Δευτέρα, 8 Αυγούστου 2016

Perceptions of undergraduate students on the use of animals in practical classes

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The brain robot "Herr Tie": discovering basic principles of brain function at primary school

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Cold pressor test using strain-gauge plethysmography

This laboratory activity is designed to teach students how to measure forearm muscle blood flow (FBF) to describe the mechanisms of peripheral blood flow thermal regulation in healthy subjects. The cold pressor test (CPT) is the clinical procedure used in the experiment to induce arterial vasoconstriction. Strain-gauge plethysmography is applied on the patient's forearm to noninvasive monitor vasoconstriction effects on local blood perfusion and physiological parameters such as blood pressure (BP) and heart rate (HR). Patients with an altered peripheral vascular resistance (e.g., in hypertension) have different responses to the CPT from healthy subjects. To date, experimental evidence remains unexplained, as we do not know if the BP and HR increase is caused by a decrease in flow rate or an increase in peripheral vascular resistance during the test. To clarify this situation, we have to quantify the parameter we assume is being conditioned by the regulatory physiological intervention, i.e., peripheral vascular resistance. Peripheral vascular resistance quantification can be calculated as the ratio between muscle flow and mean arterial pressure. Students will learn how to apply the instrumental procedure to collect and analyze data before, during, and after the CPT and to describe the physiological responses of the peripheral vascular system to external stressors. They will also learn how to distinguish healthy from pathological responses on the basis of how sympathetic nervous system reactions influence the biomechanics of peripheral vessels.



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Electrophysiology for biomedical engineering students: a practical and theoretical course in animal electrocorticography

The major challenge in laboratory teaching is the application of abstract concepts in simple and direct practical lessons. However, students rarely have the opportunity to participate in a laboratory that combines practical learning with a realistic research experience. In the Biomedical Engineering career, we offer short and optional courses to complement studies for students as they initiate their Graduation Project. The objective of these theoretical and practical courses is to introduce students to the topics of their projects. The present work describes an experience in electrophysiology to teach undergraduate students how to extract cortical information using electrocorticographic techniques. Students actively participate in some parts of the experience and then process and analyze the data obtained with different signal processing tools. In postlaboratory evaluations, students described the course as an exceptional opportunity for students interested in following a postgraduate science program and fully appreciated their contents.



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Engaging medical undergraduates in question making: a novel way to reinforcing learning in physiology

The monotony of conventional didactic lectures makes students less attentive toward learning, and they tend to memorize isolated facts without understanding, just for the sake of passing exams. Therefore, to promote a habit of gaining indepth knowledge of basic sciences in medical undergraduates along with honing of their communication and analytical skills, we introduced this more interactive way of learning. The present study was performed on 99 first-semester medical students. After conventional didactic lectures, students were asked to prepare small conceptual questions on the topic. They were divided into two teams, which were made to ask questions to each other. If a team failed to answer, the student who questioned was supposed to answer to the satisfaction of the other team's student. Data were then obtained by getting feedback from the students on a 10-item questionnaire, and statistical evaluation was done using MS Excel and SPSS. To draft questions, students went through the whole system comprehensively and made questions from every possible aspect of the topic. Some of the questions (30%) were of recall type, but most judged higher cognitive domains. Student feedback revealed that they were satisfied, motivated to read more, and were confident of applying this learning and communication skills in future clinical practice. Students also expressed their desire to implement this activity as a regular feature of the curriculum. The activity resulted in an increase in student perceptions of their knowledge on the topic as well as communicative and analytical skills. This may eventually lead to better learning.



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A method of providing engaging formative feedback to large cohort first-year physiology and anatomy students

A growing body of evidence demonstrates a critical role for effective, meaningful feedback to enhance student learning. Effective feedback can become part of the learning cycle that is not only a learning opportunity for the student but can also be used to inform the teacher and ongoing curriculum development. Feedback is considered particularly important during the first year of university and can even be viewed as a retention strategy that can help attenuate student performance anxieties and solidify perceptions of academic support. Unfortunately, the provision of individualized, timely feedback can be particularly challenging in first-year courses as they tend to be large and diverse cohort classes that pose challenges of time and logistics. Various forms of generic feedback can provide rapid and cost-effect feedback to large cohorts but may be of limited benefit to students other than signaling weaknesses in knowledge. The present study describes a method that was used to provide formative task-related feedback to a large cohort of first-year physiology and anatomy students. Based on student evaluations presented in this study, this method provided feedback in a manner that engaged students, uncovered underlying misconceptions, facilitated peer discussion, and provided opportunity for new instruction while allowing the lecturer to recognize common gaps in knowledge and inform ongoing curriculum development.



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Changing undergraduate human anatomy and physiology laboratories: perspectives from a large-enrollment course

In the present article, a veteran lecturer of human anatomy and physiology taught several sections of the laboratory component for the first time and shares his observations and analysis from this unique perspective. The article discusses a large-enrollment, content-heavy anatomy and physiology course in relationship to published studies on learning and student self-efficacy. Changes in the laboratory component that could increase student learning are proposed. The author also points out the need for research to assess whether selective curricular changes could increase the depth of understanding and retention of learned material.



