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PLOS ONE Alerts: New Articles



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Updated: 2017-12-12T04:45:46Z

 



(XML) Correction: Assessment of gold nanoparticles on human peripheral blood cells by metabolic profiling with 1H-NMR spectroscopy, a novel translational approach on a patient-specific basis

2017-12-11T22:00:00Z

by Martina Palomino-Schätzlein, Hermenegildo García, Patricia Gutiérrez-Carcedo, Antonio Pineda-Lucena, José Raul Herance

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(XML) Correction: The importance of public health, poverty reduction programs and women's empowerment in the reduction of child stunting in rural areas of Moramanga and Morondava, Madagascar

2017-12-11T22:00:00Z

by Chitale Rabaoarisoa Remonja, Rado Rakotoarison, Nivo Heritiana Rakotonirainy, Reziky Tiandraza Mangahasimbola, Alain Berthin Randrianarisoa, Ronan Jambou, Inès Vigan-Womas, Patrice Piola, Rindra Vatosoa Randremanana

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(XML) Genome-wide microarray analysis leads to identification of genes in response to herbicide, metribuzin in wheat leaves

2017-12-11T22:00:00Z

by Whitney Pilcher, Hana Zandkamiri, Kelly Arceneaux, Stephen Harrison, Niranjan Baisakh

Herbicides are an important component of weed management in wheat, particularly in the southeastern US where weeds actively compete with wheat throughout the winter for nutrients and reduce tillering and ultimately the yield of the crop. Some wheat varieties are sensitive to metribuzin, a low-cost non-selective herbicide, leading to leaf chlorosis, stand loss, and decreased yield. Knowledge of the genetics of herbicide tolerance in wheat is very limited and most new varieties have not been screened for metribuzin tolerance. The identification of genes associated with metribuzin tolerance will lead to the development of molecular markers for use in screening breeding lines for metribuzin tolerance. AGS 2035 and AGS 2060 were identified as resistant and sensitive to metribuzin in several previous field screening experiments as well as controlled condition screening of nine varieties in the present study. Genome-wide transcriptome profiling of the genes in AGS 2035 and AGS 2060 through microarray analysis identified 169 and 127 genes to be significantly (2-fold, P>0.01) up- and down-regulated, respectively in response to metribuzin. Functional annotation revealed that genes involved in cell wall biosynthesis, photosynthesis and sucrose metabolism were highly responsive to metribuzin application. (Semi)quantitative RT-PCR of seven selected differentially expressed genes (DEGs) indicated that a gene coding for alkaline alpha-galactosidase 2 (AAG2) was specifically expressed in resistant varieties only after one and two weeks of metribuzin application. Integration of the DEGs into our ongoing mapping effort and identification of the genes within the QTL region showing significant association with resistance in future will aid in development of functional markers for metribuzin resistance.(image)



(XML) Consequences of supplying methyl donors during pregnancy on the methylome of the offspring from lactating and non-lactating dairy cattle

2017-12-11T22:00:00Z

by Alex Bach, Anna Aris, Isabel Guasch

The aim of this study was to evaluate the potential effects of methyl donor supplementation of pregnant animals in the presence or absence of a concomitant lactation on the methylome of the offspring. Twenty Holstein cows, 10 nulliparous (non-lactating while pregnant) and 10 multiparous (lactating while pregnant) were blocked by parity and randomly assigned to an i.m. weekly injections of a placebo (CTRL) or a solution containing methyl donors (MET). After calving, 5 calves randomly selected from each treatment (two born to non-lactating and three to lactating dams) were blood-sampled to determine their full methylome. There were more than 2,000 CpG differentially methylated between calves born to CTRL and those born to MET, and also between calves born to lactating and non-lactating dams. Most of the differences affected genes involved in immune function, cell growth regulation and differentiation, kinase activity, and ion channeling. We conclude that the coexistence of pregnancy and lactation affects the methylome of the offspring, and that supplementation of methyl donors early in gestation has also consequences on the methylome.(image)






(XML) Tools for fairness: Increased structure in the selection process reduces discrimination

2017-12-11T22:00:00Z

by Sima Wolgast, Martin Bäckström, Fredrik Björklund

Employment discrimination causes problems at the labor market, and is hard to combat. Can increasing the degree of structure when selecting applicants increase fairness? Students were asked to perform a computerized selection task and were either provided with tools for systematizing information about the applicants (structured selection) or no such tools (unstructured selection). We hypothesized and found that a structured process, where employing recruitment tools rather than the recruiter’s impressionistic judgment is key, improves the ability to identify job-relevant criteria and hence selecting more qualified applicants, even when in-group favoritism is tempting (e.g. when the outgroup applicants are more competent). Increasing structure helped recruiters select more competent applicants and reduced ethnic discrimination. Increasing the motivation to carefully follow the structured procedure strengthened these effects further. We conclude that structure pays off, and that motivational factors should be taken into account in order for it to have the optimal effect.(image)



