Early and Midterm Outcome After Laparoscopic Fundoplication and a Minimally Invasive Endoscopic Procedure in Patients with Gastroesophageal Reflux Disease: A Prospective Observational Study.

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Early and Midterm Outcome After Laparoscopic Fundoplication and a Minimally Invasive Endoscopic Procedure in Patients with Gastroesophageal Reflux Disease: A Prospective Observational Study.

J Laparoendosc Adv Surg Tech A. 2015 Aug;25(8):657-61

Authors: Liang WT, Yan C, Wang ZG, Wu JM, Hu ZW, Zhan XL, Wang F, Ma SS, Chen MP

Abstract
BACKGROUND AND AIMS: Although the minimally invasive endoscopic Stretta procedure is being increasingly used as an alternative strategy to manage gastroesophageal reflux disease (GERD), the benefits of this procedure have to be further evaluated in clinical settings. This prospective observational study assessed the short-term and midterm outcomes associated with laparoscopic Toupet fundoplication (LTF) and the Stretta procedure.
PATIENTS AND METHODS: From January 2011 to January 2012, we allocated 80 patients to LTF and 85 to the Stretta procedure. Primary outcome measures, including symptom scores of heartburn, regurgitation, chest pain, belching, hiccup, cough, and asthma, as well as proton pump inhibitor (PPI) use, were analyzed at midterm follow-up (1-3 years).
RESULTS: Of the 165 patients, 125 patients following LTF (n=65) or the Stretta procedure (n=60) completed the designated 3-year follow-up and were included in the final analysis. At the end of the 3-year follow-up, the symptom scores were all significantly decreased compared with the corresponding values before the two procedures in both groups (P<.05). After LTF and the Stretta procedure, 47/65 (72.3%) and 41/60 (68.3%) patients, respectively, achieved complete PPI therapy independence (72.3% versus 68.3%, P=.627). Comparing with LTF, however, the Stretta procedure had less effect on improving typical symptoms of heartburn, regurgitation, and chest pain and reducing the rate of re-operation (11.8% versus 0%, P=.006).
CONCLUSIONS: LTF and the Stretta procedure were equally effective in controlling GERD symptoms and reducing PPI use. However, LTF can achieve more improvement on typical symptoms and has a lower rate of re-operation.

PMID: 26258269 [PubMed - indexed for MEDLINE]

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Laparoscopic Management of Severe Reflux After Sleeve Gastrectomy, in Selected Patients, Without Conversion to Roux-en-Y Gastric Bypass.

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Laparoscopic Management of Severe Reflux After Sleeve Gastrectomy, in Selected Patients, Without Conversion to Roux-en-Y Gastric Bypass.

J Laparoendosc Adv Surg Tech A. 2015 Aug;25(8):631-5

Authors: Hawasli A, Bush A, Hare B, Meguid A, Thatimatla N, Szpunar S

Abstract
BACKGROUND: Treatment of severe reflux after laparoscopic sleeve gastrectomy (LSG) may require conversion to Roux-en-Y gastric bypass (RYGB). We conducted a pilot study to evaluate the feasibility and effectiveness of performing laparoscopic anterior fundoplication with posterior crura approximation (LAF/pCA), in selected patients, to correct the reflux without conversion to RYGB.
PATIENTS AND METHODS: From October 2012 to April 2013, 6 patients with confirmed severe de novo reflux after LSG were treated with LAF/pCA.
RESULTS: All patients were females with a mean age of 41.5±14.2 years. All patients had lost weight after initial LSG. The percentage excess body mass index (BMI) loss (%EBL) was 61.2±33.2%. The mean time from the initial LSG to LAF/pCA was 33.2±12.5 months. Four patients had reduction of gastric fundus size. One patient required resleeving. Reflux resolved immediately in all patients with a follow-up of 18.5±2.7 months. All patients continued to lose weight, with %EBL reaching 75.5±22.9% and a mean BMI of 32±7.3 kg/m(2).
CONCLUSIONS: LAF/pCA with reduction of gastric fundus size, when needed, may be considered an alternative option to correct severe reflux after LSG in selected patients.

PMID: 26186099 [PubMed - indexed for MEDLINE]

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Impact of early enteral nutrition on short term prognosis after acute stroke.

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Impact of early enteral nutrition on short term prognosis after acute stroke.

J Clin Neurosci. 2015 Sep;22(9):1473-6

Authors: Zheng T, Zhu X, Liang H, Huang H, Yang J, Wang S

Abstract
We hypothesized that early enteral nutritional support would improve the short term prognosis of acute stroke patients with dysphagia, demonstrated by lower malnutrition rates, lower complication rates, and lower National Institutes of Health Stroke Scale (NIHSS) scores at 90 days post stroke. Nutrition support is an essential element in the care of stroke patients and many studies have investigated the effect of specific nutritional elements on stroke patients. However, few studies have looked at the impact of complete enteral nutrition on Chinese patients with acute stroke. To investigate this, we conducted a randomized controlled trial of 146 patients with acute stroke and dysphagia, among whom 75 were supported with nasogastric nutrition and 71 received family managed nutrition after randomization. Nutritional status, nosocomial infection and mortality rates were recorded on day 21 of hospitalization. Neurological deficits were evaluated by the NIHSS activities of daily living Barthel index (ADLBI) and the modified Rankin scale (mRS) and compared between the two groups. We found that the nasogastric nutrition group had a better nutritional status and reduced nosocomial infection and mortality rates after 21 days compared with patients in the family managed nutrition group. In addition, the nasogastric nutrition group showed a lower score on the NIHSS than the control group. However, the differences in the scores of the ADLBI and the 90 day mRS between the groups were not significant. Taken together, the present study shows that early enteral nutrition support improves the short term prognosis of acute stroke patients with dysphagia.

PMID: 26183306 [PubMed - indexed for MEDLINE]

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Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.

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Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.

J Immunol Res. 2015;2015:729217

Authors: Furuzawa-Carballeda J, Aguilar-León D, Gamboa-Domínguez A, Valdovinos MA, Nuñez-Álvarez C, Martín-del-Campo LA, Enríquez AB, Coss-Adame E, Svarch AE, Flores-Nájera A, Villa-Baños A, Ceballos JC, Torres-Villalobos G

Abstract
Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

PMID: 26078981 [PubMed - indexed for MEDLINE]

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Pulmonary function in infants with swallowing dysfunction.

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Pulmonary function in infants with swallowing dysfunction.

PLoS One. 2015;10(5):e0123125

Authors: Tutor JD, Srinivasan S, Gosa MM, Spentzas T, Stokes DC

Abstract
BACKGROUND: Swallowing dysfunction can lead to recurring aspiration and is frequently associated with chronic symptoms such as cough and wheezing in infants. Our objective was to describe the characteristics of infants with swallowing dysfunction, determine if pulmonary function abnormalities are detectable, and if they improve after therapy.
METHODS: We studied 38 infants with a history of coughing and wheezing who had pulmonary function tests performed within two weeks of their diagnosis of swallowing dysfunction. The raised lung volume rapid thoracoabdominal compression technique was used. After 6 months of therapy, 17 of the infants repeated the tests.
RESULTS: Initially, 25 had abnormal spirometry, 18 had abnormal plethysmography, and 15 demonstrated bronchodilator responsiveness. Six months later test were repeated for seventeen patients. Ten patients had continued abnormal spirometry, two patients remained normal, three patients' abnormal spirometry had normalized, and two patients' previously normal studies became abnormal. Eight of the 17 patients had continued abnormal plethysmography, six had continued normal plethysmography, and three patients' normal plethysmography became abnormal. After 6 months of treatment, eight patients demonstrated bronchodilator responsiveness, of which five continued to demonstrate bronchodilator responsiveness and three developed responsiveness. The remainder either continued to be non- bronchodilator responsive (two) or lost responsiveness (three.) The findings of the abnormal tests in most infants tested is complicated by frequent occurrence of other co-morbidities in this population, including gastroesophageal reflux in 23 and passive smoke exposure in 13 of the infants.
CONCLUSIONS: The interpretation of lung function changes is complicated by the frequent association of swallowing dysfunction with gastroesophageal reflux and passive smoke exposure in this population. Six months of medical therapy for swallowing dysfunction/gastroesophageal reflux did not significantly improve pulmonary function in these infants. Long-term studies will be necessary to determine which of these changes persists into adulthood.

PMID: 25978396 [PubMed - indexed for MEDLINE]

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De novo deletion of HOXB gene cluster in a patient with failure to thrive, developmental delay, gastroesophageal reflux and bronchiectasis.

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De novo deletion of HOXB gene cluster in a patient with failure to thrive, developmental delay, gastroesophageal reflux and bronchiectasis.