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Convergence of visual and whisker responses in the primary somatosensory thalamus (ventral posterior medial region) of the mouse

Sensory signals reach the cortex via sense-specific thalamic nuclei. Here we report that neurons in the primary sensory thalamus of the mouse vibrissal system (the ventral posterior medial region; VPM) can be excited by visual as well as whisker stimuli. Using extracellular electrophysiological recordings from anaesthetized mice we first show that simple light steps can excite a subset of VPM neurons. We then test the ability of the VPM to respond to spatial patterns and show that many units are excited by visual motion in a direction selective manner. Coherent movement of multiple objects (an artificial recreation of 'optic flow' that would usually occur during head rotations or body movements) best engages this visual motion response. We next show that, when co-applied with visual stimuli, the magnitude of responses to whisker deflections is highest in the presence of optic flow going in the opposite direction. Importantly, whisker response amplitude is also modulated by presentation of a movie recreating the mouse's visual experience during natural exploratory behaviour. We finally present functional and anatomical data indicating a functional connection (likely multisynaptic) from the primary visual cortex to VPM. These data provide a rare example of multisensory integration occurring at the level of the sensory thalamus, and provide evidence for dynamic regulation of whisker responses according to visual experience.

This article is protected by copyright. All rights reserved



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Granulomatosis with polyangiitis-associated acute subglottic stenosis in a 13-year-old boy: a case report

Summary

We present a case of a child with granulomatosis with polyangiitis, admitted with acute respiratory distress attributed to subglottic stenosis. The anesthetic management and potential complications are described.



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Perioperative complications and outcomes in children with cerebral palsy undergoing scoliosis surgery

Summary

Introduction

Neuromuscular scoliosis is a known risk factor for postoperative complications after corrective spine surgery. Few studies have looked at the preoperative factors affecting postoperative complications in children with cerebral palsy.

Aim

The aim of this study was to examine the factors that might influence postoperative course in patients with cerebral palsy undergoing spine surgery for scoliosis.

Methods

Nineteen case notes of children with cerebral palsy who had spine surgery (2008–2014) were reviewed retrospectively. Preoperative comorbidities and postoperative complications were noted and complications were classified as major and minor.

Results

Thirteen out of 19 (68.4%) patients had two or more systemic comorbidities. Most common comorbidities included reflux and seizure disorder. Nine patients (49%) had at least one major complication. About 5/19 patients had respiratory complications requiring ventilation and 4/19 had massive blood loss. A higher incidence of postoperative major complication was recorded in the group with two systemic comorbidities as compared to those with less than two systemic comorbidities (47% vs 16%). Both patients who had a single-stage anterior release and posterior fixation had a major complication.

Conclusion

Presence of two or more comorbidities and thoracotomy are risk factors for perioperative complications in children with cerebral palsy undergoing surgery for scoliosis correction.

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Distribution of sul genes and their variants in uropathogenic Escherichia coli isolated from two hospitals of Sabah

2016-08-08T09-49-24Z
Source: Asian Journal of Medical and Biological Research
Zaw Lin, Yun Mei Lai, Myo Thura Zaw and Ahmad Toha Samsudin.
Sulphonamides resistant strains are highly prevalent in uropathogenic Escherichia coli (UPEC) isolates. Sul genes encode sulphonamide resistance and are present on transferrable plasmids. Integrons (IGNs) are genetic elements containing integrase gene, attl site and gene cassettes which carry multiple antibiotic resistant genes. Class 1 integrons have been extensively studied because these were most prevalent among clinical isolates. In this study, UPEC isolates were determined for the antibiotic susceptibility patterns to four antibiotics commonly used for urinary tract infections, which include co-trimethoxazole (TMP-STX). Distribution of sul genes and integrase1 gene (intI1) was studied in TMP-STX resistant UPEC isolates by using multiplex polymerase chain reaction (mPCR). Sul genes variants were investigated by DNA sequencing of the whole open reading frame of sul1 and sul2 genes and PCR product of sul3 gene. Sul1, sul2 and sul3 genes were prevalent in 37 (24.7%) of 150 UPEC isolates. IntI1 is positive in 22 sul genes positive isolates. Of six isolates positive with sul2 genes, sul2(a) and sul2(b) variants, which were described in the previous study, in the four isolates and the two isolates respectively were observed. This is the first mPCR which investigates the prevalence of three sul genes and intI1 in the UPEC clinical isolates from two hospitals of Sabah.


