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The amyloid precursor family of proteins in excitatory neurons are essential for regulating cortico-hippocampal circuit dynamics in vivo
Get PDFThe amyloid precursor protein (APP) family is ubiquitously expressed in the mammalian brain and implicated in Alzheimer’s disease. APP family proteins participate in synaptic function and their absence impairs cognition. However, how these proteins regulate neural circuits and influence brain-behavior relationships remains unknown. Using in vivo two-photon Ca2+-imaging and Neuropixels, we show that APP family knockout (KO) in excitatory neocortical and hippocampal neurons suppresses neuronal dynamics across behavioral states, and results in an increased proportion of low-activity and silent neurons. Further, APP family KO leads to a reduction in synapses expressing the requisite N-methyl-D-aspartate receptor (NMDAR) subunit GluN1, with pharmacological enhancement of NMDAR function normalizing aberrant dynamics in low-activity neurons and rectifying behavioral impairments. Suppressing NMDAR function in control mice replicates the functional phenotype observed in APP family KOs. Our findings indicate a physiological role for the APP family in regulating and sustaining spontaneous neuronal activity in cortico-hippocampal circuits in vivo
High Resolution Global Environmental Stratification to Model Shifting Bioclimatic Conditions and Climate Change Impacts on Terrestrial Ecosystems
Get PDFUnderstanding climate-driven ecological change benefits from frameworks capable of translating climate model outputs into ecologically interpretable spatial patterns. This study presents a global application of the Environmental Stratification (EnS) methodology, using Maximum Likelihood Classification, and integrating outputs from 22 CMIP6 Earth System Models (ESMs) across four Shared Socioeconomic Pathways (SSP: 1-2.6; 2-4.5; 3-7.0; 5-8.5), two historical baseline climate datasets (1960–1990; 1970–2000), and two future averaged time periods (2021–2040; 2041–2060). Both “Consensus” and “High-Risk” multimodel majority ensembles were selected and used in the global analysis. The resulting Future_Global_EnS Database (https://doi.org/10.5281/zenodo.15099763), provides these highresolution EnS projections at 30 arc seconds resolution (~1km2). The global EnS analysis reveals extensive bioclimatic reorganization by mid-century. Cooler and mesic zones, particularly boreal, temperate, and montane systems, exhibit high zonal turnover, significant poleward latitudinal shifts, upslope migrations, and mountaintop extirpations. Tropical, arid, and extremely hot zones show significant spatial expansion and internal reorganization under high-emissions scenarios, including large-scale growth of drylands and intensification of extremely hot bioclimatic conditions. Results from the global EnS analyses align closely with empirical observations of bioclimatic and ecological shifts, providing spatially explicit, ecologically grounded metrics for anticipating where and how terrestrial ecosystems will change. By delineating statistically based coherent and ecologically meaningful geospatial strata, the EnS methodology provides a powerful tool for translating complex climate projections into interpretable ecological insights and enables rigorous analysis of climate impacts at decision-relevant scales. Both the EnS methodology and Future_Global_EnS Database provide a resource with immediate utility for biodiversity conservation, land-use policy, agricultural sustainability, natural resource management, and adaptation to rapid climate change, at global to regional and local scales
The Confidential Enquiry into Perioperative Equine Fatalities : phase 4 (CEPEF4) - a worldwide observational, prospective, multicentre cohort study in 2025
No full textObjective: To report on the Confidential Enquiry into Perioperative Equine Fatalities 4 (CEPEF4). Study design: Confidential, observational, prospective, multicentre, cohort study. Animals: 47,396 horses/ponies undergoing general anaesthesia (GA). Methods: Characteristics of each GA (249 variables) were collected. Outcomes after seven days were ALIVE (or discharged), EUTHANASIA or DEAD. Logistic regression analysed patient demographics and the anaesthetic drugs (p < 0.05). Results: Data were collected from 47,396 GAs in 93 centres in 28 countries. Death rates were 1.2% overall, 0.6% for cases classified as NON-COLIC and 4.2% for COLIC. For NON-COLICs (227 deaths from 39,798 NON-COLICs), the main three causes of death were fractures (35.7%), abdominal complications (18.1%) and central nervous system problems (13.2%). Logistic regression analyses revealed an increase in the odds of death for pregnant mares, geriatrics, thin horses, those with a higher American Society of Anesthesiologists grade, urgent procedures and those lasting < 1 hour or > 2 hours. Ketamine infusions and plasma lactate measurement during maintenance were associated with elevated risk. By contrast, monitoring invasive arterial pressure, end-tidal CO 2, blood gases and body temperature were each associated with reduced odds of death. Premedication with agonist-antagonist/partial-agonist opioids with non-steroidal anti-inflammatory drugs and administration of α 2-adrenoceptor agonists during recovery, alone or with acepromazine, were associated with reduced odds of death. Conclusions and clinical relevance: CEPEF4 reports a reduction in the death rate compared with CEPEF2 in 2002: overall 1.2% versus 1.9%, colic death rate 4.2% versus 7.8% and non-colic death rate 0.6% versus 0.9%. Healthy horses still die, the majority because of fractures during recovery. We identified factors that may influence clinical decision-making and enhance patient safety. The CEPEF4 database will continue to provide clinically applicable information, with potential for further insights and improvements in equine anaesthesia.</p
Can the use of silver nanoparticles in dental implants increase its antimicrobial potency? - systematic review
