293 research outputs found
Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory
Data from the Sudbury Neutrino Observatory have been used to constrain the
lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The
analysis was based on a search for gamma-rays from the de-excitation of the
residual nucleus that would result from the disappearance of either a proton or
neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90%
confidence for either neutron or proton decay modes. This is about an order of
magnitude more stringent than previous constraints on invisible proton decay
modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of
2) Submitted to Physical Review Letter
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Genetic Evidence for Repurposing of GLP1R (Glucagon-Like Peptide-1 Receptor) Agonists to Prevent Heart Failure.
Background This study was designed to investigate the genetic evidence for repurposing of GLP1R (glucagon-like peptide-1 receptor) agonists to prevent heart failure (HF) and whether the potential benefit exceeds the benefit conferred by more general glycemic control. Methods and Results We applied 2-sample Mendelian randomization of genetically proxied GLP1R agonism on HF as the main outcome and left ventricular ejection fraction as the secondary outcome. The associations were compared with those of general glycemic control on the same outcomes. Genetic associations were obtained from genome-wide association study summary statistics of type 2 diabetes mellitus (228Â 499 cases and 1Â 178Â 783 controls), glycated hemoglobin (n=344Â 182), HF (47,309 cases and 930Â 014 controls), and left ventricular ejection fraction (n=16Â 923). Genetic proxies for GLP1R agonism associated with reduced risk of HF (odds ratio per 1Â mmol/mol decrease in glycated hemoglobin 0.75; 95% CI, 0.64-0.87; P=1.69Ă—10-4), and higher left ventricular ejection fraction (SD change in left ventricular ejection fraction per 1Â mmol/mol decrease in glycated hemoglobin 0.22%; 95% CI, 0.03-0.42; P=0.03). The magnitude of these benefits exceeded those expected from improved glycemic control more generally. The results were similar in sensitivity analyses, and we did not find evidence to suggest that these associations were mediated by reduced coronary artery disease risk. Conclusions This genetic evidence supports the repurposing of GLP1R agonists for preventing HF
Lack of correlation between Ki-67 labelling index and tumor size of anterior pituitary adenomas
AIMS AND BACKGROUND: The Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its Labeling Index (LI) is considered a marker of normal and abnormal cell proliferation. Pituitary adenomas are generally well differentiated neoplasms, even if in about one third of cases they are invasive of surrounding tissues. The aim of this study is to evaluate the correlation between Ki-67 labelling index and tumor size of pituitary adenomas extimated by means CT and MRI and confirmed at operation. METHODS: Using the monoclonal antibody MIB-1, we evaluated the expression of Ki-67 in 121 anterior pituitary adenomas consecutively operated on in a 48-month period. RESULTS: In relation to neuroradiological (CT and MRI) and surgically verified tumor size, we identified 24 microadenomas, 27 intrasellar macroadenomas, 34 intra-suprasellar macroadenomas, and 36 intra-supra-parasellar macroadenomas. The adenomas were non-infiltrating (76 cases) and infiltrating (45 cases) adenomas. The wall of the cavernous sinus (CS) was infiltrated in 18 cases. Forty-eight adenomas were non-functioning and 73 functioning. The overall mean ± SD Ki-67 LI was 2.72 ± 2.49% (median 1.6). It was 2.59 ± 1.81 in microadenomas, 2.63 ± 3.45 in intrasellar macroadenomas, 1.91 ± 2.11 in intra-suprasellar macroadenomas, and 3.29 ± 5.45 in intra-supra-parasellar macroadenomas (p = 0.27). It was 3.73 ± 5.13% in infiltrating and 2.03 ± 2.41% in non-infiltrating adenomas (p = 0.02), and 5.61 ± 7.19% in CS-infiltrating versus 2.09 ± 2.37% in CS-non-infiltrating adenomas (p = 0.0005). CONCLUSIONS: Our preliminary results seem to exclude significative correlations between Ki-67 LI and tumor size of anterior pituitary adenomas, even if this index can be considered a useful marker in the determination of the infiltrative behaviour of these tumors
Diurnal Variation in Urodynamics of Rat
In humans, the storage and voiding functions of the urinary bladder have a characteristic diurnal variation, with increased voiding during the day and urine storage during the night. However, in animal models, the daily functional differences in urodynamics have not been well-studied. The goal of this study was to identify key urodynamic parameters that vary between day and night. Rats were chronically instrumented with an intravesical catheter, and bladder pressure, voided volumes, and micturition frequency were measured by continuous filling cystometry during the light (inactive) or dark (active) phases of the circadian cycle. Cage activity was recorded by video during the experiment. We hypothesized that nocturnal rats entrained to a standard 12:12 light:dark cycle would show greater ambulatory activity and more frequent, smaller volume micturitions in the dark compared to the light. Rats studied during the light phase had a bladder capacity of 1.44±0.21 mL and voided every 8.2±1.2 min. Ambulatory activity was lower in the