Over recent decades, global warming has led to sustained glacier mass reduction and the formation of glacier lakes dammed by potentially unstable moraines. When such dams break, devastating Glacial Lake Outburst Floods (GLOFs) can occur in high mountain environments with catastrophic effects on populations and infrastructure. To understand the occurrence of GLOFs in space and time, build frequency-magnitude relationships for disaster risk reduction or identify regional links between GLOF frequency and climate warming, comprehensive databases are critically needed.
View Article and Find Full Text PDFspp. are facultative pathogens that contribute to the pathogenesis of multiple bovine diseases, including the bovine respiratory disease complex, and have been shown to form biofilms. Biofilm formation is associated with increased antibiotic resistance in many organisms, but accurate determination of antimicrobial susceptibility in biofilms is challenging.
View Article and Find Full Text PDFIn recent decades significant forest expansion into treeless alpine zones has been observed across global mountain ranges, including the Alps, driven by a complex interplay of global warming and land-use changes. The upward shift of treelines has far-reaching implications for ecosystem functioning, biodiversity, and biogeochemical cycles. However, climate variables alone account for only a fraction of treeline dynamics, highlighting substantial research gaps concerning the influence of non-climatic factors.
View Article and Find Full Text PDFCetacean brains are uniquely adapted to diving, but can be affected by diseases and exposure to toxins, triggering neurodegenerative processes that may cause stranding. Some species exhibit a significant post-reproductive lifespan (PRLS), increasing the likelihood of observing cumulative and age-related pathology. Immunohistochemistry against amyloid-β and hyperphosphorylated tau proteins is increasingly implemented to assess Alzheimer's Disease-like neuropathology in cetaceans, but comparisons between geographically distinct populations, animals of different age groups, sex, and with concomitant pathologies are lacking.
View Article and Find Full Text PDFIdiopathic pulmonary fibrosis (IPF) is a lethal disorder characterized by relentless progression of lung fibrosis that causes respiratory failure and early death. Currently, no curative treatments are available, and existing therapies include a limited selection of antifibrotic agents that only slow disease progression. The development of novel therapeutics has been hindered by a limited understanding of the disease's etiology and pathogenesis.
View Article and Find Full Text PDFIntroduction: Bacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders.
View Article and Find Full Text PDFDebris-flow activity in the Alps is anticipated to undergo pronounced changes in response to a warming climate. Yet, a fundamental challenge in comprehensively assessing changes in process activity is the systematic lack of long-term observational debris-flow records. Here, we reconstruct the longest, continuous time series (1626-2020) of debris flows at Multetta, a supply-limited torrential system in the Eastern Swiss Alps.
View Article and Find Full Text PDFX-ray computed tomography (XRCT) imaging allows non-destructive visualization of the structure of various materials. Applied to wooden objects, it allows determination of their morphologies or manufacturing techniques, but also measurement of growth ring widths. We have applied XRCT to a selection of 38 mummy labels.
View Article and Find Full Text PDFAedes japonicus is an invasive Asian mosquito species, and to date it is widespread in many European countries. In Italy, it was first recorded in 2015 at the Austrian border and it then spread throughout the Northeast of the country. In 2019, it was also identified in Piedmont region, near the Swiss border.
View Article and Find Full Text PDFObjectives: Pesticide application has become necessary to increase crop productivity and reduce losses. However, the use of these products can produce toxic effects. Farmers are individuals occupationally exposed to pesticides, thus subject to associated diseases as well as cognitive impairment.
View Article and Find Full Text PDFOver large regions exposed to natural disasters, cascading effects resulting from complex or concatenated natural processes may represent a large portion of total risk. Populated high-mountain environments are a major concern, and methods for large-scale quantitative risk analyses are urgently required to improve risk mitigation. This article presents a comprehensive quantitative rockfall risk assessment over a large archetypal valley of the Andean mountains, in Central Chile, which integrates a wide spectrum of elements at risk.
View Article and Find Full Text PDFAs a key regulator of the innate immune system, the NLRP3 inflammasome responds to a variety of environmental insults through activation of caspase-1 and release of the proinflammatory cytokines IL-1β and IL-18. Aberrant NLRP3 inflammasome function is implicated in numerous inflammatory diseases, spurring drug discovery efforts at NLRP3 as a therapeutic target. A diverse array of small molecules is undergoing preclinical/clinical evaluation with a reported mode of action involving direct modulation of the NLRP3 pathway.
View Article and Find Full Text PDFDNA-encoded libraries (DELs) provide unmatched chemical diversity and starting points for novel drug modalities. Here, we describe a workflow that exploits the bifunctional attributes of DEL ligands as a platform to generate BRET probes for live cell target engagement studies. To establish proof of concept, we performed a DEL screen using aurora kinase A and successfully converted aurora DEL ligands as cell-active BRET probes.
View Article and Find Full Text PDFACS Appl Mater Interfaces
August 2023
Determining the mechanistic causes of lung diseases, developing new treatments thereof, and assessing toxicity whether from chemical exposures or engineered nanomaterials would benefit significantly from a preclinical human lung alveolar interstitium model of physiological relevance. The existing preclinical models have limitations because they fail to replicate the key anatomical and physiological characteristics of human alveoli. Thus, a human lung alveolar interstitium chip was developed to imitate key alveolar microenvironmental factors including an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels, physiologically relevant interstitial matrix stiffness, interstitial fluid flow, and 3D breathing-like mechanical stretch.
View Article and Find Full Text PDFIntermittent fasting (IF) is a diet with salutary effects on cognitive aging, Alzheimer's disease (AD), and stroke. IF restricts a number of nutrient components, including glucose. 2-deoxyglucose (2-DG), a glucose analog, can be used to mimic glucose restriction.
View Article and Find Full Text PDFPathological hallmarks of Alzheimer's disease (AD) precede clinical symptoms by years, indicating a period of cognitive resilience before the onset of dementia. Here, we report that activation of cyclic GMP-AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA.
View Article and Find Full Text PDFComplete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age.
View Article and Find Full Text PDFExplosive volcanism is a key contributor to climate variability on interannual to centennial timescales. Understanding the far-field societal impacts of eruption-forced climatic changes requires firm event chronologies and reliable estimates of both the burden and altitude (that is, tropospheric versus stratospheric) of volcanic sulfate aerosol. However, despite progress in ice-core dating, uncertainties remain in these key factors.
View Article and Find Full Text PDFThe primary goal of paleoflood hydrology is to estimate the frequency and magnitude of past floods. Botanical evidence, and particularly scars on trees, has been used repeatedly as paleostage indicators to reconstruct peak discharges and flood height. Yet, these reconstructions depend on the presence of visible scars on tree stems which tend to be masked as trees grow older.
View Article and Find Full Text PDFBackground: Central nervous system (CNS) infections in cattle are a major cause of economic loss and mortality. Machine learning (ML) techniques are gaining widespread application in solving predictive tasks in both human and veterinary medicine.
Objectives: Our primary aim was to develop and compare ML models that could predict the likelihood of a CNS disorder of infectious or inflammatory origin in neurologically-impaired cattle.