bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell adhesion through αV-containing integrins is required for efficient HIV-1 infection in macrophages
Authors: Ballana Ester , Pauls Eduardo , Senserrich Jordi , Clotet Bonaventura , Perron-Sierra Françoise , Tucker Gordon C. , Esté José A. 
Published: October 2008

AbstractMonocytes and macrophages are an important reservoir of human immunodeficiency virus (HIV) and may represent the largest reservoir of this virus in tissues. Differentiation of monocytes into macrophages leads to cell attachment and susceptibility to infection and replication of HIV. Among other cell-surface molecules, integrins are overexpressed during monocyte-macrophage differentiation and may play a role in the replication cycle of envelope viruses including HIV. Here, we show that inhibition of αV integrin in monocyte-derived macrophages, by RNA interference or their inhibition by a selective small heterocyclic RGD-mimetic nonpeptide compound, inhibited the replication of HIV in the absence of cytotoxicity. Interference or inhibition of αV integrins triggered a signal transduction pathway, leading to down-regulation of nuclear factor-κB–dependent HIV-1 transcription. Such inhibition was mediated by a MAP-kinase signaling cascade, probably involving ERK1/2, p38-mitogen–activated protein kinases, and HSP27. In conclusion, our results reveal a significant role of integrin αV-mediated adhesion in HIV-1 infection of macrophages.
Group IVA cytosolic phospholipase A2 (cPLA2α) and integrin αIIbβ3 reinforce each other's functions during αIIbβ3 signaling in platelets
Authors: Prévost Nicolas , Mitsios John V. , Kato Hisashi , Burke John E. , Dennis Edward A. , Shimizu Takao , Shattil Sanford J. 
Published: October 2008

AbstractGroup IVA cytosolic phospholipase A2 (cPLA2α) catalyzes release of arachidonic acid from glycerophospholipids, leading to thromboxane A2 (TxA2) production. Some platelet agonists stimulate cPLA2α, but others require fibrinogen binding to αIIbβ3 to elicit TxA2. Therefore, relationships between cPLA2α and αIIbβ3 were examined. cPLA2α and a cPLA2α binding partner, vimentin, coimmunoprecipitated with αIIbβ3 from platelets, independent of fibrinogen binding. Studies with purified proteins and with recombinant proteins expressed in CHO cells determined that the interaction between cPLA2α and αIIbβ3 was indirect and was dependent on the αIIb and β3 cytoplasmic tails. Fibrinogen binding to αIIbβ3 caused an increase in integrin-associated cPLA2α activity in normal platelets, but not in cPLA2α-deficient mouse platelets or in human platelets treated with pyrrophenone, a cPLA2α inhibitor. cPLA2α activation downstream of αIIbβ3 had functional consequences for platelets in that it was required for fibrinogen-dependent recruitment of activated protein kinase Cβ to the αIIbβ3 complex and for platelet spreading. Thus, cPLA2α and αIIbβ3 interact to reinforce each other's functions during αIIbβ3 signaling. This provides a plausible explanation for the role of αIIbβ3 in TxA2 formation and in the defective hemostatic function of mouse or human platelets deficient in cPLA2α.
A genome-wide scan for quantitative trait loci affecting limb bone lengths and areal bone mineral density of the distal femur in a White Duroc × Erhualian F2 population
Authors: Mao Huirong , Guo Yuanmei , Yang Guangcheng , Yang Bin , Ren Jun , Liu Sanfeng , Ai Huashui , Ma Junwu , Brenig Bertram , Huang Lusheng 
Published: October 2008

Abstract

Background
Limb bone lengths and bone mineral density (BMD) have been used to assess the bone growth and the risk of bone fractures in pigs, respectively. It has been suggested that limb bone lengths and BMD are under genetic control. However, the knowledge about the genetic basis of the limb bone lengths and mineralisatinon is limited in pigs. The aim of this study was to identify quantitative trait loci (QTL) affecting limb bone lengths and BMD of the distal femur in a White Duroc × Erhualian resource population.

