197 research outputs found
Factors associated with HIV viral load “blips” and the relationship between self-reported adherence and efavirenz blood levels on blip occurrence: a case–control study
Competition between decay and dissociation of core-excited OCS studied by X-ray scattering
We show the first evidence of dissociation during resonant inelastic soft
X-ray scattering. Carbon and oxygen K-shell and sulfur L-shell resonant and
non-resonant X-ray emission spectra were measured using monochromatic
synchrotron radiation for excitation and ionization. After sulfur, L2,3 ->
{\pi}*, {\sigma}* excitation, atomic lines are observed in the emission spectra
as a consequence of competition between de-excitation and dissociation. In
contrast the carbon and oxygen spectra show weaker line shape variations and no
atomic lines. The spectra are compared to results from ab initio calculations
and the discussion of the dissociation paths is based on calculated potential
energy surfaces and atomic transition energies.Comment: 12 pages, 6 pictures, 2 tables,
http://link.aps.org/doi/10.1103/PhysRevA.59.428
The Potential Link between Thermal Resistance and Virulence in Salmonella: A Review
In some animals, the typical body temperature can be higher than humans, for example, 42°C in poultry and 40°C in rabbits which can be a potential thermal stress challenge for pathogens. Even in animals with lower body temperatures, when infection occurs, the immune system may increase body temperature to reduce the chance of survival for pathogens. However, some pathogens can still easily overcome higher body temperatures and/or rise in body temperatures through expression of stress response mechanisms. Salmonella is the causative agent of one of the most prevalent foodborne illnesses, salmonellosis, and can readily survive over a wide range of temperatures due to the efficient expression of the heat (thermal) stress response. Therefore, thermal resistance mechanisms can provide cross protection against other stresses including the non-specific host defenses found within the human body thus increasing pathogenic potential. Understanding the molecular mechanisms associated with thermal responses in Salmonella is crucial in designing and developing more effective or new treatments for reducing and eliminating infection caused by Salmonella that have survived heat stress. In this review, Salmonella thermal resistance is assessed followed by an overview of the thermal stress responses with a focus on gene regulation by sigma factors, heat shock proteins, along with the corresponding thermosensors and their association with virulence expression including a focus on a potential link between heat resistance and potential for infection
Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours
The molecular mechanisms that underlie the development of squamous cell skin cancers (SSC) are poorly understood. We have used oligonucleotide microarrays to compare the differences in cellular gene expression between a series of keratinocyte cell that mimic disease progression with the aim of identifying genes that may potentially contribute towards squamous cell carcinoma (SCC) progression in vivo, and in particular to identify markers that may serve as potential therapeutic targets for SCC treatment. Gene expression differences were corroborated by polymerase chain reaction and Western blotting. We identified Axl, a receptor tyrosine kinase with transforming potential that has also been shown to have a role in cell survival, adhesion and chemotaxis, was upregulated in vitro in SCC-derived cells compared to premalignant cells. Extending the investigation to tumour biopsies showed that the Axl protein was overexpressed in vivo in a series of SCCs
The Relationship Between GPS Sampling Interval and Estimated Daily Travel Distances in Chacma Baboons (Papio ursinus)
Modern studies of animal movement use the Global Positioning System (GPS) to estimate animals’ distance traveled. The temporal resolution of GPS fixes recorded should match those of the behavior of interest; otherwise estimates are likely to be inappropriate. Here, we investigate how different GPS sampling intervals affect estimated daily travel distances for wild chacma baboons (Papio ursinus). By subsampling GPS data collected at one fix per second for 143 daily travel distances (12 baboons over 11–12 days), we found that less frequent GPS fixes result in smaller estimated travel distances. Moving from a GPS frequency of one fix every second to one fix every 30 s resulted in a 33% reduction in estimated daily travel distance, while using hourly GPS fixes resulted in a 66% reduction. We then use the relationship we find between estimated travel distance and GPS sampling interval to recalculate published baboon daily travel distances and find that accounting for the predicted effect of sampling interval does not affect conclusions of previous comparative analyses. However, if short-interval or continuous GPS data—which are becoming more common in studies of primate movement ecology—are compared with historical (longer interval) GPS data in future work, controlling for sampling interval is necessary
A de novo paradigm for male infertility
Genetics of Male Infertility Initiative (GEMINI) consortium: Donald F. Conrad, Liina Nagirnaja, Kenneth I. Aston, Douglas T. Carrell, James M. Hotaling, Timothy G. Jenkins, Rob McLachlan, Moira K. O’Bryan, Peter N. Schlegel, Michael L. Eisenberg, Jay I. Sandlow, Emily S. Jungheim, Kenan R. Omurtag, Alexandra M. Lopes, Susana Seixas, Filipa Carvalho, Susana Fernandes, Alberto Barros, João Gonçalves, Iris Caetano, Graça Pinto, Sónia Correia, Maris Laan, Margus Punab, Ewa Rajpert-De Meyts, Niels Jørgensen, Kristian Almstrup, Csilla G. Krausz & Keith A. Jarvi.De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness.
We hypothesize that de novo mutations play an important role in severe male infertility and
explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we
utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents.
Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations
are classified as possibly causative of the male infertility phenotype. We observed a significant
enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value =
1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant
increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes
(p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify,
RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously
implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations
affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such
mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the
role of de novo mutations in severe male infertility and point to new candidate genes affecting
fertility.This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E.info:eu-repo/semantics/publishedVersio
Nitric oxide and cyclic nucleotides: Their roles in junction dynamics and spermatogenesis
Spermatogenesis is a highly complicated process in which functional spermatozoa (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n). This process involves the differentiation and transformation of several types of germ cells as spermatocytes and spermatids undergo meiosis and differentiation. Due to its sophistication and complexity, testis possesses intrinsic mechanisms to modulate and regulate different stages of germ cell development under the intimate and indirect cooperation with Sertoli and Leydig cells, respectively. Furthermore, developing germ cells must translocate from the basal to the apical (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction restructuring must occur to assist germ cell movement. Within the seminiferous tubules, three principal types of junctions are found namely anchoring junctions, tight junctions, and gap junctions. Other less studied junctions are desmosome-like junctions and hemidesmosome junctions. With these varieties of junction types, testes are using different regulators to monitor junction turnover. Among the uncountable junction modulators, nitric oxide (NO) is a prominent candidate due to its versatility and extensive downstream network. NO is synthesized by nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently shown to have putative junction regulation properties. More important, these two NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G signaling pathway to regulate the structural components at the tight junctions and adherens junctions in the testes. Apart from the involvement in junction regulation, NOS/NO also participates in controlling the levels of cytokines and hormones in the testes. On the other hand, NO is playing a unique role in modulating germ cell viability and development, and indirectly acting on some aspects of male infertility and testicular pathological conditions. Thus, NOS/NO bears an irreplaceable role in maintaining the homeostasis of the microenvironment in the seminiferous epithelium via its different downstream signaling pathways
Association between hepatitis B vaccine antibody response and CD4 reconstitution after initiation of combination antiretroviral therapy in HIV-infected persons
A de novo paradigm for male infertility
Funding Information: (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E. Funding Information: We are grateful for the participation of all patients and their parents in this study. We thank Laurens van de Wiel (Radboudumc), Sebastian Judd-Mole (Monash University), Arron Scott and Bryan Hepworth (Newcastle University) for technical support, and Margot J Wyrwoll (University of Münster) for help with handling MERGE samples and data. This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” Publisher Copyright: © 2022, The Author(s).De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.publishersversionpublishe
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