(XML) Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans

2017-12-11T22:00:00Z

by Dmitry Smirnov, Fanny Lachat, Tomi Peltola, Juha M. Lahnakoski, Olli-Pekka Koistinen, Enrico Glerean, Aki Vehtari, Riitta Hari, Mikko Sams, Lauri Nummenmaa

Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI). The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals.(image)



(XML) Biochemical studies of two lytic polysaccharide monooxygenases from the white-rot fungus Heterobasidion irregulare and their roles in lignocellulose degradation

2017-12-11T22:00:00Z

by Bing Liu, Åke Olson, Miao Wu, Anders Broberg, Mats Sandgren

Lytic polysaccharide monooxygenases (LPMO) are important redox enzymes produced by microorganisms for the degradation of recalcitrant natural polysaccharides. Heterobasidion irregulare is a white-rot phytopathogenic fungus that causes wood decay in conifers. The genome of this fungus encodes 10 putative Auxiliary Activity family 9 (AA9) LPMOs. We describe the first biochemical characterization of H. irregulare LPMOs through heterologous expression of two CBM-containing LPMOs from this fungus (HiLPMO9H, HiLPMO9I) in Pichia pastoris. The oxidization preferences and substrate specificities of these two enzymes were determined. The two LPMOs were shown to cleave different carbohydrate components of plant cell walls. HiLPMO9H was active on cellulose and oxidized the substrate at the C1 carbon of the pyranose ring at β-1,4-glycosidic linkages, whereas HiLPMO9I cleaved cellulose with strict oxidization at the C4 carbon of glucose unit at internal bonds, and also showed activity against glucomannan. We propose that the two LPMOs play different roles in the plant-cell-wall degrading system of H. irregulare for degradation of softwood and that the lignocellulose degradation mediated by this white-rot fungus may require collective efforts from multi-types of LPMOs.(image)



(XML) Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase

2017-12-11T22:00:00Z

by Wen-Cheng Chao, Chia-Liang Yen, Cheng-Yuan Hsieh, Ya-Fang Huang, Yau-Lin Tseng, Peter Andrija Nigrovic, Chi-Chang Shieh

Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1β production. Moreover, we showed that the abundant NE and IL-1β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.(image)



(XML) Temporal dynamics of gene expression in heat-stressed Caenorhabditis elegans

2017-12-11T22:00:00Z

by Katharina Jovic, Mark G. Sterken, Jacopo Grilli, Roel P. J. Bevers, Miriam Rodriguez, Joost A. G. Riksen, Stefano Allesina, Jan E. Kammenga, L. Basten Snoek

There is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3–4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.(image)



(XML) Novel systems for the application of isolated tensile, compressive, and shearing stimulation of distraction callus tissue

2017-12-11T22:00:00Z

by Nicholaus Meyers, Julian Schülke, Anita Ignatius, Lutz Claes

Background

Distraction osteogenesis is a procedure widely used for the correction of large bone defects. However, a high complication rate persists, likely due to insufficient stability during maturation. Numerical fracture healing models predict bone regeneration under different mechanical conditions allowing fixation stiffness optimization. However, most models apply a linear elastic material law inappropriate for the transient stresses/strains present during limb lengthening or segment transport. They are also often validated using in vivo osteotomy models lacking precise mechanical regulation due to the unavoidable stimulation of secondary interfragmentary motion during ambulation under finitely stiff fixation. Therefore, in order to create a robust numerical model of distraction osteogenesis, it is necessary to both characterize the new tissue’s viscoelasticity during distraction and determine the influence of strictly isolated stimulation in each loading mode (tension, compression, and shear) to account for potential differences in mechanical and histological response.

Aim

Two electromechanical fixators with integrated load cells were designed to precisely perform and monitor in vivo lateral distraction and isolated stimulation in sheep tibiae using a mobile, hydroxyapatite-coated titanium plate. The novel surgical procedure circumvents osteotomy, eliminating the undesirable and unquantifiable mechanical stimulation during ambulation.

Methods

After a 10-day post-surgery latency period, two 0.275 mm distraction steps were performed daily for 10 days. The load cell collected data before, during, and after each distraction step and was terminated after no less than one minute from the time of distraction. A 7-day consolidation period separated the distraction phase and 18-day stimulation phase. Stimulation was carried out in isolated tension, compression, or shear while recording force/time data. Each stimulation session consisted of 120 cycles with a magnitude of either 0.1 mm or 0.6 mm in the tension and compression groups and 1.0 mm in the shear group. The animals were euthanized after a 3-day holding period following stimulation.

Results

Our initial results show that the tissue progressively stiffens and maintains an increasingly large residual traction. The force curves during compressive stimulation show a progressive drift from compression toward tension. We hypothesize that this behavior may be due to the preferential flow of fluid outward from the tissue and a greater resistance to reabsorption during the plate’s return to the starting position.

