Jet-Medium Interactions with Identified Particles

Identified particles have long been of great interest at RHIC in large part because of the baryon/meson differences observed at intermediate $p_T$ and the implications for hadronization via quark coalescence. With recent high statistics data identified particles are also now central to understanding the details of the jet-medium interactions and energy loss and hadron formation at intermediate and high $p_T$. In particular, high $p_T$ identified particle spectra along with two-particle correlations triggered with direct photons, neutral pions or electrons from heavy flavor decay with hadrons can provide information about how medium modifications to jet fragmentation depend on parton type. I will review recent results with identified particles both in heavy ion systems and the reference measurements in p+p collisions.Comment: Proceedings for Quark Matter 2009, Knoxville T

Ammonium-Acetate Is Sensed by Gustatory and Olfactory Neurons in Caenorhabditis elegans

Background: Caenorhabditis elegans chemosensation has been successfully studied using behavioral assays that treat detection of volatile and water soluble chemicals as separate senses, analogous to smell and taste. However, considerable ambiguity has been associated with the attractive properties of the compound ammonium-acetate (NH 4Ac). NH 4Ac has been used in behavioral assays both as a chemosensory neutral compound and as an attractant. Methodology/Main Findings: Here we show that over a range of concentrations NH4Ac can be detected both as a water soluble attractant and as an odorant, and that ammonia and acetic acid individually act as olfactory attractants. We use genetic analysis to show that NaCl and NH4Ac sensation are mediated by separate pathways and that ammonium sensation depends on the cyclic nucleotide gated ion channel TAX-2/TAX-4, but acetate sensation does not. Furthermore we show that sodium-acetate (NaAc) and ammonium-chloride (NH4Cl) are not detected as Na + and Cl 2 specific stimuli, respectively. Conclusions/Significance: These findings clarify the behavioral response of C. elegans to NH4Ac. The results should have an impact on the design and interpretation of chemosensory experiments studying detection and adaptation to soluble compounds in the nematode Caenorhabditis elegans

Temperature- and Touch-Sensitive Neurons Couple CNG and TRPV Channel Activities to Control Heat Avoidance in Caenorhabditis elegans

Background: Any organism depends on its ability to sense temperature and avoid noxious heat. The nematode Caenorhabditis elegans responds to noxious temperatures exceeding,35uC and also senses changes in its environmental temperature in the range between 15 and 25uC. The neural circuits and molecular mechanisms involved in thermotaxis have been successfully studied, whereas details of the thermal avoidance behavior remain elusive. In this work, we investigate neurological and molecular aspects of thermonociception using genetic, cell biological and physiological approaches. Methodology/Principal Findings: We show here that the thermosensory neurons AFD, in addition to sensing temperature within the range within which the animals can thrive, also contribute to the sensation of noxious temperatures resulting in a reflex-like escape reaction. Distinct sets of interneurons are involved in transmitting thermonociception and thermotaxis, respectively. Loss of AFD is partially compensated by the activity of a pair of multidendritic, polymodal neurons, FLP, whereas laser ablation of both types of neurons abrogated the heat response in the head of the animals almost completely. A third pair of heat sensory neurons, PHC, is situated in the tail. We find that the thermal avoidance response requires the cell autonomous function of cGMP dependent Cyclic Nucleotide-Gated (CNG) channels in AFD, and the heat- and capsaicinsensitive Transient Receptor Potential Vanilloid (TRPV) channels in the FLP and PHC sensory neurons. Conclusions/Significance: Our results identify distinct thermal responses mediated by a single neuron, but also show tha

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE - The UK National Cohort Study

Background: Children with intellectual disability (ID) frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aimed to determine the impact of genomics, inheritance and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared to the general population. Methods: IMAGINE is a prospective study using online mental health and medical assessments in a cohort of 2770 children with ID and pathogenic genomic variants, identified by the UK’s National Health Service. Outcomes: Assessments completed on 2397 young people with ID (4-19 years, M 9·2, SD 3·9) with a rare pathogenic genomic variant. 1339 (55·9%) were male. 1771 (73·9%) of participants had a pathogenic copy number variant (CNV), 626 (26·1%) a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk of co-occurring neuropsychiatric diagnoses, compared with the UK national population, was high: Autism Spectrum Disorder 29·2 (95% CI 23·9 to 36·5), Attention Deficit Hyperactivity Disorder 13·5 (95% CI 11·1 to 16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. Interpretation: Children with genomic variants and ID are at a greatly enhanced risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk

Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE, a UK national cohort study

Background Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. Methods IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. Findings We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. Interpretation Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services

A first update on mapping the human genetic architecture of COVID-19

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