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Identification of susceptibility gene associated with female primary Sjögren’s syndrome in Han Chinese by genome-wide association study

Abstract

Primary Sjögren's syndrome (PSS) is an autoimmune disease targeting exocrine glands. It ten times more dominantly affects women than men with an onset peak at menopause. The genetic factor predisposing women to PSS remains unclear. Therefore, we aimed to identify susceptibility loci for PSS in women. We performed genome-wide association study (GWAS) using 242 female PSS patients and 1444 female control in Han Chinese population residing in Taiwan. Replication was conducted in an independent cohort of 178 female PSS and 14,432 control subjects. We identified rs117026326 on GTF2I with GWAS significance (P = 1.10 × 10−15) and rs13079920 on RBMS3 with suggestive significance (P = 2.90 × 10−5) associating with PSS in women. The association of RBMS3 was further evidenced by imputation in which rs13072846 (P = 4.89 × 10−5) was identified and confirmed as female PSS associating SNP within the same LD with rs13079920. PSS pathogenesis involves both immune (effector) and exocrine (target) system. We suggested that while GTF2I is a previously reported associating gene which may function in immune system, RBMS3 is a novel susceptibility gene that predisposes women to PSS potentially through modulating acinar apoptosis and TGF-β signaling in target exocrine system.



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Interactions between Glu-1 and Glu-3 loci and associations of selected molecular markers with quality traits in winter wheat ( Triticum aestivum L.) DH lines

Abstract

The quality of wheat depends on a large complex of genes and environmental factors. The objective of this study was to identify quantitative trait loci controlling technological quality traits and their stability across environments, and to assess the impact of interaction between alleles at loci Glu-1 and Glu-3 on grain quality. DH lines were evaluated in field experiments over a period of 4 years, and genotyped using simple sequence repeat markers. Lines were analysed for grain yield (GY), thousand grain weight (TGW), protein content (PC), starch content (SC), wet gluten content (WG), Zeleny sedimentation value (ZS), alveograph parameter W (APW), hectolitre weight (HW), and grain hardness (GH). A number of QTLs for these traits were identified in all chromosome groups. The Glu-D1 locus influenced TGW, PC, SC, WG, ZS, APW, GH, while locus Glu-B1 affected only PC, ZS, and WG. Most important marker-trait associations were found on chromosomes 1D and 5D. Significant effects of interaction between Glu-1 and Glu-3 loci on technological properties were recorded, and in all types of this interaction positive effects of Glu-D1 locus on grain quality were observed, whereas effects of Glu-B1 locus depended on alleles at Glu-3 loci. Effects of Glu-A3 and Glu-D3 loci per se were not significant, while their interaction with alleles present at other loci encoding HMW and LMW were important. These results indicate that selection of wheat genotypes with predicted good bread-making properties should be based on the allelic composition both in Glu-1 and Glu-3 loci, and confirm the predominant effect of Glu-D1d allele on technological properties of wheat grains.



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Paramedic - Lifeguard Ambulance Services

SUMMARY: Administers life support care to sick and injured persons in pre-hospital setting as authorized and directed by physician. Conducts advanced life support skills as allowed by the local, state and federal protocols and assists in the delivery of seriously ill or injured patients to appropriate medical facility personnel. Provides basic information relative to identification and condition of ...

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Full-Term Small-for-Gestational-Age Newborns in the U.S.: Characteristics, Trends, and Morbidity

Abstract

Objectives The magnitude, characteristics, and morbidity of term (≥37 weeks gestation) newborns that are small-for-gestational-age (SGA) in the U.S. are underexplored. We sought to examine characteristics and trends for SGA-coded term newborns in the U.S. Methods Data were obtained from the Nationwide Inpatient Sample, a nationally representative database of hospital stays in the U.S. from 2002 to 2011. Term, singleton newborns with SGA codes were identified and examined over the study period. Demographic characteristics were compared for term newborns according to presence of SGA codes using χ2 tests. Odds ratios (OR) were calculated to compare morbidities between the two groups, adjusting for relevant demographic and clinical variables. Results In 2011, 15 per 1000 term newborns in the U.S. were coded as SGA, a 29.9 % increase since 2002. Compared with other term newborns, SGA term newborns were significantly (p < 0.05) more likely to be female, receive public insurance, and reside in lower income zip codes. Comorbidities, including perinatal complications, metabolic disorders, central nervous system diseases, infection, and neonatal abstinence syndrome were more common among SGA-coded term newborns. These newborns also had higher odds of in-hospital death (OR = 3.0 95 % confidence interval: 2.0, 4.4), longer mean length of stay (3.7 vs. 2.3 days, p < 0.001), and higher mean hospital charges ($12,621 vs. $5012, p < 0.001). Conclusions for practice Term newborns coded as SGA have higher morbidity, mortality, and incur higher hospital charges than other term newborns. More research is needed to understand causes of SGA so its incidence and effects can be reduced.



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Prehospital use of ketamine

Watch this video about the mechanism of action, indications and administration routes for prehospital use of ketamine.  After watching read the Ketamine Drug Why article and three reasons to use ketamine for prehospital analgesia. 