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(XML) Risk of thromboembolism in cisplatin versus carboplatin-treated patients with lung cancer

2017-12-11T22:00:00Z

by Eric S. Kim, Andrea M. Baran, Esther L. Mondo, Thomas D. Rodgers, Gradon C. Nielsen, David W. Dougherty, Kishan J. Pandya, David Q. Rich, Edwin van Wijngaarden

Introduction

Carboplatin is widely used to treat lung cancer in the United States as an alternative to cisplatin. Several studies have demonstrated that cisplatin-based regimen is associated with a high frequency of thromboembolic complications. However, there has been limited investigation directly comparing the risk of thromboembolic events (TEEs) between cisplatin- and carboplatin-treated patients with lung cancer.

Methods

All lung cancer patients treated with cisplatin or carboplatin at Wilmot Cancer Center, University of Rochester between 2011 and 2014 were included. Patient characteristics including exposure (cisplatin vs. carboplatin) and outcome (TEEs between the time of the first dose of cisplatin or carboplatin and 4 weeks after the last dose) were collected by reviewing electronic medical records. A Fisher’s exact test was used to compare the proportion of incident TEEs between cisplatin and carboplatin groups. The risk of TEE associated with carboplatin compared to cisplatin was assessed using multiple logistic regression.

Results

Among 415 subjects, 317 patients (76.4%) received carboplatin and 98 (23.6%) patients received cisplatin. In the carboplatin group, 10.9% (33/302) of evaluable patients developed treatment-related TEEs vs. 14.7% (14/95) in the cisplatin group. There was no significant difference in the risk of developing TEEs between the two groups (P = 0.32). However, 15.2% of carboplatin-related TEEs were arterial thromboses compared to none in the cisplatin group.

Conclusions

The incidence of carboplatin-related TEEs was high in lung cancer patients without significant difference in the risk of developing TEEs between cisplatin and carboplatin groups. Potential use of prophylactic anticoagulation in all platinum-treated patients should be further investigated.

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(XML) Market access and community size influence pastoral management of native and exotic livestock species: A case study in communities of the Cordillera Real in Bolivia's high Andean wetlands

2017-12-11T22:00:00Z

by Quentin Struelens, Karina Gonzales Pomar, Susi Loza Herrera, Gaby Nina Huanca, Olivier Dangles, François Rebaudo

Grazing areas management is of utmost importance in the Andean region. In the valleys of the Bolivian Cordillera Real near La Paz, pastoralism constitutes the traditional way for people to insure food security and economical sustainability. In these harsh mountains, unique and productive wetlands sustained by glacial water streams are of utmost importance for feeding cattle herds during the dry season. After the colonization by the Spanish, a shift in livestock species has been observed, with the introduction of exotic species such as cows and sheep, resulting in a different impact on pastures compared to native camelid species—llamas and alpacas. Here we explored some of the social-economical and environmental drivers that motivate Bolivian pastoralists to prefer exotic over native livestock species, based on 36 household surveys in the Cordillera Real. We constructed a Partial Least Squares Structural Equation Model in order to assess the relationships between these drivers. Our results suggest that the access to market influenced pastoralists to reshape their herd composition, by increasing the number of sheep. They also suggest that community size increased daily grazing time in pastures, therefore intensifying the grazing pressure. At a broader scale, this study highlights the effects of some social-economical and environmental drivers on mountain herding systems.(image)



(XML) Detection of duo-schistosome infection from filtered urine samples from school children in Zambia after MDA

2017-12-11T22:00:00Z

by Megan J. Hessler, Austin Cyrs, Steven C. Krenzke, El Shaimaa Mahmoud, Chummy Sikasunge, James Mwansa, Nilanjan Lodh

Schistosomiasis is one of the major Neglected Tropical Diseases (NTDs) in sub-Saharan Africa. In sub-Saharan Africa, two major human schistosome species namely Schistosoma mansoni and S. haematobium often occur sympatrically largely affecting children. Recognizing the public health impact of Schistosomiasis, the World Health Organization (WHO) is urging member states to regularly treat at least 75% and up to 100%, of all school-aged children at risk of morbidity. For control strategies based on targeted mass drug administration (MDA) to succeed it is essential to have a simple and sensitive test for monitoring the success of these interventions. Current available diagnostic tests, such as egg detection in stool by Kato-Katz (KK) for S. mansoni and detection of eggs or blood (hematuria) in urine for S. haematobium have reduced sensitivity in low intensity settings. The objective of the study was to evaluate active single or duo schistosome infections in school children following MDA using molecular diagnostics (PCR) on filtered urine samples and comparing that against traditional diagnostic tests. This cross-sectional study was conducted among 111 school children aged 7–15 years in Chongwe and Siavonga Districts in Zambia. Species-specific cell-free repeat DNA fragment were amplified from 111 filtered urine samples. Our approach detected eight times more positive cases (total 77) than by KK (9) for S. mansoni and six times more (total 72) than by hematuria (11) for S. haematobium and even more against urine filtration (77 compared to only 6). The same pattern was observed when stratified for age group and sex specific analysis with 100% sensitivity and specificity devoid of any cross amplification. In addition, 69 individuals (62%) were co-infected by both parasites. We have demonstrated a significantly higher prevalence of both species than indicated by the traditional tests and the persistent maintenance of reservoir of infection after MDA. Our approach is an effective means of detecting low intensity infection, which will enhance the effectiveness of surveillance and assess the impact of MDA control programs against schistosomiasis.(image)



(XML) Structure-activity studies of Mdm2/Mdm4-binding stapled peptides comprising non-natural amino acids

2017-12-11T22:00:00Z

by Sharon Min Qi Chee, Jantana Wongsantichon, Jiawei Siau, Dawn Thean, Fernando Ferrer, Robert C. Robinson, David P. Lane, Christopher J. Brown, Farid J. Ghadessy

As primary p53 antagonists, Mdm2 and the closely related Mdm4 are relevant cancer therapeutic targets. We have previously described a series of cell-permeable stapled peptides that bind to Mdm2 with high affinity, resulting in activation of the p53 tumour suppressor. Within this series, highest affinity was obtained by modification of an obligate tryptophan residue to the non-natural L-6-chlorotryptophan. To understand the structural basis for improved affinity we have solved the crystal structure of this stapled peptide (M011) bound to Mdm2 (residues 6–125) at 1.66 Å resolution. Surprisingly, near identity to the structure of a related peptide (M06) without the 6-chloro modification is observed. Further analysis of linear and stapled peptides comprising 6-Me-tryptophan provides mechanistic insight into dual Mdm2/Mdm4 antagonism and confirms L98 of Mdm4 as a mutable steric gate. The results also highlight a possible role of the flexible hinge region in determining Mdm2/Mdm4 plasticity.(image)



(XML) Birth preparedness and complication readiness (BPCR) among pregnant women in hard-to-reach areas in Bangladesh

2017-12-11T22:00:00Z

by Md Moinuddin, Aliki Christou, Dewan Md Emdadul Hoque, Tazeen Tahsina, Shumona Sharmin Salam, Sk Masum Billah, Lianne Kuppens, Md Ziaul Matin, Shams El Arifeen

Background

Birth preparedness and complication readiness aims to reduce delays in care seeking, promote skilled birth attendance, and facility deliveries. Little is known about birth preparedness practices among populations living in hard-to-reach areas in Bangladesh.

Objectives

To describe levels of birth preparedness and complication readiness among recently delivered women, identify determinants of being better prepared for birth, and assess the impact of greater birth preparedness on maternal and neonatal health practices.

Methods

A cross-sectional survey with 2,897 recently delivered women was undertaken in 2012 as part of an evaluation trial done in five hard-to-reach districts in rural Bangladesh. Mothers were considered well prepared for birth if they adopted two or more of the four birth preparedness components. Descriptive statistics and multivariable logistic regression were used for analysis.

Results

Less than a quarter (24.5%) of women were considered well prepared for birth. Predictors of being well-prepared included: husband’s education (OR = 1.3; CI: 1.1–1.7), district of residence, exposure to media in the form of reading a newspaper (OR = 2.2; CI: 1.2–3.9), receiving home visit by a health worker during pregnancy (OR = 1.5; CI: 1.2–1.8), and receiving at least 3 antenatal care visits from a qualified provider (OR = 1.4; CI: 1.0–1.9). Well-prepared women were more likely to deliver at a health facility (OR = 2.4; CI: 1.9–3.1), use a skilled birth attendant (OR = 2.4, CI: 1.9–3.1), practice clean cord care (OR = 1.3, CI: 1.0–1.5), receive post-natal care from a trained provider within two days of birth for themselves (OR = 2.6, CI: 2.0–3.2) or their newborn (OR = 2.6, CI: 2.1–3.3), and seek care for delivery complications (OR = 1.8, CI: 1.3–2.6).

Conclusion

Greater emphasis on BPCR interventions tailored for hard to reach areas is needed to improve skilled birth attendance, care seeking for complications and essential newborn care and facilitate reductions in maternal and neonatal mortality in low performing districts in Bangladesh.

