bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catching a Virus in the Act of RNA Release: a Novel Poliovirus Uncoating Intermediate Characterized by Cryo-Electron Microscopy
Authors: Levy Hazel C. , Bostina Mihnea , Filman David J. , Hogle James M. 
Published: February 2010

ABSTRACT
Poliovirus infection requires that the particle undergo a series of conformational transitions that lead to cell entry and genome release. In an effort to understand the conformational changes associated with the release of the RNA genome, we have used cryo-electron microscopy to characterize the structure of the 80S “empty” particles of poliovirus that are thought to represent the final product of the cell entry pathway. Using two-dimensional classification methods, we show that preparations of 80S particles contain at least two structures, which might represent snapshots from a continuous series of conformers. Using three-dimensional reconstruction methods, we have solved the structure of two distinct forms at subnanometric resolution, and we have built and refined pseudoatomic models into the reconstructions. The reconstructions and the derived models demonstrate that the two structural forms are both slightly expanded, resulting in partial disruption of interprotomer interfaces near their particle 2-fold axes, which may represent the site where RNA is released. The models demonstrate that each of the two 80S structures has undergone a unique set of movements of the capsid proteins, associated with rearrangement of flexible loops and amino-terminal extensions that participate in contacts between protomers, between pentamers, and with the viral RNA.
The m74 Gene Product of Murine Cytomegalovirus (MCMV) Is a Functional Homolog of Human CMV gO and Determines the Entry Pathway of MCMV
Authors: Scrivano Laura , Esterlechner Jasmina , Mühlbach Hermine , Ettischer Nicole , Hagen Christoph , Grünewald Kay , Mohr Christian A. , Ruzsics Zsolt , Koszinowski Ulrich , Adler Barbara 
Published: February 2010

ABSTRACT
The glycoprotein gO (UL74) of human cytomegalovirus (HCMV) forms a complex with gH/gL. Virus mutants with a deletion of gO show a defect in secondary envelopment with the consequence that virus spread is restricted to a cell-associated pathway. Here we report that the positional homolog of HCMV gO, m74 of mouse CMV (MCMV), codes for a glycosylated protein which also forms a complex with gH (M75). m74 knockout mutants of MCMV show the same spread phenotype as gO knockout mutants of HCMV, namely, a shift from supernatant-driven to cell-associated spread. We could show that this phenotype is due to a reduction of infectious virus particles in cell culture supernatants. m74 knockout mutants enter fibroblasts via an energy-dependent and pH-sensitive pathway, whereas in the presence of an intact m74 gene product, entry is neither energy dependent nor pH sensitive. This entry phenotype is shared by HCMV expressing or lacking gO. Our data indicate that the m74 and UL74 gene products both codetermine CMV spread and CMV entry into cells. We postulate that MCMV, like HCMV, expresses alternative gH/gL complexes which govern cell-to-cell spread of the virus.
FUZZY CAUSAL MAPPING (F-CMAP) — A PROPOSAL TO DEVELOP A NEW SYSTEMS BIOLOGY TOOL
Authors: WEINREB GABRIEL , CAO PAUL Y. 
Published: February 2010

Biological systems are complex, consisting of many elements of different nature. As a whole, they are robust, and a general system description can be done in a semi-quantitative way when it comes to phenotype behaviors. We used these properties earlier1 to develop a new systems biology method, causal mapping (CMAP). In this paper, we pinpoint some problems with the earlier version of CMAP, and develop it further. CMAP used linguistic variables (LV) to describe the behaviour of biological systems, and here we use the procedure of fuzzyfications to improve CMAP. The numerical methods to calculate the ranges of LV are agreeable to reality in a very intuitive manner. The new version of CMAP reproduced the physical data on cortical oscillations2 in spreading cells with depolymerized microtubules. Further, predictions were made on the dependency of the myosin activity on the period of oscillations. The presented development lies on the way to a more general approach that should be able to address questions of biological robustness, modularity and hierarchy.
Effects of Restless Legs Syndrome on Quality of Life and Psychological Status in Patients With Type 2 Diabetes
Authors: Merlino Giovanni , Valente Mariarosaria , Serafini Anna , Fratticci Lara , Del Giudice Angela , Piani Antonella , Noacco Claudio , Gigli Gian Luigi 
Published: February 2010

