Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.

The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function. A central finding of this investigation is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 situated within an intrinsically disordered region, as critical determinants in epichaperome assembly. Our data demonstrate that the phosphorylation of these serine residues enhances HSP90's interaction with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Furthermore, this study establishes a direct link between epichaperome function and cellular physiology, especially in contexts where robust proliferation and adaptive behavior are essential, such as cancer and stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone complexes in diseases characterized by epichaperome dysregulation, bridging the gap between fundamental research and precision medicine.

Effect of Aggregation and Molecular Size on the Ice Nucleation Efficiency of Proteins.

Aerosol acts as ice-nucleating particles (INPs) by catalyzing the formation of ice crystals in clouds at temperatures above the homogeneous nucleation threshold (-38 °C). In this study, we show that the immersion mode ice nucleation efficiency of the environmentally relevant protein, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), occurs at temperatures between -6.8 and -31.6 °C. Further, we suggest that this range is controlled by the RuBisCO concentration and protein aggregation. The warmest median nucleation temperature (-7.9 ± 0.8 °C) was associated with the highest concentration of RuBisCO (2 × 10-1 mg mL-1) and large aggregates with a hydrodynamic diameter of ∼103 nm. We investigated four additional chemically and structurally diverse proteins, plus the tripeptide glutathione, and found that each of them was a less effective INP than RuBisCO. Ice nucleation efficiency of the proteins was independent of the size (molecular weight) for the five proteins investigated in this study. In contrast to previous work, increasing the concentration and degree of aggregation did not universally increase ice nucleation efficiency. RuBisCO was the exception to this generalization, although the underlying molecular mechanism determining why aggregated RuBisCO is such an effective INP remains elusive.

Human Ageing Genomic Resources: updates on key databases in ageing research.

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).

Trucks versus treks: The relative influence of motorized versus nonmotorized recreation on a mammal community.

Outdoor recreation is increasing rapidly on public lands, with potential consequences for wildlife communities. Recreation can induce shifts in wildlife activity and habitat use, but responses vary widely even within the same species, suggesting mitigating factors that remain poorly understood. Both the type of recreation-motorized or nonmotorized-and the distance of wildlife from human disturbance may be important in developing a general understanding of recreation impacts on wildlife and making more informed management decisions. We conducted a camera-trapping survey in the Colville National Forest (CNF) of northeastern Washington in the summers of 2019 and 2020. We collected ~11,000 trap nights of spatially extensive data on nine mid-large mammalian species, simultaneously recording the presence and activity patterns of motorized (primarily vehicles on roads) and nonmotorized (primarily hikers on trails) recreation and wildlife both along trails and roads and off trails and off roads (away from most recreation). We used diel overlap analysis, time lag analysis, and single-season single-species occupancy modeling to examine the impact of recreation on the focal species. Species temporally avoided recreationists either by shifting to more nocturnal hours or delaying return to recently used recreation sites. Most species also responded spatially by altering the use or the intensity of use of camera sites due to recreation, although both positive and negative associations with recreation were documented. Species responded to nonmotorized recreation (e.g., hikers on trails) more often than motorized recreation (e.g., vehicles on roads). Most effects of recreation extended off the trail or road, although in three instances the spatiotemporal response of species to recreation along trails/roads disappeared a short distance away from those features. Our work suggests that a better understanding of landscape-scale impacts of recreation, including fitness consequences, will require additional work to disentangle the effects of different types of recreation and estimate the effective distance at which wildlife responds. Moreover, these results suggest that quiet, nonconsumptive recreation may warrant increased attention from land managers given its potential to influence the spatiotemporal ecology of numerous species.

Partial COVID-19 closure of a national park reveals negative influence of low-impact recreation on wildlife spatiotemporal ecology.