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(XML) Trends in the management levels of metabolic risk factors in middle-aged and elderly patients with type 2 diabetes mellitus: The Korean National Health and Nutrition Examination Survey 1998–2014

2017-12-11T22:00:00Z

by Sukyung Cho, Haeun Jang, Kyong Park

The present study examined the temporal trends in the management of blood pressure, glucose, and lipid levels among middle-aged and elderly patients with type 2 diabetes using data from the Korean National Health and Nutrition Examination Survey (1998–2014). A total of 3,689 patients with diabetes were included and divided into middle-aged (30–64 years old) and elderly (≥65 years old) groups. Demographic and lifestyle data were obtained using a self-reported questionnaire, and trained medical staff obtained fasting blood samples and blood pressure data. Laboratory testing was performed to determine blood glucose, cholesterol, and triglyceride levels. In the multivariable adjusted models, significant decreasing trends in the prevalences of hyperglycemia and hypertension were observed in both age groups during 1998–2014, although no trends were observed for lipid levels. Based on the most recent survey, approximately 50% of patients with diabetes had hyperglycemia, and one-third of patients with diabetes and hypertension did not appropriately manage their blood pressure. In addition, 50% of the patients in both age groups did not manage their lipid profiles, and the management of lipid profiles did not improve in recent years. These results suggest that continuous follow-up is needed to effectively manage metabolic risk factors, especially lipid profiles, among patients with diabetes.(image)



(XML) On the relation between economic bubbles and effort gaps between sellers and buyers: An experimental study

2017-12-11T22:00:00Z

by Eldad Yechiam, Amitay Kauffmann, Nathaniel J. S. Ashby, Gal Zahavi

Economic bubbles are an empirical puzzle because they do not readily fit the notion of an efficient market. We argue that bubbles are associated with a conflict and a gap in the allocation of effort during negotiation by sellers and buyers. We examined 21 experimental asset markets where in one condition players could buy and sell and in the other they could either buy or sell. The results indicated that when making concurrent buying and selling decisions the mean number of asks for sellers was 71% higher than the number of bids for buyers. Similar findings emerge in a re-analysis of data from Lei et al. (2001). Importantly, bubbles only emerged in markets where the number of asks was larger than that of bids. These findings indicate that bubbles are associated with increased negotiation effort when acting as a seller and diminished effort when acting as a buyer.(image)



(XML) Back and neck pain and function in females with adolescent idiopathic scoliosis: A follow-up at least 23 years after conservative treatment with a Milwaukee brace

2017-12-11T22:00:00Z

by Ewa Misterska, Jakub Głowacki, Adam Okręt, Maria Laurentowska, Maciej Głowacki We aimed to explore the long-term outcomes of back and neck pain and functionality in adult females with adolescent idiopathic scoliosis (AIS), who had been treated with a Milwaukee brace, in a follow-up study a minimum of 23 years after the completion of the treatment, using radiological, clinical and socio-demographical data. Thirty AIS patients (scoliosis group–SG), were included in the study based on an extensive search of Pediatric Orthopedics and Traumatology Clinic charts. All treatments were successfully completed between 1974 and 1990. In all cases, scoliosis had not been detected before the age of 10 and was not combined with any major spinal deformities at the time when the brace treatment was implemented. In those patients, the Risser sign 4 and minimum two years post-menarche was defined as a maturity, after that time the brace treatment was completed. Patients were excluded from the study if they, at the time of the follow-up examinations, suffered from any other disease leading to trunk deformity. Forty patients met the criteria for inclusion, but due to change some personal details, not all of them were contacted. Finally, 30 women returned for a follow-up evaluation. Patients’ follow-up period was mean 27.77 yrs. ± SD 3.30 (range 23–35). Curvature change from the end of the treatment until the present day was mean 9.1 degrees ± SD 7.64 (range 0–27). A control group of 42 healthy females (healthy controls group—HG) matching the age profile of the patient group was randomly selected for comparative purposes.Both SG and HG completed the Polish versions of the Revised Oswestry Lower Back Pain Disability Index (RODI), the Rolland-Morris Questionnaire (RMQ), the Quebec Back Pain Disability Scale (QDS), the Neck Disability Index (NDI) and the Copenhagen Neck Functional Disability Scale (CNFDS). Descriptive statistics were calculated for demographics and baseline questionnaire scores. To determine if the investigated sample sizes are equivalent, the chi-square test was used. The chi-square test was used to compare qualitative features between persons with scoliosis and healthy controls. In addition, a Mann-Whitney test was utilized to compare differences between both groups in regard to quantitative characteristics. To establish relations between quantitative data such as e.g. age, duration of brace application, apical translation, Cobb angle, and questionnaire results, we used Spearman's rank correlation (marked as rS). To determine dependency between quantitative and qualitative characteristics, e.g. between questionnaire numerical data and marital status, place of residence or curve type, ANOVA Kruskal-Wallis test was used. A p[...]



