bluuebunny/crossref_metadata_2025_split huggingface dataset:
The roots of Atractylodes japonica Koidzumi promote adipogenic differentiation via activation of the insulin signaling pathway in 3T3-L1 cells
Authors: Han Yunkyung , Jung Hyo Won , Park Yong-Ki 
Published: September 2012

Abstract

Background
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by insulin resistance and hyperglycemia. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcription factor and plays an important role in the regulation of genes involved in adipogenic differentiation, glucose metabolism and insulin signal transduction.

Methods
In this study, the effects of the root extract of Atractylodes japonica Koidzumi ( Atractylodis Rhizoma Alba, ARA) on the differentiation of 3T3-L1 preadipocytes and the possible mechanism of glucose transport were investigated. 3T3-L1 cells were cultured with insulin and ARA extract.

Results
In 3T3-L1 cells, ARA extract significantly enhanced adipogenic differentiation and upregulated the expression of PPARγ genes and protein in a dose-dependent manner. ARA also promoted glucose transport by increasing the glucose transporter 4 (GLUT-4), phosphatidylinositol 3-kinase (PI3K) and insulin receptor substrates-1 (IRS-1) levels.

Conclusion
Our results suggest that ARA extract may be an attractive therapeutic agent for managing T2D via promoting the differentiation of adipocytes with the upregulation of PPARγ levels and the activation of the insulin signaling pathway.
SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome
Authors: Liu Bernard A , Engelmann Brett W , Jablonowski Karl , Higginbotham Katherine , Stergachis Andrew B , Nash Piers D 
Published: September 2012

AbstractSpecific peptide ligand recognition by modular interaction domains is essential for the fidelity of information flow through the signal transduction networks that control cell behavior in response to extrinsic and intrinsic stimuli. Src homology 2 (SH2) domains recognize distinct phosphotyrosine peptide motifs, but the specific sites that are phosphorylated and the complement of available SH2 domains varies considerably in individual cell types. Such differences are the basis for a wide range of available protein interaction microstates from which signaling can evolve in highly divergent ways. This underlying complexity suggests the need to broadly map the signaling potential of systems as a prerequisite for understanding signaling in specific cell types as well as various pathologies that involve signal transduction such as cancer, developmental defects and metabolic disorders. This report describes interactions between SH2 domains and potential binding partners that comprise initial signaling downstream of activated fibroblast growth factor (FGF), insulin (Ins), and insulin-like growth factor-1 (IGF-1) receptors. A panel of 50 SH2 domains screened against a set of 192 phosphotyrosine peptides defines an extensive potential interactome while demonstrating the selectivity of individual SH2 domains. The interactions described confirm virtually all previously reported associations while describing a large set of potential novel interactions that imply additional complexity in the signaling networks initiated from activated receptors. This study of pTyr ligand binding by SH2 domains provides valuable insight into the selectivity that underpins complex signaling networks that are assembled using modular protein interaction domains.
Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (ACLF)
Authors: Yang Jiezuan , Yi Ping , Wei Li , Xu Zherong , Chen Yunbo , Tang Lingling , Li Lanjuan 
Published: September 2012

Abstract

Background
CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR) reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF). The repertoire of TCR beta chain variable (TCRBV) regions of peripheral Tregs in ACLF patients is not well understood.

Methods
Human PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS). The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB) patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP) analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak.

Results
CD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs) (P < 0.01) and CHB patients (P < 0.01). The prevalence of CD4+CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families.

Conclusions
The CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.
Stop codons in bacteria are not selectively equivalent
Authors: Povolotskaya Inna S , Kondrashov Fyodor A , Ledda Alice , Vlasov Peter K 
Published: September 2012

Abstract

Background
The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.

Results
We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.

Conclusions
Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.

Reviewers
This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section.
Nursing home administrators’ perspectives on a study feedback report: a cross sectional survey
Authors: Boström Anne-Marie , Cranley Lisa A , Hutchinson Alison M , Cummings Greta G , Norton Peter G , Estabrooks Carole A 
Published: September 2012

Abstract

Background
This project is part of the Translating Research in Elder Care (TREC) program of research, a multi-level and longitudinal research program being conducted in 36 nursing homes in three Canadian Prairie Provinces. The overall goal of TREC is to improve the quality of care for older persons living in nursing homes and the quality of work life for care providers. The purpose of this paper is to report on development and evaluation of facility annual reports (FARs) from facility administrators’ perspectives on the usefulness, meaningfulness, and understandability of selected data from the TREC survey.