No full textBACKGROUND: Silver nanoparticles (AgNPs) is a promising nanotechnological solution to prevent microbial colonization on dental implants, offering a promising avenue for combating implant-related infections and improving long-term treatment outcomes.METHODS: Using manual search and electronic databases such as PubMed Advanced Search and Google Scholar, a methodical search was carried out from 2013 to 2023 utilizing keywords, and inclusion and exclusion criteria to find pertinent papers addressing the research question "Can the use of silver nanoparticles in dental implants increase its antimicrobial potency?". Critical Appraisal analysis for this review was done using risk of bias tool for in vitro studies: QUIN tool.RESULTS: Nine of the 122 articles that were retrieved underwent the three-step screening process before being chosen for the final analysis. QUIN Tool were used to evaluate the quality of the included in vitro studies. The summarized results from nine studies reveal the efficacy of AgNPs in inhibiting microorganisms and preventing biofilm formation on dental implants. In vitro tests demonstrate AgNPs' ability to hinder bacterial growth associated with peri-implantitis. Various techniques, including surface modifications and nanostructure incorporations, exhibit promising antibacterial effects.CONCLUSIONS: AgNPs show promise in inhibiting multidrug-resistant bacteria, enhancing dental implant biocompatibility, and reducing peri-implant diseases, benefiting clinical outcomes and limiting bacterial colonization.</p
Application of new biologic disease criteria for synucleinopathies to the systemic synuclein sampling study cohort
No full textWe applied biologic criteria and NSD-ISS to Synuclein Sampling Study, a PD sample with range of durations since clinical diagnosis. 93% of evaluable participants met biologic criteria. The majority were NSD-ISS stage3 or less, including >40% of the advanced PD group. Interpretation of staging in medicated patients is challenging. Biologic criteria and clinico-biomarker staging are important steps forward, but quantitative biomarkers of disease progression, not influenced by medications, are critically needed.</p
Identification of herbal medicine species of Lysimachia L. (Primulaceae) in Southern China using genome skimming
No full textBACKGROUND: The accurate identification of herbal medicine is a prerequisite for safe and effective use. DNA barcoding has been widely used for the identification of herbal medicine. However, choosing and refining a suitable barcode is complex in plants. The genus Lysimachia includes over 180 species and is widely used as herbal medicine in China and elsewhere. Species identification within this genus based on morphological, microscopic, or chemical characters is often challenging. In this study, 44 accessions representing 17 putative species of Lysimachia from southern China were sequenced using genome skimming. Whole plastome and nrDNA sequences were successfully recovered from these data. Combining 13 published plastomes of Lysimachia, the discrimination power of standard barcodes, along with plastome and hypervariable sequences from the plastome were compared across 57 plastomes from 22 putative species.RESULTS: Standard barcodes have limitation in providing accurate species level identification; however, they can facilitate the rapid classification of unknown samples at the generic level. The plastomes exhibit a highly degree of conservation in the structure and gene content, yet they successfully identify all studied taxa. Five highly variable loci from plastomes were identified: petN-psbM, ycf1, rpl22, trnK-rps16, and ndhC-trnV. While these regions improved the discrimination power compared to standard barcodes, they still could not yield accurate identification of all taxa studied. However, when combined with ITS, ycf1 provides 100% successful species identification.CONCLUSIONS: We recommend that the use of whole plastome and the combination of ycf1 + ITS as accurate and effective barcodes for species identification in Lysimachia. This study also highlights the potential for effective use of genome skimming data.</p
Public health agencies need to be 'Kennedy ready'
Get PDFThe Secretary of the US Department of Health & Human Services, Robert Kennedy Jr is leading a political agenda against vaccination. This is undermining the delivery of life-saving vaccination programmes and provision of evidence-based information on the safety and effectiveness of vaccines for the public and health professionals. Inconsistent and conflicting messaging between health practitioners and government health agencies erodes trust in public health programmes, creating a vacuum which is often filled with mis/disinformation that presents severe consequences for families. Due to the transnational spread of diseases, we consider the implications of events in the US for routine childhood vaccination programmes in the UK. Public health agencies across the world need to be ‘Kennedy ready’; pragmatic steps must be taken to mitigate threats posed to vaccine confidence and the control of vaccine preventable diseases
Towards eco-social contracts through an entangled manifestation of digital litter
Get PDFMany of the current debates in technology concern the extractive practices around planetary resources and data, which produce electronic waste as well as everyday sense of clutter among media channels and files. In this paper, we engage with this problem space through a specific focus on Terms of Service agreements, which have become a prerequisite for even the most rudimentary use of technology. We do this by presenting an exploded view of an existing Terms of Service policy ecosystem, in the form of an outdoor installation, temporarily littering a patch of nature. Through this installation, we expose eco-social contracts as a design opening for more-than-human data governance, ecological temporalities, and the right to patchwork as generative concepts
A twenty-first century prodigal son:Donation between family members
Get PDFCase analysis of Russell's Executors v Russell's Executrix [2025] SC GLA 1
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