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Maternal uniparental disomy for chromosome 6 in a patient with IUGR, ambiguous genitalia, and persistent mullerian structures

Maternal uniparental disomy of chromosome 6 [upd(6)mat] is rare and has only been previously reported 13 times with the main associated phenotype being IUGR. We present a case of a male patient with isodisomy upd(6)mat resulting in severe IUGR and ambiguous genitalia, a phenotype not previously described in association with this chromosome finding. The patient initially presented prenatally with IUGR at 19 weeks gestation with placental dysfunction and ambiguous genitalia noted at 27 weeks. Postnatally, the patient had external genital abnormalities, the gonads were in the inguinal canal and there was a rudimentary appearing vagina and uterus. Karyotype is 46, XY and SNP array revealed maternal isodisomy of 171 Mb at 6p25.3q27 with no pathogenic copy number variants. To our best knowledge, this is the first case of an XY patient with upd(6)mat with IUGR and ambiguous genitalia, further supporting previous reports regarding an association between upd(6)mat and IUGR. This patient also presented with a disorder of sex development (46, XY DSD) with the sex chromosome being male and positive for the SRY gene, testicular gonadal sex and abnormal external and internal genitalia. © 2016 Wiley Periodicals, Inc.



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Prehospital use of ketamine

Watch this video about the mechanism of action, indications and administration routes for prehospital use of ketamine.  After watching read the Ketamine Drug Why article and three reasons to use ketamine for prehospital analgesia. 

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Prehospital use of ketamine

Watch this video about the mechanism of action, indications and administration routes for prehospital use of ketamine.  After watching read the Ketamine Drug Why article and three reasons to use ketamine for prehospital analgesia. 

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Prehospital use of ketamine

Watch this video about the mechanism of action, indications and administration routes for prehospital use of ketamine.  After watching read the Ketamine Drug Why article and three reasons to use ketamine for prehospital analgesia. 

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Epigenetic regulation of the formyl peptide receptor 2 gene

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Felice Simiele, Antonio Recchiuti, Sara Patruno, Roberto Plebani, Anna Maria Pierdomenico, Marilina Codagnone, Mario Romano
Lipoxin (LX) A4, a main stop signal of inflammation, exerts potent bioactions by activating a specific G protein-coupled receptor, termed formyl peptide receptor 2 and recently renamed ALX/FPR2. Knowledge of the regulatory mechanisms that drive ALX/FPR2 gene expression is key for the development of innovative anti-inflammatory pharmacology. Here, we examined chromatin patterns of the ALX/FPR2 gene. We report that in MDA-MB231 breast cancer cells, the ALX/FPR2 gene undergoes epigenetic silencing characterized by low acetylation at lysine 27 and trimethylation at lysine 4, associated with high methylation at lysine 27 of histone 3. This pattern, which is consistent with transcriptionally inaccessible chromatin leading to low ALX/FPR2 mRNA and protein expression, is reversed in polymorphonuclear leukocytes that express high ALX/FPR2 levels. Activation of p300 histone acetyltransferase and inhibition of DNA methyltransferase restored chromatin accessibility and significantly increased ALX/FPR2 mRNA transcription and protein levels in MDA-MB231 cells, as well as in pulmonary artery endothelial cells. In both cells types, changes in the histone acetylation/methylation status enhanced ALX/FPR2 signaling in response to LXA4. Collectively, these results uncover unappreciated epigenetic regulation of ALX/FPR2 expression that can be exploited for innovative approaches to inflammatory disorders.



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Effects of σ factor competition are promoter initiation kinetics dependent

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Vinodh K. Kandavalli, Huy Tran, Andre S. Ribeiro
In Escherichia coli, the expression of a σ factor is expected to indirectly down-regulate the expression of genes recognized by another σ factor, due to σ factor competition for a limited pool of RNA polymerase core enzymes. Evidence suggests that the sensitivity of genes to indirect down-regulation differs widely. We studied the variability in this sensitivity in promoters primarily recognized by RNAP holoenzymes carrying σ70. From qPCR and live single-cell, single-RNA measurements of the transcription kinetics of several σ70-dependent promoters in various conditions and from the analysis of σ factors population-dependent models of transcription initiation, we find that, the smaller is the time-scale of the closed complex formation relative to the open complex formation, the weaker is a promoter's responsiveness to changes in σ38 numbers. We conclude that, in E. coli, a promoter's responsiveness to indirect regulation by σ factor competition is determined by the sequence-dependent kinetics of the rate limiting steps of transcription initiation.

Graphical abstract

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Histone variants in plant transcriptional regulation

Publication date: Available online 10 July 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Danhua Jiang, Frédéric Berger
Chromatin based organization of eukaryotic genome plays a profound role in regulating gene transcription. Nucleosomes form the basic subunits of chromatin by packaging DNA with histone proteins, impeding the access of DNA to transcription factors and RNA polymerases. Exchange of histone variants in nucleosomes alters the properties of nucleosomes and thus modulates DNA exposure during transcriptional regulation. Growing evidence indicates the important function of histone variants in programming transcription during developmental transitions and stress response. Here we review how histone variants and their deposition machineries regulate the nucleosome stability and dynamics, and discuss the link between histone variants and transcriptional regulation in plants. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.