Eur J Med Genet. 2015 Jun-Jul;58(6-7):336-40

Authors: Pajusalu S, Reimand T, Uibo O, Vasar M, Talvik I, Zilina O, Tammur P, Õunap K

Abstract
We report a female patient with a complex phenotype consisting of failure to thrive, developmental delay, congenital bronchiectasis, gastroesophageal reflux and bilateral inguinal hernias. Chromosomal microarray analysis revealed a 230 kilobase deletion in chromosomal region 17q21.32 (arr[hg19] 17q21.32(46 550 362-46 784 039)×1) encompassing only 9 genes - HOXB1 to HOXB9. The deletion was not found in her mother or father. This is the first report of a patient with a HOXB gene cluster deletion involving only HOXB1 to HOXB9 genes. By comparing our case to previously reported five patients with larger chromosomal aberrations involving the HOXB gene cluster, we can suppose that HOXB gene cluster deletions are responsible for growth retardation, developmental delay, and specific facial dysmorphic features. Also, we suppose that bilateral inguinal hernias, tracheo-esophageal abnormalities, and lung malformations represent features with incomplete penetrance. Interestingly, previously published knock-out mice with targeted heterozygous deletion comparable to our patient did not show phenotypic alterations.

PMID: 25907420 [PubMed - indexed for MEDLINE]

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Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

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Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

J Clin Gastroenterol. 2015 Jul;49(6):451-60

Authors: Zerbib F, Roman S

Abstract
With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.

PMID: 25844840 [PubMed - indexed for MEDLINE]

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Images in vascular medicine. Dysphagia aortica with left atrial compression.

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Images in vascular medicine. Dysphagia aortica with left atrial compression.

Vasc Med. 2015 Jun;20(3):266-7

Authors: Al-Quthami A, Albloushi A, Alquthami AH

PMID: 25776850 [PubMed - indexed for MEDLINE]

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In vitro biocompatibility of nickel-titanium esthetic orthodontic archwires.

In vitro biocompatibility of nickel-titanium esthetic orthodontic archwires.

Angle Orthod. 2016 Mar 4;

Authors: Rongo R, Valletta R, Bucci R, Rivieccio V, Galeotti A, Michelotti A, D'Antò V

Abstract
OBJECTIVE:   To investigate the cytotoxicity of nickel-titanium (NiTi) esthetic orthodontic archwires with different surface coatings.
MATERIALS AND METHODS:   Three fully coated, tooth-colored NiTi wires (BioCosmetic, Titanol Cosmetic, EverWhite), two ion-implanted wires (TMA Purple, Sentalloy High Aesthetic), five uncoated NiTi wires (BioStarter, BioTorque, Titanol Superelastic, Memory Wire Superelastic, and Sentalloy), one β-titanium wire (TMA), and one stainless steel wire (Stainless Steel) were considered for this study. The wire samples were placed at 37°C in airtight test tubes containing Dulbecco's Modified Eagle's Medium (0.1 mg/mL) for 1, 7, 14, and 30 days. The cell viability of human gingival fibroblasts (HGFs) cultured with this medium was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Data were analyzed by a two-way analysis of variance (α  =  .05).
RESULTS:   The highest cytotoxic effect was reached on day 30 for all samples. The archwires exhibited a cytotoxicity on HGFs ranging from "none" to "slight," with the exception of the BioTorque, which resulted in moderate cytotoxicity on day 30. Significant differences were found between esthetic archwires and their uncoated pairs only for BioCosmetic (P  =  .001) and EverWhite (P < .001).
CONCLUSIONS:   Under the experimental conditions, all of the NiTi esthetic archwires resulted in slight cytotoxicity, as did the respective uncoated wires. For this reason their clinical use may be considered to have similar risks to the uncoated archwires.

PMID: 26942561 [PubMed - as supplied by publisher]

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Nonsurgical miniscrew-assisted rapid maxillary expansion results in acceptable stability in young adults.

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Nonsurgical miniscrew-assisted rapid maxillary expansion results in acceptable stability in young adults.

Angle Orthod. 2016 Mar 3;

Authors: Choi SH, Shi KK, Cha JY, Park YC, Lee KJ

Abstract
OBJECTIVE:   To evaluate the stability of nonsurgical miniscrew-assisted rapid maxillary expansion (MARME) in young adults with a transverse maxillary deficiency.
MATERIALS AND METHODS:   From a total of 69 adult patients who underwent MARME followed by orthodontic treatment with a straight-wire appliance, 20 patients (mean age, 20.9 ± 2.9 years) with follow-up records (mean, 30.2 ± 13.2 months) after debonding were selected. Posteroanterior cephalometric records and dental casts were obtained at the initial examination (T0), immediately after MARME removal (T1), immediately after debonding (T2), and at posttreatment follow-up (T3).
RESULTS:   Suture separation was observed in 86.96% of subjects (60/69). An increase in the maxillary width (J-J; 1.92 mm) accounted for 43.34% of the total expansion with regard to the intermolar width (IMW) increase (4.43 mm; P < .001) at T2. The amounts of J-J and IMW posttreatment changes were -0.07 mm (P > .05) and -0.42 mm (P  =  .01), respectively, during retention. The postexpansion change in middle alveolus width increased with age (P < .05). The postexpansion change of interpremolar width (IPMW) was positively correlated with the amount of IPMW expansion (P < .05) but not with IMW. The changes of the clinical crown heights in the maxillary canines, first premolars, and first molars were not significant at each time point.
CONCLUSIONS:   Nonsurgical MARME can be a clinically acceptable and stable treatment modality for young adults with a transverse maxillary deficiency.

PMID: 26938955 [PubMed - as supplied by publisher]

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The treatment timing of labial inversely impacted maxillary central incisors: A prospective study.

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The treatment timing of labial inversely impacted maxillary central incisors: A prospective study.

Angle Orthod. 2016 Mar 3;

Authors: Sun H, Hu R, Ren M, Lin Y, Wang X, Sun C, Wang Y

Abstract
OBJECTIVE:   To determine the timing of treatment for the labial inversely impacted maxillary central incisors.
METHODS:   Twenty-eight patients (mean age, 8.2 years) with labial inversely impacted maxillary central incisors were divided into early-treated and later-treated groups according to their dental age. All of the patients were treated with a combination of surgery and orthodontic traction using the Guide rod appliance. Cone-beam computed tomography images were taken immediately after treatment for assessing the root morphology, root length, and alveolar bone loss. Sagittal slices were evaluated at the widest labial-lingual width of the tooth in the axial view. All variables were evaluated by Simplant 13.0 software (Materialise Dental NV, Leuven, Belgium).
RESULTS:   The rank sum test indicated that the root length of two groups showed a statistically significant difference between the impacted and homonym tooth, with a shorter length in the impacted tooth (P < .05). The D-value (difference of root length between the impacted and homonym tooth) and alveolar bone loss on the labial side of the impacted incisor are significantly less in the early-treated groups when compared with the later-treated groups (P < .05). Spearman rank correlation analysis showed a statistically positive association between the treatment timing and D-value (r  =  .623, P < .05). The chi-square test for morphology of root apex indicated that the incidence of the root-apex-directed labial side is significantly higher in the later-treated groups when compared with the early-treated groups.
CONCLUSION:   The labial inversely impacted maxillary central incisors should be treated early to promote root development by achieving a better morphology of root apex, thus reducing the risk of alveolar bone loss on the labial side.

PMID: 26938954 [PubMed - as supplied by publisher]

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Pulsed electromagnetic field (PEMF) prevents pro-oxidant effects of H2O2 in SK-N-BE(2) human neuroblastoma cells

10.3109/09553002.2016.1150619<br/>Stefano Falone

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Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity.

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Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity.

J Neural Eng. 2016 Mar 2;13(2):026029

Authors: Migliorelli C, Alonso JF, Romero S, Mañanas MA, Nowak R, Russi A

Abstract
OBJECTIVE: Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference.
APPROACH: A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results.
MAIN RESULTS: The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches.
SIGNIFICANCE: The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.

PMID: 26934426 [PubMed - as supplied by publisher]

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Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts.

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Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts.

J Neural Eng. 2016 Mar 2;13(2):026028

Authors: Geeter N, Dupré L, Crevecoeur G

Abstract
OBJECTIVE: Transcranial magnetic stimulation (TMS) is a promising non-invasive tool for modulating the brain activity. Despite the widespread therapeutic and diagnostic use of TMS in neurology and psychiatry, its observed response remains hard to predict, limiting its further development and applications. Although the stimulation intensity is always maximum at the cortical surface near the coil, experiments reveal that TMS can affect deeper brain regions as well.
APPROACH: The explanation of this spread might be found in the white matter fiber tracts, connecting cortical and subcortical structures. When applying an electric field on neurons, their membrane potential is altered. If this change is significant, more likely near the TMS coil, action potentials might be initiated and propagated along the fiber tracts towards deeper regions. In order to understand and apply TMS more effectively, it is important to capture and account for this interaction as accurately as possible. Therefore, we compute, next to the induced electric fields in the brain, the spatial distribution of the membrane potentials along the fiber tracts and its temporal dynamics.
MAIN RESULTS: This paper introduces a computational TMS model in which electromagnetism and neurophysiology are combined. Realistic geometry and tissue anisotropy are included using magnetic resonance imaging and targeted white matter fiber tracts are traced using tractography based on diffusion tensor imaging. The position and orientation of the coil can directly be retrieved from the neuronavigation system. Incorporating these features warrants both patient- and case-specific results.
SIGNIFICANCE: The presented model gives insight in the activity propagation through the brain and can therefore explain the observed clinical responses to TMS and their inter- and/or intra-subject variability. We aspire to advance towards an accurate, flexible and personalized TMS model that helps to understand stimulation in the connected brain and to target more focused and deeper brain regions.

