bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins
Authors: Lek Angela , Lek Monkol , North Kathryn N , Cooper Sandra T 
Published: July 2010

Abstract

Background
The ferlin gene family possesses a rare and identifying feature consisting of multiple tandem C2 domains and a C-terminal transmembrane domain. Much currently remains unknown about the fundamental function of this gene family, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease. The availability of genome sequences from a wide range of species makes it possible to explore the evolution of the ferlin family, providing contextual insight into characteristic features that define the ferlin gene family in its present form in humans.

Results
Ferlin genes were detected from all species of representative phyla, with two ferlin subgroups partitioned within the ferlin phylogenetic tree based on the presence or absence of a DysF domain. Invertebrates generally possessed two ferlin genes (one with DysF and one without), with six ferlin genes in most vertebrates (three DysF, three non-DysF). Expansion of the ferlin gene family is evident between the divergence of lamprey (jawless vertebrates) and shark (cartilaginous fish). Common to almost all ferlins is an N-terminal C2-FerI-C2 sandwich, a FerB motif, and two C-terminal C2 domains (C2E and C2F) adjacent to the transmembrane domain. Preservation of these structural elements throughout eukaryotic evolution suggests a fundamental role of these motifs for ferlin function. In contrast, DysF, C2DE, and FerA are optional, giving rise to subtle differences in domain topologies of ferlin genes. Despite conservation of multiple C2 domains in all ferlins, the C-terminal C2 domains (C2E and C2F) displayed higher sequence conservation and greater conservation of putative calcium binding residues across paralogs and orthologs. Interestingly, the two most studied non-mammalian ferlins (Fer-1 and Misfire) in model organisms C. elegans and D. melanogaster, present as outgroups in the phylogenetic analysis, with results suggesting reproduction-related divergence and specialization of species-specific functions within their genus.

Conclusions
Our phylogenetic studies provide evolutionary insight into the ferlin gene family. We highlight the existence of ferlin-like proteins throughout eukaryotic evolution, from unicellular phytoplankton and apicomplexan parasites, through to humans. We characterise the preservation of ferlin structural motifs, not only of C2 domains, but also the more poorly characterised ferlin-specific motifs representing the DysF, FerA and FerB domains. Our data suggest an ancient role of ferlin proteins, with lessons from vertebrate biology and human disease suggesting a role relating to vesicle fusion and plasma membrane specialization.
Genetic and phenotypic diversity in Burkholderia: contributions by prophage and phage-like elements
Authors: Ronning Catherine M , Losada Liliana , Brinkac Lauren , Inman Jason , Ulrich Ricky L , Schell Mark , Nierman William C , DeShazer David 
Published: July 2010

Abstract

Background

Burkholderia species exhibit enormous phenotypic diversity, ranging from the nonpathogenic, soil- and water-inhabiting Burkholderia thailandensis to the virulent, host-adapted mammalian pathogen B. mallei. Genomic diversity is evident within Burkholderia species as well. Individual isolates of Burkholderia pseudomallei and B. thailandensis, for example, carry a variety of strain-specific genomic islands (GIs), including putative pathogenicity and metabolic islands, prophage-like islands, and prophages. These GIs may provide some strains with a competitive advantage in the environment and/or in the host relative to other strains.

Results
Here we present the results of analysis of 37 prophages, putative prophages, and prophage-like elements from six different Burkholderia species. Five of these were spontaneously induced to form bacteriophage particles from B. pseudomallei and B. thailandensis strains and were isolated and fully sequenced; 24 were computationally predicted in sequenced Burkholderia genomes; and eight are previously characterized prophages or prophage-like elements. The results reveal numerous differences in both genome structure and gene content among elements derived from different species as well as from strains within species, due in part to the incorporation of additional DNA, or 'morons' into the prophage genomes. Implications for pathogenicity are also discussed. Lastly, RNAseq analysis of gene expression showed that many of the genes in ϕ1026b that appear to contribute to phage and lysogen fitness were expressed independently of the phage structural and replication genes.