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Integrator complex and transcription regulation: Recent findings and pathophysiology

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Monica Rienzo, Amelia Casamassimi
In the last decade, a novel molecular complex has been added to the RNA polymerase II-mediated transcription machinery as one of the major components. This multiprotein complex, named Integrator, plays a pivotal role in the regulation of most RNA Polymerase II-dependent genes. This complex consists of at least 14 different subunits. However, studies investigating its structure and composition are still lacking. Although it was originally discovered as a complex implicated in the 3′-end formation of noncoding small nuclear RNAs, recent studies indicate additional roles for Integrator in transcription regulation, for example during transcription pause-release and elongation of polymerase, in the biogenesis of transcripts derived from enhancers, as well as in DNA and RNA metabolism for some of its components. Noteworthy, several subunits have been emerging to play roles during development and differentiation; more importantly, their alterations are likely to be involved in several human pathologies, including cancer and lung diseases.



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Plant responses to abiotic stress: The chromatin context of transcriptional regulation

Publication date: Available online 31 July 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): María-Amparo Asensi-Fabado, Anna Amtmann, Giorgio Perrella
The ability of plants to cope with abiotic environmental stresses such as drought, salinity, heat, cold or flooding relies on flexible mechanisms for re-programming gene expression. Over recent years it has become apparent that transcriptional regulation needs to be understood within its structural context. Chromatin, the assembly of DNA with histone proteins, generates a local higher-order structure that impacts on the accessibility and effectiveness of the transcriptional machinery, as well as providing a hub for multiple protein interactions. Several studies have shown that chromatin features such as histone variants and post-translational histone modifications are altered by environmental stress, and they could therefore be primary stress targets that initiate transcriptional stress responses. Alternatively, they could act downstream of stress-induced transcription factors as an integral part of transcriptional activity. A few experimental studies have addressed this 'hen-an-egg' problem in plants and other systems, but to date the causal relationship between dynamic chromatin changes and transcriptional responses under stress is still unclear. In this review we have collated the existing information on concurrent epigenetic and transcriptional responses of plants to abiotic stress, and we have assessed the evidence using a simple theoretical framework of causality scenarios.



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Editorial Board

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Publication date: August 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 8





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Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Anton M. Schwartz, Lidia V. Putlyaeva, Milica Covich, Anna V. Klepikova, Kseniya A. Akulich, Ilya E. Vorontsov, Kirill V. Korneev, Sergey E. Dmitriev, Oleg L. Polanovsky, Svetlana P. Sidorenko, Ivan V. Kulakovskiy, Dmitry V. Kuprash
Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation. Mutations of SP1, STAT6, IRF4, NF-kB, ELF1, TCF3, and SPI1/PU.1 sites resulted in significantly decreased promoter activity of varying magnitude, depending on the cell line tested. The most profound effect on the promoter strength was observed upon mutation of the binding site for Early B-cell factor 1 (EBF1). This mutation produced a 10–20 fold drop in promoter activity and pinpointed EBF1 as the master regulator of human SLAMF1 gene in B cells. We also identified three potent transcriptional enhancers in human SLAMF1 locus, each containing functional EBF1 binding sites. Thus, EBF1 interacts with specific binding sites located both in the promoter and in the enhancer regions of the SLAMF1 gene and is critical for its expression in human B cells.



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Global regulation of alternative RNA splicing by the SR-rich protein RBM39

Publication date: August 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 8
Author(s): Sanyue Mai, Xiuhua Qu, Ping Li, Qingjun Ma, Cheng Cao, Xuan Liu
BackgroundRBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood.MethodsIn this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39-RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells.ResultsRBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5′ and 3′ splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65.ConclusionsRBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.General significanceThe current study offers a genome-wide view of RBM39's regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels.



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ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation

Publication date: Available online 21 July 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Hu Chen, Renqiang Yuan, Ying Zhang, Xumeng Zhang, Luxi Chen, Xingyu Zhou, Zhuning Yuan, Yaping Nie, Ming Li, Delin Mo, Yaosheng Chen
Activating transcription factor 4 (ATF4), which is highly expressed in 3T3-L1 adipocytes after adipogenic induction, is essential for adipocytes differentiation. ATF4 also plays a vital role in regulating fatty acids biosynthesis, whereas the detailed mechanism of this process is still unclear. Here we demonstrated that siRNA-based ATF4 depletion in 3T3-L1 adipocytes significantly reduced the accumulation of fatty acids and triglycerides. Moreover, SREBP1c protein, which is an important transcription factor of lipogenesis, appreciably decreased while Srebp1c mRNA increased. Then we identified that ATF4 could maintain SREBP1c protein stability by directly activating the expression of USP7 which deubiquitinates SREBP1c and increases its protein content in cell. Besides, USP7 could restore the synthesis of fatty acids and triglycerides in the absence of ATF4. On the other hand, we found that ATF4 might inhibit the transcription of Srebp1c through TRB3, which is repressed by IBMX and DEX during early adipogenesis. Thus, our data indicate that ATF4 regulates SREBP1c expression to control fatty acids synthesis.



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Activation of Tag1 transposable elements in Arabidopsis dedifferentiating cells and their regulation by CHROMOMETHYLASE 3-mediated CHG methylation

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Asif Khan, Narendra Singh Yadav, Yaakov Morgenstern, Assaf Zemach, Gideon Grafi
Dedifferentiation, that is, the acquisition of stem cell-like state, commonly induced by stress (e.g., protoplasting), is characterized by open chromatin conformation, a chromatin state that could lead to activation of transposable elements (TEs). Here, we studied the activation of the Arabidopsis class II TE Tag1, in which two copies, situated close to each other (near genes) on chromosome 1 are found in Landsberg erecta (Ler) but not in Columbia (Col). We first transformed protoplasts with a construct in which a truncated Tag1 (ΔTag1 non-autonomous) blocks the expression of a reporter gene AtMBD5-GFP and found a relatively high ectopic excision of ΔTag1 accompanied by expression of AtMBD5-GFP in protoplasts derived from Ler compared to Col; further increase was observed in ddm1 (decrease in DNA methylation1) protoplasts (Ler background). Ectopic excision was associated with transcription of the endogenous Tag1 and changes in histone H3 methylation at the promoter region. Focusing on the endogenous Tag1 elements we found low level of excision in Ler protoplasts, which was slightly and strongly enhanced in ddm1 and cmt3 (chromomethylase3) protoplasts, respectively, concomitantly with reduction in Tag1 gene body (GB) CHG methylation and increased Tag1 transcription; strong activation of Tag1 was also observed in cmt3 leaves. Notably, in cmt3, but not in ddm1, Tag1 elements were excised out from their original sites and transposed elsewhere in the genome. Our results suggest that dedifferentiation is associated with Tag1 activation and that CMT3 rather than DDM1 plays a central role in restraining Tag1 activation via inducing GB CHG methylation.



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The complexity of the translation ability of circRNAs

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Javier T. Granados-Riveron, Guillermo Aquino-Jarquin
Circular RNAs (circRNAs) are a new class of long non-coding RNAs that play a potential role in gene expression regulation, acting as efficient microRNAs sponges. The latest surprise concerning circRNAs is that we now know that they can serve as transcriptional activators in human cells, indicating that circRNAs are involved in important regulatory tasks. Recently, new insight has been gained about the coding potential of circular viroid RNAs, as well as the presence of Internal Ribosomal Entry Sites (IRES) allowing the formation of peptides or proteins from circular RNA. Here, we discuss the current state of our knowledge regarding evidence supporting the hypothesis that circRNAs serve as protein-coding sequences in vitro and in vivo. Also, we remark on the difficulties of their identification and highlight some tools currently available for exploring the coding potential of circRNA.



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The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Patrick Connerty, Sarah Bajan, Judit Remenyi, Frances V. Fuller-Pace, Gyorgy Hutvagner
MicroRNAs (miRNAs) are short (21–23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors.Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.



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A 3′UTR polymorphism marks differential KLRG1 mRNA levels through disruption of a miR-584-5p binding site and associates with pemphigus foliaceus susceptibility

Publication date: October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 10
Author(s): Gabriel A. Cipolla, Jong Kook Park, Liana A. de Oliveira, Sara Cristina Lobo-Alves, Rodrigo C. de Almeida, Ticiana D.J. Farias, Débora de S. Lemos, Danielle Malheiros, Robert M. Lavker, Maria Luiza Petzl-Erler
Genetic variations mapping to 3′ untranslated regions (3′UTRs) may overlap with microRNA (miRNA) binding sites, therefore potentially interfering with translation inhibition or messenger RNA (mRNA) degradation. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) located within the 3′UTRs of six candidate genes and predicted to interfere with miRNA ligation could account for disease-relevant differential mRNA levels. Focusing on pemphigus foliaceus (PF) – an autoimmune blistering skin condition with unique endemic patterns – we investigated whether nine 3′UTR SNPs from the CD1D, CTLA4, KLRD1, KLRG1, NKG7, and TNFSF13B genes differentially expressed in PF were disease-associated. The heterozygous genotype of the KLRG1 rs1805672 polymorphism was associated with increased predisposition to PF (A/G vs. A/A: P=0.038; OR=1.60), and a trend for augmented susceptibility was observed for carriers of the G allele (P=0.094; OR=1.44). In silico analyses suggested that rs1805672 G allele could disrupt binding of miR-584-5p, and indicated rs1805672 as an expression Quantitative Trait Locus (eQTL), with an effect on KLRG1 gene expression. Dual-luciferase assay showed that miR-584-5p mediated approximately 50% downregulation of the reporter gene's activity through the 3′UTR of KLRG1 harboring rs1805672 A allele (vs. miRNA-negative condition, P=0.006). This silencing relationship was lost after site-directed mutation to G allele (vs. miRNA-negative condition, P=0.391; vs. rs1805672 A allele, P=0.005). Collectively, these results suggest that a disease-associated SNP located within the 3′UTR of KLRG1 directly interferes with miR-584-5p binding, allowing for KLRG1 mRNA differential accumulation, which in turn may contribute to pathogenesis of autoimmune diseases, such as pemphigus.