PMID: 26934301 [PubMed - as supplied by publisher]

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The impact of a breast cancer diagnosis on health-related quality of life. A prospective comparison among middle-aged to elderly women with and without breast cancer.

The impact of a breast cancer diagnosis on health-related quality of life. A prospective comparison among middle-aged to elderly women with and without breast cancer.

Acta Oncol. 2016 Mar 4;:1-8

Authors: Karlsen RV, Frederiksen K, Larsen MB, von Heymann-Horan AB, Appel CW, Christensen J, Tjønneland A, Ross L, Johansen C, Bidstrup PE

Abstract
Background The improved survival after breast cancer has prompted knowledge on the effect of a breast cancer diagnosis on health-related quality of life (HQoL). This study compared changes in HQoL among women from before to after breast cancer diagnosis with longitudinal changes among women who remained breast cancer-free. Material and methods The Danish Diet, Cancer and Health study included 57 053 cancer-free persons aged 50-64 years at baseline (1993-1997). We used data from first follow-up (1999-2002) and second follow-up (2010-2012) on HQoL [Medical Outcomes Survey, short form (SF-36)] obtained from 542 women aged 64-82 years with primary breast cancer (stages I-III) and a randomly matched sample of 729 women who remained breast cancer-free. Linear regression models were used to estimate the differences in changes in HQoL between women with and without breast cancer; the analyses were repeated with stratification according to age, comorbidity, partner support and time since diagnosis. Results Women with breast cancer reported significantly larger decreases in HQoL from before to after diagnosis than those who remained breast cancer-free (physical component summary, -2.0; 95% CI -2.8; -1.2, mental component summary, -1.5, 95% CI -2.3; -0.6). This association was significantly modified by comorbidity and time since diagnosis. Conclusions Women with breast cancer reported significantly larger HQoL declines than breast cancer-free women. Breast cancer diagnosis seems to have the greatest impact on HQoL closest to diagnosis and in women with comorbidity indicating that this group should be offered timely and appropriate follow-up care to prevent HQoL declines.

PMID: 26942569 [PubMed - as supplied by publisher]

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Fear of cancer recurrence in prostate cancer survivors.

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Fear of cancer recurrence in prostate cancer survivors.

Acta Oncol. 2016 Mar 3;:1-7

Authors: van de Wal M, van Oort I, Schouten J, Thewes B, Gielissen M, Prins J

Abstract
Background High fear of cancer recurrence (FCR) is an understudied topic in prostate cancer (PCa) survivors. This study aimed to detect the prevalence, consequences and characteristics associated with high FCR in PCa survivors. Material and methods This cross-sectional study included patients diagnosed with localized PCa and treated with curative radical prostatectomy between 1992 and 2012. We administered the Cancer Worry Scale (CWS) to assess FCR severity (primary outcome measure). Secondary outcomes included distress, quality of life (QOL), post-traumatic symptoms, and multidimensional aspects of FCR. χ(2)-tests, t-tests and Pearson's correlations examined the relationship between FCR and medical/demographic characteristics. MANOVA analyses and χ2-tests identified differences between PCa survivors with high and low FCR. Results Two hundred eighty-three PCa survivors (median age of 70.0 years) completed the questionnaires a median time of 7.1 years after surgery. About a third (36%) of all PCa survivors experienced high FCR. High FCR was associated with lower QOL, more physical problems, higher distress and more post-traumatic stress symptoms. PCa survivors with high FCR reported disease-related triggers (especially medical examinations), felt helpless and experienced problems in social relationships. High FCR was associated with a younger age and having received adjuvant radiotherapy. Conclusions Results illustrate that FCR is a significant problem in PCa survivors. Younger men and those treated with adjuvant radiotherapy are especially at risk. Those with high FCR experience worse QOL and higher symptom burden. Health care providers should pay specific attention to this problem and provide appropriate psychosocial care when needed.

PMID: 26935517 [PubMed - as supplied by publisher]

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Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality.

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Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality.

Acta Oncol. 2016 Mar 3;:1-8

Authors: Strömberg U, Peterson S, Holmberg E, Holmén A, Persson B, Sandberg C, Nilbert M

Abstract
Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis and outcome. Material and methods All patients with primary invasive CMM diagnosed in 2004-2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality. Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage-specific incidence of CMM. The incidence of stage I-II tumors was higher in the western health care region, whereas the incidence of stage III-IV CMMs was higher in the southern region. The divergent incidence patterns per stage at diagnosis were consistent across population strata based on educational level. The geographic disparities in CMM stage influenced relative survival with an excess five-year mortality ratio in the southern region versus the western region of 1.49 (95% confidence interval 1.22-1.82). The excess mortality ratio for patients with low versus high educational level was 1.81 (1.37-2.40). Conclusion Residential region and educational level influenced CMM stage and, thereby, excess mortality. These observations suggest that geographic as well as socioeconomic data should be considered in prevention of CMM.

PMID: 26935355 [PubMed - as supplied by publisher]

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Effect of socioeconomic position on survival after childhood cancer in Denmark.

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Effect of socioeconomic position on survival after childhood cancer in Denmark.

Acta Oncol. 2016 Mar 3;:1-9

Authors: Simony SB, Lund LW, Erdmann F, Andersen KK, Winther JF, Schüz J, Johansen C, Schmiegelow K, Dalton SO

Abstract
Background One fifth of all deaths among children in Europe are accounted for by cancer. If this is to be reduced there is a need for studies on not only biology and treatment approaches but also on how social factors influence cure rates. We investigated how various socioeconomic characteristics were associated with survival after childhood cancer. Material and methods In a nationwide cohort of 3797 children diagnosed with cancer [hematological cancer, central nervous system (CNS) tumors, non-CNS solid tumors] before age 20 between 1990 and 2009 we identified parents and siblings and obtained individual level parental socioeconomic variables and vital status through 2012 by linkage to population-based registries. Hazard ratios (HR) and 95% confidence intervals (CI) for dying were estimated using multivariate Cox proportional hazard models. Results For all children with cancer combined, survival was slightly but not statistically significantly better the higher the education of the mother or the father, and with maternal income. Significantly better survival was observed when parents were living together compared to living alone and worse survival when the child had siblings compared to none. Young (<20) or older (≥40) maternal age showed non-significant associations, but based on small numbers. For hematological cancers, no significant associations were observed. For CNS tumors, better survival was seen with parents living together (HR 0.70, CI 0.51-0.97). For non-CNS solid tumors, survival was better with high education of the mother (HR 0.66, CI 0.44-0.99) compared to basic and worse for children with one (HR 1.45, CI 1.11-1.89) or two or more siblings (HR 1.29, CI 0.93-1.79) (p for trend 0.02) compared to none. Conclusion The impact of socioeconomic characteristics on childhood cancer survival, despite equal access to protocolled and free-of-charge treatment, warrants further and more direct studies of underlying mechanisms in order to target these as a means to improve survival rates.

PMID: 26935257 [PubMed - as supplied by publisher]

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Risk structures for radiation-induced trismus in head and neck cancer.

Related Articles

Risk structures for radiation-induced trismus in head and neck cancer.

Acta Oncol. 2016 Mar 3;:1-5

Authors: Pauli N, Olsson C, Pettersson N, Johansson M, Haugen H, Wilderäng U, Steineck G, Finizia C

PMID: 26935147 [PubMed - as supplied by publisher]

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Deep inspiration breath-hold volumetric modulated arc radiotherapy decreases dose to mediastinal structures in locally advanced lung cancer.

Related Articles

Deep inspiration breath-hold volumetric modulated arc radiotherapy decreases dose to mediastinal structures in locally advanced lung cancer.

Acta Oncol. 2016 Mar 3;:1-4

Authors: Persson GF, Scherman Rydhög J, Josipovic M, Maraldo MV, Nygård L, Costa J, Berthelsen AK, Specht L, Aznar MC

PMID: 26935017 [PubMed - as supplied by publisher]

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Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

Related Articles

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

Acta Oncol. 2016 Mar 3;:1-8

Authors: Izewska J, Wesolowska P, Azangwe G, Followill DS, Thwaites DI, Arib M, Stefanic A, Viegas C, Suming L, Ekendahl D, Bulski W, Georg D

Abstract
The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs.
MATERIAL AND METHODS: The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants.
RESULTS: The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements.
DISCUSSION: Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

PMID: 26934916 [PubMed - as supplied by publisher]

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Dosimetric advantages of proton therapy compared with photon therapy using an adaptive strategy in cervical cancer.

