bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency and spectrum of mitochondrial 12S rRNA variants in 440 Han Chinese hearing impaired pediatric subjects from two otology clinics
Authors: Shen Zhisen , Zheng Jing , Chen Bobei , Peng Guanghua , Zhang Ting , Gong Shasha , Zhu Yi , Zhang Chuqin , Li Ronghua , Yang Li , Zhou Jianjin , Cai Ting , Jin Lihua , Lu Jianxin , Guan Min-Xin 
Published: January 2011

Abstract

Background
Aminoglycoside ototoxicity is one of the common health problems. Mitochondrial 12S rRNA mutations are one of the important causes of aminoglycoside ototoxicity. However, the incidences of 12S rRNA mutations associated with aminoglycoside ototoxicity are less known.

Methods
A total of 440 Chinese pediatric hearing-impaired subjects were recruited from two otology clinics in the Ningbo and Wenzhou cities of Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of mitochondrial 12S rRNA. Resultant mtDNA variants were evaluated by structural and phylogenetic analysis.

Results
The study samples consisted of 227 males and 213 females. The age of all participants ranged from 1 years old to 18 years, with the median age of 9 years. Ninety-eight subjects (58 males and 40 females) had a history of exposure to aminoglycosides, accounting for 22.3% cases of hearing loss in this cohort. Molecular analysis of 12S rRNA gene identified 41 (39 known and 2 novel) variants. The incidences of the known deafness-associated 1555A > G, 1494C > T and 1095T > C mutations were 7.5%, 0.45% and 0.91% in this entire hearing-impaired subjects, respectively, and 21.4%, 2% and 2% among 98 subjects with aminoglycoside ototoxicity, respectively. The structural and phylogenetic evaluations showed that a novel 747A > G variant and known 839A > G, 1027A > G, 1310C > T and 1413T > C variants conferred increased sensitivity to aminoglycosides or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants were polymorphisms. Of 44 subjects carrying one of definite or putative deafness-related 12S rRNA variants, only one subject carrying the 1413T > C variant harbored the 235DelC/299DelAT mutations in the GJB2 gene, while none of mutations in GJB2 gene was detected in other 43 subjects.

Conclusions
Mutations in mitochondrial 12S rRNA accounted for ~30% cases of aminoglycoside-induced deafness in this cohort. Our data strongly support the idea that the mitochondrial 12S rRNA is the hot spot for mutations associated with aminoglycoside ototoxicity. These data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.
A high-throughput chemically induced inflammation assay in zebrafish
Authors: d'Alençon Claudia A , Peña Oscar A , Wittmann Christine , Gallardo Viviana E , Jones Rebecca A , Loosli Felix , Liebel Urban , Grabher Clemens , Allende Miguel L 
Published: January 2011

Abstract

Background
Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening.

Results
Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction.

Conclusions
This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay.
See Commentary article: http://www.biomedcentral.com/1741-7007/8/148.
The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop
Authors: Stoye Jonathan P , Silverman Robert H , Boucher Charles A , Le Grice Stuart FJ 
Published: January 2011

Abstract
The 1st International Workshop on Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV), co-sponsored by the National Institutes of Health, The Department of Health and Human Services and Abbott Diagnostics, was convened on September 7/8, 2010 on the NIH campus, Bethesda, MD. Attracting an international audience of over 200 participants, the 2-day event combined a series of plenary talks with updates on different aspects of XMRV research, addressing basic gammaretrovirus biology, host response, association of XMRV with chronic fatigue syndrome and prostate cancer, assay development and epidemiology. The current status of XMRV research, concerns among the scientific community and suggestions for future actions are summarized in this meeting report.
Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1
Authors: White Laura F , Pagano Marcello 
Published: January 2011

AbstractBackgroundEffectively responding to infectious disease outbreaks requires a well-informed response. Quantitative methods for analyzing outbreak data and estimating key parameters to characterize the spread of the outbreak, including the reproductive number and the serial interval, often assume that the data collected is complete. In reality reporting delays, undetected cases or lack of sensitive and specific tests to diagnose disease lead to reporting errors in the case counts. Here we provide insight on the impact that such reporting errors might have on the estimation of these key parameters.ResultsWe show that when the proportion of cases reported is changing through the study period, the estimates of key epidemiological parameters are biased. Using data from the Influenza A/H1N1 outbreak in La Gloria, Mexico, we provide estimates of these parameters, accounting for possible reporting errors, and show that they can be biased by as much as 33%, if reporting issues are not accounted for.ConclusionsFailure to account for missing data can lead to misleading and inaccurate estimates of epidemic parameters.
Neural networks engaged in tactile object manipulation: patterns of expression among healthy individuals
Authors: Kägi Georg , Missimer John H , Abela Eugenio , Seitz Rüdiger J , Weder Bruno J 
Published: January 2011

Abstract

Background
Somatosensory object discrimination has been shown to involve widespread cortical and subcortical structures in both cerebral hemispheres. In this study we aimed to identify the networks involved in tactile object manipulation by principal component analysis (PCA) of individual subjects. We expected to find more than one network.

