Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

<b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

Predictors of nursing home admission of individuals without a dementia diagnosis before admission - results from the Leipzig Longitudinal Study of the Aged (LEILA 75+)

<p>Abstract</p> <p>Background</p> <p>In previous decades a substantial number of community-based studies mostly including dementia cases examined predictors of nursing home admission (NHA) among elderly people. However, no one study has analysed predictors of NHA for individuals without developing dementia before NHA.</p> <p>Methods</p> <p>Data were derived from the Leipzig Longitudinal Study of the Aged, a population-based study of individuals aged 75 years and older. 1,024 dementia-free older adults were interviewed six times on average every 1.4 years. Socio-demographic, clinical, and psychometric variables were obtained. Kaplan-Meier estimates were used to determine mean time to NHA. Cox proportional hazards regression was used to examine predictors of long-term NHA.</p> <p>Results</p> <p>Of the overall sample, 7.8 percent of the non-demented elderly (n = 59) were admitted to nursing home (NH) during the study period. The mean time to NHA in the dementia-free sample was 7.6 years. Characteristics associated with a shorter time to NHA were increased age, living alone, functional and cognitive impairment, major depression, stroke, myocardial infarction, a low number of specialist visits and paid home helper use.</p> <p>Conclusions</p> <p>Severe physical or psychiatric diseases and living alone have a significant effect on NHA for dementia-free individuals. The findings offer potentialities of secondary prevention to avoid or delay NHA for these elderly individuals. Further investigation of predictors of institutionalization is warranted to advance understanding of the process leading to NHA for this important group.</p

The Effect of Climate Fluctuation on Chimpanzee Birth Sex Ratio

Climate and weather conditions, such as the North Atlantic Oscillation, precipitation and temperature influence the birth sex ratio (BSR) of various higher latitude species, including deer, elephant seals or northern human populations. Although, tropical regions show only little variation in temperature, climate and weather conditions can fluctuate with consequences for phenology and food resource availability. Here, we evaluate, whether the BSR of chimpanzees, inhabiting African tropical forests, is affected by climate fluctuations as well. Additionally, we evaluate, if variation in consumption of a key food resource with high nutritional value, Coula edulis nuts, is linked to both climate fluctuations and variation in BSR. We use long-term data from two study groups located in Taï National Park, Côte d'Ivoire to assess the influence of local weather conditions and the global climate driver El Niño Southern Oscillation (ENSO) on offspring sex. Côte d'Ivoire has experienced considerable climate variation over the last decades, with increasing temperature and declining precipitation. For both groups we find very similar time windows around the month of conception, in which offspring sex is well predicted by ENSO, with more males following low ENSO values, corresponding to periods of high rainfall. Furthermore, we find that the time spent cracking and feeding on Coula nuts is strongly influenced by climate conditions. Although, some of our analysis suggest that a higher proportion of males is born after periods with higher nut consumption frequency, we cannot conclude decisively at this point that nut consumption may influence shifts in BSR. All results combined suggest that also chimpanzees may experience climate related shifts in offspring sex ratios as response to climate fluctuation

Fluidal pyroclasts reveal the intensity of peralkaline rhyolite pumice cone eruptions

This work is a contribution to the Natural Environment Research Council (NERC) funded RiftVolc project (NE/L013932/1, Rift volcanism: past, present and future) through which several of the authors are supported. In addition, Clarke was funded by a NERC doctoral training partnership grant (NE/L002558/1).Peralkaline rhyolites are medium to low viscosity, volatile-rich magmas typically associated with rift zones and extensional settings. The dynamics of peralkaline rhyolite eruptions remain elusive with no direct observations recorded, significantly hindering the assessment of hazard and risk. Here we describe uniquely-preserved, fluidal-shaped pyroclasts found within pumice cone deposits at Aluto, a peralkaline rhyolite caldera in the Main Ethiopian Rift. We use a combination of field-observations, geochemistry, X-ray computed microtomography (XCT) and thermal-modelling to investigate how these pyroclasts are formed. We find that they deform during flight and, depending on size, quench prior to deposition or continue to inflate then quench in-situ. These findings reveal important characteristics of the eruptions that gave rise to them: that despite the relatively low viscosity of these magmas, and similarities to basaltic scoria-cone deposits, moderate to intense, unstable, eruption columns are developed; meaning that such eruptions can generate extensive tephra-fall and pyroclastic density currents.Publisher PDFPeer reviewe