Related Articles

Dosimetric advantages of proton therapy compared with photon therapy using an adaptive strategy in cervical cancer.

Acta Oncol. 2016 Mar 3;:1-8

Authors: van de Schoot AJ, de Boer P, Crama KF, Visser J, Stalpers LJ, Rasch CR, Bel A

Abstract
Background Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation therapy (RT). In this study, the potential dosimetric advantages of IGAPT compared with photon-based image-guided adaptive RT (IGART) were investigated. Material and methods For 13 cervical cancer patients, full and empty bladder planning computed tomography (CT) images and weekly CTs were acquired. Based on both primary clinical target volumes (pCTVs) [i.e. gross tumor volume (GTV), cervix, corpus-uterus and upper part of the vagina] on planning CTs, the pretreatment observed full range primary internal target volume (pITV) was interpolated to derive pITV subranges. Given corresponding ITVs (i.e. pITVs including lymph nodes), patient-specific photon and proton plan libraries were generated. Using all weekly CTs, IGART and IGAPT treatments were simulated by selecting library plans and recalculating the dose. For each recalculated IGART and IGAPT fraction, CTV (i.e. pCTV including lymph nodes) coverage was assessed and differences in fractionated substitutes of dose-volume histogram (DVH) parameters (V15Gy, V30Gy, V45Gy, Dmean, D2cc) for bladder, bowel and rectum were tested for significance (Wilcoxon signed-rank test). Also, differences in toxicity-related DVH parameters (rectum V30Gy, bowel V45Gy) were approximated based on accumulated dose distributions. Results In 92% (96%) of all recalculated IGAPT (IGART) fractions adequate CTV coverage (V95% >98%) was obtained. All dose parameters for bladder, bowel and rectum, except the fractionated substitute for rectum V45Gy, were improved using IGAPT. Also, IGAPT reduced the mean dose to bowel, bladder and rectum significantly (p < 0.01). In addition, an average decrease of rectum V30Gy and bowel V45Gy indicated reductions in toxicity probabilities when using IGAPT. Conclusion This study demonstrates the feasibility of IGAPT in cervical cancer using a plan-library based plan-of-the-day approach. Compared to photon-based IGART, IGAPT maintains target coverage while significant dose reductions for the bladder, bowel and rectum can be achieved.

PMID: 26934821 [PubMed - as supplied by publisher]

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Type distribution of lymphoid leukemia from Cancer Incidence in Five Continents Vol. X.

Type distribution of lymphoid leukemia from Cancer Incidence in Five Continents Vol. X.

Jpn J Clin Oncol. 2016 Mar;46(3):290

Authors: Matsuda T, Niino M

PMID: 26941374 [PubMed - in process]

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Obituary.

Obituary.

Jpn J Clin Oncol. 2016 Mar;46(3):287

Authors: Kakizoe T

PMID: 26941373 [PubMed - in process]

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Cigarette smoking and bladder cancer risk: an evaluation based on a systematic review of epidemiologic evidence in the Japanese population.

Cigarette smoking and bladder cancer risk: an evaluation based on a systematic review of epidemiologic evidence in the Japanese population.

Jpn J Clin Oncol. 2016 Mar;46(3):273-83

Authors: Masaoka H, Matsuo K, Ito H, Wakai K, Nagata C, Nakayama T, Sadakane A, Tanaka K, Tamakoshi A, Sugawara Y, Mizoue T, Sawada N, Inoue M, Tsugane S, Sasazuki S, Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan

Abstract
OBJECTIVE: Although several epidemiological studies have demonstrated that cigarette smoking is an important risk factor for bladder cancer, no systematic review in the Japanese population has yet been performed. Accurate evaluation of bladder cancer risk in relation to smoking for Japanese populations can provide necessary information for Japanese policy-makers and doctors to enlighten the importance of smoking cessation. We reviewed epidemiologic data to estimate the strength of the association between cigarette smoking and bladder cancer in the Japanese population.
METHODS: We identified previous cohort and case-control studies, extracting data from databases in the MEDLINE (PubMed) and Ichushi. The magnitude of association and strength of evidence were evaluated in each study, and a meta-analysis was conducted to obtain summary estimates for the overall magnitude of association.
RESULTS: Three cohort and eight case-control studies were identified. Except for one case-control study, all studies showed a strong positive association between cigarette smoking and bladder cancer. The summary relative risk for ever smokers relative to never smokers was 2.14 (95% confidence interval 1.87-2.44) in a fixed-effect model.
CONCLUSIONS: We conclude that cigarette smoking is a convincing risk factor for bladder cancer among Japanese.

PMID: 26941372 [PubMed - in process]

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upper respiratory tract infection; +103 new citations

103 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2016/03/05

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Pseudoaneurysm of the internal maxillary artery: A case report of facial trauma and recurrent bleeding.

Pseudoaneurysm of the internal maxillary artery: A case report of facial trauma and recurrent bleeding.

Int J Surg Case Rep. 2016 Feb 21;21:63-66

Authors: Alonso N, de Oliveira Bastos E, Massenburg BB

Abstract
INTRODUCTION: Pseudoaneurysms occur when there is a partial disruption in the wall of a blood vessel, causing a hematoma that is either contained by the vessel adventitia or the perivascular soft tissue.
PRESENTATION OF CASE: A 32-year-old male presented to the emergency department presented with comminuted fractures in the left zygoma, ethmoids, and the right ramus of the mandible following a gunshot wound. The patient underwent open reduction of his fractures and the patient was discharged on the eighth day after the trauma. Thirteen days after the discharge and 21 days after the gunshot wound, the patient returned to the ER due to heavy nasopharyngeal bleeding that compromised the patency of the patient's airways and caused hemodynamic instability. Arteriography of the facial blood vessels revealed a pseudoaneurysm of the maxillary artery. Endovascular embolization with a synthetic embolic agent resulted in adequate hemostasis, and nine days after embolization the patient was discharged.
DISCUSSION: The diagnosis of pseudoaneurysm is suggested by history and physical examination, and confirmed by one of several imaging methods, such as CT scan with contrast. Progressive enlargement of the lesion may lead to several complications, including rupture of the aneurysm and hemorrhage, compression of adjacent nerves, or release of embolic thrombi.
CONCLUSION: This case reports the long-term follow up and natural history of a patient with a post-traumatic pseudoaneurysm of the internal maxillary artery and the successful use of endovascular embolization to treat the lesion.

PMID: 26942333 [PubMed - as supplied by publisher]

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Treatment of ununited femoral neck fractures in young adults using low-intensity pulsed ultrasound: Report of 2 cases.

Treatment of ununited femoral neck fractures in young adults using low-intensity pulsed ultrasound: Report of 2 cases.

Int J Surg Case Rep. 2016 Feb 20;21:59-62

Authors: Lee SY, Niikura T, Iwakura T, Kuroda R, Kurosaka M

Abstract
INTRODUCTION: Delayed union and non-union of displaced femoral neck fractures remains a difficult clinical problem for orthopaedic surgeons. In the physiologically young patient, every effort should be made to preserve the native hip joint. We present two cases of ununited femoral neck fractures in young adults who were successfully treated with low-intensity pulsed ultrasound (LIPUS) and showed satisfactory results. PRESENTATION OF CASE 1: A 41-year-old woman was involved in a motor vehicle crash and was diagnosed with displaced femoral neck fracture. Eleven months after internal fixation, a computed tomography (CT) scan revealed the presence of non-union of the femoral neck. LIPUS treatment was therefore initiated. After eight months, the fracture was completely consolidated. PRESENTATION OF CASE 2: A 39-year-old man was involved in a cycling accident and was diagnosed with displaced femoral neck fracture. Thirteen weeks after internal fixation, a CT scan revealed delayed union of the femoral neck. LIPUS treatment was therefore initiated. After six months, the fracture was completely consolidated.
CONCLUSION: We suggest use of LIPUS as a possible treatment approach for delayed union and non-union of displaced femoral neck fractures in young patients before considering further surgical intervention.

PMID: 26942332 [PubMed - as supplied by publisher]

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Control-group feature normalization for multivariate pattern analysis of structural MRI data using the support vector machine

Publication date: 15 May 2016
Source:NeuroImage, Volume 132
Author(s): Kristin A. Linn, Bilwaj Gaonkar, Theodore D. Satterthwaite, Jimit Doshi, Christos Davatzikos, Russell T. Shinohara
Normalization of feature vector values is a common practice in machine learning. Generally, each feature value is standardized to the unit hypercube or by normalizing to zero mean and unit variance. Classification decisions based on support vector machines (SVMs) or by other methods are sensitive to the specific normalization used on the features. In the context of multivariate pattern analysis using neuroimaging data, standardization effectively up- and down-weights features based on their individual variability. Since the standard approach uses the entire data set to guide the normalization, it utilizes the total variability of these features. This total variation is inevitably dependent on the amount of marginal separation between groups. Thus, such a normalization may attenuate the separability of the data in high dimensional space. In this work we propose an alternate approach that uses an estimate of the control-group standard deviation to normalize features before training. We study our proposed approach in the context of group classification using structural MRI data. We show that control-based normalization leads to better reproducibility of estimated multivariate disease patterns and improves the classifier performance in many cases.