(XML) Inheritance mode and mechanisms of resistance to imidacloprid in the house fly Musca domestica (Diptera:Muscidae) from China

2017-12-11T22:00:00Z

by Zhuo Ma, Jing Li, Yi Zhang, Chao Shan, Xiwu Gao

Imidacloprid is a neonicotinoid insecticide that is effective against house fly, Musca domestica L., which is a major pest with the ability to develop resistance to insecticides. In the present study, we investigated the inheritance mode, the cross-resistance pattern and the mechanisms of resistance to imidacloprid. A near-isogenic house fly line (N-IRS) with 78-fold resistance to imidacloprid was used to demonstrate the mode of inheritance. The overlapping confidence limits of LC50 values and the slopes of the log concentration-probit lines between the reciprocal F1 and F1’ progenies suggest that imidacloprid resistance is inherited autosomally in the house fly. There was incomplete dominant inheritance in the F1 and F1’ progenies, based on dominance values of 0.77 and 0.75, respectively. A monogenic inheritance model revealed that imidacloprid resistance is governed by more than one factor. Compared to the field strain (CFD), the N-IRS strain developed more cross-resistance to chlorfenapyr and no cross-resistance to chlorpyrifos and acetamiprid, but showed negative cross-resistance to beta-cypermethrin and azamethiphos. Three synergists, diethyl malate (DEM), s,s,s-tributylphosphorotrithioate (DEF), and piperonyl butoxide (PBO), showed significant synergism against to imidacloprid (4.55-, 4.46- and 3.34-fold respectively) in the N-IRS strain. However, both DEM and PBO had no synergism and DEF only exhibited slight synergism in the CSS strain. The activities of carboxylesterase (CarE), glutathione S-transferases (GSTs) and cytochrome P450 in the N-IRS strain were significantly higher than in the CSS strain. But similar synergistic potential of DEF to imidacloprid between the CSS and N-IRS strain suggested that GSTs and cytochrome P450 played much more important role than esterase for the N-IRS strain resistance to imidacloprid. These results should be helpful for developing an improved management strategy to delay the development of imidacloprid resistance in house fly.(image)



(XML) A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure

2017-12-11T22:00:00Z

by Christina Y. Hung, Barbara Volkmar, James D. Baker, Johann W. Bauer, Emanuela Gussoni, Stefan Hainzl, Alfred Klausegger, Jose Lorenzo, Ivana Mihalek, Olaf Rittinger, Mustafa Tekin, Julia E. Dallman, Olaf A. Bodamer

Primordial growth failure has been linked to defects in the biology of cell division and replication. The complex processes involved in microtubule spindle formation, organization and function have emerged as a dominant patho-mechanism in these conditions. The majority of reported disease genes encode for centrosome and centriole proteins, leaving kinetochore proteins by which the spindle apparatus interacts with the chromosomes largely unaccounted for. We report a novel disease gene encoding the constitutive inner kinetochore member CENPT, which is involved in kinetochore targeting and assembly, resulting in severe growth failure in two siblings of a consanguineous family. We herein present studies on the molecular and cellular mechanisms that explain how genetic mutations in this gene lead to primordial growth failure. In both, affected human cell lines and a zebrafish knock-down model of Cenpt, we observed aberrations in cell division with abnormal accumulation of micronuclei and of nuclei with increased DNA content arising from incomplete and/or irregular chromosomal segregation. Our studies underscore the critical importance of kinetochore function for overall body growth and provide new insight into the cellular mechanisms implicated in the spectrum of these severe growth disorders.(image)



(XML) Genome-wide association study identifies a locus associated with rotator cuff injury

2017-12-11T22:00:00Z

by Thomas R. Roos, Andrew K. Roos, Andrew L. Avins, Marwa A. Ahmed, John P. Kleimeyer, Michael Fredericson, John P. A. Ioannidis, Jason L. Dragoo, Stuart K. Kim

Rotator cuff tears are common, especially in the fifth and sixth decades of life, but can also occur in the competitive athlete. Genetic differences may contribute to overall injury risk. Identifying genetic loci associated with rotator cuff injury could shed light on the etiology of this injury. We performed a genome-wide association screen using publically available data from the Research Program in Genes, Environment and Health including 8,357 cases of rotator cuff injury and 94,622 controls. We found rs71404070 to show a genome-wide significant association with rotator cuff injury with p = 2.31x10-8 and an odds ratio of 1.25 per allele. This SNP is located next to cadherin8, which encodes a protein involved in cell adhesion. We also attempted to validate previous gene association studies that had reported a total of 18 SNPs showing a significant association with rotator cuff injury. However, none of the 18 SNPs were validated in our dataset. rs71404070 may be informative in explaining why some individuals are more susceptible to rotator cuff injury than others.(image)



(XML) A novel indel variant in LDLR responsible for familial hypercholesterolemia in a Chinese family

2017-12-11T22:00:00Z

by Hongyan Shu, Jingwei Chi, Jing Li, Wei Zhang, Wenshan Lv, Jie Wang, Yujie Deng, Xu Hou, Yangang Wang