Results
Limb bone lengths and femoral bone mineral density (fBMD) were measured in a total of 1021 and 116 F2 animals, respectively. There were strong positive correlations among the lengths of limb bones and medium positive correlations between the lengths of limb bones and fBMD. A whole-genome scan involving 183 microsatellite markers across the pig genome revealed 35 QTL for the limb bone lengths and 2 for femoral BMD. The most significant QTL for the lengths of five limb bones were mapped on two chromosomes affecting all 5 limb bones traits. One was detected around 57 cM on pig chromosome (SSC) 7 with the largest F-value of more than 26 and 95% confidence intervals of less than 5 cM, providing a crucial start point to identify the causal genes for these traits. The Erhualian alleles were associated with longer limb bones. The other was located on SSCX with a peak at 50–53 cM, whereas alleles from the White Duroc breed increased the bone length. Many QTL identified are homologous to the human genomic regions containing QTL for bone-related traits and a list of interesting candidate genes.

Conclusion
This study detected the QTL for the lengths of scapula, ulna, humerus and tibia and fBMD in the pig for the first time. Moreover, several new QTL for the pig femoral length were found. As correlated traits, QTL for the lengths of five limb bones were mainly located in the same genomic regions. The most promising QTL for the lengths of five limb bones on SSC7 merits further investigation.
Deciphering the genetic basis for polyketide variation among mycobacteria producing mycolactones
Authors: Pidot Sacha J , Hong Hui , Seemann Torsten , Porter Jessica L , Yip Marcus J , Men Artem , Johnson Matthew , Wilson Peter , Davies John K , Leadlay Peter F , Stinear Timothy P 
Published: October 2008

Abstract

Background
Mycolactones are immunosuppressive and cytotoxic polyketides, comprising five naturally occurring structural variants (named A/B, C, D, E and F), produced by different species of very closely related mycobacteria including the human pathogen, Mycobacterium ulcerans. In M. ulcerans strain Agy99, mycolactone A/B is produced by three highly homologous type I polyketide megasynthases (PKS), whose genes (mlsA1: 51 kb, mlsA2: 7.2 kb and mlsB: 42 kb) are found on a 174 kb plasmid, known as pMUM001.

Results
We report here comparative genomic analysis of pMUM001, the complete DNA sequence of a 190 kb megaplasmid (pMUM002) from Mycobacterium liflandii 128FXT and partial sequence of two additional pMUM replicons, combined with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These data reveal how PKS module and domain differences affecting MlsB correlate with the production of mycolactones E and F. For mycolactone E these differences from MlsB in M. ulcerans Agy99 include replacement of the AT domain of the loading module (acetate to propionate) and the absence of an entire extension module. For mycolactone F there is also a reduction of one extension module but also a swap of ketoreductase domains that explains the characteristic stereochemistry of the two terminal side-chain hydroxyls, an arrangement unique to mycolactone F

Conclusion
The mycolactone PKS locus on pMUM002 revealed the same large, three-gene structure and extraordinary pattern of near-identical PKS domain sequence repetition as observed in pMUM001 with greater than 98.5% nucleotide identity among domains of the same function. Intra- and inter-strain comparisons suggest that the extreme sequence homogeneity seen among the mls PKS genes is caused by frequent recombination-mediated domain replacement. This work has shed light on the evolution of mycolactone biosynthesis among an unusual group of mycobacteria and highlights the potential of the mls locus to become a toolbox for combinatorial PKS biochemistry.
Development of a real-time multiplex PCR assay for the detection of multiple Salmonella serotypes in chicken samples
Authors: O'Regan Edel , McCabe Evonne , Burgess Catherine , McGuinness Sheila , Barry Thomas , Duffy Geraldine , Whyte Paul , Fanning Séamus 
Published: October 2008

Abstract

Background
A real-time multiplex PCR assay was developed for the detection of multiple Salmonella serotypes in chicken samples. Poultry-associated serotypes detected in the assay include Enteritidis, Gallinarum, Typhimurium, Kentucky and Dublin. The traditional cultural method according to EN ISO 6579:2002 for the detection of Salmonella in food was performed in parallel. The real-time PCR based method comprised a pre-enrichment step in Buffered Peptone Water (BPW) overnight, followed by a shortened selective enrichment in Rappaport Vasilliadis Soya Broth (RVS) for 6 hours and subsequent DNA extraction.

Results
The real-time multiplex PCR assay and traditional cultural method showed 100% inclusivity and 100% exclusivity on all strains tested. The real-time multiplex PCR assay was as sensitive as the traditional cultural method in detecting Salmonella in artificially contaminated chicken samples and correctly identified the serotype. Artificially contaminated chicken samples resulted in a detection limit of between 1 and 10 CFU per 25 g sample for both methods. A total of sixty-three naturally contaminated chicken samples were investigated by both methods and relative accuracy, relative sensitivity and relative specificity of the real-time PCR method were determined to be 89, 94 and 87%, respectively. Thirty cultures blind tested were correctly identified by the real-time multiplex PCR method.

Conclusion
Real-time PCR methodology can contribute to meet the need for rapid identification and detection methods in food testing laboratories.
Global transcriptional response to mammalian temperature provides new insight into Francisella tularensis pathogenesis
Authors: Horzempa Joseph , Carlson Paul E , O'Dee Dawn M , Shanks Robert MQ , Nau Gerard J 
Published: October 2008

Abstract

Background
After infecting a mammalian host, the facultative intracellular bacterium, Francisella tularensis, encounters an elevated environmental temperature. We hypothesized that this temperature change may regulate genes essential for infection.

Results
Microarray analysis of F. tularensis LVS shifted from 26°C (environmental) to 37°C (mammalian) showed ~11% of this bacterium's genes were differentially-regulated. Importantly, 40% of the protein-coding genes that were induced at 37°C have been previously implicated in virulence or intracellular growth of Francisella in other studies, associating the bacterial response to this temperature shift with pathogenesis. Forty-four percent of the genes induced at 37°C encode proteins of unknown function, suggesting novel Francisella virulence traits are regulated by mammalian temperature. To explore this possibility, we generated two mutants of loci induced at 37°C [FTL_1581 and FTL_1664 (deoB)]. The FTL_1581 mutant was attenuated in a chicken embryo infection model, which was likely attributable to a defect in survival within macrophages. FTL_1581 encodes a novel hypothetical protein that we suggest naming temperature-induced, virulence-associated locus A, tivA. Interestingly, the deoB mutant showed diminished entry into mammalian cells compared to wild-type LVS, including primary human macrophages and dendritic cells, the macrophage-like RAW 264.7 line, and non-phagocytic HEK-293 cells. This is the first study identifying a Francisella gene that contributes to uptake into both phagocytic and non-phagocytic host cells.

Conclusion
Our results provide new insight into mechanisms of Francisella virulence regulation and pathogenesis. F. tularensis LVS undergoes considerable gene expression changes in response to mammalian body temperature. This temperature shift is important for the regulation of genes that are critical for the pathogenesis of Francisella. Importantly, the compilation of temperature-regulated genes also defines a rich collection of novel candidate virulence determinants, including tivA (FTL_1581). An analysis of tivA and deoB (FTL_1664) revealed that these genes contribute to intracellular survival and entry into mammalian cells, respectively.
The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis
Authors: Wang Aijin , Arantes Stacey , Yan Leqin , Kiguchi Kaoru , McArthur Mark J , Sahin Aysegul , Thames Howard D , Aldaz C Marcelo , MacLeod Michael C 
Published: October 2008

AbstractBackgroundOverexpression of the bZip transcription factor, ATF3, in basal epithelial cells of transgenic mice under the control of the bovine cytokeratin-5 (CK5) promoter has previously been shown to induce epidermal hyperplasia, hair follicle anomalies and neoplastic lesions of the oral mucosa including squamous cell carcinomas. CK5 is known to be expressed in myoepithelial cells of the mammary gland, suggesting the possibility that transgenic BK5.ATF3 mice may exhibit mammary gland phenotypes.MethodsMammary glands from nulliparous mice in our BK5.ATF3 colony, both non-transgenic and transgenic, were examined for anomalies by histopathology and immunohistochemistry. Nulliparous and biparous female mice were observed for possible mammary tumor development, and suspicious masses were analyzed by histopathology and immunohistochemistry. Human breast tumor samples, as well as normal breast tissue, were similarly analyzed for ATF3 expression.ResultsTransgenic BK5.ATF3 mice expressed nuclear ATF3 in the basal layer of the mammary ductal epithelium, and often developed squamous metaplastic lesions in one or more mammary glands by 25 weeks of age. No progression to malignancy was seen in nulliparous BK5.ATF3 or non-transgenic mice held for 16 months. However, biparous BK5.ATF3 mice developed mammary carcinomas with squamous metaplasia between 6 months and one year of age, reaching an incidence of 67%. Cytokeratin expression in the tumors was profoundly disturbed, including expression of CK5 and CK8 (characteristic of basal and luminal cells, respectively) throughout the epithelial component of the tumors, CK6 (potentially a stem cell marker), CK10 (a marker of interfollicular epidermal differentiation), and mIRSa2 and mIRSa3.1 (markers of the inner root sheath of hair follicles). Immunohistochemical studies indicated that a subset of human breast tumors exhibit high levels of nuclear ATF3 expression.ConclusionOverexpression of ATF3 in CK5-expressing cells of the murine mammary gland results in the development of squamous metaplastic lesions in nulliparous females, and in mammary tumors in biparous mice, suggesting that ATF3 acts as a mammary oncogene. A subset of human breast tumors expresses high levels of ATF3, suggesting that ATF3 may play an oncogenic role in human breast tumorigenesis, and therefore may be useful as either a biomarker or therapeutic target.
Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China
Authors: Wang Jianming , Fei Yang , Shen Hongbing , Xu Biao 
Published: October 2008

AbstractBackgroundTuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors.MethodsTwo cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly.ResultsAmong general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores.ConclusionTB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.
Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure
Authors: Lenaerts Tom , Ferkinghoff-Borg Jesper , Stricher Francois , Serrano Luis , Schymkowitz Joost WH , Rousseau Frederic 
Published: October 2008

Abstract

Background
Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking.

Results
Here we introduce a method to analyze protein dynamics within the framework of information theory and show that signal transduction within proteins can be considered as a particular instance of communication over a noisy channel. In particular, we analyze the conformational correlations between protein residues and apply the concept of mutual information to quantify information exchange. Mapping out changes of mutual information on the protein structure then allows visualizing how distal communication is achieved. We illustrate the approach by analyzing information transfer by the SH2 domain of Fyn tyrosine kinase, obtained from Monte Carlo dynamics simulations. Our analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located in the phosphopeptide and specificity binding sites and a number of residues at the other side of the domain near the linkers that connect the SH2 domain to the SH3 and kinase domains. We find that for this particular domain, communication is affected by a series of contiguous residues that connect distal sites by crossing the core of the SH2 domain.

Conclusion
As a result, our method provides a means to directly map the exchange of biological information on the structure of protein domains, making it clear how binding triggers conformational changes in the protein structure. As such it provides a structural road, next to the existing attempts at sequence level, to predict long-range interactions within protein structures.
Factors influencing the participation of gastroenterologists and hepatologists in clinical research
Authors: Dev Anouk T , Kauf Teresa L , Zekry Amany , Patel Keyur , Heller Karen , Schulman Kevin A , McHutchison John G 
Published: October 2008

Abstract

Background
Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.

Methods
We surveyed 1050 members of the American Association for the Study of Liver Diseases regarding their participation in clinical research. We compared the survey responses by specialty and level of clinical trial experience.

Results
A majority of the respondents (71.6%) reported involvement in research activities. Factors most influential in clinical trial participation included funding and compensation (88.3%) and intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n = 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced (n = 159) clinical researchers. These barriers included uncompensated research costs and lack of specialized support. Industry marketing was a greater influence among respondents with less trial experience, compared to those with extensive experience (15.7% vs 1.6%; P < .01). Hepatologists and respondents with extensive clinical trial experience tended to be more interested in phase 1 and 2 studies, whereas gastroenterologists and less experienced investigators were more interested in phase 4 studies.

Conclusion
This study suggests that the greatest barrier to participation in clinical research is lack of adequate resources. Respondents also favored industry-sponsored research with less complex trial protocols and studies of relatively short duration.
Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans
Authors: Sela Noa , Stern Adi , Makalowski Wojciech , Pupko Tal , Ast Gil 
Published: October 2008

Abstract
Transposable elements may acquire unrelated gene fragments into their sequences in a process called transduplication. Transduplication of protein-coding genes is common in plants, but is unknown of in animals. Here, we report that the Turmoil-1 transposable element in C. elegans has incorporated two protein-coding sequences into its inverted terminal repeat (ITR) sequences. The ITRs of Turmoil-1 contain a conserved RNA recognition motif (RRM) that originated from the rsp-2 gene and a fragment from the protein-coding region of the cpg-3 gene. We further report that an open reading frame specific to C. elegans may have been created as a result of a Turmoil-1 insertion. Mutations at the 5' splice site of this open reading frame may have reactivated the transduplicated RRM motif.

Reviewers

This article was reviewed by Dan Graur and William Martin. For the full reviews, please go to the Reviewers' Reports section.