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Editorial Board

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Publication date: September 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 9





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More than meets the eye: Emergent properties of transcription factors networks in Arabidopsis

Publication date: Available online 30 July 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Durreshahwar Muhammad, Selene Schmittling, Cranos Williams, Terri A. Long
Uncovering and mathematically modeling Transcription Factors Networks (TFNs) are the first steps in engineering plants with traits that are better equipped to respond to changing environments. Although several plant TFNs are well known, the framework for systematically modeling complex characteristics such as switch-like behavior, oscillations, and homeostasis that emerge from TFNs remain elusive. This review highlights literature that provides, in part, experimental and computational techniques for characterizing TFNs. This review also outlines methodologies that have been used to mathematically model the dynamic characteristics of TFNs. We present several examples of TFNs in plants that are involved in developmental and stress response. In several cases, advanced algorithms capture or quantify emergent properties that serve as the basis for robustness and adaptability in plant responses. Increasing the use of mathematical approaches will shed new light on these regulatory properties that control plant growth and development, leading to mathematical models that predict plant behavior. "This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer".



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Transcriptional and post-transcriptional control of the plant circadian gene regulatory network

Publication date: Available online 10 July 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): C. Esteban Hernando, Andrés Romanowski, Marcelo J. Yanovsky
The circadian clock drives rhythms in multiple physiological processes allowing plants to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of thousands of genes linked to the control of photosynthesis, cell elongation, biotic and abiotic stress responses, developmental processes such as flowering, and the clock itself. Given its pervasive effects on plant physiology, it is not surprising that circadian clock genes have played an important role in the domestication of crop plants and in the improvement of crop productivity. Therefore, identifying the principles governing the dynamics of the circadian gene regulatory network in plants could strongly contribute to further speed up crop improvement. Here we provide an historical as well as a current description of our knowledge of the molecular mechanisms underlying circadian rhythms in plants. This work focuses on the transcriptional and post-transcriptional regulatory layers that control the very core of the circadian clock, and some of its complex interactions with signaling pathways that help synchronize plant growth and development to daily and seasonal changes in the environment.This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.



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Temporal Control of Dickeya dadantii Main Virulence Gene Expression by Growth Phase-Dependent Alteration of Regulatory Nucleoprotein Complexes

Publication date: Available online 5 August 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Alexandre Duprey, Georgi Muskhelishvili, Sylvie Reverchon, William Nasser
In bacteria, important genes are often controlled at the transcriptional level by several factors, forming a complex and intertwined web of interactions. Yet, transcriptional regulators are often studied separately and little information is available concerning their interactions. In this work, we dissect the regulation of the major virulence gene pelD in D. dadantii by taking into account the effects of individual binding sites for regulatory proteins FIS and CRP, and the impact of a newly discovered divergent promoter div. Using a combination of biochemistry and genetics approaches we provide an unprecedented level of detail on the multifactorial regulation of bacterial transcription. We show that the growth phase dependent regulation of pelD is under the control of changing composition of higher-order nucleoprotein complexes between FIS, CRP, div and pelD during the growth cycle that allow sequential expression of div and pelD in the early and late exponential growth phases, respectively. This work highlights the importance of "orphan" promoters in gene regulation and that the individual binding sites for a regulator can serve several purposes and have different effects on transcription, adding a new level of complexity to bacterial transcriptional regulation.

Graphical abstract

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Plant Elongator-mediated transcriptional control in a chromatin and epigenetic context

Publication date: August 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 8
Author(s): Magdalena Woloszynska, Sabine Le Gall, Mieke Van Lijsebettens
Elongator (Elp) genes were identified in plants by the leaf growth-altering elo mutations in the yeast (Saccharomyces cerevisiae) gene homologs. Protein purification of the Elongator complex from Arabidopsis thaliana cell cultures confirmed its conserved structure and composition. The Elongator function in plant growth, development, and immune response is well-documented in the elp/elo mutants and correlated with the histone acetyl transferase activity of the ELP3/ELO3 subunit at the coding part of key regulatory genes of developmental and immune response pathways. Here we will focus on additional roles in transcription, such as the cytosine demethylation activity of ELP3/ELO3 at gene promoter regions and primary microRNA transcription and processing through the ELP2 subunit interaction with components of the small interference RNA machinery. Furthermore, specific interactions and upstream regulators support a role for Elongator in transcription and might reveal mechanistic insights into the specificity of the histone acetyl transferase and cytosine demethylation activities for target genes.



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MDR1 mediated chemoresistance: BMI1 and TIP60 in action

Publication date: August 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1859, Issue 8
Author(s): Soumyajit Banerjee Mustafi, Prabir Kumar Chakraborty, Sarwat Naz, Shailendra Kumar Dhar Dwivedi, Mark Street, Rumki Basak, Da Yang, Kai Ding, Priyabrata Mukherjee, Resham Bhattacharya
Chemotherapy-induced emergence of drug resistant cells is frequently observed and is exemplified by the expression of family of drug resistance proteins including, multidrug resistance protein 1 (MDR1). However, a concise mechanism for chemotherapy-induced MDR1 expression is unclear. Mechanistically, mutational selection, epigenetic alteration, activation of the Wnt pathway or impaired p53 function have been implicated. The present study describes that the surviving fraction of cisplatin resistant cells co- upregulate MDR1, BMI1 and acetyl transferase activity of TIP60. Using complementary gain and loss of function approaches, we demonstrate that the expression of MDR1 is positively regulated by BMI1, a stem-cell factor classically known as a transcriptional repressor. Our study establishes a functional interaction between TIP60 and BMI-1 resulting in upregulation of MDR1 expression. Chromatin immunoprecipitation (ChIP) assays further establish that the proximal MDR1 promoter responds to cisplatin in a BMI1 dependent manner. BMI1 interacts with a cluster of E-box elements on the MDR1 promoter and recruits TIP60 resulting in acetylation of histone H2A and H3. Collectively, our data establish a hitherto unknown liaison among MDR1, BMI1 and TIP60 and provide mechanistic insights into cisplatin-induced MDR1 expression resulting in acquired cross-resistance against paclitaxel, doxorubicin and likely other drugs. In conclusion, our results advocate utilizing anti-BMI1 strategies to alleviate acquired resistance to chemotherapy.

Graphical abstract

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Gene-regulatory networks controlling inflorescence and flower development in Arabidopsis thaliana

Publication date: Available online 31 July 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Christopher Ralf Wils, Kerstin Kaufmann
Reproductive development in plants is controlled by complex and intricate gene-regulatory networks of transcription factors. These networks integrate the information from endogenous, hormonal and environmental regulatory pathways. Many of the key players have been identified in Arabidopsis and other flowering plant species, and their interactions and molecular modes of action are being elucidated. An emerging theme is that there is extensive crosstalk between different pathways, which can be accomplished at the molecular level by modulation of transcription factor activity or of their downstream targets. In this review, we aim to summarize current knowledge on transcription factors and epigenetic regulators that control basic developmental programs during inflorescence and flower morphogenesis in the model plant Arabidopsis thaliana.This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.



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Sprinkling of neural dust opens door to electroceuticals

University of California Berkeley Health News

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Diagnosis accuracy of transcutaneous bilirubinometry in very preterm newborns

Neonatology

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Sofosbuvir plus daclatasvir with or without ribavirin for chronic hepatitis C infection: Impact of drug concentration on viral load decay

Digestive and Liver Diseases

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Prediction models of mortality in acute pancreatitis in adults: a systematic review

Annals of Internal Medicine

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Vitamin D deficiency in non-alcoholic fatty liver disease

Clinical Nutrition

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Methylation quantitative trait loci within the TOMM20 gene are associated with metabolic syndrome-related lipid alterations in severely obese subjects

Diabetology & Metabolic Syndrome

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Use of antibiotics among patients with cirrhosis and upper gastrointestinal bleeding is associated with reduced mortality

Clinical Gastroenterology and Hepatology

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A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn’s disease

The American Journal of Gastroenterology

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Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome

Alimentary Pharmacology and Therapeutics

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Role of conserved E2 residue W420 in receptor binding and hepatitis C virus infection

Journal of Virology

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Risk of gastric cancer among patients with intestinal metaplasia of the stomach in a United States integrated healthcare system

Clinical Gastroenterology and Hepatology

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Relation of serum irisin level with metabolic and antropometric parameters in obese children

Journal of Diabetes and its Complications

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Association between results of a gene expression signature assay and recurrence-free interval in patients with stage II colon cancer in cancer and leukemia group B 9581

Journal of Clinical Oncology

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A case of acute esophageal necrosis and duodenal disease in a patient with adrenal insufficiency

Clinical Gastroenterology and Hepatology

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Epidemiology of hepatitis C virus and genotype distribution in immigrants crossing to Europe from north and sub-Saharan Africa

Travel Medicine and Infectious Disease

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AGA establishes NIH-funded registry to track fecal microbiota transplants

American Gastroenterological Association News

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