2,556 research outputs found
A modern multicentennial record of radiocarbon variability from an exactly dated bivalve chronology at the Tree Nob site (Alaska coastal current)
This is the final version. Available from Cambridge University Press via the DOI in this record.β―Quantifying the marine radiocarbon reservoir effect, offsets (ΞR), and ΞR variability over time is critical to improving dating estimates of marine samples while also providing a proxy of water mass dynamics. In the northeastern Pacific, where no high-resolution time series of ΞR has yet been established, we sampled radiocarbon (14C) from exactly dated growth increments in a multicentennial chronology of the long-lived bivalve, Pacific geoduck (Paneopea generosa) at the Tree Nob site, coastal British Columbia, Canada. Samples were taken at approximately decadal time intervals from 1725 CE to 1920 CE and indicate average ΞR values of 256 Β± 22 years (1Ο) consistent with existing discrete estimates. Temporal variability in ΞR is small relative to analogous Atlantic records except for an unusually old-water event, 1802β1812. The correlation between ΞR and sea surface temperature (SST) reconstructed from geoduck increment width is weakly significant (r2 = .29, p = .03), indicating warm water is generally old, when the 1802β1812 interval is excluded. This interval contains the oldest (β2.1Ο) anomaly, and that is coincident with the coldest (β2.7Ο) anomalies of the temperature reconstruction. An additional 32 14C values spanning 1952β1980 were detrended using a northeastern Pacific bomb pulse curve. Significant positive correlations were identified between the detrended 14C data and annual El NiΓ±o Southern Oscillation (ENSO) and summer SST such that cooler conditions are associated with older water. Thus, 14C is generally relatively stable with weak, potentially inconsistent associations to climate variables, but capable of infrequent excursions as illustrated by the unusually cold, old-water 1802β1812 interval.National Science FoundationNational Science Foundatio
Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy
This study describes a novel type of interstitial (stromal) cell β telocytes (TCs) β in the human and mouse respiratory tree (terminal and respiratory bronchioles, as well as alveolar ducts). TCs have recently been described in pleura, epicardium, myocardium, endocardium, intestine, uterus, pancreas, mammary gland, etc. (see www.telocytes.com). TCs are cells with specific prolongations called telopodes (Tp), frequently two to three per cell. Tp are very long prolongations (tens up to hundreds of ΞΌm) built of alternating thin segments known as podomers (β€ 200Β nm, below the resolving power of light microscope) and dilated segments called podoms, which accommodate mitochondria, rough endoplasmic reticulum and caveolae. Tp ramify dichotomously, making a 3-dimensional network with complex homo- and heterocellular junctions. Confocal microscopy reveals that TCs are c-kit- and CD34-positive. Tp release shed vesicles or exosomes, sending macromolecular signals to neighboring cells and eventually modifying their transcriptional activity. At bronchoalveolar junctions, TCs have been observed in close association with putative stem cells (SCs) in the subepithelial stroma. SCs are recognized by their ultrastructure and Sca-1 positivity. Tp surround SCs, forming complex TC-SC niches (TC-SCNs). Electron tomography allows the identification of bridging nanostructures, which connect Tp with SCs. In conclusion, this study shows the presence of TCs in lungs and identifies a TC-SC tandem in subepithelial niches of the bronchiolar tree. In TC-SCNs, the synergy of TCs and SCs may be based on nanocontacts and shed vesicles
The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model
As maladaptive disgust responses are linked to mental health problems, and cancer patients
may experience heightened disgust as a result of treatments they receive, we explored the
associations between disgust-related side-effects and symptoms of depression and anxiety in
people treated for cancer. One hundred and thirty two (83 women, Mage = 57.48 years)
participants answered questions about their treatments, side-effects, disgust responding, and
mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred
to here as βcoreβ disgust-related side-effects) was significantly related to greater symptoms of
depression and borderline increased anxiety. Further, these links were explained by a
moderated mediation model, whereby the effects of core disgust side-effects on depression
and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust
propensity moderated the effect of core disgust side-effects on self-disgust. These findings
stress the importance of emotional responses, like disgust, in psychological adaptation to the
side-effects of cancer treatments
Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers
This work was supported by the Fundação Carlos Chagas de Amparo Γ Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento CientΓfico e TecnolΓ³gico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
Deletion of the GABAA Ξ±2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking
Rationale
GABAA receptors containing Ξ±2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the Ξ±2-subunit results in an absence of sensitisation to cocaine.
Objective
We investigated the reinforcing properties of cocaine in GABAA Ξ±2-subunit knockout (KO) mice using an intravenous self-administration procedure.
Methods
Ξ±2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg).
Results
No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not.
Conclusions
Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the Ξ±2-subunit may be involved in modulating the βenergisingβ aspect of cocaineβs effects on reward-seeking
Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report
<p>Abstract</p> <p>Introduction</p> <p>Although the adverse effects of cocaine use in pregnancy are well recognised, we believe this case highlights the importance of considering the route of administration, and suggests the possibility of multifocal damage relating to intravenous use.</p> <p>Case presentation</p> <p>A Caucasian female baby of 29-weeks' gestation was spontaneously delivered and subsequently developed multi-organ failure considered unrelated to simple prematurity. Intensive care was re-orientated following the development of massive intraventricular haemorrhage.</p> <p>Conclusion</p> <p>This case illustrates the need for regular cranial ultrasound in babies of pregnancies at risk due to intravenous cocaine use and also the necessity of counselling women who misuse cocaine in the antenatal period. As such, this article will be of most interest to paediatric and obstetric staff.</p
Radio emission from Supernova Remnants
The explosion of a supernova releases almost instantaneously about 10^51 ergs
of mechanic energy, changing irreversibly the physical and chemical properties
of large regions in the galaxies. The stellar ejecta, the nebula resulting from
the powerful shock waves, and sometimes a compact stellar remnant, constitute a
supernova remnant (SNR). They can radiate their energy across the whole
electromagnetic spectrum, but the great majority are radio sources. Almost 70
years after the first detection of radio emission coming from a SNR, great
progress has been achieved in the comprehension of their physical
characteristics and evolution. We review the present knowledge of different
aspects of radio remnants, focusing on sources of the Milky Way and the
Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief
overview of theoretical background, analyze morphology and polarization
properties, and review and critical discuss different methods applied to
determine the radio spectrum and distances. The consequences of the interaction
between the SNR shocks and the surrounding medium are examined, including the
question of whether SNRs can trigger the formation of new stars. Cases of
multispectral comparison are presented. A section is devoted to reviewing
recent results of radio SNRs in the Magellanic Clouds, with particular emphasis
on the radio properties of SN 1987A, an ideal laboratory to investigate
dynamical evolution of an SNR in near real time. The review concludes with a
summary of issues on radio SNRs that deserve further study, and analyzing the
prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure
Identifying Ligand Binding Conformations of the Ξ²2-Adrenergic Receptor by Using Its Agonists as Computational Probes
Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, Ξ²2-adrenergic receptor (Ξ²2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of Ξ²2AR. We show that the select ligands bind preferentially to different predicted conformers of Ξ²2AR, and identify a role of Ξ²2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. Β© 2012 Isin et al
Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells
Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction
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