Purpose The purpose of this study was to evaluate the effects of restless legs syndrome (RLS) on quality of life (QoL), anxiety, and depression in people with type 2 diabetes. Methods One hundred twenty-four patients with type 2 diabetes were enrolled in this study. RLS was diagnosed by a neurologist masked on psychological evaluation. Data on severity, frequency, and duration of the sleep disorder were collected. The Italian version of the SF-36 was used to assess QoL. Psychological status was investigated by a neuropsychologist masked on RLS diagnosis. Patients with a diagnosis of generalized anxiety disorder (GAD) and major depressive disorder (MDD) were considered affected by anxiety and depression, respectively. A modified version of the Hamilton Anxiety and Depression Rating Scales (HARS and HDRS) was also administered. Results RLS was an independent predictor for several mental domains of the SF-36 and for the mental component summary. Multivariate analysis showed that RLS was an independent predictor of anxiety and depression. RLS severity correlated with HARS and HDRS scores, whereas frequency per week of RLS had a significant correlation only with HARS score. Conclusions Among individuals with diabetes, RLS can impair mental health, increasing the risk for anxiety and depression. Since RLS consequences on nocturnal rest and psychological status may impair glycemic control in this population, diabetologists and diabetes educators should investigate for the presence of RLS in their patients and treat them.
Autologous Chondrocyte Implantation
Authors: Peterson Lars , Vasiliadis Haris S. , Brittberg Mats , Lindahl Anders 
Published: February 2010

Background: The medium-term results of autologous chondrocyte implantation (ACI) have shown good to excellent outcomes for the majority of patients. However, no long-term results 10 to 20 years after the surgery have been reported. Hypothesis: Autologous chondrocyte implantation provides a durable solution to the treatment of full-thickness cartilage lesions of the knee, maintaining good clinical results even 10 to 20 years after implantation. Study Design: Case series; Level of evidence, 4. Methods: In this uncontrolled study, questionnaires with the Lysholm, Tegner-Wallgren, Brittberg-Peterson, modified Cincinnati (Noyes), and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were sent to 341 patients. Preoperative Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were also retrieved when possible from patients’ files. The patients were asked to grade their status during the past 10 years as better, worse, or unchanged. Finally, they were asked if they would do the operation again. Results: There were 224 of 341 patients who replied to our posted questionnaires and were assessed. The mean cartilage lesion size was 5.3 cm2. Ten to 20 years after the implantation (mean, 12.8 years), 74% of the patients reported their status as better or the same as the previous years. There were 92% who were satisfied and would have the ACI again. The Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were improved compared with the preoperative values. The average Lysholm score improved from 60.3 preoperatively to 69.5 postoperatively, the Tegner from 7.2 to 8.2, and the Brittberg-Peterson from 59.4 to 40.9. At the final measurement, the KOOS score was on average 74.8 for pain, 63 for symptoms, 81 for activities of daily living (ADL), 41.5 for sports, and 49.3 for quality of life (QOL). The average Noyes score was 5.4. Patients with bipolar lesions had a worse final outcome than patients with multiple unipolar lesions. The presence of meniscal injuries before ACI or history of bone marrow procedures before the implantation did not appear to affect the final outcomes. The age at the time of the operation or the size of lesion did not seem to correlate with the final outcome. Conclusion: Autologous chondrocyte implantation has emerged as an effective and durable solution for the treatment of large full-thickness cartilage and osteochondral lesions of the knee joint. Our study suggests that the clinical and functional outcomes remain high even 10 to 20 years after the implantation.
Professional Growth in Turbulent Times
Authors: Baum Nehami , Ramon Shulamit 
Published: February 2010

