Genes influencing milk production traits predominantly affect one of four biological pathways

In this study we introduce a method that accounts for false positive and false negative results in attempting to estimate the true proportion of quantitative trait loci that affect two different traits. This method was applied to data from a genome scan that was used to detect QTL for three independent milk production traits, Australian Selection Index (ASI), protein percentage (P%) and fat percentage corrected for protein percentage (F% – P%). These four different scenarios are attributed to four biological pathways: QTL that (1) increase or decrease total mammary gland production (affecting ASI only); (2) increase or decrease lactose synthesis resulting in the volume of milk being changed but without a change in protein or fat yield (affecting P% only); (3) increase or decrease protein synthesis while milk volume remains relatively constant (affecting ASI and P% in the same direction); (4) increase or decrease fat synthesis while the volume of milk remains relatively constant (affecting F% – P% only). The results indicate that of the positions that detected a gene, most affected one trait and not the others, though a small proportion (2.8%) affected ASI and P% in the same direction

What’s so “proper” about translation? Or interlingual translation and interpretative semiotics

Jakobson’s famous classification of three types of translation is the point of departure for a discussion of “translation proper,” or translation from one natural historical language to another. Eco’s comparison of the terms interpretation and translation show that they overlap but are not synonymous as there is a limit to translation that does not hold for interpretation. A translation strategy that aims for equivalent effect is guided by the intentio operis as well as by the regulative hypothesis of the encyclopedia, which takes into account the inferential and pragmatic conditions of communication that are implied but not explicit in the text. The paper compares insights from what has been called the “cultural turn” in Translation Studies with Eco’s regulative hypothesis of the Encyclopedia as a dynamic interpretative strategy.peer-reviewe

Toll-like receptor 3 activation impairs excitability and synaptic activity via TRIF signalling in immature rat and human neurons

Toll like receptor 3 (TLR3) belongs to a family of pattern recognition receptors that recognise molecules found on pathogens referred to as pathogen associated molecular patterns (PAMPs). Its involvement in innate immunity is well known but despite its presence in the central nervous system (CNS), our knowledge of its function is limited. Here, we have investigated whether TLR3 activation modulates synaptic activity in primary hippocampal cultures and induced pluripotent stem cell (iPSC)-derived neurons. Synaptically driven spontaneous action potential (AP) firing was significantly reduced by the TLR3 specific activator, poly I:C, in a concentration-dependent manner following both short (5 min) and long exposures (1h) in rat hippocampal cultures. Notably, the consequence of TLR3 activation on neuronal function was reproduced in iPSC-derived cortical neurons, with poly I:C (25µg/ml, 1h) significantly inhibiting sAP firing. We examined the mechanisms underlying these effects, with poly I:C significantly reducing peak sodium current, an effect dependent on the MyD88-independent TRIF dependent pathway. Furthermore, poly I:C (25µg/ml, 1h) resulted in a significant reduction in miniature excitatory postsynaptic potential (mEPSC) frequency and amplitude and significantly reduced surface AMPAR expression. These novel findings reveal that TLR3 activation inhibits neuronal excitability and synaptic activity through multiple mechanisms, with this being observed in both rat and human iPSC-derived neurons. These data might provide further insight into how TLR3 activation may contribute to neurodevelopmental disorders following maternal infection and in patients with increased susceptibility to herpes simplex encephalitis

A model for the waveform behavior of accreting millisecond pulsars: Nearly aligned magnetic fields and moving emission regions

We investigate further a model of the accreting millisecond X-ray pulsars we proposed earlier. In this model, the X-ray-emitting regions of these pulsars are near their spin axes but move. This is to be expected if the magnetic poles of these stars are close to their spin axes, so that accreting gas is channeled there. As the accretion rate and the structure of the inner disk vary, gas is channeled along different field lines to different locations on the stellar surface, causing the X-ray-emitting areas to move. We show that this "nearly aligned moving spot model" can explain many properties of the accreting millisecond X-ray pulsars, including their generally low oscillation amplitudes and nearly sinusoidal waveforms; the variability of their pulse amplitudes, shapes, and phases; the correlations in this variability; and the similarity of the accretion- and nuclear-powered pulse shapes and phases in some. It may also explain why accretion-powered millisecond pulsars are difficult to detect, why some are intermittent, and why all detected so far are transients. This model can be tested by comparing with observations the waveform changes it predicts, including the changes with accretion rate.Comment: 21 pages, 6 figures; includes 3 new sections, 14 additional pages, 4 additional figures with 11 new plots, and additional references; accepted for publication in Ap

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Towards a model of contemporary parenting: The parenting behaviours and dimensions questionnaire

The assessment of parenting has been problematic due to theoretical disagreement, concerns over generalisability, and problems with the psychometric properties of current parenting measures. The aim of this study was to develop a comprehensive, psychometrically sound self-report parenting measure for use with parents of preadolescent children, and to use this empirical scale development process to identify the core dimensions of contemporary parenting behaviour. Following item generation and parent review, 846 parents completed an online survey comprising 116 parenting items. Exploratory and confirmatory factor analyses supported a six factor parenting model, comprising Emotional Warmth, Punitive Discipline, Anxious Intrusiveness, Autonomy Support, Permissive Discipline and Democratic Discipline. This measure will allow for the comprehensive and consistent assessment of parenting in future research and practice

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation