Prey Records for the Eastern Indigo Snake (Drymarchon couperi)

Prey items for the federally protected Eastern Indigo Snake (Drymarchon couperi) were compiled from published and gray literature, field observations, necropsies, dissection of museum specimens, and personal communications from reliable sources. One hundred and eighty-six records were obtained for 48 different prey species. Anurans, Gopher Tortoises, snakes, and rodents comprised ca. 85% of the prey items. Most records (n = 143) that mentioned size were from adult indigos; 17 were from juveniles. Prey records were collected from 1940-2008 and were available for all months of the year. These data confirm that Eastern Indigo Snakes eat a wide assortment of prey of varying sizes. This strategy allows D. couperi to potentially forage successfully in many different types of habitats and under fluctuating environmental conditions, a valuable trait for a top-level predator that requires a large home range

CXCR4 involvement in neurodegenerative diseases

Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a 'network' of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases

Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA\xe2\x80\x99s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Home Range and Habitat Use of The Eastern Box Turtle (Terrapene carolina) in the Northern Georgia Piedmont

The Eastern Box Turtle (Terrapene carolina) is a terrestrial species found throughout the Eastern United States. The species is considered vulnerable according to the International Union for the Conservation of Nature, yet data regarding habitat use, home range, and impacts of invasive plant species is limited, especially in the northern Piedmont region of Georgia. For this research, Box Turtles were hand captured at Tumbling Creek Nature Preserve on the Gainesville campus of The University of North Georgia in Oakwood, GA and located on foot using radiotelemetry 1-2 times per week from spring 2013 to fall 2015. At radiolocations, we collected GPS location and microhabitat data, including vegetation cover, environmental temperatures, and forest stand basal area. We used 100% minimum complex polygons (MCP) and kernel density to estimate individual home range area. To date, we have collected 5-134 radiolocations per individual turtle, with MCP home ranges variying from 0.16-6.10 ha. Overall patterns of habitat use indicate use of upland habitats dominated by native vegetation (37% of radiolocations), uplands dominated by Chinese Privet (Ligustrum sinense; 50%), cleared land (9%), and wetland habitats (4%). Assessment of home ranges and habitat use will continue through 2015-2016 as we maintain tracking efforts

AQUATIC HABITAT RESOURCE USE OF EASTERN BOX TURTLES IN NORTHEASTERN GEORGIA**

Abstract: Anthropogenic habitat loss, fragmentation, and degradation lead to decreases in resources, biodiversity, and ecosystem services; thus, understanding how species use specific resources is vital to conservation and restoration efforts. Eastern Box Turtles (Terrapene carolina carolina) are a primarily terrestrial species native to the eastern United States that has experienced population declines throughout its native range largely due to habitat loss and alterations. Although the species is considered primarily terrestrial, phylogenetic studies indicate Eastern Box Turtles (EBT) evolved from an aquatic turtle species, suggesting that aquatic habitats may represent an important resource for the species when considering conservation efforts. To investigate this use in northeastern Georgia, we analyzed habitat use of 50 individual EBT (29 M, 21 F) located using radiotelemetry 1-2 times per month for periods of 9-110 months between 2013-2022. Aquatic habitats at our study site included freshwater forested/shrub wetlands created by beaver activity along a permanent creek in addition to multiple, unconnected seepage wetland areas dominated by either Chinese Privet (Ligustrum sinense) or native woody and herbaceous vegetation. About a quarter of all radiolocations were recorded in wetland or seepage habitats; however individual use of these aquatic resources varied, with about 20% of the turtles having no locations recorded in a wetland or seepage area. The high percentage of EBT using aquatic habitats supports the need for consideration of aquatic habitat in conservation efforts

VARIATION IN GROWTH RATES OF EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) IN AN INVASIVE-DOMINATED HABITAT IN NORTH GEORGIA**

Habitat destruction, fragmentation, and degradation often leads to an increase in invasive, non-native plant species which can compete with native species for limiting resources, often reducing native biodiversity. Chinese privet (Ligustrom sinense) was introduced to the United States from China as an ornamental in the 19th century and is now a common invasive plant from Florida to Virginia and as far west as Texas and Oklahoma. Uncontrolled, Chinese privet (privet) can form dense understory stands that frequently shade out native plants and tree seedlings. The resulting monoculture may alter many ecological factors including hydrology, soil composition, vegetative food resources, and invertebrate community composition. Eastern box turtles (Terrapene carolina carolina), native to the eastern United States, are in decline throughout much of their range. Evidence shows that habitat loss and degradation are major contributing factors in the diminishing populations of Eastern Box Turtles (EBT). Habitat alterations have occurred in areas where Chinese privet and EBT ranges overlap; however, little data has been published regarding the impacts of privet on EBT ecology and physiology. Using morphological measurements collected on 37 EBT (19M, 18 F) radiotracked in northeastern Georgia between 2013-2022, we examined growth differences by sex and age class of individuals using habitats with varying amounts of privet coverage. Understanding how invasive habitats affect box turtle growth may be used to guide future conservation efforts and management decisions

PRELIMINARY ANALYSIS OF THE EFFECT OF TEMPERATURE ON OVERWINTERING PATTERNS IN EASTERN BOX TURTLES (TERRAPENE CAROLINA) **

In ectothermic animals, environmental temperatures cause alterations in activity, cellular metabolism, and physiological processes. To compensate for nonoptimal temperatures and resource scarcity that often accompany seasonal patterns, some ectotherms undergo brumation, during which their metabolism is slowed to conserve energy needed for future emergence, growth, and reproduction. Globally, winter temperatures are becoming milder, with January 2020 being the hottest January on record, and January 2016 the second hottest. Warmer temperatures during brumation can increase mortality or decrease fitness in ectotherms by increasing metabolism during over-wintering, which can cause significant body mass loss. Mild temperatures may also interfere with physiological mechanisms that regulate emergence from over-wintering. Early emergence presents a risk to ectotherms as spring food sources may not be available, and they may be unable to burrow to safe depths to avoid sudden decreases in temperature that can occur in spring. Body mass losses compounded with early emergence could hinder reproduction which could affect population persistence. Turtles make up a large group of ecologically significant ectotherms since they contribute a wide variety of ecosystem services, including soil maintenance, ecosystem restoration, and seed disbursement. Despite their importance however, many turtle populations are experiencing declines and research on turtles is lacking, especially during overwintering periods. Since 2013, we have documented overwintering patterns and locations in a population of Eastern Box Turtles (Terrapene carolina) in northeastern Georgia using radiotelemetry. In 2019, we added temperature data loggers (iButtons ®) that record environmental and individual turtle temperatures every 3 hours. We plan to observe emergence from brumation and its relationship with temperature in Eastern Box Turtles to increase our understanding of how temperature fluctuations could influence overwintering activities in ectotherms