• Summary: This article examines professional growth among Jewish and Arab social workers in Israel in the wake of the Second Intifada. The paper is based on a further in-depth analysis of data from semi-structured face to face and telephone interviews with 58 social workers. • Findings: The findings show professional growth, in the form of increased skills and knowledge, improved professional identity, and greater team cohesion. The major facilitators of these developments were the recognition and resources the workers received from their society and the support provided by and within their place of employment for coping with their distress and with the tasks they had to perform. Such growth was found among two-thirds of the Jewish workers, and none among the Arab workers. The data analysis outlines likely reasons for these main findings, as well as what facilitates pride in one’s work within the context of violent political conflict, and what does not. • Applications : Implications for future practice and research are highlighted.
RUNX1/core binding factor A2 regulates platelet 12-lipoxygenase gene (ALOX12): studies in human RUNX1 haplodeficiency
Authors: Kaur Gurpreet , Jalagadugula Gauthami , Mao Guangfen , Rao A. Koneti 
Published: February 2010

AbstractHaploinsufficiency of RUNX1 (also known as CBFA2/AML1) is associated with familial thrombocytopenia, platelet dysfunction, and predisposition to acute leukemia. We have reported on a patient with thrombocytopenia and impaired agonist-induced aggregation, secretion, and protein phosphorylation associated with a RUNX1 mutation. Expression profiling of platelets revealed approximately 5-fold decreased expression of 12-lipoxygenase (12-LO, gene ALOX12), which catalyzes 12-hydroxyeicosatetraenoic acid production from arachidonic acid. We hypothesized that ALOX12 is a direct transcriptional target gene of RUNX1. In present studies, agonist-induced platelet 12-HETE production was decreased in the patient. Four RUNX1 consensus sites were identified in the 2-kb promoter region of ALOX12 (at −1498, −1491, −708, −526 from ATG). In luciferase reporter studies in human erythroleukemia cells, mutation of each site decreased activity; overexpression of RUNX1 up-regulated promoter activity, which was abolished by mutation of RUNX1 sites. Gel shift studies, including with recombinant protein, revealed RUNX1 binding to each site. Chromatin immunoprecipitation revealed in vivo RUNX1 binding in the region of interest. siRNA knockdown of RUNX1 decreased RUNX1 and 12-LO proteins. ALOX12 is a direct transcriptional target of RUNX1. Our studies provide further proof of principle that platelet expression profiling can elucidate novel alterations in platelets with inherited dysfunction.
Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma
Authors: Fan Gaofeng , Simmons Matthew J. , Ge Sheng , Dutta-Simmons Jui , Kucharczak Jérôme , Ron Yacov , Weissmann David , Chen Chiann-Chyi , Mukherjee Chandreyee , White Eileen , Gélinas Céline 
Published: February 2010

Abstract
The antiapoptotic Bcl-2 family member Bfl-1 is up-regulated in many human tumors in which nuclear factor-κB (NF-κB) is implicated and contributes significantly to tumor cell survival and chemoresistance. We previously found that NF-κB induces transcription of bfl-1 and that the Bfl-1 protein is also regulated by ubiquitin-mediated proteasomal degradation. However, the role that dysregulation of Bfl-1 turnover plays in cancer is not known. Here we show that ubiquitination-resistant mutants of Bfl-1 display increased stability and greatly accelerated tumor formation in a mouse model of leukemia/lymphoma. We also show that tyrosine kinase Lck is up-regulated and activated in these tumors and leads to activation of the IkappaB kinase, Akt, and extracellular signal-regulated protein kinase signaling pathways, which are key mediators in cancer. Coexpression of Bfl-1 and constitutively active Lck promoted tumor formation, whereas Lck knockdown in tumor-derived cells suppressed leukemia/lymphomagenesis. These data demonstrate that ubiquitination is a critical tumor suppression mechanism regulating Bfl-1 function and suggest that mutations in bfl-1 or in the signaling pathways that control its ubiquitination may predispose one to cancer. Furthermore, because bfl-1 is up-regulated in many human hematopoietic tumors, this finding suggests that strategies to promote Bfl-1 ubiquitination may improve therapy.
Germ band retraction as a landmark in glucose metabolism during Aedes aegypti embryogenesis
Authors: Vital Wagner , Rezende Gustavo Lazzaro , Abreu Leonardo , Moraes Jorge , Lemos Francisco JA , Vaz Itabajara da Silva , Logullo Carlos 
Published: February 2010