Human presence exerts complex effects on the ecology of species, which has implications for biodiversity persistence in protected areas experiencing increasing human recreation levels. However, the difficulty of separating the effect on species of human presence from other environmental or disturbance gradients remains a challenge. The cessation of human activity that occurred with COVID-19 restrictions provides a 'natural experiment' to better understand the influence of human presence on wildlife. Here, we use a COVID-19 closure within a heavily visited and highly protected national park (Glacier National Park, MT, USA) to examine how 'low-impact' recreational hiking affects the spatiotemporal ecology of a diverse mammal community. Based on data collected from camera traps when the park was closed and then subsequently open to recreation, we found consistent negative responses to human recreation across most of our assemblage of 24 species, with fewer detections, reduced site use, and decreased daytime activity. Our results suggest that the dual mandates of national parks and protected areas to conserve biodiversity and promote recreation have potential to be in conflict, even for presumably innocuous recreational activities. There is an urgent need to understand the fitness consequences of these spatiotemporal changes to inform management decisions in protected areas.

Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes.

Naked mole-rats (NMRs) (Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span >30 years. In this study, using immunohistochemical and RNA-sequencing analyses, we compare skin morphology, cellular composition, and global transcriptome signatures between young and aged (aged 3‒4 vs. 19‒23 years, respectively) NMRs. We show that similar to aging in human skin, aging in NMRs is accompanied by a decrease in epidermal thickness; keratinocyte proliferation; and a decline in the number of Merkel cells, T cells, antigen-presenting cells, and melanocytes. Similar to that in human skin aging, expression levels of dermal collagens are decreased, whereas matrix metalloproteinase 9 and matrix metalloproteinase 11 levels increased in aged versus in young NMR skin. RNA-sequencing analyses reveal that in contrast to human or mouse skin aging, the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) genes are increased in aged NMR skin. Overall, these data suggest that specific features in the NMR skin aging transcriptome might contribute to the resistance of NMRs to spontaneous skin carcinogenesis and provide a platform for further investigations of NMRs as a model organism for studying the biology and disease resistance of human skin.

Food quality, security, and thermal refuge influence the use of microsites and patches by pygmy rabbits (Brachylagus idahoensis) across landscapes and seasons.

How intensely animals use habitat features depends on their functional properties (i.e., how the feature influences fitness) and the spatial and temporal scale considered. For herbivores, habitat use is expected to reflect the competing risks of starvation, predation, and thermal stress, but the relative influence of each functional property is expected to vary in space and time. We examined how a dietary and habitat specialist, the pygmy rabbit (Brachylagus idahoensis), used these functional properties of its sagebrush habitat-food quality, security, and thermal refuge-at two hierarchical spatial scales (microsite and patch) across two seasons (winter and summer). At the microsite and patch scales, we determined which plant functional traits predicted the number of bites (i.e., foraging) by pygmy rabbits and the number of their fecal pellets (i.e., general habitat use). Pygmy rabbits used microsites and patches more intensely that had higher crude protein and aerial concealment cover and were closer to burrows. Food quality was more influential when rabbits used microsites within patches. Security was more influential in winter than summer, and more at Cedar Gulch than Camas. However, the influence of functional properties depended on phytochemical and structural properties of sagebrush and was not spatiotemporally consistent. These results show function-dependent habitat use that varied according to specific activities by a central-place browsing herbivore. Making spatially explicit predictions of the relative value of habitat features that influence different types of habitat use (i.e., foraging, hiding, and thermoregulating) will improve how we predict patterns of habitat use by herbivores and how we monitor and manage functional traits within habitats for wildlife.

Ocean Aerobiology.

Ocean aerobiology is defined here as the study of biological particles of marine origin, including living organisms, present in the atmosphere and their role in ecological, biogeochemical, and climate processes. Hundreds of trillions of microorganisms are exchanged between ocean and atmosphere daily. Within a few days, tropospheric transport potentially disperses microorganisms over continents and between oceans. There is a need to better identify and quantify marine aerobiota, characterize the time spans and distances of marine microorganisms' atmospheric transport, and determine whether microorganisms acclimate to atmospheric conditions and remain viable, or even grow. Exploring the atmosphere as a microbial habitat is fundamental for understanding the consequences of dispersal and will expand our knowledge of biodiversity, biogeography, and ecosystem connectivity across different marine environments. Marine organic matter is chemically transformed in the atmosphere, including remineralization back to CO2. The magnitude of these transformations is insignificant in the context of the annual marine carbon cycle, but may be a significant sink for marine recalcitrant organic matter over long (∼104 years) timescales. In addition, organic matter in sea spray aerosol plays a significant role in the Earth's radiative budget by scattering solar radiation, and indirectly by affecting cloud properties. Marine organic matter is generally a poor source of cloud condensation nuclei (CCN), but a significant source of ice nucleating particles (INPs), affecting the formation of mixed-phase and ice clouds. This review will show that marine biogenic aerosol plays an impactful, but poorly constrained, role in marine ecosystems, biogeochemical processes, and the Earth's climate system. Further work is needed to characterize the connectivity and feedbacks between the atmosphere and ocean ecosystems in order to integrate this complexity into Earth System models, facilitating future climate and biogeochemical predictions.

