In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.

Considering collaborative incident management: A study of the COVID-19 response and initial recovery in a rural West Virginia community.

Hierarchical command-style structures are commonplace in the management of disasters, though researchers have begun to recommend the exploration of networked approaches to incident management. Furthermore, few studies are explicitly looking at the rural context of disaster management. This study seeks to contribute to both topics by examining the motivations for emergent collaboration in the direction of the response and initial recovery to the coronavirus disease 2019 pandemic in a rural West Virginia community.

The transitory origins of rivers.

Streams that only flow occasionally are major contributors to river flow.

Chlorophyll a in lakes and streams of the United States (2005-2022).

The concentration of chlorophyll a in phytoplankton and periphyton represents the amount of algal biomass. We compiled an 18-year record (2005-2022) of pigment data from water bodies across the United States (US) to support efforts to develop process-based, machine learning, and remote sensing models for prediction of harmful algal blooms (HABs). To our knowledge, this dataset of nearly 84,000 sites and over 1,374,000 pigment measurements is the largest compilation of harmonized discrete, laboratory-extracted chlorophyll data for the US.

Atypical granulation in neutrophils of a domestic shorthair cat.

A 13-year-old male domestic short-hair cat presented for evaluation of labored breathing, hyporexia, and lethargy. Pertinent initial diagnostics yielded leukocytosis, characterized by neutrophilia and monocytosis. Numerous small, round, magenta granules were observed within all neutrophils in Wright-Giemsa-stained blood films on the day of presentation and the day thereafter.

An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier. BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40 to 50 times greater reporter expression in the CNS of human knockin mice.

Metabolism Regimes in Regulated Rivers of the Illinois River Basin, USA.

Metabolism estimates organic carbon accumulation by primary productivity and removal by respiration. In rivers it is relevant to assessing trophic status and threats to river health such as hypoxia as well as greenhouse gas fluxes. We estimated metabolism in 17 rivers of the Illinois River basin (IRB) for a total of 15,176 days, or an average of 2.

Prioritizing river basins for nutrient studies.

Increases in fluxes of nitrogen (N) and phosphorus (P) in the environment have led to negative impacts affecting drinking water, eutrophication, harmful algal blooms, climate change, and biodiversity loss. Because of the importance, scale, and complexity of these issues, it may be useful to consider methods for prioritizing nutrient research in representative drainage basins within a regional or national context. Two systematic, quantitative approaches were developed to (1) identify basins that geospatial data suggest are most impacted by nutrients and (2) identify basins that have the most variability in factors affecting nutrient sources and transport in order to prioritize basins for studies that seek to understand the key drivers of nutrient impacts.

Macroscale controls determine the recovery of river ecosystem productivity following flood disturbances.

River ecosystem function depends on flow regimes that are increasingly modified by changes in climate, land use, water extraction, and flow regulation. Given the wide range of variation in flow regime modifications and autotrophic communities in rivers, it has been challenging to predict which rivers will be more resilient to flow disturbances. To better understand how river productivity is disturbed by and recovers from high-flow disturbance events, we used a continental-scale dataset of daily gross primary production time series from 143 rivers to estimate growth of autotrophic biomass and ecologically relevant flow disturbance thresholds using a modified population model.

An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an AAV capsid, BI-hTFR1, that binds human Transferrin Receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40-50 times greater reporter expression in the CNS of human knock-in mice.

Cytochemical staining of leukocytes and platelets in the Florida manatee (): identification of a bilobed monocyte similar to other members of the .

Manatees (Antillean-, Amazonian, and African-) and dugongs belong to the Order , and when combined with elephants and rock hyraxes, form the . A bilobed mononuclear cell has previously been identified in elephants and rock hyraxes, but not in manatees and dugongs, with cytochemical staining identifying these cells as bilobed monocytes in elephants. The objective of this study was to characterize leukocytes (white blood cells, WBC) and platelets in blood films of Florida manatees (;  = 8) using one routine hematological (Wright-Giemsa) and eight cytochemical stains: alkaline phosphatase (ALP), α-naphthyl butyrate esterase (ANBE), chloroacetate esterase (CAE), Luna, myeloperoxidase (MPx), periodic acid-Schiff (PAS), Sudan black B (SBB), and toluidine blue (TB).