Synaptic tagging and capture in the living rat

In isolated hippocampal slices, decaying long-term potentiation can be stabilized and converted to late long-term potentiation lasting many hours, by prior or subsequent strong high-frequency tetanization of an independent input to a common population of neurons—a phenomenon known as ‘synaptic tagging and capture’. Here we show that the same phenomenon occurs in the intact rat. Late long-term potentiation can be induced in CA1 during the inhibition of protein synthesis if an independent input is strongly tetanized beforehand. Conversely, declining early long-term potentiation induced by weak tetanization can be converted into lasting late long-term potentiation by subsequent strong tetanization of a separate input. These findings indicate that synaptic tagging and capture is not limited to in vitro preparations; the past and future activity of neurons has a critical role in determining the persistence of synaptic changes in the living animal, thus providing a bridge between cellular studies of protein synthesis-dependent synaptic potentiation and behavioural studies of memory persistence

Severely Impaired Learning and Altered Neuronal Morphology in Mice Lacking NMDA Receptors in Medium Spiny Neurons

The striatum is composed predominantly of medium spiny neurons (MSNs) that integrate excitatory, glutamatergic inputs from the cortex and thalamus, and modulatory dopaminergic inputs from the ventral midbrain to influence behavior. Glutamatergic activation of AMPA, NMDA, and metabotropic receptors on MSNs is important for striatal development and function, but the roles of each of these receptor classes remain incompletely understood. Signaling through NMDA-type glutamate receptors (NMDARs) in the striatum has been implicated in various motor and appetitive learning paradigms. In addition, signaling through NMDARs influences neuronal morphology, which could underlie their role in mediating learned behaviors. To study the role of NMDARs on MSNs in learning and in morphological development, we generated mice lacking the essential NR1 subunit, encoded by the Grin1 gene, selectively in MSNs. Although these knockout mice appear normal and display normal 24-hour locomotion, they have severe deficits in motor learning, operant conditioning and active avoidance. In addition, the MSNs from these knockout mice have smaller cell bodies and decreased dendritic length compared to littermate controls. We conclude that NMDAR signaling in MSNs is critical for normal MSN morphology and many forms of learning

Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia

<p>Abstract</p> <p>Background</p> <p>Although most guidelines recommend the use of cholinesterase inhibitors (ChEIs) for mild to moderate Alzheimer's Disease, only a small proportion of affected patients receive these drugs. We aimed to study if geriatric comorbidity and polypharmacy influence the prescription of ChEIs in patients with dementia in Germany.</p> <p>Methods</p> <p>We used claims data of 1,848 incident patients with dementia aged 65 years and older. Inclusion criteria were first outpatient diagnoses for dementia in at least three of four consecutive quarters (incidence year). Our dependent variable was the prescription of at least one ChEI in the incidence year. Main independent variables were polypharmacy (defined as the number of prescribed medications categorized into quartiles) and measures of geriatric comorbidity (levels of care dependency and 14 symptom complexes characterizing geriatric patients). Data were analyzed by multivariate logistic regression.</p> <p>Results</p> <p>On average, patients were 78.7 years old (47.6% female) and received 9.7 different medications (interquartile range: 6-13). 44.4% were assigned to one of three care levels and virtually all patients (92.0%) had at least one symptom complex characterizing geriatric patients. 13.0% received at least one ChEI within the incidence year. Patients not assigned to the highest care level were more likely to receive a prescription (e.g., no level of care dependency vs. level 3: adjusted Odds Ratio [OR]: 5.35; 95% CI: 1.61-17.81). The chance decreased with increasing numbers of symptoms characterizing geriatric patients (e.g., 0 vs. 5+ geriatric complexes: OR: 4.23; 95% CI: 2.06-8.69). The overall number of prescribed medications had no influence on ChEI prescription and a significant effect of age could only be found in the univariate analysis. Living in a rural compared to an urban environment and contacts to neurologists or psychiatrists were associated with a significant increase in the likelihood of receiving ChEIs in the multivariate analysis.</p> <p>Conclusions</p> <p>It seems that not age as such but the overall clinical condition of a patient including care dependency and geriatric comorbidities influences the process of decision making on prescription of ChEIs.</p