light phase, and rats slept during the recording period, awakening only to urinate. In contrast, rats studied during the dark were more active, had a lower bladder capacities (0.65±0.18 mL), and urinated more often (every 3.7±0.9 min). Average bladder pressures were not significantly different between the light and dark (13.40±2.49 and 12.19±2.85 mmHg, respectively). These results identify a day-night difference in bladder capacity and micturition frequency in chronically-instrumented nocturnal rodents that is phase-locked to the normal circadian locomotor activity rhythm of the animal. Furthermore, since it has generally been assumed that the daily hormonal regulation of renal function is a major driver of the circadian rhythm in urination, and few studies have addressed the involvement of the lower urinary tract, these results establish the bladder itself as a target for circadian regulation
Supervolcanoes Within an Ancient Volcanic Province in Arabia Terra, Mars
Several irregularly shaped craters located within Arabia Terra, Mars represent a new type of highland volcanic construct and together constitute a previously unrecognized martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae display a range of geomorphic features related to structural collapse, effusive volcanism, and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulfur and erupted fine-grained pyroclastics from these calderas likely fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. Discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars
Interactome Analyses Identify Ties of PrPC and Its Mammalian Paralogs to Oligomannosidic N-Glycans and Endoplasmic Reticulum-Derived Chaperones
The physiological environment which hosts the conformational conversion of the cellular prion protein (PrPC) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrPC interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrPC paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrPC and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrPC with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrPSc. A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrPC organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins
Edaravone Guards Dopamine Neurons in a Rotenone Model for Parkinson's Disease
3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), an effective free radical scavenger, provides neuroprotection in stroke models and patients. In this study, we investigated its neuroprotective effects in a chronic rotenone rat model for Parkinson's disease. Here we showed that a five-week treatment with edaravone abolished rotenone's activity to induce catalepsy, damage mitochondria and degenerate dopamine neurons in the midbrain of rotenone-treated rats. This abolishment was attributable at least partly to edaravone's inhibition of rotenone-induced reactive oxygen species production or apoptotic promoter Bax expression and its up-regulation of the vesicular monoamine transporter 2 (VMAT2) expression. Collectively, edaravone may provide novel clinical therapeutics for PD
Systematic Genetic Nomenclature for Type VII Secretion Systems
CITATION: Bitter, W., et al. 2009. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathogens, 5(10): 1-6, doi: 10.1371/journal.ppat.1000507.The original publication is available at http://journals.plos.org/plospathogensMycobacteria, such as the etiological
agent of human tuberculosis, Mycobacterium
tuberculosis, are protected by an impermeable
cell envelope composed of an inner
cytoplasmic membrane, a peptidoglycan
layer, an arabinogalactan layer, and an
outer membrane. This second membrane
consists of covalently linked, tightly packed
long-chain mycolic acids [1,2] and noncovalently
bound shorter lipids involved in
pathogenicity [3–5]. To ensure protein
transport across this complex cell envelope,
mycobacteria use various secretion pathways,
such as the SecA1-mediated general
secretory pathway [6,7], an alternative
SecA2-operated pathway [8], a twin-arginine
translocation system [9,10], and a
specialized secretion pathway variously
named ESAT-6-, SNM-, ESX-, or type
VII secretion [11–16]. The latter pathway,
hereafter referred to as type VII secretion
(T7S), has recently become a large and
competitive research topic that is closely
linked to studies of host–pathogen interactions
of M. tuberculosis [17] and other
pathogenic mycobacteria [16]. Molecular
details are just beginning to be revealed
[18–22] showing that T7S systems are
complex machineries with multiple components
and multiple substrates. Despite
their biological importance, there has been
a lack of a clear naming policy for the
components and substrates of these systems.
As there are multiple paralogous T7S
systems within the Mycobacteria and
orthologous systems in related bacteria,
we are concerned that, without a unified
nomenclature system, a multitude of redundant
and obscure gene names will be
used that will inevitably lead to confusion
and hinder future progress. In this opinion
piece we will therefore propose and introduce
a systematic nomenclature with
guidelines for name selection of new
components that will greatly facilitate
communication and understanding in this
rapidly developing field of research.http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1000507Publisher's versio
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