Chromophoric dissolved organic matter (CDOM) in a subtropical estuary (Galveston Bay, USA) and the impact of Hurricane Harvey.

The landfall of Hurricane Harvey in August 2017 provided the opportunity to study the impact of extreme freshwater discharge on chromophoric dissolved organic matter (CDOM) properties in a subtropical estuary (Galveston Bay, Texas). Both fluorescence spectroscopy (excitation-emission matrices) and a three-component parallel factor analysis (PARAFAC) model identified changes in CDOM properties. Comparing to Coble's peaks, component 1 was similar to peak C, component 2 to peak M, and component 3 to peak B. Results clearly show three periods with distinct CDOM properties: a dry season, a wet season, and Hurricane Harvey. The dry season was characterized by higher values of the spectral slope and fluorescence and biological indices. The wet season was characterized by high values of PARAFAC components 1 and 2 (humic-like) and the absorption coefficient at 350 nm. Some CDOM components were highly correlated with salinity, indicating conservative mixing. Component 3 (protein-like) had a low correlation to salinity, suggesting degradation or production processes in the bay. Silicates and NO3- + NO2- had negative relationships with salinity and a positive one with PARAFAC components 1 and 2. PARAFAC component 3 was correlated with dissolved oxygen and chlorophyll a, suggesting a relationship between CDOM fluorescent components and phytoplankton activity. High values of the humification index were observed immediately after Hurricane Harvey, indicating increased input of terrestrial organic matter into the bay. Hurricane Harvey increased CDOM levels and humification, and the variability and changes seem to be mostly due to freshwater discharge from the San Jacinto River and not the Trinity River. The influx of freshwater was sufficient to eliminate the salinity gradient in Galveston Bay and significantly change CDOM properties. Galveston Bay recovered quickly from the hurricane and associated flux of freshwater, returning to pre-hurricane CDOM characteristics in less than 2 months.

Improved prediction of Canada lynx distribution through regional model transferability and data efficiency.

The application of species distribution models (SDMs) to areas outside of where a model was created allows informed decisions across large spatial scales, yet transferability remains a challenge in ecological modeling. We examined how regional variation in animal-environment relationships influenced model transferability for Canada lynx (Lynx canadensis), with an additional conservation aim of modeling lynx habitat across the northwestern United States. Simultaneously, we explored the effect of sample size from GPS data on SDM model performance and transferability. We used data from three geographically distinct Canada lynx populations in Washington (n = 17 individuals), Montana (n = 66), and Wyoming (n = 10) from 1996 to 2015. We assessed regional variation in lynx-environment relationships between these three populations using principal components analysis (PCA). We used ensemble modeling to develop SDMs for each population and all populations combined and assessed model prediction and transferability for each model scenario using withheld data and an extensive independent dataset (n = 650). Finally, we examined GPS data efficiency by testing models created with sample sizes of 5%-100% of the original datasets. PCA results indicated some differences in environmental characteristics between populations; models created from individual populations showed differential transferability based on the populations' similarity in PCA space. Despite population differences, a single model created from all populations performed as well, or better, than each individual population. Model performance was mostly insensitive to GPS sample size, with a plateau in predictive ability reached at ~30% of the total GPS dataset when initial sample size was large. Based on these results, we generated well-validated spatial predictions of Canada lynx distribution across a large portion of the species' southern range, with precipitation and temperature the primary environmental predictors in the model. We also demonstrated substantial redundancy in our large GPS dataset, with predictive performance insensitive to sample sizes above 30% of the original.

