A New Long-tailed Weasel County Record in Shenandoah National Park

Though abundant throughout much of its range, the ecology and local geographic distribution of Mustela frenata (Long-tailed Weasel) is not well-known, especially in the central Appalachian Mountains. In 2015, we conducted a camera study in rock outcrop habitats within Shenandoah National Park, Virginia. Our objective was to determine the presence of mammals considered uncommon in these habitats. After 2,016 trap nights, we report eleven photographic captures of Long-tailed Weasels at eight sites. Two of these sites represent the first record of this species in Rappahannock County, Virginia. These detections represent the first record of Long-tailed Weasels in Shenandoah National Park in 60 years and extend their known range within the Park

Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy

The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (∼70% versus ∼10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrPres type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance

Emergence of Classical BSE Strain Properties during Serial Passages of H-BSE in Wild-Type Mice

BACKGROUND: Two distinct forms of atypical spongiform encephalopathies (H-BSE and L-BSE) have recently been identified in cattle. Transmission studies in several wild-type or transgenic mouse models showed that these forms were associated with two distinct major strains of infectious agents, which also differed from the unique strain that had been isolated from cases of classical BSE during the food-borne epizootic disease. METHODOLOGY/PRINCIPAL FINDINGS: H-BSE was monitored during three serial passages in C57BL/6 mice. On second passage, most of the inoculated mice showed molecular features of the abnormal prion protein (PrP(d)) and brain lesions similar to those observed at first passage, but clearly distinct from those of classical BSE in this mouse model. These features were similarly maintained during a third passage. However, on second passage, some of the mice exhibited distinctly different molecular and lesion characteristics, reminiscent of classical BSE in C57Bl/6 mice. These similarities were confirmed on third passage from such mice, for which the same survival time was also observed as with classical BSE adapted to C57Bl/6 mice. Lymphotropism was rarely detected in mice with H-BSE features. In contrast, PrP(d) was detectable, on third passage, in the spleens of most mice exhibiting classical BSE features, the pattern being indistinguishable from that found in C57Bl/6 mice infected with classical BSE. CONCLUSION/SIGNIFICANCE: Our data demonstrate the emergence of a prion strain with features similar to classical BSE during serial passages of H-BSE in wild-type mice. Such findings might help to explain the origin of the classical BSE epizootic disease, which could have originated from a putatively sporadic form of BSE

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: A cross-sectional analysis

Background: Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (. GRN), microtubule-associated protein tau (. MAPT), or chromosome 9 open reading frame 72 (. C9orf72). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. Methods: We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT, or C9orf72, or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. Findings: Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test -0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all -0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference -0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference -0·2, SE 0·1). Interpretation: Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. Funding: Centres of Excellence in Neurodegenerati

Impairment of episodic memory in genetic frontotemporal dementia : a GENFI study

© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72- and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. J. D. Rohrer is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1); the Bluefield Project; the JPND GENFI-PROX grant (2019-02248); the Dioraphte Foundation (grant numbers 09-02-00); the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO; grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie, project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). J. M. Poos is supported by a Fellowship award from Alzheimer Nederland (WE.15-2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.info:eu-repo/semantics/publishedVersio

Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort

© 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Background: Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. Methods: Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants from the Genetic FTD Initiative: 216 mutation-negative controls, 192 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. Using global scores from the CDR® plus NACC FTLD, mutation carriers were divided into three groups, asymptomatic (0), very mildly symptomatic/prodromal (.5), or fully symptomatic (1 or more). The mIRI Total score, as well as the subscores of Empathic Concern (EC) and Perspective Taking (PT) were assessed. Linear regression models with bootstrapping were used to assess empathy ratings across genetic groups, as well as across phenotypes in the symptomatic carriers. Neural correlates of empathy deficits were examined using a voxel-based morphometry (VBM) analysis. Results: All fully symptomatic groups scored lower on the mIRI Total, EC, and PT when compared to controls and their asymptomatic or prodromal counterparts (all p < .001). Prodromal C9orf72 expansion carriers also scored significantly lower than controls on the mIRI Total score (p = .046). In the phenotype analysis, all groups (behavioural variant FTD, primary progressive aphasia and FTD with amyotrophic lateral sclerosis) scored significantly lower than controls (all p < .007). VBM revealed an overlapping neural correlate of the mIRI Total score across genetic groups in the orbitofrontal lobe but with additional involvement in the temporal lobe, insula and basal ganglia in both the GRN and MAPT groups, and uniquely more posterior regions such as the parietal lobe and thalamus in the GRN group, and medial temporal structures in the MAPT group. Conclusions: Significant empathy deficits present in genetic FTD, particularly in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf72 expansion carriers.This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). MB's work is also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organisation for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V is supported by an Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2), and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Wellcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme – Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc).info:eu-repo/semantics/publishedVersio

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO