1,474 research outputs found
Recommended from our members
Enhanced macrophage tropism of HIV in brain and lymphoid tissues is associated with sensitivity to the broadly neutralizing CD4 binding site antibody b12
Macrophages in the central nervous system (CNS) and other tissues are an important cellular reservoir for human immunodeficiency virus type 1 (HIV) infection, particularly in the later stages of disease. Macrophage-tropic HIV strains have an enhanced capacity to enter cells expressing low levels of CD4 through mechanisms that are not well understood. Here, we use a panel of primary HIV envelopes from brain and lymphoid tissues to examine the relationship between neutralization sensitivity to reagents targeting the CD4 binding site and virus entry into macrophages. Neutralization assays using pseudotyped viruses showed an association between the capacity of HIV to enter macrophages and increased sensitivity to the broadly neutralizing monoclonal antibody (mAb) b12, which recognizes a conserved epitope overlapping the CD4 binding site, but not sensitivity to soluble CD4 (sCD4) or b6, a non-neutralizing CD4 binding site mAb. Furthermore, loss of an N-linked glycosylation site at position 386 in the V4 region of Env enhanced macrophage tropism together with b12 sensitivity, but not neutralization by sCD4, b6, or a broadly neutralizing AIDS patient serum. These findings suggest that exposure of the b12 epitope, rather than exposure of the CD4 binding site per se, enhances HIV macrophage tropism, possibly by exposing a region on the outer domain of gp120 that is initially recognized by CD4. These findings suggest overlap between specific gp120 determinants in or near the b12 epitope and those conferring macrophage tropism
Recommended from our members
Acceleration Through a Holistic Support Model: An Implementation and Outcomes Analysis of FastStart@CCD
Originally designed for students who test into at least two levels of developmental education in a particular subject area, FastStart is a compressed course program model launched in 2005 at the Community College of Denver (CCD). The program combines multiple semester-length courses into a single intensive semester, while providing case management, career exploration, and educational planning services.
This report discusses the development of FastStart, its program features, and student perspectives, and it presents findings from a quantitative analysis of the FastStart math program. The authors find that participation is associated with higher rates of enrolling in and passing college-level math courses but not with increased persistence or with increased accumulation of college-level credits. The analysis suggests that FastStart makes it possible for students to complete the developmental math sequence and required gatekeeper math course more quickly than would otherwise be possible, without harming other long-term academic outcomes. The report also analyzes pedagogical features of FastStart drawn from classroom observations and interviews
Effects of Exogenous Yeast and Bacteria on the Microbial Population Dynamics and Outcomes of Olive Fermentations.
In this study, we examined Sicilian-style green olive fermentations upon the addition of Saccharomyces cerevisiae UCDFST 09-448 and/or Pichia kudriazevii UCDFST09-427 or the lactic acid bacteria (LAB) Lactobacillus plantarum AJ11R and Leuconostoc pseudomesenteroides BGM3R. Olives containing S. cerevisiae UCDFST 09-448, a strain able to hydrolyze pectin, but not P. kudriazevii UCDFST 09-427, a nonpectinolytic strain, exhibited excessive tissue damage within 4 weeks. DNA sequencing of fungal internal transcribed spacer (ITS) regions and comparisons to a yeast-specific ITS sequence database remarkably showed that neither S. cerevisiae UCDFST 09-448 nor P. kudriazevii UCDFST 09-427 resulted in significant changes to yeast species diversity. Instead, Candida boidinii constituted the majority (>90%) of the total yeast present, independent of whether S. cerevisiae or P. kudriazevii was added. By comparison, Lactobacillus species were enriched in olives inoculated with potential starter LAB L. plantarum AJ11R and L. pseudomesenteroides BGM3R according to community 16S rRNA gene sequence analysis. The bacterial diversity of those olives was significantly reduced and resembled control fermentations incubated for a longer period of time. Importantly, microbial populations were highly dynamic at the strain level, as indicated by the large variations in AJ11R and BGM3R cell numbers over time and reductions in the numbers of yeast isolates expressing polygalacturonase activity. These findings show the distinct effects of exogenous spoilage and starter microbes on indigenous communities in plant-based food fermentations that result in very different impacts on product quality. IMPORTANCE Food fermentations are subject to tremendous selective pressures resulting in the growth and persistence of a limited number of bacterial and fungal taxa. Although these foods are vulnerable to spoilage by unintended contamination of certain microorganisms, or alternatively, can be improved by the deliberate addition of starter culture microbes that accelerate or beneficially modify product outcomes, the impact of either of those microbial additions on community dynamics within the fermentations is not well understood at strain-specific or global scales. Herein, we show how exogenous spoilage yeast or starter lactic acid bacteria confer very different effects on microbial numbers and diversity in olive fermentations. Introduced microbes have long-lasting consequences and result in changes that are apparent even when levels of those inoculants and their major enzymatic activities decline. This work has direct implications for understanding bacterial and fungal invasions of microbial habitats resulting in pivotal changes to community structure and function
Recommended from our members
FUS Binds the CTD of RNA Polymerase II and Regulates its Phosphorylation at Ser2
Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. We found that FUS binds the C-terminal domain (CTD) of RNA polymerase II (RNAP2) and prevents inappropriate hyperphosphorylation of Ser2 in the RNAP2 CTD at thousands of human genes. The loss of FUS leads to RNAP2 accumulation at the transcription start site and a shift in mRNA isoform expression toward early polyadenylation sites. Thus, in addition to its role in alternative RNA splicing, FUS has a general function in orchestrating CTD phosphorylation during RNAP2 transcription
Recommended from our members
FUS is sequestered in nuclear aggregates in ALS patient fibroblasts
Mutations in the RNA-binding protein FUS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We investigate whether mutant FUS protein in ALS patient–derived fibroblasts affects normal FUS functions in the nucleus. We investigated fibroblasts from two ALS patients possessing different FUS mutations and a normal control. Fibroblasts from these patients have their nuclear FUS protein trapped in SDS-resistant aggregates. Genome-wide analysis reveals an inappropriate accumulation of Ser-2 phosphorylation on RNA polymerase II (RNA Pol II) near the transcription start sites of 625 genes for ALS patient cells and after small interfering RNA (siRNA) knockdown of FUS in normal fibroblasts. Furthermore, both the presence of mutant FUS protein and siRNA knockdown of wild-type FUS correlate with altered distribution of RNA Pol II within fibroblast nuclei. A loss of FUS function in orchestrating Ser-2 phosphorylation of the CTD of RNA Pol II is detectable in ALS patient–derived fibroblasts expressing mutant FUS protein, even when the FUS protein remains largely nuclear. A likely explanation for this loss of function is the aggregation of FUS protein in nuclei. Thus our results suggest a specific mechanism by which mutant FUS can have biological consequences other than by the formation of cytoplasmic aggregates
- …