Vulnerability of progeroid smooth muscle cells to biomechanical forces is mediated by MMP13.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments.

A multidimensional systems biology analysis of cellular senescence in aging and disease.

BACKGROUND: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. RESULTS: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. CONCLUSIONS: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

Time to surgery for open hand injuries and the risk of surgical site infection: a prospective multicentre cohort study.

Whether delaying surgery increases the risk of infection in open hand injuries is an important but unresolved topic. This prospective cohort study included 983 consecutive adults with open hand injuries treated surgically over 1 year. The risk ratio (RR) for surgical site infection was estimated by logistic regression. The median time from injury to surgery was 20 hours (range 4-90). Forty-one patients (4%) developed an infection. The risk of infection was not affected by the time to surgery (adjusted risk ratio 1.0 [95% CI: 1.0 to 1.0]) or preoperative antibiotics (adjusted risk ratio 1.8 [95% CI: 0.2 to 13]), which were provided to 95% of patients. Skin loss increased the risk of infection (adjusted risk ratio 2.6 [95% CI: 1.3 to 5.0]). Delaying surgery for open hand injuries by 4 days does not appear to increase the risk of surgical site infection. Level of evidence: II.

Distribution and connectivity of protected areas in the Americas facilitates transboundary conservation.

Large-scale anthropogenic changes to landscapes will cause species to move and shift their ranges against a backdrop of international political boundaries. Transboundary conservation efforts are therefore key to preserving intact and connected landscapes, particularly if such efforts can be implemented within the framework of protected area networks that provide for resiliency and persistence in the face of threats such as climate change. We studied the distribution, connectivity, and integrity of protected areas in regions near international borders within the Americas. We found that there is a greater proportion of land protected near vs. far from borders, with this effect extending approximately 125 km from the border. This trend was most pronounced when considering multiuse categories of protected areas in the analysis. We also found that there is greater connectivity of protected areas in border regions than more internally within countries, and relatively low rates of habitat loss within border-situated and internal protected areas. Our results indicate that protected area networks are larger and more connected if considered in a transboundary context and that efforts to conserve species and mitigate effects of long-term stressors like climate change will be most successful when planning includes neighboring countries. Despite a relative lack of attention to transboundary conservation in the Americas, our results suggest substantial opportunities for linking landscapes via a focus on international border regions and coordination across borders in protected areas management.

Neotropical carnivores: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non‐detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non‐governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peerreviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non‐detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio‐temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other largescale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data.

Reassessing the success of experts and nonexperts at correctly differentiating between closely related species from camera trap images: A reply to Gooliaff and Hodges.

We present a reply to a recent article in Ecology and Evolution ("Measuring agreement among experts in classifying camera images of similar species" by Gooliaff and Hodges) that demonstrated a lack of consistency in expert-based classification of images of similar-looking species. We disagree with several conclusions from the study, and show that with some training, and use of multiple images that is becoming standard practice in camera-trapping studies, even nonexperts can identify similar sympatric species with high consistency.

Chemical cross-linking in the structural analysis of protein assemblies.

For decades, chemical cross-linking of proteins has been an established method to study protein interaction partners. The chemical cross-linking approach has recently been revived by mass spectrometric analysis of the cross-linking reaction products. Chemical cross-linking and mass spectrometric analysis (CXMS) enables the identification of residues that are close in three-dimensional (3D) space but not necessarily close in primary sequence. Therefore, this approach provides medium resolution information to guide de novo structure prediction, protein interface mapping and protein complex model building. The robustness and compatibility of the CXMS approach with multiple biochemical methods have made it especially appealing for challenging systems with multiple biochemical compositions and conformation states. This review provides an overview of the CXMS approach, describing general procedures in sample processing, data acquisition and analysis. Selection of proper chemical cross-linking reagents, strategies for cross-linked peptide identification, and successful application of CXMS in structural characterization of proteins and protein complexes are discussed.

A Reassessment of Genes Modulating Aging in Mice Using Demographic Measurements of the Rate of Aging.

