bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction
Authors: Nguyen Ba Alex N , Pogoutse Anastassia , Provart Nicholas , Moses Alan M 
Published: June 2009

Abstract

Background
Nuclear localization signals (NLSs) are stretches of residues within a protein that are important for the regulated nuclear import of the protein. Of the many import pathways that exist in yeast, the best characterized is termed the 'classical' NLS pathway. The classical NLS contains specific patterns of basic residues and computational methods have been designed to predict the location of these motifs on proteins. The consensus sequences, or patterns, for the other import pathways are less well-understood.

Results
In this paper, we present an analysis of characterized NLSs in yeast, and find, despite the large number of nuclear import pathways, that NLSs seem to show similar patterns of amino acid residues. We test current prediction methods and observe a low true positive rate. We therefore suggest an approach using hidden Markov models (HMMs) to predict novel NLSs in proteins. We show that our method is able to consistently find 37% of the NLSs with a low false positive rate and that our method retains its true positive rate outside of the yeast data set used for the training parameters.

Conclusion
Our implementation of this model, NLStradamus, is made available at: http://www.moseslab.csb.utoronto.ca/NLStradamus/
The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse
Authors: Zheng Ke , Wu Xin , Kaestner Klaus H , Wang Peijing Jeremy 
Published: June 2009

AbstractBackgroundLife-long production of spermatozoa depends on spermatogonial stem cells. Spermatogonial stem cells exist among the most primitive population of germ cells – undifferentiated spermatogonia. Transplantation experiments have demonstrated the functional heterogeneity of undifferentiated spermatogonia. Although the undifferentiated spermatogonia can be topographically divided into As(single), Apr(paired), and Aal(aligned) spermatogonia, subdivision of this primitive cell population using cytological markers would greatly facilitate characterization of their functions.ResultsIn the present study, we show that LIN28, a pluripotency factor, is specifically expressed in undifferentiated spermatogonia (As, Apr, and Aal) in mouse.Ngn3also specifically labels undifferentiated spermatogonia. We usedNgn3-GFP knockin mice, in which GFP expression is under the control of allNgn3transcription regulatory elements. Remarkably,Ngn3-GFP is only expressed in ~40% of LIN28-positive As(single) cells. The percentage ofNgn3-GFP-positive clusters increases dramatically with the chain length of interconnected spermatogonia.ConclusionOur study demonstrates that LIN28 specifically marks undifferentiated spermatogonia in mice. These data, together with previous studies, suggest that the LIN28-expressing undifferentiated spermatogonia exist as two subpopulations:Ngn3-GFP-negative (high stem cell potential) andNgn3-GFP-positive (high differentiation commitment). Furthermore,Ngn3-GFP-negative cells are found in chains ofNgn3-GFP-positive spermatogonia, suggesting that cells in the Aalspermatogonia could revert to a more primitive state.
Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
Authors: Doley Robin , Mackessy Stephen P , Kini R Manjunatha 
Published: June 2009

Abstract

Background
Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET) might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins.

Results
Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites.

Conclusion
ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions.
Genome-wide transcriptomic profiling of Anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and Plasmodium berghei infection
Authors: Baton Luke A , Robertson Anne , Warr Emma , Strand Michael R , Dimopoulos George 
Published: June 2009

Abstract

Background
The mosquito Anopheles gambiae is a major vector of human malaria. Increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. To further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female An. gambiae hemocytes following infection by two species of bacteria and a malaria parasite.

Results
We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium.

Conclusion
Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies.
Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors
Authors: Tritto Simona , Botta Laura , Zampini Valeria , Zucca Gianpiero , Valli Paolo , Masetto Sergio 
Published: June 2009

Abstract

Background
Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia.

Results
RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin.

Conclusion
The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.
Effect of questionnaire structure on recall of drug utilization in a population of university students
Authors: Gama Helena , Correia Sofia , Lunet Nuno 
Published: June 2009

Abstract

Background
Self-reported data are a common source of information about drug exposure. Modes of data collection differ considerably and the questionnaire's structure may affect prevalence estimates. We compared the recall of medication use evaluated by means of two questionnaires differing in structure and length.

Methods
Drug utilization was assessed by two alternative versions of a questionnaire (A – 4 pages, including specific questions for 12 indications/pharmacological groups and one question for "other medicines"; B – 1 page, including 1 open-ended question to cover overall drug consumption). Each of 32 classes in a private University in Maputo, Mozambique, was randomly assigned questionnaire A (233 participants) or B (276 participants). Logistic regression (allowing for clustering by classroom) was used to compare the two groups in terms of socio-demographic characteristics and medication used during the previous month.

