Observation of ballistic phonons in silicon crystals induced by α particles

We have observed the ballistic-phonon-focusing pattern along the [100] axis of a 1-mm-thick silicon crystal using α-particle bombardment as the phonon source. These experiments on phonon-mediated particle detection are performed in vacuum at about 400 mK and use titanium-superconducting-transition-edge phonon sensors on the crystal surfaces. The ballistic time of flight is confirmed in one experiment and the focusing patterns are spatially resolved in another. These data indicate that about 1/3 of the phonon energy striking the back face during the first μsec is ballistic

The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

International audienceBackground: Paracetamol’s (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans.Methods and results: This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter.Conclusion: These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain

Youth mental health first aid: a description of the program and an initial evaluation

<p>Abstract</p> <p>Background</p> <p>Adolescence is the peak age of onset for mental illness, with half of all people who will ever have a mental illness experiencing their first episode prior to 18 years of age. Early onset of mental illness is a significant predictor for future episodes. However, adolescents and young adults are less likely than the population as a whole to either seek or receive treatment for a mental illness. The knowledge and attitudes of the adults in an adolescent's life may affect whether or not help is sought, and how quickly. In 2007, the Youth Mental Health First Aid Program was launched in Australia with the aim to teach adults, who work with or care for adolescents, the skills needed to recognise the early signs of mental illness, identify potential mental health-related crises, and assist adolescents to get the help they need as early as possible. This paper provides a description of the program, some initial evaluation and an outline of future directions.</p> <p>Methods</p> <p>The program was evaluated in two ways. The first was an uncontrolled trial with 246 adult members of the Australian public, who completed questionnaires immediately before attending the 14 hour course, one month later and six months later. Outcome measures were: recognition of schizophrenia or depression; intention to offer and confidence in offering assistance; stigmatising attitudes; knowledge about adolescent mental health problems and also about the Mental Health First Aid action plan. The second method of evaluation was to track the uptake of the program, including the number of instructors trained across Australia to deliver the course, the number of courses they delivered, and the uptake of the YMHFA Program in other countries.</p> <p>Results</p> <p>The uncontrolled trial found improvements in: recognition of schizophrenia; confidence in offering help; stigmatising attitudes; knowledge about adolescent mental health problems and application of the Mental Health First Aid action plan. Most results were maintained at follow-up. Over the first 3 years of this program, a total of 318 instructors were trained to deliver the course and these instructors have delivered courses to 10,686 people across all states and territories in Australia. The program has also spread to Canada, Singapore and England, and will spread to Hong Kong, Sweden and China in the near future.</p> <p>Conclusions</p> <p>Initial evaluation suggests that the Youth Mental Health First Aid course improves participants' knowledge, attitudes and helping behaviour. The program has spread successfully both nationally and internationally.</p> <p>Trial registration</p> <p><a href="http://www.anzctr.org.au/ACTRN12609000033246.aspx">ACTRN12609000033246</a></p

Dementia Risk Models in an Australian First Nations Population: Cross-Sectional Associations and Preparation for Follow-Up

Background: Reducing the burden of dementia in First Nations populations may be addressed through developing population specific methods to quantify future risk of dementia. Objective: To adapt existing dementia risk models to cross-sectional dementia prevalence data from a First Nations population in the Torres Strait region of Australia in preparation for follow-up of participants. To explore the diagnostic utility of these dementia risk models at detecting dementia. Methods: A literature review to identify existing externally validated dementia risk models. Adapting these models to cross-sectional data and assessing their diagnostic utility through area under the receiver operating characteristic curve (AUROC) analyses and calibration using Hosmer-Lemeshow Chi2. Results: Seven risk models could be adapted to the study data. The Aging, Cognition and Dementia (AgeCoDe) study, the Framingham Heart Study (FHS), and the Brief Dementia Screening Indicator (BDSI) had moderate diagnostic utility in identifying dementia (i.e., AUROC >0.70) before and after points for older age were removed. Conclusion: Seven existing dementia risk models could be adapted to this First Nations population, and three had some cross-sectional diagnostic utility. These models were designed to predict dementia incidence, so their applicability to identify prevalent cases would be limited. The risk scores derived in this study may have prognostic utility as participants are followed up over time. In the interim, this study highlights considerations when transporting and developing dementia risk models for First Nations populations

Distinct roles of Argonaute in the green alga Chlamydomonas reveal evolutionary conserved mode of miRNA-mediated gene expression