AbstractBackgroundThe mosquitoA. aegyptiis vector of dengue and other viruses. New methods of vector control are needed and can be achieved by a better understanding of the life cycle of this insect. Embryogenesis is a part ofA. aegyptylife cycle that is poorly understood. In insects in general and in mosquitoes in particular energetic metabolism is well studied during oogenesis, when the oocyte exhibits fast growth, accumulating carbohydrates, lipids and proteins that will meet the regulatory and metabolic needs of the developing embryo. On the other hand, events related with energetic metabolism duringA. aegyptiembryogenesis are unknown.ResultsGlucose metabolism was investigated throughoutAedes aegypti(Diptera) embryonic development. Both cellular blastoderm formation (CBf, 5 h after egg laying - HAE) and germ band retraction (GBr, 24 HAE) may be considered landmarks regarding glucose 6-phosphate (G6P) destination. We observed high levels of glucose 6-phosphate dehydrogenase (G6PDH) activity at the very beginning of embryogenesis, which nevertheless decreased up to 5 HAE. This activity is correlated with the need for nucleotide precursors generated by the pentose phosphate pathway (PPP), of which G6PDH is the key enzyme. We suggest the synchronism of egg metabolism with carbohydrate distribution based on the decreasing levels of phosphoenolpyruvate carboxykinase (PEPCK) activity and on the elevation observed in protein content up to 24 HAE. Concomitantly, increasing levels of hexokinase (HK) and pyruvate kinase (PK) activity were observed, and PEPCK reached a peak around 48 HAE. Glycogen synthase kinase (GSK3) activity was also monitored and shown to be inversely correlated with glycogen distribution during embryogenesis.ConclusionsThe results herein support the hypothesis that glucose metabolic fate changes according to developmental embryonic stages. Germ band retraction is a moment that was characterized as a landmark in glucose metabolism duringAedes aegyptiembryogenesis. Furthermore, the results also suggest a role for GSK3 in glycogen balance/distribution during morphological modifications.
Comparative genomics of VirR regulons in Clostridium perfringens strains
Authors: Frandi Antonio , Mengoni Alessio , Brilli Matteo 
Published: February 2010

Abstract

Background

Clostridium perfringens is a Gram-positive anaerobic bacterium causing severe diseases such as gas gangrene and pseudomembranosus colitis, that are generally due to the secretion of powerful extracellular toxins. The expression of toxin genes is mainly regulated by VirR, the response regulator of a two-component system. Up to now few targets only are known for this regulator and mainly in one strain (Strain 13). Due to the high genomic and phenotypic variability in toxin production by different strains, the development of effective strategies to counteract C. perfringens infections requires methodologies to reconstruct the VirR regulon from genome sequences.

Results
We implemented a two step computational strategy allowing to consider available information concerning VirR binding sites in a few species to scan all genomes of the same species, assuming the VirR targets are at least partially conserved across these strains. Results obtained are in agreement with previous works where experimental validation of the promoters have been performed and showed the presence of a core and an accessory regulon of VirR in C. perfringens strains with three target genes also located on plasmids. Moreover, the type E strain JGS1987 has the largest predicted regulon with as many as 10 VirR targets not found in the other genomes.