Results
Overall, 67.4% of the subjects had used at least one drug during the previous month. The following prevalences were greater among participants completing questionnaire A: use of drugs from two or more pharmacological groups (60.5% vs. 34.4%, p < 0.001), use of two or more drugs (66.2% vs. 43.0%, p < 0.001), and use of antibiotics (14.6% vs. 6.9%, p = 0.001), antifungals (9.4% vs. 4.0%, p = 0.013), antiparasitics (5.6% vs. 1.8%, p = 0.031) and antacids (8.6% vs. 3.6%, p = 0.024). Information about duration of treatment and medical advice was more complete with version A.

Conclusion
The indication/drug-specific questions (questionnaire A) revealed a significantly higher prevalence of use of medicines – antibiotics, antifungals, antiparasitics and antacids – without compromising the completeness of the information.
Role of pathogenic oral flora in postoperative pneumonia following brain surgery
Authors: Bágyi Kinga , Haczku Angela , Márton Ildikó , Szabó Judit , Gáspár Attila , Andrási Melinda , Varga Imre , Tóth Judit , Klekner Almos 
Published: June 2009

Abstract

Background
Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.

Methods
A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.

Results
The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.

Conclusion
Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.
Association study of SHANK3 gene polymorphisms with autism in Chinese Han population
Authors: Qin Jian , Jia Meixiang , Wang Lifang , Lu Tianlan , Ruan Yan , Liu Jing , Guo Yanqing , Zhang Jishui , Yang Xiaoling , Yue Weihua , Zhang Dai 
Published: June 2009

Abstract

Background
Autism, a heterogeneous disease, is described as a genetic psychiatry disorder. Recently, abnormalities at the synapse are supposed to be important for the etiology of autism.SHANK3 (SH3 and multiple ankyrin repeat domains protein) gene encodes a master synaptic scaffolding protein at postsynaptic density (PSD) of excitatory synapse. Rare mutations and copy number variation (CNV) evidence suggested SHANK3 as a strong candidate gene for the pathogenesis of autism.

Methods
We performed an association study between SHANK3 gene polymorphisms and autism in Chinese Han population. We analyzed the association between five single nucleotide polymorphisms (SNPs) of the SHANK3 gene and autism in 305 Chinese Han trios, using the family based association test (FBAT). Linkage disequilibrium (LD) analysis showed the presence of LD between pairwise markers across the locus. We also performed mutation screening for the rare de novo mutations reported previously.

Results
No significant evidence between any SNPs of SHANK3 and autism was observed. We did not detect any mutations described previously in our cohort.

Conclusion
We suggest that SHANK3 might not represent a major susceptibility gene for autism in Chinese Han population.
Lack of association of TIM3polymorphisms and allergic phenotypes
Authors: Zhang Jian , Daley Denise , Akhabir Loubna , Stefanowicz Dorota , Chan-Yeung Moira , Becker Allan B , Laprise Catherine , Paré Peter D , Sandford Andrew J 
Published: June 2009

Abstract

Background
T-cell immunoglobulin mucin-3 (TIM3) is a TH1-specific type 1 membrane protein that regulates TH1 proliferation and the development of immunological tolerance. TIM3 and its genetic variants have been suggested to play a role in regulating allergic diseases. Polymorphisms in the TIM3 promoter region have been reported to be associated with allergic phenotypes in several populations. The aims of this study were to examine whether genetic variation in the promoter region of TIM3 influenced transcription of the gene and risk for allergic phenotypes.

Methods
We performed 5' rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. We screened for polymorphisms in the promoter region. Deletion analysis was used to localize the promoter region of TIM3. Genotyping was performed by TaqMan assays in three asthma/allergy population samples.

Results
We found two regions with promoter activity in TIM3. One region was from -214 bp to +58 bp and the other from -1.6 kb to -914 bp relative to the transcription start site. None of the single nucleotide polymorphisms (SNPs) or haplotypes affected the transcriptional activity in reporter gene assays. No association between the SNPs and any phenotype was observed in the study cohorts.

Conclusion
Our findings indicate that SNPs and haplotypes in the TIM3 promoter region do not have a functional effect in vitro and are not associated with allergic diseases. These data suggest that polymorphisms in the TIM3 promoter region are unlikely to play an important role in susceptibility to allergic diseases.
Age-related associations of hypertension and diabetes mellitus with chronic kidney disease
Authors: Islam Tareq M , Fox Caroline S , Mann Devin , Muntner Paul 
Published: June 2009

Abstract

Background
Studies suggest end-stage renal disease incidence and all-cause mortality rates among patients with chronic kidney disease (CKD) differ by age. The association of diabetes mellitus and hypertension with CKD across the adult lifespan is not well established.

Methods
Data from NHANES 1999–2004 were used to determine the association of risk factors for stage 3 or 4 CKD (n = 12,518) and albuminuria (n = 12,778) by age grouping (20 to 49, 50 to 69, and ≥70 years). Stage 3 or 4 CKD was defined as an estimated glomerular filtration rate of 15 to 59 ml/min/1.73 m2 and albuminuria as an albumin to creatinine ratio ≥30 mg/g.

Results
For adults 20 to 49, 50 to 69 and ≥70 years of age, the prevalence ratios (95% confidence interval) of stage 3 or 4 CKD associated with hypertension were 1.94 (0.86 – 4.35), 1.51 (1.09 – 2.07), 1.31 (1.15 – 1.49), respectively (p-trend = 0.038). The analogous prevalence ratios (95% confidence interval) were 3.01 (1.35 – 6.74), 1.61 (1.15 – 2.25), 1.40 (1.15 – 1.69), respectively, for diagnosed diabetes mellitus (p-trend = 0.067); and 2.67 (0.53 – 13.4), 1.35 (0.69 – 2.63), 1.08 (0.78 – 1.51), respectively, for undiagnosed diabetes mellitus (p-trend = 0.369). The prevalence ratios of albuminuria associated with hypertension and diagnosed and undiagnosed diabetes mellitus were lower at older age (each p < 0.05).

Conclusion
Among US adults, diabetes mellitus and hypertension are associated with CKD and albuminuria regardless of age. However, the associations were stronger at younger ages.
A simple method for co-segregation analysis to evaluate the pathogenicity of unclassified variants; BRCA1 and BRCA2 as an example
Authors: Mohammadi Leila , Vreeswijk Maaike P , Oldenburg Rogier , van den Ouweland Ans , Oosterwijk Jan C , van der Hout Annemarie H , Hoogerbrugge Nicoline , Ligtenberg Marjolijn , Ausems Margreet G , van der Luijt Rob B , Dommering Charlotte J , Gille Johan J , Verhoef Senno , Hogervorst Frans B , van Os Theo A , Gómez García Encarna , Blok Marinus J , Wijnen Juul T , Helmer Quinta , Devilee Peter , van Asperen Christi J , van Houwelingen Hans C 
Published: June 2009

Abstract

Background
Assessment of the clinical significance of unclassified variants (UVs) identified in BRCA1 and BRCA2 is very important for genetic counselling. The analysis of co-segregation of the variant with the disease in families is a powerful tool for the classification of these variants. Statistical methods have been described in literature but these methods are not always easy to apply in a diagnostic setting.

Methods
We have developed an easy to use method which calculates the likelihood ratio (LR) of an UV being deleterious, with penetrance as a function of age of onset, thereby avoiding the use of liability classes. The application of this algorithm is publicly available http://www.msbi.nl/cosegregation. It can easily be used in a diagnostic setting since it requires only information on gender, genotype, present age and/or age of onset for breast and/or ovarian cancer.

Results
We have used the algorithm to calculate the likelihood ratio in favour of causality for 3 UVs in BRCA1 (p.M18T, p.S1655F and p.R1699Q) and 5 in BRCA2 (p.E462G p.Y2660D, p.R2784Q, p.R3052W and p.R3052Q). Likelihood ratios varied from 0.097 (BRCA2, p.E462G) to 230.69 (BRCA2, p.Y2660D). Typing distantly related individuals with extreme phenotypes (i.e. very early onset cancer or old healthy individuals) are most informative and give the strongest likelihood ratios for or against causality.

Conclusion
Although co-segregation analysis on itself is in most cases insufficient to prove pathogenicity of an UV, this method simplifies the use of co-segregation as one of the key features in a multifactorial approach considerably.
The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells
Authors: Li Jun , Qin Zhenghong , Liang Zhongqin 
Published: June 2009

Abstract

Background
Previous study reported that resveratrol has anti-tumor activity. In this study, we investigated the involvement of autophagy in the resveratrol-induced apoptotic death of human U251 glioma cells.

Methods
The growth inhibition of U251 cells induced by resveratrol was assessed with methyl thiazolyl tetrazolium (MTT). The activation of autophagy and proapoptotic effect were characterized by monodansylcadaverine labeling and Hoechst stain, respectively. Mitochondrialtransmembrane potential (ΔΨm) was measured as a function of drug treatment using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). The role of autophagy and apoptosis in the resveratrol-induced death of U251 cells was assessed using autophagic and caspase inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms.

Results
Methyl thiazolyl tetrazolium (MTT) assays indicated that resveratrol decreased the viability of U251 cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that resveratrol increased cell population at sub-G1 phase, an index of apoptosis. Furthermore, resveratrol-induced cell death was associated with a collapse of the mitochondrial membrane potential. The pan-caspase inhibitor Z-VAD-fmk suppressed resveratrol-induced U251 cell death. Resveratrol stimulated autophagy was evidenced by punctuate monodansylcadaverine(MDC) staining and microtubule-associated protein light chain 3 (LC3) immunoreactivty. Resveratrol also increased protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitors 3-methylademine (3-MA) and bafilomycin A1 sensitized the cytotoxicity of resveratrol.

Conclusion
Together, these findings indicate that resveratrol induces autophagy in human U251 glioma cells and autophagy suppressed resveratrol-induced apoptosis. This study thus suggests that autophagy inhibitors can increase the cytotoxicity of resveratrol to glioma cells.