The Effects of Copper Pollution on Fouling Assemblage Diversity: A Tropical-Temperate Comparison

BACKGROUND: The invasion of habitats by non-indigenous species (NIS) occurs at a global scale and can generate significant ecological, evolutionary, economic and social consequences. Estuarine and coastal ecosystems are particularly vulnerable to pollution from numerous sources due to years of human-induced degradation and shipping. Pollution is considered as a class of disturbance with anthropogenic roots and recent studies have concluded that high frequencies of disturbance may facilitate invasions by increasing the availability of resources. METHODOLOGY/PRINCIPAL FINDINGS: To examine the effects of heavy metal pollution as disturbance in shaping patterns of exotic versus native diversity in marine fouling communities we exposed fouling communities to different concentrations of copper in one temperate (Virginia) and one tropical (Panama) region. Diversity was categorized as total, native and non-indigenous and we also incorporated taxonomic and functional richness. Our findings indicate that total fouling diversity decreased with increasing copper pollution, whether taxonomic or functional diversity is considered. Both native and non-indigenous richness decreased with increasing copper concentrations at the tropical site whereas at the temperate site, non-indigenous richness was too low to detect any effect. CONCLUSIONS/SIGNIFICANCE: Non-indigenous richness decreased with increasing metal concentrations, contradicting previous investigations that evaluate the influence of heavy metal pollution on diversity and invasibility of fouling assemblages. These results provide first insights on how the invasive species pool in a certain region may play a key role in the disturbance vs. non-indigenous diversity relationship

Macroalgal morphogenesis induced by waterborne compounds and bacteria in coastal seawater

Axenic gametes of the marine green macroalga Ulva mutabilis Foyn (Ria Formosa, locus typicus) exhibit abnormal development into slow-growing callus-like colonies with aberrant cell walls. Under laboratory conditions, it was previously demonstrated that all defects in growth and thallus development can be completely abolished when axenic gametes are inoculated with a combination of two specific bacterial strains originally identified as Roseo-bacter sp. strain MS2 and Cytophaga sp. strain MS6. These bacteria release diffusible morphogenetic compounds (= morphogens), which act similar to cytokinin and auxin. To investigate the ecological relevance of the waterborne bacterial morphogens, seawater samples were collected in the Ria Formosa lagoon (Algarve, Southern Portugal) at 20 sampling sites and tidal pools to assess their morphogenetic effects on the axenic gametes of U. mutabilis. Specifically the survey revealed that sterile-filtered seawater samples can completely recover growth and morphogenesis of U. mutabilis under axenic conditions. Morphogenetic activities of free-living and epiphytic bacteria isolated from the locally very abundant Ulva species (i.e., U. rigida) were screened using a multiwell-based testing system. The most represented genera isolated from U. rigida were Alteromonas, Pseudoalteromonas and Sulfitobacter followed by Psychrobacter and Polaribacter. Several naturally occurring bacterial species could emulate MS2 activity (= induction of cell divisions) regardless of taxonomic affiliation, whereas the MS6 activity (= induction of cell differentiation and cell wall formation) was species-specific and is probably a feature of difficult-to-culture bacteria. Interestingly, isolated bacteroidetes such as Algoriphagus sp. and Polaribacter sp. could individually trigger complete Ulva morphogenesis and thus provide a novel mode of action for bacterial-induced algal development. This study also highlights that the accumulation of algal growth factors in a shallow water body separated from the open ocean by barrier islands might have strong implications to, for example, the wide usage of natural coastal seawater in algal (land based) aquacultures of Ulva