Whole-stream metabolism: strategies for measuring and modeling diel trends of dissolved oxygen

Stream metabolism is used to characterize the allochthonous and autochthonous basis of stream foodweb production. The metabolic rates of respiration and gross primary production often are estimated from changes in dissolved O2 concentration in the stream over time. An upstream–downstream O2 accounting method (2-station) is used commonly to estimate metabolic rates in a defined length of stream channel. Various approaches to measuring and analyzing diel O2 trends have been used, but a detailed comparison of different approaches (e.g., required reach length, method of measuring aeration rate [k], and use of temperature-corrected metabolic rates) is needed. We measured O2 upstream and downstream of various reaches in Kings Creek, Kansas. We found that 20 m was the approximate minimum reach length required to detect a significant change in O2, a result that matched the prediction of a calculation method to determine minimum reach length. We assessed the ability of models based on 2-station diel O2 data and k measurements in various streams around Manhattan, Kansas, to predict k accurately, and we tested the importance of accounting for temperature effects on metabolic rates. We measured gas exchange directly with an inert gas and used a tracer dye to account for dilution and to measure velocity and discharge. Modeled k was significantly correlated with measured k (Kendall's τ, p < 0.001; regression adjusted R²  =  0.70), but 19 published equations for estimating k generally provided poor estimates of measured k (only 6 of 19 equations were significantly correlated). Temperature correction of metabolic rates allowed us to account for increases in nighttime O2, and temperature-corrected metabolic rates fit the data somewhat better than uncorrected estimates. Use of temperature-correction estimates could facilitate cross-site comparisons of metabolism

Uterine Torsion Dystocia Complicated by Perosomus Elumbis in an Angus Calf Associated with a Consanguineous Mating

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the dam, sire, and ten half siblings were collected for genetic testing and parentage verification. Necropsy, radiographic, and computed tomography examinations all supported a diagnosis of perosomus elumbis. Perosomus elumbis is a congenital abnormality of unknown origin(s), and this is the first report of a case associated with a consanguineous mating

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases

Introduction Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods We analyzed data from the DIRECT study (NCT02159209), an international, multi-center, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least one nephrotoxic drug for a minimum of 24 hours prior to acute kidney injury (AKI) onset. Cases were clinically adjudicated and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), non-steroidal anti-inflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine trends, and contrast media as significant predictors of DI-AKI with good performance, ROC AUC 0.86. Conclusions The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Uterine Torsion Dystocia Complicated by Perosomus Elumbis in an Angus Calf Associated with a Consanguineous Mating

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the dam, sire, and ten half siblings were collected for genetic testing and parentage verification. Necropsy, radiographic, and computed tomography examinations all supported a diagnosis of perosomus elumbis. Perosomus elumbis is a congenital abnormality of unknown origin(s), and this is the first report of a case associated with a consanguineous mating

Whole-genome sequencing to investigate a possible genetic basis of perosomus elumbis in a calf resulting from a consanguineous mating

Perosomus elumbis (PE) is a lethal, congenital defect marked by aplasia of the lumbar and sacral spine and spinal cord. Contracture of the hind limbs is also commonly observed in affected individuals. PE has been reported in many domestic species, with numerous case reports in Holstein cattle in the past two decades (Jones, 1999; Karakaya et al., 2013; Agerholm et al., 2014). The etiology of PE remains unknown. In one instance, a stillborn Holstein calf with PE was found to be infected with Bovine Viral Diarrhea Virus (BVDV) (Karakaya et al., 2013), and thus, it is possible that PE may be due to genetic and/or environmental factors. Recently, a stillborn Angus calf was diagnosed with PE following an accidental mother-son mating (Helms et al., 2020). BVDV was not detected in the affected Angus calf, dam, nor sire. Due to the relationship between the sire and dam, it was hypothesized that a novel, recessive genetic variant may be responsible for the development of PE in this Angus calf. The objective of this study was to use whole-genome sequencing to address this hypothesis and identify candidate variants for PE in this calf

Uterine Torsion Dystocia Complicated by Perosomus Elumbis in an Angus Calf Associated with a Consanguineous Mating

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the dam, sire, and ten half siblings were collected for genetic testing and parentage verification. Necropsy, radiographic, and computed tomography examinations all supported a diagnosis of perosomus elumbis. Perosomus elumbis is a congenital abnormality of unknown origin(s), and this is the first report of a case associated with a consanguineous mating

Eutrophication of US Freshwaters: Analysis of Potential Economic Damages

Human-induced eutrophication degrades freshwater systems worldwide by reducing water quality and altering ecosystem structure and function. We compared current total nitrogen (TN) and phosphorus (TP) concentrations for the U.S. Environmental Protection Agency nutrient ecoregions with estimated reference conditions. In all nutrient ecoregions, current median TN and TP values for rivers and lakes exceeded reference median values. In 12 of 14 ecoregions, over 90% of rivers currently exceed reference median values. We calculated potential annual value losses in recreational water usage, waterfront real estate, spending on recovery of threatened and endangered species, and drinking water. The combined costs were approximately $2.2 billion annually as a result of eutrophication in U.S. freshwaters. The greatest economic losses were attributed to lakefront property values ($0.3?2.8 billion per year, although this number was poorly constrained) and recreational use ($0.37?1.16 billion per year). Our evaluation likely underestimates economic losses incurred from freshwater eutrophication. We document potential costs to identify where restoring natural nutrient regimes can have the greatest economic benefits. Our research exposes gaps in current records (e.g., accounting for frequency of algal blooms and fish kills) and suggests further research is necessary to refine cost estimates