Conclusions
This study provides the first estimate of the relative contribution of prophages to the vast phenotypic diversity found among the Burkholderiae.
Structure-function relationships of wheat flavone O-methyltransferase: Homology modeling and site-directed mutagenesis
Authors: Zhou Jian-Min , Lee Eunjung , Kanapathy-Sinnaiaha Francesca , Park Younghee , Kornblatt Jack A , Lim Yoongho , Ibrahim Ragai K 
Published: July 2010

Abstract

Background
Wheat (Triticum aestivum L.) O-methyltransferase (TaOMT2) catalyzes the sequential methylation of the flavone, tricetin, to its 3'-methyl- (selgin), 3',5'-dimethyl- (tricin) and 3',4',5'-trimethyl ether derivatives. Tricin, a potential multifunctional nutraceutical, is the major enzyme reaction product. These successive methylations raised the question as to whether they take place in one, or different active sites. We constructed a 3-D model of this protein using the crystal structure of the highly homologous Medicago sativa caffeic acid/5-hydroxyferulic acid O-methyltransferase (MsCOMT) as a template with the aim of proposing a mechanism for multiple methyl transfer reactions in wheat.

Results
This model revealed unique structural features of TaOMT2 which permit the stepwise methylation of tricetin. Substrate binding is mediated by an extensive network of H-bonds and van der Waals interactions. Mutational analysis of structurally guided active site residues identified those involved in binding and catalysis. The partly buried tricetin active site, as well as proximity and orientation effects ensured sequential methylation of the substrate within the same pocket. Stepwise methylation of tricetin involves deprotonation of its hydroxyl groups by a His262-Asp263 pair followed by nucleophilic attack of SAM-methyl groups. We also demonstrate that Val309, which is conserved in a number of graminaceous flavone OMTs, defines the preference of TaOMT2 for tricetin as the substrate.

Conclusions
We propose a mechanism for the sequential methylation of tricetin, and discuss the potential application of TaOMT2 to increase the production of tricin as a nutraceutical. The single amino acid residue in TaOMT2, Val309, determines its preference for tricetin as the substrate, and may define the evolutionary differences between the two closely related proteins, COMT and flavone OMT.
Lymphocyte and monocyte flow cytometry immunophenotyping as a diagnostic tool in uncharacteristic inflammatory disorders
Authors: Janols Helena , Bredberg Anders , Thuvesson Irene , Janciauskiene Sabina , Grip Olof , Wullt Marlene 
Published: July 2010

Abstract

Background
Patients with uncharacteristic inflammatory symptoms such as long-standing fatigue or pain, or a prolonged fever, constitute a diagnostic and therapeutic challenge. The aim of the present study was to determine if an extended immunophenotyping of lymphocytes and monocytes including activation markers can define disease-specific patterns, and thus provide valuable diagnostic information for these patients.

Methods
Whole blood from patients with gram-negative bacteraemia, neuroborreliosis, tuberculosis, acute mononucleosis, influenza or a mixed connective tissue disorders, as diagnosed by routine culture and serology techniques was analysed for lymphocyte and monocyte cell surface markers using a no-wash, no-lyse protocol for multi-colour flow cytometry method. The immunophenotyping included the activation markers HLA-DR and CD40. Plasma levels of soluble TNF alpha receptors were analysed by ELISA.

Results
An informative pattern was obtained by combining two of the analysed parameters: (i), the fractions of HLA-DR-expressing CD4+ T cells and CD8+ T cells, respectively, and (ii), the level of CD40 on CD14+ CD16- monocytes. Patients infected with gram-negative bacteria or EBV showed a marked increase in monocyte CD40, while this effect was less pronounced for tuberculosis, borrelia and influenza. The bacterial agents could be distinguished from the viral agents by the T cell result; CD4+ T cells reacting in bacterial infection, and the CD8+ T cells dominating for the viruses. Patients with mixed connective tissue disorders also showed increased activation, but with similar engagement of CD4+ and CD8+ T cells. Analysis of soluble TNF alpha receptors was less informative due to a large inter-individual variation.