Conclusions
In this work we exploited available experimental information concerning the targets of the VirR toxin regulator in one C. perfringens strain to obtain plausible predictions concerning target genes in genomes and plasmids of nearby strains. Our predictions are available for wet-lab researchers working on less characterized C. perfringens strains that can thus design focused experiments reducing the search space of their experiments and increasing the probability of characterizing positive targets with less efforts. Main result was that the VirR regulon is variable in different C. perfringens strains with 4 genes controlled in all but one strains and most genes controlled in one or two strains only.
The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity
Authors: Chen Wanqun , Zhang Xinhua , Shang Xuan , Cai Ren , Li Liyan , Zhou Tianhong , Sun Manna , Xiong Fu , Xu Xiangmin 
Published: February 2010

Abstract

Background
The clinical syndrome of thalassemia intermedia (TI) results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF) and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients.

Methods
We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations.

Results
A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20) in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited αααanti-3.7 triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β+-thalassemia mutation was the most common (49/97), hemoglobin E (HbE) variants was second (27/97), and deletional hereditary persistence of fetal hemoglobin (HPFH) or δβ-thalassemia was third (11/97). Two novel mutations, Term CD+32(A→C) and Cap+39(C→T), have been detected.

Conclusions
Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β0/βN and 1 β+/βN) with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β0/β0), the existence of other causative genetic determinants is remaining to be molecularly defined.
The 4q27 locus and prostate cancer risk
Authors: Tindall Elizabeth A , Hoang Hoa N , Southey Melissa C , English Dallas R , Hopper John L , Giles Graham G , Severi Gianluca , Hayes Vanessa M 
Published: February 2010

Abstract

Background
Chronic inflammation is considered to be implicated in the development of prostate cancer. In this study we are the first to investigate a potential association between variants in an autoimmune related region on chromosome 4q27 and prostate cancer risk. This region harbors two cytokine genes IL-2 and the recently described IL-21.

Methods
We genotyped six variants previously associated with autoimmune disease (namely rs13151961, rs13119723, rs17388568, rs3136534, rs6822844 and rs6840978) and one functional IL-2 promoter variant (rs2069762) for possible association with prostate cancer risk using the Australian Risk Factors for Prostate Cancer case-control Study.

Results
Overall, our results do not support an association between the seven variants at position 4q27 and prostate cancer risk. Per allele odds ratios (ORs) were not significantly different from 1 (all P-values = 0.06). However, we found suggestive evidence for a significant association between the presence of the rs13119723 variant (located in a protein of unknown function) and men with a family history of prostate cancer in first-degree relatives (P-value for interaction 0.02). The per allele OR associated with this variant was significantly higher than 1 (2.37; 95% C.I. = 1.01-5.57).

Conclusions
We suggest that genetic variation within the chromosome 4q27 locus might be associated with prostate cancer susceptibility in men with a family history of the disease. Furthermore, our study alludes to a potential role of unknown protein KIAA1109 in conferring this risk.
Nav2 is necessary for cranial nerve development and blood pressure regulation
Authors: McNeill Elizabeth M , Roos Kenneth P , Moechars Dieder , Clagett-Dame Margaret 
Published: February 2010

Abstract
Background
All-trans retinoic acid (atRA) is required for nervous system development, including the developing hindbrain region. Neuron navigator 2 (Nav2) was first identified as an atRA-responsive gene in human neuroblastoma cells (retinoic acid-induced in neuroblastoma 1, Rainb1), and is required for atRA-mediated neurite outgrowth. In this paper, we explore the importance of Nav2 in nervous system development and function in vivo.

Results
Nav2 hypomorphic homozygous mutants show decreased survival starting at birth. Nav2 mutant embryos show an overall reduction in nerve fiber density, as well as specific defects in cranial nerves IX (glossopharyngeal) and X (vagus). Nav2 hypomorphic mutant adult mice also display a blunted baroreceptor response compared to wild-type controls.

Conclusions
Nav2 functions in mammalian nervous system development, and is required for normal cranial nerve development and blood pressure regulation in the adult.