Methods
Seven healthy right-handed male volunteers (aged 22 to 44 yrs) manipulated with their right hand aluminium spheres during 5 s with a repetition frequency of 0.5-0.7 Hz. The correlation coefficients between the principal component temporal expression coefficients and the hemodynamic response modelled by SPM (ecc) determined the task-related components. To establish reproducibility within subjects and similarity of functional connectivity patterns among subjects, regional correlation coefficients (rcc) were computed between task-related component image volumes. By hierarchically categorizing, selecting and averaging the task-related component image volumes across subjects according to the rccs, mean component images (MCIs) were derived describing neural networks associated with tactile object manipulation.

Results
Two independent mean component images emerged. Each included the primary sensorimotor cortex contralateral to the manipulating hand. The region extended to the premotor cortex in MCI 1, whereas it was restricted to the hand area of the primary sensorimotor cortex in MCI 2. MCI 1 showed bilateral involvement of the paralimbic anterior cingulate cortex (ACC), whereas MCI 2 implicated the midline thalamic nuclei and two areas of the rostral dorsal pons.

Conclusions
Two distinct networks participate in tactile object manipulation as revealed by the intra- and interindividual comparison of individual scans. Both were employed by most subjects, suggesting that both are involved in normal somatosensory object discrimination.
pH-sensitivity of YFP provides an intracellular indicator of programmed cell death
Authors: Young Bennett , Wightman Raymond , Blanvillain Robert , Purcel Sydney B , Gallois Patrick 
Published: January 2011

Abstract

Background
Programmed cell death (PCD) is an essential process for the life cycle of all multicellular organisms. In higher plants however, relatively little is known about the cascade of genes and signalling molecules responsible for the initiation and execution of PCD. To aid with the discovery and analysis of plant PCD regulators, we have designed a novel cell death assay based on low cytosolic pH as a marker of PCD.

Results
The acidification that occurs in the cytosol during plant PCD was monitored by way of the extinction of YFP fluorescence at low pH. This fluorescence was recovered experimentally when bringing the intracellular pH back to 7, demonstrating that there was no protein degradation of YFP. Because it uses YFP, the assay is none-destructive, does not interfere with the PCD process and allows time-lapse studies to be carried out. In addition, changes of sub-cellular localisation can be visualised during PCD using the protein of interest fused to RFP. Coupled to a transient expression system, this pH-based assay can be used to functionally analyse genes involved in PCD, using point mutations or co-expressing PCD regulators. Transfecting mBAX and AtBI-1 in onion epidermal cells showed that the pH shift is downstream of PCD suppression by AtBI-1. In addition, this method can be used to score PCD in tissues of stably transformed transgenic lines. As proof of principle, we show the example of YFP extinction during xylogenesis in Arabidopsis. This demonstrates that the assay is applicable to PCD studies in a variety of tissues.

Conclusions
The observation that YFP fluorescence is lost during the plant PCD process provides a new tool to study the genetic regulation and cell biology of the process. In addition, plant cell biologists should make a note of this effect of PCD on YFP fluorescence to avoid misinterpretation of their data and to select a pH insensitive reporter if appropriate. This method represents an efficient and streamlined tool expected to bring insights on the process leading to the pH shift occurring during PCD.
Protocol: using virus-induced gene silencing to study the arbuscular mycorrhizal symbiosis in Pisum sativum
Authors: Grønlund Mette , Olsen Anne , Johansen Elisabeth I , Jakobsen Iver 
Published: January 2011

Abstract
Virus-induced gene silencing (VIGS) is an alternative reverse genetics tool for silencing of genes in some plants, which are difficult to transform. The pea early-browning virus (PEBV) has been developed as a VIGS vector and used in pea for functional analysis of several genes. However, the available PEBV-VIGS protocols are inadequate for studying genes involved in the symbiosis with arbuscular mycorrhizal fungi (AMF).
Here we describe a PEBV-VIGS protocol suitable for reverse genetics studies in pea of genes involved in the symbiosis with AMF and show its effectiveness in silencing genes involved in the early and late stages of AMF symbiosis.
Defining the antigen receptor-dependent regulatory network that induces arrest of cycling immature B-lymphocytes
Authors: Jamal Mohammad Sarwar , Ravichandran Srikanth , Jailkhani Noor , Chatterjee Samrat , Dua Raina , Rao Kanury VS 
Published: January 2011