Conclusion
Immunophenotyping including the combination of the fractions of HLA-DR expressing T cell subpopulations with the level of CD40 on monocytes produces an informative pattern, differentiating between infections of bacterial and viral origin. Furthermore, a quantitative analysis of these parameters revealed the novel finding of characteristic patterns indicating a subacute bacterial infection, such as borreliosis or tuberculosis, or a mixed connective tissue disorder. The employed flow cytometric method is suitable for clinical diagnostic laboratories, and may help in the assessment of patients with uncharacteristic inflammatory symptoms.
Prevalence, concordance and determinants of human papillomavirus infection among heterosexual partners in a rural region in central Mexico
Authors: Parada Rocio , Morales Rosalba , Giuliano Anna R , Cruz Aurelio , Castellsagué Xavier , Lazcano-Ponce Eduardo 
Published: July 2010

AbstractBackgroundAlthough human papillomavirus (HPV) infection in heterosexual couples has been sparsely studied, it is relevant to understand disease burden and transmission mechanisms. The present study determined the prevalence and concordance of type-specific HPV infection as well as the determinants of infection in heterosexual couples in a rural area of Mexico.MethodsA cross-sectional study was conducted in 504 clinically healthy heterosexual couples from four municipalities in the State of Mexico, Mexico. HPV testing was performed using biotinylated L1 consensus primers and reverse line blot in cervical samples from women and in genital samples from men. Thirty-seven HPV types were detected, including high-risk oncogenic types and low-risk types. Multivariate logistic regression models were utilized to evaluate factors associated with HPV.ResultsThe prevalence of HPV infection was 20.5% in external male genitals and 13.7% in cervical samples. In 504 sexual couples participating in the study, concordance of HPV status was 79%; 34 partners (6.7%) were concurrently infected, and 21 out of 34 partners where both were HPV positive (61.8%) showed concordance for one or more HPV types. The principal risk factor associated with HPV DNA detection in men as well as women was the presence of HPV DNA in the respective regular sexual partner (OR = 5.15, 95%CI 3.01-8.82). In men, having a history of 10 or more sexual partners over their lifetime (OR 2.5, 95%CI 1.3 - 4.8) and having had sexual relations with prostitutes (OR 1.7, 95%CI 1.01 - 2.8) increased the likelihood of detecting HPV DNA.ConclusionsIn heterosexual couples in rural regions in Mexico, the prevalence of HPV infection and type-specific concordance is high. High-risk sexual behaviors are strong determinants of HPV infection in men.
Gorlin syndrome associated with small bowel carcinoma and mesenchymal proliferation of the gastrointestinal tract: case report and review of literature
Authors: Prodinger Peter M , Sarbia Mario , Maßmann Jörg , Straka Christian , Meyer Günther , Steinlein Ortrud K 
Published: July 2010

Abstract

Background and Case Presentation
A patient with nevoid basal cell carcinoma syndrome (Gorlin syndrome) presented with two unusual clinical features, i.e. adenocarcinoma of the small bowel and extensive mesenchymal proliferation of the lower gastrointestinal tract.

Conclusions
We discuss the possibility that these two features are pathogenetically linked to the formerly undescribed patient's PTCH germ line mutation.
Knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical Singapore: a cross-sectional survey
Authors: Yap Jonathan , Lee Vernon J , Yau Teng Yan , Ng Tze Pin , Tor Phern-Chern 
Published: July 2010

Abstract

Background
Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes and practices in various different cohorts and explore the pertinent factors that influenced behavior in tropical Singapore.

Methods
We performed a cross-sectional knowledge, attitudes and practices survey in the Singapore military from mid-August to early-October 2009, among 3054 personnel in four exposure groups - laboratory-confirmed H1N1-2009 cases, close contacts of cases, healthcare workers, and general personnel.

Results
1063 (34.8%) participants responded. The mean age was 21.4 (SE 0.2) years old. Close contacts had the highest knowledge score (71.7%, p = 0.004) while cases had the highest practice scores (58.8%, p < 0.001). There was a strong correlation between knowledge and practice scores (r = 0.27, p < 0.01) and knowledge and attitudes scores (r = 0.21, p < 0.01). The significant predictors of higher practice scores were higher knowledge scores (p < 0.001), Malay ethnicity (p < 0.001), exposure group (p < 0.05) and lower education level (p < 0.05). The significant predictors for higher attitudes scores were Malay ethnicity (p = 0.014) and higher knowledge scores (p < 0.001). The significant predictor for higher knowledge score was being a contact (p = 0.007).

