297 research outputs found
Evidence of an active volcanic heat source beneath the Pine Island Glacier
Tectonic landforms reveal that the West Antarctic Ice Sheet (WAIS) lies atop a major volcanic rift system. However, identifying subglacial volcanism is challenging. Here we show geochemical evidence of a volcanic heat source upstream of the fast-melting Pine Island Ice Shelf, documented by seawater helium isotope ratios at the front of the Ice Shelf cavity. The localization of mantle helium to glacial meltwater reveals that volcanic heat induces melt beneath the grounded glacier and feeds the subglacial hydrological network crossing the grounding line. The observed transport of mantle helium out of the Ice Shelf cavity indicates that volcanic heat is supplied to the grounded glacier at a rate of ~ 2500 ± 1700 MW, which is ca. half as large as the active Grimsvötn volcano on Iceland. Our finding of a substantial volcanic heat source beneath a major WAIS glacier highlights the need to understand subglacial volcanism, its hydrologic interaction with the marine margins, and its potential role in the future stability of the WAIS
Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation
In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments
A boundary delimitation algorithm to approximate cell soma volumes of bipolar cells from topographical data obtained by scanning probe microscopy
Climate Change and the Future of California's Endemic Flora
The flora of California, a global biodiversity hotspot, includes 2387 endemic plant taxa. With anticipated climate change, we project that up to 66% will experience >80% reductions in range size within a century. These results are comparable with other studies of fewer species or just samples of a region's endemics. Projected reductions depend on the magnitude of future emissions and on the ability of species to disperse from their current locations. California's varied terrain could cause species to move in very different directions, breaking up present-day floras. However, our projections also identify regions where species undergoing severe range reductions may persist. Protecting these potential future refugia and facilitating species dispersal will be essential to maintain biodiversity in the face of climate change
Effect of apomorphine on cognitive performance and sensorimotor gating in humans
Contains fulltext :
88792.pdf (publisher's version ) (Closed access)INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.1 januari 201
Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits
Background
Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation.
Objective
The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry.
Results
The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior.
Conclusions
Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression
What have birth cohort studies asked about genetic, pre- and perinatal exposures and child and adolescent onset mental health outcomes? A systematic review
Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses
The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV
- …