Abstract: The unicellular green alga Chlamydomonas reinhardtii is evolutionarily divergent from higher plants, but has a fully functional silencing machinery including microRNA (miRNA)-mediated translation repression and mRNA turnover. However, distinct from the metazoan machinery, repression of gene expression is primarily associated with target sites within coding sequences instead of 3′UTRs. This feature indicates that the miRNA-Argonaute (AGO) machinery is ancient and the primary function is for post transcriptional gene repression and intermediate between the mechanisms in the rest of the plant and animal kingdoms. Here, we characterize AGO2 and 3 in Chlamydomonas, and show that cytoplasmically enriched Cr-AGO3 is responsible for endogenous miRNA-mediated gene repression. Under steady state, mid-log phase conditions, Cr-AGO3 binds predominantly miR-C89, which we previously identified as the predominant miRNA with effects on both translation repression and mRNA turnover. In contrast, the paralogue Cr-AGO2 is nuclear enriched and exclusively binds to 21-nt siRNAs. Further analysis of the highly similar Cr-AGO2 and Cr-AGO 3 sequences (90% amino acid identity) revealed a glycine-arginine rich N-terminal extension of ~100 amino acids that, given previous work on unicellular protists, may associate AGO with the translation machinery. Phylogenetic analysis revealed that this glycine-arginine rich N-terminal extension is present outside the animal kingdom and is highly conserved, consistent with our previous proposal that miRNA-mediated CDS-targeting operates in this green alga

Potentially preventable dementia in a First Nations population in the Torres Strait and Northern Peninsula Area of North Queensland, Australia: A cross sectional analysis using population attributable fractions

Dementia is highly prevalent among Australia's First Nations peoples, including Torres Strait Islander and Aboriginal peoples in Far North Queensland (FNQ). It is likely that historically recent exposure to modifiable risk factors underlies these rates, and a large proportion of dementia may be potentially preventable. Data from two adult community health checks (2015-2018) were analyzed to determine the prevalence of 11 modifiable dementia risk factors among the First Nations residents of the Torres Strait and Northern Peninsula Area of FNQ. Population attributable fractions (PAF%) for dementia were calculated using age-standardized prevalence estimates derived from these health checks and relative risks obtained from previous meta-analyses in other populations. PAF% estimates were weighted for communality to account for overlap of risk factors. Half (52·1%) of the dementia burden in this population may be attributed to 11 potentially modifiable risk factors. Hypertension (9·4%), diabetes mellitus (9·0%), obesity (8·0%), and smoking (5·3%) were the highest contributing risk factors. The contribution of depression (2·0%) and alcohol (0·3%) was lower than other global and national estimates. While the adjusted PAF% for social isolation was low based on the adult community health check data (1·6%), it was higher (4·2%) when official census data were analyzed. These results suggest that a substantial proportion of dementia in FNQ First Nations peoples could potentially be prevented. Government investment in preventative health now is essential to reduce the future burden of dementia

Primary care biomarkers and dementia in people of the Torres Strait, Australia: extended data analysis

Objective: Dementia disproportionately affects First Nations populations. Biomarkers collected in primary care may assist with determining dementia risk. Our previous underpowered study showed some suggestive associations between baseline biomarkers with follow-up dementia or cognitive impairment. The current study extended this work with a larger linked dataset. Study design and setting: Probabilistic data linkage was used to combine four baseline datasets with one follow-up assessment of dementia status 0–20 years later in a First Nations population in Australia. Mixed Effects Generalized Linear Regression models were used to test associations between baseline measures and follow-up status, accounting for repeated measures within individuals. Results: Linked data were available for 88 individuals, with 101–279 baseline observations, depending on the type of measure. Higher urinary albumin to creatine ratio was associated with greater risk of cognitive impairment/dementia, whereas body weight and key lipid markers were negatively associated. There was no clear trend when these associations were examined by timing of measurement (i.e., ≤10 years or >10 years before a dementia assessment). Conclusions: The results of this study support findings from our previous work and indicate that microalbuminuria can be an early indicator of dementia risk in this population. The weight and lipid profile findings reflect the mixed results in the published literature and require further investigation and interpretation

Most microRNAs in the single-cell alga Chlamydomonas reinhardtii are produced by Dicer-like 3-mediated cleavage of introns and untranslated regions of coding RNAs.

We describe here a forward genetic screen to investigate the biogenesis, mode of action, and biological function of miRNA-mediated RNA silencing in the model algal species,Chlamydomonas reinhardtii Among the mutants from this screen, there were three at Dicer-like 3 that failed to produce both miRNAs and siRNAs and others affecting diverse post-biogenesis stages of miRNA-mediated silencing. The DCL3-dependent siRNAs fell into several classes including transposon- and repeat-derived siRNAs as in higher plants. The DCL3-dependent miRNAs differ from those of higher plants, however, in that many of them are derived from mRNAs or from the introns of pre-mRNAs. Transcriptome analysis of the wild-type and dcl3 mutant strains revealed a further difference from higher plants in that the sRNAs are rarely negative switches of mRNA accumulation. The few transcripts that were more abundant in dcl3 mutant strains than in wild-type cells were not due to sRNA-targeted RNA degradation but to direct DCL3 cleavage of miRNA and siRNA precursor structures embedded in the untranslated (and translated) regions of the mRNAs. Our analysis reveals that the miRNA-mediated RNA silencing in C. reinhardtii differs from that of higher plants and informs about the evolution and function of this pathway in eukaryotes.Work in the Baulcombe laboratory is supported by the Balzan Prize award and the ERC Advanced Investigator Grant ERC-2013-AdG 340642 TRIBE. AAV was supported by a Marie-Curie fellowship (PIEF-GA-2010-276037). BYC was supported by an EMBL long-term postdoctoral fellowship and a Sir Henry Wellcome Fellowship (096082). DCB is the Royal Society Edward Penley Abraham Research Professor.This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via https://doi.org/10.1101/gr.199703.11