Conclusion
Knowledge is a significant influence on attitudes and practices in a pandemic, and personal experience influences practice behaviors. Efforts should be targeted at educating the general population to improve practices in the current pandemic, as well as for future epidemics.
Coping flexibility in college students with depressive symptoms
Authors: Zong Ji-Gang , Cao Xiao-Yan , Cao Yuan , Shi Yan-Fang , Wang Yu-Na , Yan Chao , Abela John RZ , Gan Yi-Qun , Gong Qi-Yong , Chan Raymond CK 
Published: July 2010

Abstract

Background
The current study explored the prevalence of depressed mood among Chinese undergraduate students and examined the coping patterns and degree of flexibility of flexibility of such patterns associated with such mood.

Methods
A set of questionnaire assessing coping patterns, coping flexibility, and depressive symptoms were administered to 428 students (234 men and 194 women).

Results
A total of 266 participants both completed the entire set of questionnaires and reported a frequency of two or more stressful life events (the criterion needed to calculate variance in perceived controllability). Findings showed that higher levels of depressive symptoms were significantly associated with higher levels of both event frequency (r = .368, p < .001) and event impact (r = .245, p < .001) and lower levels of perceived controllability (r = -.261, p < .001), coping effectiveness (r = -.375, p < .001), and ratio of strategy to situation fit (r = -.108, p < .05). Depressive symptoms were not significantly associated with cognitive flexibility (variance of perceived controllability; r = .031, p = .527), Gender was not a significant moderator of any of the reported associations.

Conclusions
Findings indicate that Chinese university students with depressive symptoms reported experiencing a greater number of negative events than did non-depressed university students. In addition, undergraduates with depressive symptoms were more likely than other undergraduates to utilize maladaptive coping methods. Such findings highlight the potential importance of interventions aimed at helping undergraduate students with a lower coping flexibility develop skills to cope with stressful life events.
Functional expression and intracellular signaling of UTP-sensitive P2Y receptors in theca-interstitial cells
Authors: Vázquez-Cuevas Francisco G , Zárate-Díaz Erika P , Garay Edith , Arellano Rogelio O 
Published: July 2010

AbstractBackgroundPurinergic receptors are expressed in the ovary of different species; their physiological roles remain to be elucidated. UTP-sensitive P2Y receptor activity may regulate cell proliferation. The aim of the present work was to study the functional expression of these receptors in theca/interstitial cells (TIC).MethodsTIC were isolated by centrifugation in a Percoll gradient. P2Y receptors and cellular markers in TIC were detected by RT-PCR and Western blot. Intracellular calcium mobilization induced by purinergic drugs was evaluated by fluorescence microscopy, phosphorylation of MAPK p44/p42 and of cAMP response element binding protein (CREB) was determined by Western blot and proliferation was quantified by [3H]-thymidine incorporation into DNA.ResultsRT-PCR showed expression of p2y2r and p2y6r transcripts, expression of the corresponding proteins was confirmed. UTP and UDP, agonists for P2Y2 and P2Y6 receptors, induced an intracellular calcium increase with a maximum of more than 400% and 200% of basal level, respectively. The response elicited by UTP had an EC50 of 3.5 +/- 1.01 μM, while that for UDP was 3.24 +/- 0.82 μM. To explore components of the pathway activated by these receptors, we evaluated the phosphorylation induced by UTP or UDP of MAPK p44 and p42. It was found that UTP increased MAPK phosphorylation by up to 550% with an EC50 of 3.34 +/- 0.92 and 1.41 +/- 0.67 μM, for p44 and p42, respectively; these increases were blocked by suramin. UDP also induced p44/p42 phosphorylation, but at high concentrations. Phosphorylation of p44/p42 was dependent on PKC and intracellular calcium. To explore possible roles of this pathway in cell physiology, cell proliferation and hCG-induced CREB-phosphorylation assays were performed; results showed that agonists increased cell proliferation and prevented CREB-phosphorylation.ConclusionHere, it is shown that UTP-sensitive P2Y receptors are expressed in cultured TIC and that these receptors had the ability to activate mitogenic signaling pathways and to promote cell proliferation, as well as to prevent CREB-phosphorylation by hCG. Regulation of TIC proliferation and steroidogenesis is relevant in ovarian pathophysiology since theca hyperplasia is involved in polycystic ovarian syndrome. Purinergic receptors described might represent an important new set of molecular therapeutic targets.
Development and pilot testing of HEXORR: Hand EXOskeleton Rehabilitation Robot
Authors: Schabowsky Christopher N , Godfrey Sasha B , Holley Rahsaan J , Lum Peter S 
Published: July 2010