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Magnetic susceptibility of brain iron is associated with childhood spatial IQ

Publication date: 15 May 2016
Source:NeuroImage, Volume 132
Author(s): Kimberly L.H. Carpenter, Wei Li, Hongjiang Wei, Bing Wu, Xue Xiao, Chunlei Liu, Gordon Worley, Helen Link Egger
Iron is an essential micronutrient for healthy brain function and development. Because of the importance of iron in the brain, iron deficiency results in widespread and lasting effects on behavior and cognition. We measured iron in the basal ganglia of young children using a novel MRI method, quantitative susceptibility mapping, and examined the association of brain iron with age and cognitive performance. Participants were a community sample of 39 young children recruited from pediatric primary care who were participating in a 5-year longitudinal study of child brain development and anxiety disorders. The children were ages 7 to 11years old (mean age: 9.5years old) at the time of the quantitative susceptibility mapping scan. The differential abilities scale was administered when the children were 6years old to provide a measure of general intelligence and verbal (receptive and expressive), non-verbal, and spatial performance. Magnetic susceptibility values, which are linearly related to iron concentration in iron-rich areas, were extracted from regions of interest within iron-rich deep gray matter nuclei from the basal ganglia, including the caudate, putamen, substantia nigra, globus pallidus, and thalamus. Controlling for scan age, there was a significant positive association between iron in the basal ganglia and spatial IQ, with this effect being driven by iron in the right caudate We also replicated previous findings of a significant positive association between iron in the bilateral basal ganglia and age. Our finding of a positive association between spatial IQ and mean iron in the basal ganglia, and in the caudate specifically, suggests that iron content in specific regions of the iron-rich deep nuclei of the basal ganglia influences spatial intelligence. This provides a potential neurobiological mechanism linking deficits in spatial abilities reported in children who were severely iron deficient as infants to decreased iron within the caudate.



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Predicting ground contact events for a continuum of gait types: An application of targeted machine learning using principal component analysis

Publication date: Available online 4 March 2016
Source:Gait & Posture
Author(s): Sean T. Osis, Blayne A. Hettinga, Reed Ferber
An ongoing challenge in the application of gait analysis to clinical settings is the standardized detection of temporal events, with unobtrusive and cost-effective equipment, for a wide range of gait types. The purpose of the current study was to investigate a targeted machine learning approach for the prediction of timing for foot strike (or initial contact) and toe-off, using only kinematics for walking, forefoot running, and heel-toe running. Data were categorized by gait type and split into a training set (∼30%) and a validation set (∼70%). A principal component analysis was performed, and separate linear models were trained and validated for foot strike and toe-off, using ground reaction force data as a gold-standard for event timing. Results indicate the model predicted both foot strike and toe-off timing to within 20ms of the gold-standard for more than 95% of cases in walking and running gaits. The machine learning approach continues to provide robust timing predictions for clinical use, and may offer a flexible methodology to handle new events and gait types.



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Allelic expression of mammalian imprinted genes in a matrotrophic lizard, Pseudemoia entrecasteauxii

Abstract

Genomic imprinting is a process that results in the differential expression of genes depending on their parent of origin. It occurs in both plants and live-bearing mammals, with imprinted genes typically regulating the ability of an embryo to manipulate the maternal provision of nutrients. Genomic imprinting increases the potential for selection to act separately on paternally and maternally expressed genes, which increases the number of opportunities that selection can facilitate embryonic control over maternal nutrient provision. By looking for imprinting in an independent matrotrophic lineage, the viviparous lizard Pseudemoia entrecasteauxii (Scincidae), we test the hypothesis that genomic imprinting facilitates the evolution of substantial placental nutrient transport to embryos (matrotrophy). We sequenced transcriptomes from the embryonic component of lizard placentae to determine whether there are parent-of-origin differences in expression of genes that are imprinted in mammals. Of these genes, 19 had sufficiently high expression in the lizard to identify polymorphisms in transcribed sequences. We identified bi-allelic expression in 17 genes (including insulin-like growth factor 2), indicating that neither allele was imprinted. These data suggest that either genomic imprinting has not evolved in this matrotrophic skink or, if it has, it has evolved in different genes to mammals. We outline how these hypotheses can be tested. This study highlights important differences between mammalian and reptile pregnancy and the absence of any shared imprinting genes reflects fundamental differences in the way that pregnancy has evolved in these two lineages.

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Healthcare Cost of Over-Diagnosis of Low-Grade Dysplasia in Barrett’s Esophagus

Abstract

Introduction

Published reports have demonstrated that many Barrett's esophagus patients are over-diagnosed as low-grade dysplasia (BE-LGD). We performed an analysis of the surveillance and treatment costs associated with the over-diagnosis of BE-LGD.

Methods

As the principal cost variables, we used endoscopic and histologic procedures performed during the recommended surveillance intervals for patients with BE-LGD, the national average Medicare reimbursement for the Current Procedural Terminology codes of the procedures performed, and a spreadsheet-based tool we created to determine the overall healthcare cost associated with the over-diagnosis of BE-LGD in the US population.

Results

The average excess cost (range) for every patient in the US who is over-diagnosed with BE-LGD is estimated to be $5557 ($3115 to $8072). The principal contributors to the excess cost of over-diagnosis of BE-LGD in these patients are: endoscopy ($2626 to $4639), pathologist biopsy review ($275 to $2185), and esophagogastroduodenoscopy-guided endoscopic ablation ($214 to $1249).

Conclusions

The healthcare cost of over-diagnosis of BE-LGD is significant. To reduce the overall healthcare cost impact of over-diagnosis of BE-LGD, strict adherence to the recommendations of the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy that pathology review of all BE biopsy specimens be performed by a gastrointestinal pathologist is warranted.

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Current and Emerging Therapies for IgE-Mediated Food Allergy

Abstract

Food allergies are a growing clinical problem leading to increased health care utilization and decreases in patient quality of life. Current treatment recommendations include strict dietary avoidance of the offending food as well as use of self-injectable epinephrine in case of accidental exposure with allergic reaction. Although many individuals will eventually outgrow their food allergies, a substantial number will not. Significant effort has been made to find novel treatments that protect patients from food-triggered reactions as well as to develop immune-modulating therapies that could lead to tolerance. In this review, three therapies that have shown the most promise for the treatment of food allergies are highlighted: oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy.

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The variations in the nuclear proteome reveal new transcription factors and mechanisms involved in UV stress response in Pinus radiata

Publication date: Available online 4 March 2016
Source:Journal of Proteomics
Author(s): Jesús Pascual, Sara Alegre, Matthias Nagler, Mónica Escandón, María Luz Annacondia, Wolfram Weckwerth, Luis Valledor, María Jesús Cañal
The importance of UV stress and its side-effects over the loss of plant productivity in forest species demands a deeper understanding of how pine trees respond to UV irradiation. Although the response to UV stress has been characterized at system and cellular levels, the dynamics within the nuclear proteome triggered by UV is still unknown despite that they are essential for gene expression and regulation of plant physiology. To fill this gap this work aims to characterize the variations in the nuclear proteome as a response to UV irradiation by using state-of-the-art mass spectrometry-based methods combined with novel bioinformatics workflows. The combination of SEQUEST, de novo sequencing, and novel annotation pipelines allowed cover sensing and transduction pathways, endoplasmic reticulum-related mechanisms and the regulation of chromatin dynamism and gene expression by histones, histone-like NF-Ys, and other transcription factors previously unrelated to this stress source, as well as the role of alternative splicing and other mechanisms involved in RNA translation and protein synthesis. The determination of 33 transcription factors, including NF-YB13, Pp005698_3 (NF-YB) and Pr009668_2 (WD-40), which are correlated to stress responsive mechanisms like an increased accumulation of photoprotective pigments and reduced photosynthesis, pointing them as strong candidate biomarkers for breeding programs aimed to improve UV resistance of pine trees.SignificanceThe description of the nuclear proteome of Pinus radiata combining a classic approach based on the use of SEQUEST and the use of a mass accuracy precursor alignment (MAPA) allowed an unprecedented protein coverage. This workflow provided the methodological basis for characterizing the changes in the nuclear proteome triggered by UV irradiation, allowing the depiction of the nuclear events involved in stress response and adaption. The relevance of some of the discovered proteins will suppose a major advance in stress biology field, also providing a set of transcription factors that can be considered as strong biomarker candidates to select trees more tolerant to UV radiation in forest upgrade programs.

Graphical abstract

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Editorial Board

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136





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Sensing parasites: Proteomic and advanced bio-detection alternatives

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Carlos Sánchez-Ovejero, Fernando Benito-Lopez, Paula Díez, Adriano Casulli, Mar Siles-Lucas, Manuel Fuentes, Raúl Manzano-Román
Parasitic diseases have a great impact in human and animal health. The gold standard for the diagnosis of the majority of parasitic infections is still conventional microscopy, which presents important limitations in terms of sensitivity and specificity and commonly requires highly trained technicians. More accurate molecular-based diagnostic tools are needed for the implementation of early detection, effective treatments and massive screenings with high-throughput capacities. In this respect, sensitive and affordable devices could greatly impact on sustainable control programmes which exist against parasitic diseases, especially in low income settings.Proteomics and nanotechnology approaches are valuable tools for sensing pathogens and host alteration signatures within microfluidic detection platforms. These new devices might provide novel solutions to fight parasitic diseases. Newly described specific parasite derived products with immune-modulatory properties have been postulated as the best candidates for the early and accurate detection of parasitic infections as well as for the blockage of parasite development.This review provides the most recent methodological and technological advances with great potential for bio-sensing parasites in their hosts, showing the newest opportunities offered by modern "-omics" and platforms for parasite detection and control.

Graphical abstract

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Proteomic analysis of dystrophin deficiency and associated changes in the aged mdx-4cv heart model of dystrophinopathy-related cardiomyopathy

Publication date: Available online 4 March 2016
Source:Journal of Proteomics
Author(s): Sandra Murphy, Paul Dowling, Margit Zweyer, Rustam R. Mundegar, Michael Henry, Paula Meleady, Dieter Swandulla, Kay Ohlendieck
Cardiomyopathy is a serious complication in Duchenne muscular dystrophy, an X-linked neuromuscular disease of childhood that is triggered by primary abnormalities in the dystrophin gene. In order to directly correlate the deficiency in the membrane cytoskeletal protein dystrophin to secondary abnormalities in the dystrophic heart, this study has used label-free mass spectrometry to compare protein expression patterns in the aged mdx-4cv heart model of dystrophinopathy versus wild type heart. This report is the first successful identification of members of the cardiac dystrophin–glycoprotein complex by comparative whole tissue proteomics. The mass spectrometric analysis confirmed the loss of dystrophin and concomitant reduction of syntrophin and sarcoglycans in the dystrophin-deficient heart. Proteomic profiling of secondary changes identified distinct alterations in the basal lamina component laminin, the Ca²⁺-binding protein sarcalumenin, the matricellular protein periostin, the proteoglycans asporin and lumican, the cardiac-specific myosin light chain kinase, heat shock proteins and a large number of mitochondrial and glycolytic enzymes. The proteomic findings indicate that the molecular pathogenesis of muscular dystrophy-associated cardiomyopathy is highly complex and involves impairments, modulations and/or adaptations of mitochondrial metabolism, glycolysis, protein chaperoning and ion homeostasis, as well as the maintenance of the contractile apparatus, the intracellular cytoskeleton and the extracellular matrisome.SignificanceThe X-linked inherited disorder Duchenne muscular dystrophy is the most frequently inherited neuromuscular disease of childhood. Primary abnormalities in the dystrophin gene trigger progressive skeletal muscle wasting and impaired cardiorespiratory functions. In order to improve our general understanding of the molecular pathogenesis of muscular dystrophy-associated cardiomyopathy and to identify new marker candidates of cardiac changes in dystrophinopathy, we have carried out a comparative proteomic study of the mdx-4cv mouse model of Duchenne muscular dystrophy. The mass spectrometric profiling of whole heart preparations has identified the reduction in the dystrophin–glycoprotein complex and a large variety of secondary changes in the dystrophic heart. Cardiac proteins with a changed abundance were shown to be involved in fibre contraction, energy metabolism, cellular signalling, the cytoskeletal network, the extracellular matrix and the stress response. In the future, the newly identified cardiac proteins may be useful to improve predictive, diagnostic, prognostic or therapy-monitoring approaches in the field of muscular dystrophy and cardiomyopathy.



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Proteomic analysis of the TerC interactome: Novel links to tellurite resistance and pathogenicity

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): L. Turkovicova, R. Smidak, G. Jung, J. Turna, G. Lubec, J. Aradska
The tellurite resistance gene operon (ter) is widely spread among bacterial species, particularly pathogenic species. The ter operon has been implicated in tellurite resistance, phage inhibition, colicine resistance, and pathogenicity. The TerC protein represents one of the key proteins in tellurite resistance and shows no significant homology to any protein of known function. So far, there is no experimental evidence for TerC interaction partners. In this study, proteomic-based methods, including blue native electrophoresis and co-immunoprecipitation combined with LC–MS/MS, have been used to identify TerC interaction partners and thus providing indirect evidence for tentative functions of TerC in Escherichia coli.An interactome has been constructed and robust physical interaction of integral membrane protein TerC with TerB, DctA, PspA, HslU, and RplK has been shown. The TerC–TerB complex appears to act as a central unit that may link different functional modules with biochemical activities of C4-dicarboxylate transport, inner membrane stress response (phage shock protein regulatory complex), ATPase/chaperone activity, and proteosynthesis. In previous reports, it was hypothesized that a transmembrane unit formed by TerC protein may interact with the TerD family, but herein neither TerD nor TerE proteins were identified as TerC complex components. We propose that TerD/TerE participates in tellurite resistance through TerC-independent action.

Graphical abstract

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Tandem affinity purification of histones, coupled to mass spectrometry, identifies associated proteins and new sites of post-translational modification in Saccharomyces cerevisiae

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): M. Luz Valero, Ramon Sendra, Mercè Pamblanco
Histones and their post-translational modifications contribute to regulating fundamental biological processes in all eukaryotic cells. We have applied a conventional tandem affinity purification strategy to histones H3 and H4 of the yeast Saccharomyces cerevisiae. Mass spectrometry analysis of the co-purified proteins revealed multiple associated proteins, including core histones, which indicates that tagged histones may be incorporated to the nucleosome particle. Among the many other co-isolated proteins there are histone chaperones, elements of chromatin remodeling, of nucleosome assembly/disassembly, and of histone modification complexes. The histone chaperone Rtt106p, two members of chromatin assembly FACT complex and Psh1p, an ubiquitin ligase, were the most abundant proteins obtained with both H3-TAP and H4-TAP, regardless of the cell extraction medium stringency. Our mass spectrometry analyses have also revealed numerous novel post-translational modifications, including 30 new chemical modifications in histones, mainly by ubiquitination. We have discovered not only new sites of ubiquitination but that, besides lysine, also serine and threonine residues are targets of ubiquitination on yeast histones. Our results show the standard tandem affinity purification procedure is suitable for application to yeast histones, in order to isolate and characterize histone-binding proteins and post-translational modifications, avoiding the bias caused by histone purification from a chromatin-enriched fraction.

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Application of MeCAT-Click labeling for protein abundance characterization of E. coli after heat shock experiments

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Yide He, Diego Esteban-Fernández, Boris Neumann, Ulf Bergmann, Frank Bierkandt, Michael W. Linscheid
In a proof of concept study, metal-coded affinity tags based on click chemistry (MeCAT-Click) were used to analyze the proteome of Escherichia coli (E. coli) in response to heat stress. This allows high labeling efficiency, high detection sensitivity, and multiplex capabilities, which are pivotal for its application to protein quantification.Two approaches are presented for relative quantification of differentially lanthanide-labeled proteins. The first approach uses isotope-labeling, where ESI–MS was utilized to quantify the differentially labeled proteins from different states of E. coli. With this approach, 14 proteins were found with changed abundance, among them five proteins upregulated.In the second approach, differentially labeled samples were separated by two dimensional gel electrophoresis (2-DE) and scanned by laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS). Comparison of the signal intensities of the different lanthanides was used to quantify different sample states. Based on this information, ESI–MS was used to identify the proteins with different abundance. The sensitivity of LA–ICP–MS allowed us to find one upregulated protein that was nearly invisible by silver staining ("Probable replication endonuclease from retron EC67"). The advantage of this approach is to locate low abundant proteins with differential expression using LA–ICP–MS, which may be overlooked otherwise.Biological significanceThis paper demonstrates the successful application of a novel metal labeling strategy to quantify the proteins from complex biological samples. In comparison with former metal labeling strategies, it reduces the steric hindrance and improves the labeling efficiency during the labeling process, which ensure its successful application. This methodology is compatible with both molecular and elemental mass spectrometry. ESI–MS/MS in combination with software-based search allows the identification and relative quantification of labeled proteins. In addition, LA–ICP–MS helps to locate the labeled proteins in 2-DE gels with superior detection capability, thus, target proteins with low abundance can be precisely followed. Its excellent sensitivity allows one to track the proteins of interest that are barely visible by silver staining.

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Identification and verification of transgelin-2 as a potential biomarker of tumor-derived lung-cancer endothelial cells by comparative proteomics

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Hongwei Jin, Xiao Cheng, Yihua Pei, Jianguo Fu, Zhi Lyu, Huifang Peng, Qin Yao, Yu Jiang, Lianzhong Luo, Huiqin Zhuo
To investigate heterogeneity of endothelial cells (ECs) in the tumor microenvironment and biomarkers for antitumor angiogenesis therapy, high-purity (>98%) normal (NECs) and tumor-derived CD105⁺ ECs (TECs) were purified from a mouse Lewis lung carcinoma model bearing 0.5cm tumors by immunomagnetic separation. Proteomics analysis revealed that 48 proteins (28 upregulated and 20 downregulated) were differentially regulated by at least 1.5-fold in TECs, and that these proteins were involved in metabolism, energy pathways, protein folding, cell growth and/or functioned as structural constituents of the cytoskeleton. Upregulation of heat shock protein 60 (Hspd1) and transgelin-2 (Tagln2) was revealed in TECs, and by immunohistochemistry (IHC) in paired tissues from 30 consecutive lung cancer (LC) patients. Higher expression levels of Hspd1, Tagln2 were detected in microvascular ECs of paratumor and tumor tissues than in paired normal counterparts. Stronger Tagln2 staining was associated with clinical stage, tumor size, and histological neural invasion. Higher Hspd1 (area under the curve [AUC], 0.82) and lower Tagln2 (AUC, 0.90) levels were detected in LC patient sera. Pearson correlation analysis revealed a positive correlation between serum Hspd1 and Tagln2 levels. In conclusion, higher Tagln2 levels were associated with tumor development, lymph node metastasis, and neural invasion in LC and may thus serve as a potential biomarker of tumor angiogenesis.SignificanceHigh-purity endothelial cells (normal and tumor derived) were prepared to characterize ECs heterogeneity in the tumor microenvironment and to explore biomarkers of early stages of tumor development by proteomics. Candidate proteins Hspd1 and Tagln2, were further verification in the sera and tumor tissues of lung cancer patients. Moreover, higher Tagln2 was significantly associated with clinical tumor development, metastasis, and neural invasion. All these results indicated a crucial role for Tagln2 in TECs for tumor development and metastasis.

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Peptidome profiling of umbilical cord plasma associated with gestational diabetes-induced fetal macrosomia

Publication date: Available online 4 March 2016
Source:Journal of Proteomics
Author(s): Fei Liu, Chun Zhao, Lan Liu, Hongjuan Ding, Ran Huo, Zhonghua Shi
Fetal macrosomia, defined as a birth weight ≥4000g, may affect 15–45% of newborns of women with gestational diabetes mellitus (GDM). The associations between endogenous peptides and gestational diabetes-induced macrosomia have not been investigated extensively by peptidome analysis. Here, we analyzed the umbilical cord plasma by combining ultrafiltration using molecular weight cut-off filters and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to investigate potential associations of GDM with macrosomia. As macrosomic babies have increased susceptibility to obesity, diabetes and cardiovascular diseases in later life, we also aimed to identify specific biomarkers to detect these future diseases. Thirty pairs of GDM mothers and controls were randomly divided into three subgroups. We identified 235 peptides of around 1000–3000Da, originating from 115 proteins. Analyzing the cleavage sites revealed that these peptides were cleaved in regulation, which may reflect the protease activity and distribution in umbilical cord plasma. Four identified peptides, of 2471.7, 1077.2, 1446.5 and 2372.7Da, were significantly differentially expressed in the GDM macrosomia groups compared with controls, whose precursors may play a critical role in developing GDM macrosomia. We provide for the first time a validated GDM macrosomia peptidome profile and identify potential biomarkers linking the effects of macrosomia to later-life diseases.Biological significanceFetal macrosomia is the predominant adverse outcome of gestational diabetes mellitus (GDM), which is a frequent medical condition during pregnancy. Till now, the detailed molecular mechanisms underlying gestational diabetes-induced macrosomia are still not elucidated. With high detection sensitivity and high throughput of peptidome technology, it is now possible to systemically identify peptides possibly involved in the umbilical cord plasma of GDM induced macrosomia cases. With LC–MS/MS based quantification, totally, we identified 235 peptides originated from 115 precursor proteins. And four peptides of 2471.7, 1077.2, 1446.5 and 2372.7Da differentially expressed between GDM cases and compared controls. A precursor protein of 1077.2Da was fibrinogen alpha chain (FGA), which was also identified in the Ai et al. [29] study with a downregulated manner in the serum samples of GDM cases. And further analysis the cleavage pattern of the identified peptides revealed that the enzymes in tissues cleaved the protein according to their rules. Thus, this quantitative peptidome approach can identify related peptides that may play a role in the gestational diabetes-induced macrosomia, and give candidate biomarkers contributing to the development of later-life diseases in macrosomic babies.

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The iron-responsive microsomal proteome of Aspergillus fumigatus

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Nicola M. Moloney, Rebecca A. Owens, Paula Meleady, Michael Henry, Stephen K. Dolan, Eoin Mulvihill, Martin Clynes, Sean Doyle
Aspergillus fumigatus is an opportunistic fungal pathogen. Siderophore biosynthesis and iron acquisition are essential for virulence. Yet, limited data exist with respect to the adaptive nature of the fungal microsomal proteome under iron-limiting growth conditions, as encountered during host infection. Here, we demonstrate that under siderophore biosynthetic conditions — significantly elevated fusarinine C (FSC) and triacetylfusarinine C (TAFC) production (p<0.0001), extensive microsomal proteome remodelling occurs. Specifically, a four-fold enrichment of transmembrane-containing proteins was observed with respect to whole cell lysates following ultracentrifugation-based microsomal extraction. Comparative label-free proteomic analysis of microsomal extracts, isolated following iron-replete and -deplete growth, identified 710 unique proteins. Scatterplot analysis (MaxQuant) demonstrated high correlation amongst biological replicates from each growth condition (Pearson correlation >0.96 within groups; biological replicates (n=4)). Quantitative and qualitative comparison revealed 231 proteins with a significant change in abundance between the iron-replete and iron-deplete conditions (p<0.05, fold change ≥2), with 96 proteins showing increased abundance and 135 with decreased abundance following iron limitation, including predicted siderophore transporters. Fluorescently labelled FSC was only sequestered following A. fumigatus growth under iron-limiting conditions. Interestingly, human sera exhibited significantly increased reactivity (p<0.0001) against microsomal protein extracts obtained following iron-deplete growth.Biological significanceThe opportunistic fungal pathogen Aspergillus fumigatus must acquire iron to facilitate growth and pathogenicity. Iron-chelating non-ribosomal peptides, termed siderophores, mediate iron uptake via membrane-localised transporter proteins. Here we demonstrate for the first time that growth of A. fumigatus under iron-deplete conditions, concomitant with siderophore biosynthesis, leads to an extensive remodelling of the microsomal proteome which includes significantly altered levels of 231 constituent proteins (96 increased and 135 decreased in abundance), many of which have not previously been localised to the microsome. We also demonstrate the first synthesis of a fluorescent version of fusarinine C, an extracellular A. fumigatus siderophore, and its uptake and localization under iron-restricted conditions. This infers the use of an A. fumigatus siderophore as a 'Trojan horse' to potentiate the efficacy of anti-fungal drugs. Finally, in addition to revealing the Aspergillus-specific IgG reactivity in normal human sera against microsomal proteins, there appears to be a significantly increased reactivity against microsomal proteins obtained following iron-restricted growth. We hypothesise that iron-limiting environment in humans, which has evolved to nutritionally limit pathogen growth in vivo, may also alter the fungal microsomal proteome.

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Identification of cypermethrin induced proteins changes in green algae by iTRAQ quantitative proteomics

Publication date: Available online 4 March 2016
Source:Journal of Proteomics
Author(s): Yan Gao, Teck Kwang Lim, Qingsong Lin, Sam Fong Yau Li
Cypermethrin (CYP) is one of the most widely used pesticides in large scale for agricultural and domestic purpose and the residue often seriously affects aquatic system. Environmental pollutants induced protein changes in organisms could be detected by proteomics, leading to discovery of potential biomarkers and understanding of mode of action. While proteomics investigations of CYP stress in some animal models have been well studied, few reports about the effects of exposure to CYP on algae proteome were published. To determine CYP effect in algae, the impact of various dosages (0.001μg/L, 0.01μg/L and 1μg/L) of CYP on green algae Chlorella vulgaris for 24h and 96h were investigated by using iTRAQ quantitative proteomics technique. A total of 162 and 198 proteins were significantly altered after CYP exposure for 24h and 96h, respectively. Overview of iTRAQ results indicated that the influence of CYP on algae protein might be dosage-dependent. Functional analysis of differentially expressed proteins showed that CYP could induce protein alterations related to photosynthesis, stress responses and carbohydrates metabolism. This study provides a comprehensive view of complex mode of action of algae under CYP stress and highlights several potential biomarkers for further investigation of pesticides exposed plant and algae.Biological SignificanceThe effect of cypermethrin on algae proteome in term of exposure concentrations and durations has been determined using quantitative iTRAQ technique. The results showed that cypermethrin affects proteins related with photosynthesis, stress responsive and carbohydrate metabolism. Overall, this study provides comprehensive analysis of green algae protein profiles in response to cypermethrin exposure and presents some new information about plant and algae exposure to pesticide.