Many studies have reported genetic interventions that have an effect on mouse life span; however, it is crucial to discriminate between manipulations of aging and aging-independent causes of life extension. Here, we used the Gompertz equation to determine whether previously reported aging-related mouse genes statistically affect the demographic rate of aging. Of 30 genetic manipulations previously reported to extend life span, for only two we found evidence of retarding demographic aging: Cisd2 and hMTH1 Of 24 genetic manipulations reported to shorten life span and induce premature aging features, we found evidence of five accelerating demographic aging: Casp2, Fn1, IKK-ß, JunD, and Stub1 Overall, our reassessment found that only 15% of the genetic manipulations analyzed significantly affected the demographic rate of aging as predicted, suggesting that a relatively small proportion of interventions affecting longevity do so by regulating the rate of aging. By contrast, genetic manipulations affecting longevity tend to impact on aging-independent mortality. Our meta-analysis of multiple mouse longevity studies also reveals substantial variation in the controls used across experiments, suggesting that a short life span of controls is a potential source of bias. Overall, the present work leads to a reassessment of genes affecting the aging process in mice, with broad implications for our understanding of the genetics of mammalian aging and which genes may be more promising targets for drug discovery.

Using population-based routinely collected data from the Sentinel Stroke National Audit Programme to investigate factors associated with discharge to care home after rehabilitation.

OBJECTIVES: We investigated factors associated with Care Home (CH) discharge following stroke using routinely collected data in unselected patients and assessed the relevance of previous research findings to such patients seen in routine clinical practice. DESIGN: Retrospective analysis of data from the Sentinel Stroke National Audit Programme using univariate analysis and logistic regression. SETTING: A large acute and rehabilitation UK stroke unit with access to early supported discharge. SUBJECTS: All patients with stroke treated from 1 January 2014 to 1 January 2017. MAIN MEASURES: National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). RESULTS: Of 2584 patients (median age 78 years, interquartile range (IQR) 69-86; 50.6% male; 86.7% infarcts; median admission NIHSS 4, IQR 2-9), 401 (15.5%) died in hospital and 203 patients (7.9%) were permanently discharged to CH for the first time. Most had pre-discharge mRS scores of 4/5. Factors (odds ratios; 95% confidence intervals) associated with CH discharge included age (1.07; 1.05-1.10), incontinence (11.5; 7.13-19.25), dysphagia (2.13; 1.39-3.29), severe weakness (1.93; 1.28-2.92), pneumonia (1.68; 1.13-2.50), urinary tract infection (UTI) (1.70; 1.04-2.75) and depression (1.65; 1.00-2.72). In a subgroup of all patients with a pre-discharge mRS of 4/5, age (1.04; 1.02-1.06), incontinence (4.87; 2.39-11.02), UTI (2.0; 1.09-3.71) and pneumonia (1.59; 1.02-2.50) were the only factors associated with CH discharge. CONCLUSION: Potentially modifiable variables like incontinence, UTI and pneumonia were associated with CH discharge, particularly in the severely disabled.

Human Ageing Genomic Resources: new and updated databases.

In spite of a growing body of research and data, human ageing remains a poorly understood process. Over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), a collection of databases and tools for studying the biology and genetics of ageing. Here, we present HAGR's main functionalities, highlighting new additions and improvements. HAGR consists of six core databases: (i) the GenAge database of ageing-related genes, in turn composed of a dataset of >300 human ageing-related genes and a dataset with >2000 genes associated with ageing or longevity in model organisms; (ii) the AnAge database of animal ageing and longevity, featuring >4000 species; (iii) the GenDR database with >200 genes associated with the life-extending effects of dietary restriction; (iv) the LongevityMap database of human genetic association studies of longevity with >500 entries; (v) the DrugAge database with >400 ageing or longevity-associated drugs or compounds; (vi) the CellAge database with >200 genes associated with cell senescence. All our databases are manually curated by experts and regularly updated to ensure a high quality data. Cross-links across our databases and to external resources help researchers locate and integrate relevant information. HAGR is freely available online (http://genomics.senescence.info/).