AbstractBackgroundFollowing acute therapeutic interventions, the majority of stroke survivors are left with a poorly functioning hemiparetic hand. Rehabilitation robotics has shown promise in providing patients with intensive therapy leading to functional gains. Because of the hand's crucial role in performing activities of daily living, attention to hand therapy has recently increased.MethodsThis paper introduces a newly developed Hand Exoskeleton Rehabilitation Robot (HEXORR). This device has been designed to provide full range of motion (ROM) for all of the hand's digits. The thumb actuator allows for variable thumb plane of motion to incorporate different degrees of extension/flexion and abduction/adduction. Compensation algorithms have been developed to improve the exoskeleton's backdrivability by counteracting gravity, stiction and kinetic friction. We have also designed a force assistance mode that provides extension assistance based on each individual's needs. A pilot study was conducted on 9 unimpaired and 5 chronic stroke subjects to investigate the device's ability to allow physiologically accurate hand movements throughout the full ROM. The study also tested the efficacy of the force assistance mode with the goal of increasing stroke subjects' active ROM while still requiring active extension torque on the part of the subject.ResultsFor 12 of the hand digits'15 joints in neurologically normal subjects, there were no significant ROM differences (P > 0.05) between active movements performed inside and outside of HEXORR. Interjoint coordination was examined in the 1stand 3rddigits, and no differences were found between inside and outside of the device (P > 0.05). Stroke subjects were capable of performing free hand movements inside of the exoskeleton and the force assistance mode was successful in increasing active ROM by 43 ± 5% (P < 0.001) and 24 ± 6% (P = 0.041) for the fingers and thumb, respectively.ConclusionsOur pilot study shows that this device is capable of moving the hand's digits through nearly the entire ROM with physiologically accurate trajectories. Stroke subjects received the device intervention well and device impedance was minimized so that subjects could freely extend and flex their digits inside of HEXORR. Our active force-assisted condition was successful in increasing the subjects' ROM while promoting active participation.
MacroH2A subtypes contribute antagonistically to the transcriptional regulation of the ribosomal cistron during seasonal acclimatization of the carp fish
Authors: Araya I , Nardocci G , Morales JP , Vera MI , Molina A , Alvarez M 
Published: July 2010

Abstract

Background
Incorporation of histone variants into chromatin is one of the epigenetic mechanisms used for regulation of gene expression. Macro (m)H2A is a histone variant that has two different subtypes in vertebrates: mH2A1 and mH2A2. It is known that mH2A is associated with gene silencing, but recent studies indicate that these mH2A subtypes could contribute more widely to transcriptional regulation. We have previously demonstrated that the gene-reprogramming response mediates adaptation of the carp fish to its environment, and that ribosomal gene transcription is seasonally regulated in carp. However, there have been few studies investigating how epigenetic mechanisms contribute to environmental adaptation and, in particular, to ribosomal cistron regulation.

Results
In this paper, we report the occurrence of differential incorporation of mH2A subtypes into chromatin during seasonal adaptation in the carp, an event that concurs with opposing transcriptional states. Moreover, we observed that enrichment of mH2A1 in the ribosomal cistron during winter, and conversely, enrichment of mH2A2 during summer. mH2A1 consistently colocalizes with a heterochromatin marker (H3K27me2; histone H3 trimethylated at lysine 27) and mH2A2 with a euchromatin marker (H3K4me3; histone H3 trimethylated at lysine 4). Similar results were found for the L41gene, with enrichment of mH2A in the promoter region.

Conclusions
We have characterized both mH2A subtypes from carp fish, and evaluated their participation in the regulation of the ribosomal cistron. Our findings indicate that differential incorporation of mH2A subtypes into the ribosome could regulate gene expression during the acclimatization process in carp. Our results reveal differential chromatin incorporation of the mH2A subtypes during the environmental adaptation process, correlating wtih antagonistic transcriptional states in the carp ribosomal cistron.