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iTRAQ-based quantitative proteomic analysis of Macrobrachium rosenbergii hemocytes during Spiroplasma eriocheiris infection

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Libo Hou, Yunji Xiu, Jian Wang, Xiaoqian Liu, Yuhan Liu, Wei Gu, Wen Wang, Qingguo Meng
Spiroplasma eriocheiris, as a novel aquaculture pathogen, has led into catastrophic economic losses in aquaculture. The Macrobrachium rosenbergii hemocytes were major target cells in S. eriocheiris infection. Our study was designed to examine the hemocytes' immune response at the protein levels. The differential proteomes of the prawn hemocytes were analyzed immediately prior to injection with the pathogen, and at 192h post-injection by isobaric tags for relative and absolute quantization (iTRAQ) labeling, followed by liquid chromatogramphytandem mass spectrometry (LC–MS/MS). A total of 69 differentially expressed proteins were identified. Forty-nine proteins were up-regulated and 20 proteins were down-regulated resulting from a S. eriocheiris infection. Up-regulated proteins included vertebrate gliacolin-like protein, vitellogenin, Gram-negative binding protein 1, alpha2 macroglobulin isoform 2 (a2M), etc. Down-regulated proteins, involved with beta-1,3-glucan-binding protein (BGBP), immunoglobulin like, Rab7, lipopolysaccharide and β-1,3-glucan (LGBP), actin-related protein, etc. Selected bioactive factors (tachylectin, α2M and vitellogenin, BGBP, C-type lectin, LGBP and Rab7) were verified by their immune roles in the S. eriocheiris infection using real-time PCR. The present work could serve as a basis for future studies on the proteins implicated in the susceptibility/resistance of M. rosenbergii to S. eriocheiris, as well as contribute to our understanding of disease processes in prawns.Biological significanceThis is the first time using an iTRAQ approach to analyze proteomes of M. rosenbergii mobilized against S. eriocheiris infection and substantiated the hemocytes' proteomic changes in M. rosenbergii using an infection model. The results reported here can provide a significant step forward toward a more complete elucidation of the immune relationship between M. rosenbergii and the pathogen S. eriocheiris.

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Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Alexander S. Streng, Douwe de Boer, Freek G. Bouwman, Edwin C.M. Mariman, Arjen Scholten, Marja P. van Dieijen-Visser, Will K.W.H. Wodzig
Cardiac troponin T (cTnT) is a highly cardiospecific protein commonly used in the diagnosis of acute myocardial infarction (AMI), but is subject to proteolytic degradation upon its release in the circulation. In this study, a targeted mass spectrometry assay was developed to detect peptides which are differentially present within the different degradation products. cTnT was spiked in human serum and incubated at 37°C to induce proteolytic degradation. Isolation and fractionation of cTnT and its fragments from serum were performed using immunoprecipitation and SDS-PAGE. Bands migrating to 37kDa (intact cTnT), 29kDa (primary fragment), and 19, 18, and 16kDa (secondary fragments) were excised, digested, and subsequently analysed using targeted selected ion monitoring on a UHPLC-coupled quadrupole-Orbitrap mass spectrometer. Sixteen precursor ions from a total of 11 peptides unique to cTnT were targeted. Precursor ions were detectable up until 1200ng/L cTnT, which is a typical cTnT concentration after AMI. With tandem-MS and relative quantification, we proved the formation of cTnT fragments upon incubation in human serum and identified differentially present peptides in the fragment bands, indicative of N- and C-terminal proteolytic cleavage. These findings are of importance for the development of future cTnT assays, calibrators, and quality control samples.Biological significanceIn this study we have developed a gel-based targeted mass spectrometry assay which is able to differentiate between different molecular forms of cTnT. The unravelling of the molecular presentation of cTnT in human serum is of importance in the field of clinical chemistry, where this highly specific and sensitive biomarker is being measured on a routinely basis in patient samples. Knowledge of the amino acid sequence of the different cTnT fragments may aid in the development of improved calibrators and quality control samples. In addition, different fragmentation patterns may be indicative of different underlying pathologies. New antibodies for future assays targeting specific areas of cTnT can thus be created based on this information. This assay will be used in future experiments to assess the fragmentation pattern of cTnT in serum of multiple patient groups in our laboratory.

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A minimal molecular toolkit for mineral deposition? Biochemistry and proteomics of the test matrix of adult specimens of the sea urchin Paracentrotus lividus

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Konstantinos Karakostis, Isabelle Zanella-Cléon, Françoise Immel, Nathalie Guichard, Philippe Dru, Thierry Lepage, Laurent Plasseraud, Valeria Matranga, Frédéric Marin
The sea urchin endoskeleton consists of a magnesium-rich biocalcite comprising a small amount of occluded organic macromolecules. This structure constitutes a key-model for understanding the mineral — organics interplay, and for conceiving in vitro bio-inspired materials with tailored properties. Here we employed a deep-clean technique to purify the occluded proteins from adult Paracentrotus lividus tests. We characterized them by 1- and 2D-electrophoreses, ELISA and immunoblotting, and using liquid chromatography coupled with Mass Spectrometry (nanoLC-MS/MS), we identified two metalloenzymes (carbonic anhydrase and MMP), a set of MSP130 family members, several C-type lectins (SM29, SM41, PM27) and cytoskeletal proteins. We demonstrate the effect of the protein extract on the crystals, with an in vitro crystallization assay. We suggest that this small set of biomineralization proteins may represent a 'minimal molecular crystallization toolkit'.SignificanceBiominerals often exhibit superior chemical properties, when compared to their inorganic counterparts. This is due pro parte to the proteins that are occluded in the mineral. However, the limited available studies on biomineralization have not yet succeeded in identifying a minimal set of proteins directly involved in the formation of the biomineral in vivo and sufficiently required for in vitro precipitation. Indeed, the high number of proteins identified by high-throughput screening in the recent years does not encourage the possibility of recreating or tailoring the mineral in vitro. Thus, the identification of biomineralization proteins involved in protein–mineral interactions is highly awaited. In the present study, we used the sea urchin, Paracentrotus lividus (P. lividus), to identify the native proteins directly taking part in protein–mineral interactions. We employed an improved deep-clean technique to extract and purify the native occluded skeletal matrix proteins from the test and identified them by the highly sensitive technique of nanoLC-MS/MS. We show that this minimal set of proteins has a shaping effect on the formation of biocalcite in vitro. This work gives insights on the biomineralization of the sea urchin, while it paves the way for the identification of biomineralization proteins in other biomineralizing systems. Understanding the 'biologically controlled mineralization' will facilitate the in vitro formation and tailoring of biominerals in mild conditions for applications in medicine and materials science.

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Characterization of proteins involved in early stage of wheat grain development by iTRAQ

Publication date: 16 March 2016
Source:Journal of Proteomics, Volume 136
Author(s): Mingming Yang, Jian Dong, Wanchun Zhao, Xiang Gao
Wheat (Triticum aestivum L.) is one of the most important crops in the world due to its value as a major food source. To explore the protein synthesis, accumulation and regulation during grain development are more complex because of its large genome. In this study, grains from wheat cultivar Chinese Spring were harvested at three development stages (DAA4, DAA8 and DAA12) and were used to display variable expressed proteins during these stages. iTRAQ-based quantitative proteomic and LC–MS/MS methods were used in this study. A total of 1762 proteins showed that at least 1.5-fold differences in abundance were found during these stages; most of the differential expressed proteins (DEPs) were involved in the metabolism process, which includes carbohydrate metabolism, cell division, cytoskeleton, lipid metabolism, nitrogen metabolism, protein synthesis, signal transduction, translation and transport. The results provide insight into biochemical events taking place during the early wheat grain development and highlight the value of proteomics in characterizing complex biochemical processes. Our results also showed that the photosynthesis played an important role for implying energy during the early grain development.SignificanceWheat (T. aestivum L., 2n=6X=42, AABBDD) is one of the most important crops in the world. The early phase of seed grain development mainly involved active cell enlargement, leading to a rapid increase in seed size available for further accumulation of starch of storage proteins. We applied the iTRAQ proteomic analysis to decipher the mechanism of wheat grain development during the early stage. Numerous differentially expressed proteins were identified; most of which were related to carbohydrate metabolism, cell division, cytoskeleton, lipid metabolism, nitrogen metabolism, protein synthesis, signal transduction, translation and transport. Results also showed that the photosynthesis played an important role for implying energy during the early grain development. Taken together, our results provide comprehensive proteome insights into the early wheat grain development.

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