AbstractBackgroundEngagement of the antigen receptor on immature B-lymphocytes leads to cell cycle arrest, and subsequent apoptosis. This is an essential process for eliminating self reactive B cells during its different stages of development. However, the mechanism by which it is achieved is not completely understood.ResultsHere we employed a systems biology approach that combined extensive experimentation within silicomethodologies to chart the network of receptor-activated pathways that mediated the arrest of immature B cells in the G1 phase of the cell cycle. Interestingly, we found that only a sparse network of signaling intermediates was recruited upon engagement of the antigen receptor. This then led to the activation of a restricted subset of transcription factors, with the consequent induction of genes primarily involved in the cell death pathway. Subsequent experiments revealed that the weak initiation of intracellular signaling pathways derived from desensitization of the receptor-proximal protein tyrosine kinase Lyn, to receptor-dependent activation. Intriguingly, the desensitization was a result of the constitutive activation of this kinase in unstimulated cells, which was likely maintained through a regulatory feedback loop involving the p38 MAP kinase. The high basal activity then attenuated the ability of the antigen receptor to recruit Lyn, and thereby also the downstream signaling intermediates. Finally, integration of these results into a mathematical model provided further substantiation to the novel finding that the ground state of the intracellular signaling machinery constitutes an important determinant of the outcome of receptor-induced cellular responses.ConclusionsOur results identify the global events leading to the G1 arrest and subsequent apoptosis in immature B cells upon receptor activation.
Features analysis for identification of date and party hubs in protein interaction network of Saccharomyces Cerevisiae
Authors: Mirzarezaee Mitra , Araabi Babak N , Sadeghi Mehdi 
Published: January 2011

Abstract

Background
It has been understood that biological networks have modular organizations which are the sources of their observed complexity. Analysis of networks and motifs has shown that two types of hubs, party hubs and date hubs, are responsible for this complexity. Party hubs are local coordinators because of their high co-expressions with their partners, whereas date hubs display low co-expressions and are assumed as global connectors. However there is no mutual agreement on these concepts in related literature with different studies reporting their results on different data sets. We investigated whether there is a relation between the biological features of Saccharomyces Cerevisiae's proteins and their roles as non-hubs, intermediately connected, party hubs, and date hubs. We propose a classifier that separates these four classes.

Results
We extracted different biological characteristics including amino acid sequences, domain contents, repeated domains, functional categories, biological processes, cellular compartments, disordered regions, and position specific scoring matrix from various sources. Several classifiers are examined and the best feature-sets based on average correct classification rate and correlation coefficients of the results are selected. We show that fusion of five feature-sets including domains, Position Specific Scoring Matrix-400, cellular compartments level one, and composition pairs with two and one gaps provide the best discrimination with an average correct classification rate of 77%.

Conclusions
We study a variety of known biological feature-sets of the proteins and show that there is a relation between domains, Position Specific Scoring Matrix-400, cellular compartments level one, composition pairs with two and one gaps of Saccharomyces Cerevisiae' s proteins, and their roles in the protein interaction network as non-hubs, intermediately connected, party hubs and date hubs. This study also confirms the possibility of predicting non-hubs, party hubs and date hubs based on their biological features with acceptable accuracy. If such a hypothesis is correct for other species as well, similar methods can be applied to predict the roles of proteins in those species.
Models of sequestration and receptor cross-talk for explaining multiple mutants in plant stem cell regulation
Authors: Sahlin Patrik , Melke Pontus , Jönsson Henrik 
Published: January 2011

Abstract

Background
Stem cells reside in a plant's shoot meristem throughout its life and are main regulators of above-ground plant development. The stem cell maintenance depends on a feedback network between the CLAVATA and WUSCHEL genes. The CLAVATA3 peptide binds to the CLAVATA1 receptor leading to WUSCHEL inhibition. WUSCHEL, on the other hand, activates CLAVATA3 expression. Recent experiments suggest a second pathway where CLAVATA3 inhibits WUSCHEL via the CORYNE receptor pathway. An interesting question, central for understanding the receptor signaling, is why the clavata1-11 null mutant has a weaker phenotype compared with the clavata1-1 non-null mutant. It has been suggested that this relies on interference from the mutated CLAVATA1 acting on the CORYNE pathway.

