828 research outputs found
HAG1 and SWI3A/B control of male germ line development in P. patens suggests conservation of epigenetic reproductive control across land plants
Bryophytes as models to study the male germ line: loss-of-function mutants of epigenetic regulators HAG1 and SWI3a/b demonstrate conserved function in sexual reproduction
Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to longterm angiographic outcome
Background. The renarrowing process after successful percutaneous transluminal coronary angioplasty
(PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this
process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The
aim of the present study was to find independent patient-related, lesion-related, and procedure-related
risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal
narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment
of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce
overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen
diameter. This population could then constitute the target population for pharmacological intervention
studies.
Methods and Results. Quantitative angiography was performed on 666 successfully dilated lesions at
angioplasty and at 6-month follow-up. Multivaria
Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients
The tumor suppressors Tsc1 and Tsc2 form the tuberous sclerosis complex (TSC), a regulator of mTOR activity. Tsc1 stabilizes Tsc2; however, the precise mechanism involved remains elusive. The molecular chaperone heat-shock protein 90 (Hsp90) is an essen- tial component of the cellular homeostatic machinery in eukary- otes. Here, we show that Tsc1 is a new co-chaperone for Hsp90 that inhibits its ATPase activity. The C-terminal domain of Tsc1 (998â1,164 aa) forms a homodimer and binds to both protomers of the Hsp90 middle domain. This ensures inhibition of both subunits of the Hsp90 dimer and prevents the activating co- chaperone Aha1 from binding the middle domain of Hsp90. Conversely, phosphorylation of Aha1-Y223 increases its affinity for Hsp90 and displaces Tsc1, thereby providing a mechanism for equilibrium between binding of these two co-chaperones to Hsp90. Our findings establish an active role for Tsc1 as a facilita- tor of Hsp90-mediated folding of kinase and non-kinase clientsâ including Tsc2âthereby preventing their ubiquitination and proteasomal degradation
Genomic Islands Confer Heavy Metal Resistance in <i>Mucilaginibacter kameinonensis</i> and <i>Mucilaginibacter rubeus</i> Isolated from a Gold/Copper Mine.
Heavy metals (HMs) are compounds that can be hazardous and impair growth of living organisms. Bacteria have evolved the capability not only to cope with heavy metals but also to detoxify polluted environments. Three heavy metal-resistant strains of <i>Mucilaginibacer rubeus</i> and one of <i>Mucilaginibacter kameinonensis</i> were isolated from the gold/copper Zijin mining site, Longyan, Fujian, China. These strains were shown to exhibit high resistance to heavy metals with minimal inhibitory concentration reaching up to 3.5 mM Cu <sup>(II)</sup> , 21 mM Zn <sup>(II)</sup> , 1.2 mM Cd <sup>(II)</sup> , and 10.0 mM As <sup>(III)</sup> . Genomes of the four strains were sequenced by Illumina. Sequence analyses revealed the presence of a high abundance of heavy metal resistance (HMR) determinants. One of the strain, <i>M. rubeus</i> P2, carried genes encoding 6 putative P <sub>IB-1</sub> -ATPase, 5 putative P <sub>IB-3</sub> -ATPase, 4 putative Zn <sup>(II)</sup> /Cd <sup>(II)</sup> P <sub>IB-4</sub> type ATPase, and 16 putative resistance-nodulation-division (RND)-type metal transporter systems. Moreover, the four genomes contained a high abundance of genes coding for putative metal binding chaperones. Analysis of the close vicinity of these HMR determinants uncovered the presence of clusters of genes potentially associated with mobile genetic elements. These loci included genes coding for tyrosine recombinases (integrases) and subunits of mating pore (type 4 secretion system), respectively allowing integration/excision and conjugative transfer of numerous genomic islands. Further in silico analyses revealed that their genetic organization and gene products resemble the <i>Bacteroides</i> integrative and conjugative element CTnDOT. These results highlight the pivotal role of genomic islands in the acquisition and dissemination of adaptive traits, allowing for rapid adaption of bacteria and colonization of hostile environments
Treponema Infection Associated With Genital Ulceration in Wild Baboons
The authors describe genital alterations and detailed histologic findings in
baboons naturally infected with Treponema pallidum. The disease causes
moderate to severe genital ulcerations in a population of olive baboons (Papio
hamadryas anubis) at Lake Manyara National Park in Tanzania. In a field survey
in 2007, 63 individuals of all age classes, both sexes, and different grades
of infection were chemically immobilized and sampled. Histology and molecular
biological tests were used to detect and identify the organism responsible: a
strain similar to T pallidum ssp pertenue, the cause of yaws in humans.
Although treponemal infections are not a new phenomenon in nonhuman primates,
the infection described here appears to be strictly associated with the
anogenital region and results in tissue alterations matching those found in
human syphilis infections (caused by T pallidum ssp pallidum), despite the
causative pathogenâs greater genetic similarity to human yaws-causing strains
Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty
Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after â„1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p 45 ° (OR 2.34; p 45 ° (OR 2.87; p 45 ° (OR 2.54; p < 0.006) were independent predictors of major adverse cardiac events
Robustness of circadian clocks to daylight fluctuations: hints from the picoeucaryote Ostreococcus tauri
The development of systemic approaches in biology has put emphasis on
identifying genetic modules whose behavior can be modeled accurately so as to
gain insight into their structure and function. However most gene circuits in a
cell are under control of external signals and thus quantitative agreement
between experimental data and a mathematical model is difficult. Circadian
biology has been one notable exception: quantitative models of the internal
clock that orchestrates biological processes over the 24-hour diurnal cycle
have been constructed for a few organisms, from cyanobacteria to plants and
mammals. In most cases, a complex architecture with interlocked feedback loops
has been evidenced. Here we present first modeling results for the circadian
clock of the green unicellular alga Ostreococcus tauri. Two plant-like clock
genes have been shown to play a central role in Ostreococcus clock. We find
that their expression time profiles can be accurately reproduced by a minimal
model of a two-gene transcriptional feedback loop. Remarkably, best adjustment
of data recorded under light/dark alternation is obtained when assuming that
the oscillator is not coupled to the diurnal cycle. This suggests that coupling
to light is confined to specific time intervals and has no dynamical effect
when the oscillator is entrained by the diurnal cycle. This intringuing
property may reflect a strategy to minimize the impact of fluctuations in
daylight intensity on the core circadian oscillator, a type of perturbation
that has been rarely considered when assessing the robustness of circadian
clocks
Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest
Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation
AKT activity orchestrates marginal zone B cell development in mice and humans.
The signals controlling marginal zone (MZ) and follicular (FO) B cell development remain incompletely understood. Here, we show that AKT orchestrates MZ B cell formation in mice and humans. Genetic models that increase AKT signaling in B cells or abolish its impact on FoxO transcription factors highlight the AKT-FoxO axis as an on-off switch for MZ B cell formation in mice. In humans, splenic immunoglobulin (Ig) D <sup>+</sup> CD27 <sup>+</sup> B cells, proposed as an MZ B cell equivalent, display higher AKT signaling than naive IgD <sup>+</sup> CD27 <sup>-</sup> and memory IgD <sup>-</sup> CD27 <sup>+</sup> B cells and develop in an AKT-dependent manner from their precursors in vitro, underlining the conservation of this developmental pathway. Consistently, CD148 is identified as a receptor indicative of the level of AKT signaling in B cells, expressed at a higher level in MZ B cells than FO B cells in mice as well as humans
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