Methods
A cross sectional survey design was used in this study. The feedback reports were developed in collaboration with participating facility administrators. FARs presented results in four contextual areas: workplace culture, feedback processes, job satisfaction, and staff burnout. Six weeks after FARs were mailed to each administrator, we conducted structured telephone interviews with administrators to elicit their evaluation of the FARs. Administrators were also asked if they had taken any actions as a result of the FAR. Descriptive and inferential statistics, as well as content analysis for open-ended questions, were used to summarize findings.

Results
Thirty-one facility administrators (representing thirty-two facilities) participated in the interviews. Six administrators had taken action and 18 were planning on taking action as a result of FARs. The majority found the four contextual areas addressed in FAR to be useful, meaningful, and understandable. They liked the comparisons made between data from years one and two and between their facility and other TREC study sites in their province. Twenty-two indicated that they would like to receive information on additional areas such as aggressive behaviours of residents and information sharing. Twenty-four administrators indicated that FARs contained enough information, while eight found FARs ‘too short’. Administrators who reported that the FAR contained enough information were more likely to take action within their facilities than administrators who reported that they needed more information.

Conclusions
Although the FAR was brief, the presentation of the four contextual areas was relevant to the majority of administrators and prompted them to plan or to take action within their facility.
Ceramide sphingolipid signaling mediates Tumor Necrosis Factor (TNF)-dependent toxicity via caspase signaling in dopaminergic neurons
Authors: Martinez Terina N , Chen Xi , Bandyopadhyay Sibali , Merrill Alfred H , Tansey Malú G 
Published: September 2012

AbstractBackgroundDopaminergic (DA) neurons in the ventral midbrain selectively degenerate in Parkinson’s disease (PD) in part because their oxidative environment in the substantia nigra (SN) may render them vulnerable to neuroinflammatory stimuli. Chronic inhibition of soluble Tumor Necrosis Factor (TNF) with dominant-negative TNF inhibitors protects DA neurons in rat models of parkinsonism, yet the molecular mechanisms and pathway(s) that mediate TNF toxicity remain(s) to be clearly identified. Here we investigated the contribution of ceramide sphingolipid signaling in TNF-dependent toxicity.ResultsCeramide dose-dependently reduced the viability of DA neuroblastoma cells and primary DA neurons and pharmacological inhibition of sphingomyelinases (SMases) with three different inhibitors during TNF treatment afforded significant neuroprotection by attenuating increased endoplasmic reticulum (ER) stress, loss of mitochondrial membrane potential, caspase-3 activation and decreases in Akt phosphorylation. Using lipidomics mass spectrometry we confirmed that TNF treatment not only promotes generation of ceramide, but also leads to accumulation of several atypical deoxy-sphingoid bases (DSBs). Exposure of DA neuroblastoma cells to atypical DSBs in the micromolar range reduced cell viability and inhibited neurite outgrowth and branching in primary DA neurons, suggesting that TNF-inducedde novosynthesis of atypical DSBs may be a secondary mechanism involved in mediating its neurotoxicity in DA neurons.ConclusionsWe conclude that TNF/TNFR1-dependent activation of SMases generates ceramide and sphingolipid species that promote degeneration and caspase-dependent cell death of DA neurons. Ceramide and atypical DSBs may represent novel drug targets for development of neuroprotective strategies that can delay or attenuate the progressive loss of nigral DA neurons in patients with PD.
A simple knowledge-based mining method for exploring hidden key molecules in a human biomolecular network
Authors: Tsuji Shingo , Ihara Sigeo , Aburatani Hiroyuki 
Published: September 2012

Abstract

Background
In the functional genomics analysis domain, various methodologies are available for interpreting the results produced by high-throughput biological experiments. These methods commonly use a list of genes as an analysis input, and most of them produce a more complicated list of genes or pathways as the results of the analysis. Although there are several network-based methods, which detect key nodes in the network, the results tend to include well-studied, major hub genes.

Results
To mine the molecules that have biological meaning but to fewer degrees than major hubs, we propose, in this study, a new network-based method for selecting these hidden key molecules based on virtual information flows circulating among the input list of genes. The human biomolecular network was constructed from the Pathway Commons database, and a calculation method based on betweenness centrality was newly developed. We validated the method with the ErbB pathway and applied it to practical cancer research data. We were able to confirm that the output genes, despite having fewer edges than major hubs, have biological meanings that were able to be invoked by the input list of genes.