Results
We present two models for the CLAVATA-WUSCHEL feedback network including two receptor pathways for WUSCHEL repression and differing only by the hypothesized mechanisms for the clavata1-1 non-null mutant. The first model is an implementation of the previously suggested interference mechanism. The other model assumes an unaltered binding between CLAVATA3 and the mutated CLAVATA1 but with a loss of propagated signal into the cell. We optimize the models using data from wild type and four single receptor mutant experiments and use data from two receptor double mutant experiments in a validation step. Both models are able to explain all seven phenotypes and in addition qualitatively predict CLAVATA3 perturbations. The two models for the clavata1-1 mutant differ in the direct mechanism of the mutant, but they also predict other differences in the dynamics of the stem cell regulating network. We show that the interference hypothesis leads to an abundance of receptors, while the loss-of-signal hypothesis leads to sequestration of CLAVATA3 and relies on degradation or internalization of the bound CLAVATA1 receptor.

Conclusions
Using computational modeling, we show that an interference hypothesis and a more parsimonious loss-of-signal hypothesis for a clavata1 non-null mutant both lead to behaviors predicting wild type and six receptor mutant experiments. Although the two models have identical implementations of the unperturbed feedback network for stem cell regulation, we can point out model-predicted differences that may be resolved in future experiments.
Successful treatment of metastatic hepatic epithelioid hemangioendothelioma with thalidomide: a case report
Authors: Raphael Claire , Hudson Emma , Williams Leslie , Lester Jason F , Savage Philip M 
Published: January 2011

Abstract

Introduction
Hepatic epithelioid hemangioendothelioma is a rare malignancy arising from the vascular endothelial cells within the liver. Historically, the disease is characterized as being poorly responsive to both chemotherapy and radiotherapy, with liver resection or transplantation the treatment of choice when feasible. For patients with advanced disease, reports of long-term therapeutic benefits from conventional cytotoxic treatments are very limited. Owing to the rarity of this malignancy, there is no structured therapeutic research, but a small number of cases have been reported to respond well to treatment with inhibitors of angiogenesis. Thalidomide was originally developed as an anti-emetic but is a potent inhibitor of vascular neogenesis, and could offer potential in the treatment of hepatic epithelioid hemangioendothelioma by blocking the proliferation of the malignant vascular endothelial cells.

Case presentation
We describe the case of a Caucasian British woman who presented at the age of 53 years with a hepatic mass, malignant lymphadenopathy and pulmonary metastases, which were confirmed as hepatic epithelioid hemangioendothelioma on biopsy. After unproductive treatment with interferon, our patient was started on thalidomide 400 mg daily. She has been successfully managed on this therapy for the past seven years, and has remained asymptomatic, with radiologically stable disease and minimal treatment-related side effects.

Conclusion
At present, there is no standard therapy for advanced hepatic epithelioid hemangioendothelioma. Our case supports the role for thalidomide and potentially other inhibitors of vascular neogenesis in the treatment of patients with metastatic hepatic epithelioid hemangioendothelioma.
Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
Authors: Rodríguez-Acebes Sara , Palacios Nuria , Botella-Carretero José I , Olea Nuria , Crespo Lorena , Peromingo Roberto , Gómez-Coronado Diego , Lasunción Miguel A , Vázquez Clotilde , Martínez-Botas Javier 
Published: January 2011

AbstractBackgroundObesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was to analyze the expression profile of cell-cycle- and lipid-metabolism-related genes of adipose tissue in morbid obesity.MethodsWe used a custom-made focused cDNA microarray to determine the adipose tissue mRNA expression profile. Gene expression of subcutaneous abdominal fat samples from 15 morbidly obese women was compared with subcutaneous fat samples from 10 nonobese control patients. The findings were validated in an independent population of 31 obese women and 9 obese men and in an animal model of obesity (Lepob/obmice) by real-time RT-PCR.ResultsMicroarray analysis revealed that transcription factors that regulate the first stages of adipocyte differentiation, such as CCAAT/enhancer binding protein beta (C/EBPβ) and JUN, were upregulated in the adipose tissues of morbidly obese patients. The expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor which controls lipid metabolism and the final steps of preadipocyte conversion into mature adipocytes, was downregulated. The expression of three cyclin-dependent kinase inhibitors that regulate clonal expansion and postmitotic growth arrest during adipocyte differentiation was also altered in obese subjects: p18 and p27 were downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which regulates angiogenesis, lipid and glucose metabolism and it is know to increase dramatically in the early stages of adipocyte differentiation, was upregulated. The expression of C/EBPβ, p18, p21, JUN, and ANGPTL4 presented similar alterations in subcutaneous adipose tissue of Lepob/obmice.ConclusionsOur microarray gene profiling study revealed that the expression of genes involved in adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly obese subjects. This expression pattern is consistent with an immature adipocyte phenotype that could reflect the expansion of the adipose tissue during obesity.