Microgravity triggers ferroptosis and accelerates senescence in the MG-63 cell model of osteoblastic cells.

peer reviewedIn space, cells sustain strong modifications of their mechanical environment. Mechanosensitive molecules at the cell membrane regulate mechanotransduction pathways that induce adaptive responses through the regulation of gene expression, post-translational modifications, protein interactions or intracellular trafficking, among others. In the current study, human osteoblastic cells were cultured on the ISS in microgravity and at 1 g in a centrifuge, as onboard controls. RNAseq analyses showed that microgravity inhibits cell proliferation and DNA repair, stimulates inflammatory pathways and induces ferroptosis and senescence, two pathways related to ageing. Morphological hallmarks of senescence, such as reduced nuclear size and changes in chromatin architecture, proliferation marker distribution, tubulin acetylation and lysosomal transport were identified by immunofluorescence microscopy, reinforcing the hypothesis of induction of cell senescence in microgravity during space flight. These processes could be attributed, at least in part, to the regulation of YAP1 and its downstream effectors NUPR1 and CKAP2L.Cytoskeleto

A Regional Red List of Montane Tree Species of the Tropical Andes: Trees at the top of the world

Andean montane forests are a major global conservation priority owing to their biological richness and high level of species endemism. Botanically the Andes are very rich in species but they remain relatively unstudied. In common with montane forests elsewhere in the world, Andean forests are of great value for the provision of ecosystem services relating to water supply, regulation of regional climate and the capture and storage of carbon. The forests and their component species are however under threat. This report summarises information drawn from a wide variety of sources to provide a regional Red List of trees of Andean tropical montane forests. The species evaluation process has drawn on published national red lists of threatened species, botanical literature, specimen databases, forestry information and expert knowledge. The IUCN Red List Categories and Criteria have been used for the evaluation and a component of Natalia?s PhD study has been to evaluate their use for species with limited and dispersed data. Understanding the geographical distribution of the species is very important in conservation assessment. The maps produced for this study are a valuable starting point for the Red Listing and a baseline for monitoring impacts of climate change. In this assessment 70 species are recorded as globally threatened based on the IUCN Red List of Categories and Criteria out of 127 tree species evaluated. In addition 165 national endemic trees of the region have previously been evaluated as globally threatened based on the same IUCN process. In total therefore 235 tree species are currently considered to be threatened with extinction within the Andean montane forests.Fil: Tejedor Garavito , Natalia. Bournemouth University; Reino UnidoFil: Álvarez Dávila, Esteban. Jardín Botánico de Medellín; ColombiaFil: Caro, Sandra Arango. Missouri Botanical Garden; Estados UnidosFil: Murakami, Alejandro Araujo. Museo de Historia Natural Noel Kempff Mercado; BoliviaFil: Baldeón, Severo. Universidad Nacional Mayor de San Marcos; PerúFil: Beltrán, Hamilton. Universidad Nacional Mayor de San Marcos; PerúFil: Blundo, Cecilia Mabel. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Laboratorio de Investigaciones Ecológicas de las Yungas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Boza Espinoza, Tatiana Erika. Missouri Botanical Garden; Estados UnidosFil: Fuentes Claros, Alfredo. Herbario Nacional de Bolivia; BoliviaFil: Gaviria, Juan. Universidad de Los Andes; VenezuelaFil: Gutiérrez, Néstor. Universidad de Los Andes; VenezuelaFil: Khela, Sonia. Botanic Gardens Conservation International; Reino UnidoFil: León, Blanca. University of Texas at Austin; Estados UnidosFil: la Torre Cuadros, Maria De Los Angeles. Universidad Nacional Agraria; PerúFil: López Camacho, René. Universidad Distrital; ColombiaFil: Malizia, Lucio Ricardo. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias. Centro de Estudios Ambientales Territoriales y Sociales; ArgentinaFil: Millán, Betty. Universidad Nacional Mayor de San Marcos; PerúFil: Moraes R., Mónica. Herbario Nacional de Bolivia; BoliviaFil: Newton, Adrian C.. Bournemouth University; Reino UnidoFil: Pacheco, Silvia. Fundación Proyungas; ArgentinaFil: Reynel, Carlos. Universidad Nacional Agraria; PerúFil: Ulloa Ulloa, Carmen. Missouri Botanical Garden; Estados UnidosFil: Vacas Cruz,Omar. Pontificia Universidad Católica del Ecuador; Ecuado