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevation of serum cholesterol bound to low-density lipoprotein. Mutations in LDLR are the major factors responsible for FH. In this study, we recruited a four-generation Chinese family with FH and identified the clinical features of hypercholesterolemia. All affected individuals shared a novel indel mutation (c.1885_1889delinsGATCATCAACC) in exon 13 of LDLR. The mutation segregated with the hypercholesterolemia phenotype in the family. To analyze the function of the indel, we established stable clones of mutant and wild-type LDLR in Hep G2 cells. The mutant LDLR was retained in the endoplasmic reticulum (ER) and failed to glycosylate via the Golgi. Moreover, the membrane LDLR was reduced and lost the ability to take up LDL. Our data also expand the spectrum of known LDLR mutations.(image)



(XML) Does access to clinical study reports from the European Medicines Agency reduce reporting biases? A systematic review and meta-analysis of randomized controlled trials on the effect of erythropoiesis-stimulating agents in cancer patients

2017-12-11T22:00:00Z

by Eliane Rohner, Michael Grabik, Thomy Tonia, Peter Jüni, Frank Pétavy, Francesco Pignatti, Julia Bohlius

Since 2010, the European Medicines Agency (EMA) has provided access to clinical study reports (CSRs). We requested CSRs for randomized controlled trials (RCTs) of erythropoiesis-stimulating agents (ESAs) in cancer patients from EMA and identified RCT publications with literature searches. We assessed CSR availability and completeness, the impact of unreported and unpublished data obtained from CSRs on the effects of ESAs on quality of life (QoL) of cancer patients, and discrepancies between data reported in the public domain and in CSRs. We used random-effects meta-analyses to evaluate the effect of ESAs on QoL measured with Functional Assessment of Cancer Therapy-Anemia (FACT-An), FACT-Fatigue (FACT-F) and FACT-Anemia Total (FACT-An Total) stratified by data source and the impact of discrepancies on QoL, mortality, adverse events, and clinical effectiveness outcomes. We identified 94 eligible RCTs; CSRs or other study documentation were available for 17 (18%) RCTs at EMA. Median report length was 1,825 pages (range 72–14,569). Of 180 outcomes of interest reported in the EMA documentation, 127 (71%) were publicly available. For 80 of those (63%) we noted discrepancies, but these had little impact on the pooled effect estimates. Of 27 QoL outcomes reported in the CSRs, 17 (63%) were unpublished. Including six unpublished comparisons (pooled mean difference [MD] 0.20; 95% confidence interval [CI] -1.93, 2.33) reduced the pooled effect of ESAs for FACT-An from MD 5.51 (95% CI 4.20, 6.82) in published data to MD 3.21 (95% CI 1.38, 5.03), which is below a clinically important difference (defined as MD ≥4). Effects were similar for FACT-F and FACT-An Total. Access to CSRs from EMA reduced reporting biases for QoL outcomes. However, EMA received documentation for a fraction of all RCTs on effects of ESAs in cancer patients. Additional efforts by other agencies and institutions are needed to make CSRs universally available for all RCTs.(image)



(XML) Transcriptional profiling of sugarcane leaves and roots under progressive osmotic stress reveals a regulated coordination of gene expression in a spatiotemporal manner

2017-12-11T22:00:00Z

by Alejandro Pereira-Santana, Edyciel J. Alvarado-Robledo, Jesus A. Zamora-Briseño, Jorge T. Ayala-Sumuano, Victor M. Gonzalez-Mendoza, Francisco Espadas-Gil, Luis D. Alcaraz, Enrique Castaño, Miguel A. Keb-Llanes, Felipe Sanchez-Teyer, Luis Carlos Rodriguez-Zapata

Sugarcane is one of the most important crops worldwide and is a key plant for the global production of sucrose. Sugarcane cultivation is severely affected by drought stress and it is considered as the major limiting factor for their productivity. In recent years, this plant has been subjected to intensive research focused on improving its resilience against water scarcity; particularly the molecular mechanisms in response to drought stress have become an underlying issue for its improvement. To better understand water stress and the molecular mechanisms we performed a de novo transcriptomic assembly of sugarcane (var. Mex 69–290). A total of 16 libraries were sequenced in a 2x100 bp configuration on a HiSeq-Illumina platform. A total of 536 and 750 genes were differentially up-regulated along with the stress treatments for leave and root tissues respectively, while 1093 and 531 genes were differentially down-regulated in leaves and roots respectively. Gene Ontology functional analysis showed that genes related to response of water deprivation, heat, abscisic acid, and flavonoid biosynthesis were enriched during stress treatment in our study. The reliability of the observed expression patterns was confirmed by RT-qPCR. Additionally, several physiological parameters of sugarcane were significantly affected due to stress imposition. The results of this study may help identify useful target genes and provide tissue-specific data set of genes that are differentially expressed in response to osmotic stress, as well as a complete analysis of the main groups is significantly enriched under this condition. This study provides a useful benchmark for improving drought tolerance in sugarcane and other economically important grass species.(image)



(XML) White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks

2017-12-11T22:00:00Z

by Jin Woo Choi, Yunseo Ku, Byeong Wook Yoo, Jung-Ah Kim, Dong Soon Lee, Young Jun Chai, Hyoun-Joong Kong, Hee Chan Kim

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method as an automated white blood cell differential count system.(image)



(XML) Genome-wide identification of WRKY genes and their expression profiles under different abiotic stresses in Elaeis guineensis

2017-12-11T22:00:00Z

by Yong Xiao, Lixia Zhou, Xintao Lei, Hongxing Cao, Yong Wang, Yajing Dou, Wenqi Tang, Wei Xia

African oil palm (Elaeis guineensis) is an important oil crop grown in tropical region and sensitive to low temperature along with high tolerance to salt and drought stresses. Since the WRKY transcription factor family plays central roles in the regulation of plant stress tolerance, 95 genes belonging to the WRKY family were identified and characterized in oil palm genome. Gene structure analysis showed that EgWRKY genes have considerable variation in intron number (0 to 12) and gene length (477bp to 89,167 bp). Duplicated genes identification indicated 32 EgWRKY genes originated from segmental duplication and two from tandem duplication. Based on transcriptome data, most EgWRKY genes showed tissue-specific expression patterns and their expression could be induced under cold stress. Furthermore, six EgWRKY genes with more than two-folded increased expression level under cold stress were validated by RT-qPCR, which has higher expression level in cold, drought and high salinity treatment. The identification and characterization of WRKY gene family showed that EgWRKY were associated with a wide range of abiotic stress responses in Elaeis guineensis and some EgWRKY members with high expression levels could be selected for further research in analyzing their functions in the stress response in African oil palm.(image)



(XML) N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation

2017-12-11T22:00:00Z

by Xiao Gao, Eirini-Maria Lampraki, Sarwah Al-Khalidi, Muhammad Asif Qureshi, Rhea Desai, Joanna Beatrice Wilson

Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body’s natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure therapies for chronic inflammation.(image)



(XML) Altered intragenic DNA methylation of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes

2017-12-11T22:00:00Z

by Sandra Rodríguez-Rodero, Edelmiro Menéndez-Torre, Gustavo Fernández-Bayón, Paula Morales-Sánchez, Lourdes Sanz, Estrella Turienzo, Juan José González, Ceferino Martinez-Faedo, Lorena Suarez-Gutiérrez, Jessica Ares, Lucia Díaz-Naya, Alicia Martin-Nieto, Juan L. Fernández-Morera, Mario F. Fraga, Elías Delgado-Álvarez

Aims/Hypothesis

Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D).

Methods

More than 485,000 CpG genome sites from VAT samples from women with obesity undergoing gastric bypass (n = 18), and classified as suffering from type 2 diabetes (T2D) or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays.

Results

We found significant differential methylation between T2D and NT2D samples in 24 CpGs that map with sixteen genes, one of which, HOOK2, demonstrated a significant correlation between differentially hypermethylated regions on the gene body and the presence of type 2 diabetes. This was validated by pyrosequencing in a population of 91 samples from both males and females with obesity. Furthermore, when these results were analyzed by gender, female T2D samples were found hypermethylated at the cg04657146-region and the cg 11738485-region of HOOK2 gene, whilst, interestingly, male samples were found hypomethylated in this latter region.

Conclusion

The differential methylation profile of the HOOK2 gene in individuals with T2D and obesity might be related to the attendant T2D, but further studies are required to identify the potential role of HOOK2 gene in T2D disease. The finding of gender differences in T2D methylation of HOOK2 also warrants further investigation.

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(XML) Pockets as structural descriptors of EGFR kinase conformations

2017-12-11T22:00:00Z

by Marcia Anahi Hasenahuer, German Patricio Barletta, Sebastián Fernandez-Alberti, Gustavo Parisi, María Silvina Fornasari

Epidermal Growth Factor Receptor (EGFR), a tyrosine kinase receptor, is one of the main tumor markers in different types of cancers. The kinase native state is mainly composed of two populations of conformers: active and inactive. Several sequence variations in EGFR kinase region promote the differential enrichment of conformers with higher activity. Some structural characteristics have been proposed to differentiate kinase conformations, but these considerations could lead to ambiguous classifications. We present a structural characterisation of EGFR kinase conformers, focused on active site pocket comparisons, and the mapping of known pathological sequence variations. A structural based clustering of this pocket accurately discriminates active from inactive, well-characterised conformations. Furthermore, this main pocket contains, or is in close contact with, ≈65% of cancer-related variation positions. Although the relevance of protein dynamics to explain biological function has been extensively recognised, the usage of the ensemble of conformations in dynamic equilibrium to represent the functional state of proteins and the importance of pockets, cavities and/or tunnels was often neglected in previous studies. These functional structures and the equilibrium between them could be structurally analysed in wild type as well as in sequence variants. Our results indicate that biologically important pockets, as well as their shape and dynamics, are central to understanding protein function in wild-type, polymorphic or disease-related variations.(image)