Conclusions
The developed method, named NetHiKe (Network-based Hidden Key molecule miner), was able to detect potential key molecules by utilizing the human biomolecular network as a knowledge base. Thus, it is hoped that this method will enhance the progress of biological data analysis in the whole-genome research era.
Preoperative diagnosis of a breast hydatid cyst using fine-needle aspiration cytology: a case report and review of the literature
Authors: Cancelo Maria Jesus , Martín Maria , Mendoza Nicolas 
Published: September 2012

Abstract

Introduction
A hydatid cyst of the breast is rare and often goes unnoticed by mammography and ultrasound. Preoperative diagnosis may be performed using fine-needle aspiration cytology, which also minimizes the risk of intraoperative rupture.

Case presentation
We report the case of a 70-year-old Spanish woman who was diagnosed with a hydatid cyst using fine-needle aspiration cytology before surgery.

Conclusion
Fine-needle aspiration cytology is an accurate and safe technique that can allow surgery to be avoided, especially in older patients or patients with high surgical risk.
Docosahexaenoic acid complexed to human albumin in experimental stroke: neuroprotective efficacy with a wide therapeutic window
Authors: Eady Tiffany N , Khoutorova Larissa , Atkins Kristal D , Bazan Nicolas G , Belayev Ludmila 
Published: September 2012

Abstract

Background
Docosahexaenoic acid (DHA) complexed to human serum albumin (Alb) is neuroprotective after experimental stroke. Here we tested using lower concentrations of albumin as part of the complex to achieve neuroprotection. We found that lower Alb concentrations extend the therapeutic window of protection beyond 5 h after stroke onset.

Methods
Sprague–Dawley rats were received 2 h middle cerebral artery occlusion (MCAo). The behavior was evaluated on day 1, 2, 3 and 7 after MCAo. In the dose–response study, animals were given either DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg + 0.32, 0.63 or 1.25 g/kg) or saline, i.v. 3 h after onset of stroke (n=6-8 per group). In the therapeutic window study, DHA-Alb (5mg/kg + 1.25g/kg) was administered i.v. at either 3, 4, 5, 6 or 7 h after onset of stroke (n=7-9 per group). Alb (1.25g/kg) was given at 3 h or 5 h and saline at 3h after onset of reperfusion. Seven days after MCAo, infarct volumes and number of GFAP, ED-1, NeuN, SMI-71 positive cells and vessels were counted.

Results
Moderate DHA-Alb doses (0.63 and 1.25 g/kg) improved neurological scores compared to albumin-treated rats on days 1, 2, 3 and 7. All DHA-Alb doses (0.32, 0.63 and 1.25 g/kg) markedly reduced cortical (by 65-70%), striatal (by 52-63%) and total infarct volumes (by 60-64%) compared to native Alb group. In the therapeutic window study DHA-Alb led to improved neurological score and significant reductions of infarct volumes (especially in the cortical or penumbral region), even when treatment was initiated as late as 7 hours after onset of MCAo.

Conclusions
The DHA-Alb complex affords high-grade neurobehavioral neuroprotection in focal cerebral ischemia, equaling or exceeding that afforded by native Alb or DHA, at considerably moderate doses. It has a broad therapeutic window extending to 7 h after stroke onset. Taken together, these finding support the potential clinical feasibility of administering DHA-Alb therapy to patients with acute ischemic stroke.
The production of β-glucosidases by Fusarium proliferatum NBRC109045 isolated from Vietnamese forest
Authors: Gao Ziqing , Van Hop Duong , Yen Le Thi Hoang , Ando Katsuhiko , Hiyamuta Shuichi , Kondo Ryuichiro 
Published: September 2012

Abstract

Fusarium proliferatum NBRC109045 is a filamentous fungus isolated from Vietnamese forest due to high production of β-glucosidases. Production of the enzyme was studied on varied carbon source based mediums. The highest activity was obtained in medium containing 1% corn stover + 1% wheat bran (3.31 ± 0.14 U/ml). It is interesting to note that glucose (0.69 ± 0.02 U/ml) gave higher activity and just followed by cellobiose among the di- and mono-saccharides, which is generally regarded as a universal repressor of hydrolases. We improved the zymogram method to prove that in response to various carbon sources, F. proliferatum could express various β-glucosidases. One of the β-glucosidases produced by F. proliferatum growing in corn stover + wheat bran based medium was partially purified and proved to have high catalytic ability.
Reference Ranges and Determinants of Testosterone, Dihydrotestosterone, and Estradiol Levels Measured using Liquid Chromatography-Tandem Mass Spectrometry in a Population-Based Cohort of Older Men
Authors: Yeap Bu B. , Alfonso Helman , Chubb S. A. Paul , Handelsman David J. , Hankey Graeme J. , Norman Paul E. , Flicker Leon 
Published: September 2012

Context:
Testosterone (T) levels decline with increasing age. Controversy exists over the threshold for classifying T as low vs. normal in older men. The relevance of assessing dihydrotestosterone (DHT) and estradiol (E2) remains unclear.