GW/SW-MST: A Groundwater/Surface-Water Method Selection Tool.

Groundwater/surface-water (GW/SW) exchange and hyporheic processes are topics receiving increasing attention from the hydrologic community. Hydraulic, chemical, temperature, geophysical, and remote sensing methods are used to achieve various goals (e.g.

Left shift and toxic change in heterophils and neutrophils of non-mammalian vertebrates: A comparative review, image atlas, and practical considerations.

Heterophils and neutrophils are important first cellular responders to inflammatory conditions. In addition to quantitative shifts in the numbers of these cells in blood, inflammatory disease states often have accompanying increases in immature precursor stages (left shift) and/or evidence of toxic change on blood film evaluation. Recognition of left shift and toxic change morphologies is a salient diagnostic finding with clinical relevance across species.

Light and flow regimes regulate the metabolism of rivers.

Mean annual temperature and mean annual precipitation drive much of the variation in productivity across Earth's terrestrial ecosystems but do not explain variation in gross primary productivity (GPP) or ecosystem respiration (ER) in flowing waters. We document substantial variation in the magnitude and seasonality of GPP and ER across 222 US rivers. In contrast to their terrestrial counterparts, most river ecosystems respire far more carbon than they fix and have less pronounced and consistent seasonality in their metabolic rates.

Clinical, metabolic, and molecular genetic characterization of hereditary methemoglobinemia caused by cytochrome b reductase deficiency in 30 dogs.

Genotype-phenotype correlations of humans and dogs with hereditary methemoglobinemia are not yet well characterized. We determined total hemoglobin and methemoglobin (MetHb) concentrations, cytochrome b reductase (CYB5R) enzyme activities, genotypes, and clinical signs in 30 dogs with persistent cyanosis without cardiopulmonary disease. Erythrocytic CYB5R enzyme activities were low in all dogs assayed.

Serum Iron Analytes in Healthy and Diseased Florida Manatees (Trichechus manatus latirostris).

Serum iron concentration is usually decreased in true iron deficiency and with inflammatory disease in man and domestic animals. Serum total iron binding capacity (TIBC) may be increased in true iron deficiency and decreased with inflammatory disease. This prospective study was designed to measure serum iron analytes in healthy free-ranging and housed Florida manatees (Trichechus manatus latirostris) of both sexes and various ages and to evaluate the effects of diseases common to manatees on these analytes.

Floodplain inundation spectrum across the United States.

Floodplain inundation poses both risks and benefits to society. In this study, we characterize floodplain inundation across the United States using 5800 stream gages. We find that between 4% and 12.

The metabolic regimes of 356 rivers in the United States.

A national-scale quantification of metabolic energy flow in streams and rivers can improve understanding of the temporal dynamics of in-stream activity, links between energy cycling and ecosystem services, and the effects of human activities on aquatic metabolism. The two dominant terms in aquatic metabolism, gross primary production (GPP) and aerobic respiration (ER), have recently become practical to estimate for many sites due to improved modeling approaches and the availability of requisite model inputs in public datasets. We assembled inputs from the U.

Thresholds of lake and reservoir connectivity in river networks control nitrogen removal.

Lakes, reservoirs, and other ponded waters are ubiquitous features of the aquatic landscape, yet their cumulative role in nitrogen removal in large river basins is often unclear. Here we use predictive modeling, together with comprehensive river water quality, land use, and hydrography datasets, to examine and explain the influences of more than 18,000 ponded waters on nitrogen removal through river networks of the Northeastern United States. Thresholds in pond density where ponded waters become important features to regional nitrogen removal are identified and shown to vary according to a ponded waters' relative size, network position, and degree of connectivity to the river network, which suggests worldwide importance of these new metrics.