Objective:
We assessed the associations of T, DHT, and E2 in men aged 70 yr or older and established reference ranges for these in healthy older men.

Participants:
Community-dwelling men aged 70–89 yr residing in Perth, Western Australia, Australia, participated in the study.

Main Outcome Measures:
Plasma T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples from 3690 men.

Results:
Increasing age, higher body mass index and waist to hip ratio, dyslipidemia, diabetes, and higher LH were independently associated with lower levels of T and DHT. Increasing age, diabetes, and higher LH were associated with lower E2. In a reference group of 394 men aged 76.1 ± 3.2 yr reporting excellent or very good health with no history of smoking, diabetes, cardiovascular disease, cancer, depression, or dementia, the 2.5th percentile for T was 6.4 nmol/liter (184 ng/dl); DHT, 0.49 nmol/liter; and E2, 28 pmol/liter. Applying these cutoffs to all 3690 men, those with low T or DHT had an increased odds ratio for frailty, diabetes, and cardiovascular disease. Men with both low T and DHT had a higher odds ratio for these outcomes.

Conclusions:
The 2.5th percentile in a reference group of healthy older men provides age-appropriate thresholds for defining low T, DHT, and E2. Additional studies are needed to test their potential applicability and clinical utility in older men.
Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation
Authors: Twiss Floor , Le Duc Quint , Van Der Horst Suzanne , Tabdili Hamid , Van Der Krogt Gerard , Wang Ning , Rehmann Holger , Huveneers Stephan , Leckband Deborah E. , De Rooij Johan 
Published: September 2012

Summary
Proper regulation of the formation and stabilization of epithelial cell–cell adhesion is crucial in embryonic morphogenesis and tissue repair processes. Defects in this process lead to organ malformation and defective epithelial barrier function. A combination of chemical and mechanical cues is used by cells to drive this process. We have investigated the role of the actomyosin cytoskeleton and its connection to cell–cell junction complexes in the formation of an epithelial barrier in MDCK cells. We find that the E-cadherin complex is sufficient to mediate a functional link between cell–cell contacts and the actomyosin cytoskeleton. This link involves the actin binding capacity of α-catenin and the recruitment of the mechanosensitive protein Vinculin to tensile, punctate cell–cell junctions that connect to radial F-actin bundles, which we name Focal Adherens Junctions (FAJ). When cell–cell adhesions mature, these FAJs disappear and linear junctions are formed that do not contain Vinculin. The rapid phase of barrier establishment (as measured by Trans Epithelial Electrical Resistance (TER)) correlates with the presence of FAJs. Moreover, the rate of barrier establishment is delayed when actomyosin contraction is blocked or when Vinculin recruitment to the Cadherin complex is prevented. Enhanced presence of Vinculin increases the rate of barrier formation. We conclude that E-cadherin-based FAJs connect forming cell–cell adhesions to the contractile actomyosin cytoskeleton. These specialized junctions are sites of Cadherin mechanosensing, which, through the recruitment of Vinculin, is a driving force in epithelial barrier formation.
A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome
Authors: Neary Marianne T. , Mohun Timothy J. , Breckenridge Ross A. 
Published: September 2012

Summary
The pathology of sudden infant death syndrome (SIDS) is poorly understood. Many risk factors, including hypoxia, have been identified. Prolongation of the ECG QTc interval is associated with elevated risk of SIDS but its aetiology in most cases remains unknown. We have characterised ECG changes in the newborn mouse in the hours and days following birth. There was a steady increase in heart rate alongside significant decreases in QTc interval, QRS duration and QTc dispersion over the first 10 postnatal days. Birth into hypoxia (10% FiO2) prevented electrocardiac maturation, downregulated cardiac ion-channel expression and led to neonatal death. We found that risk of death decreased with increasing age of exposure to hypoxia. Genetic elevation of cardiac hypoxia-signalling after birth in αMHC-Cre::VHLfl/fl mice also prevented electrocardiographic maturation, leading to arrhythmia and death before weaning. Immunohistochemistry and western blotting revealed internalisation and dephosphorylation of Connexin43. We conclude that increased ambient oxygen concentration after birth drives maturation of the cardiac electrical conduction system, failure of which leads to aberrant ion channel and Connexin43 expression and predisposes to arrhythmia and sudden death. This is consistent with known risk factors of SIDS and provides a link between neonatal hypoxia, ECG abnormalities and sudden death.