A Study of the Unionidae of Tinkers Creek, Ohio

We present data on freshwater mussel (Mollusca: Bivalvia: Unionidae) distributions for Tinkers Creek, a small Ohio stream that previously had not been surveyed for its unionid fauna. The distribution of these mussels was mapped against the changing habitat of the stream, with special attention paid to two zones of human manipulation, a wastewater treatment plant and a stretch of the river where the bed was relocated to enable development. At least five unionid species live in Tinkers Creek. These are Pyganodon grandis, Lampsilis radiata luteola, Fusconaiajlava, Lasmigona costata, and Lasmigona compressa. Fresh shells suggested the presence of three others: Strophitus undulatus, Toxolasma parvus, and Alasmidonta marginata. The region of Tinkers Creek where the mussels are most common extends through Twinsburg, Ohio, and upstream to a waterfall just below the confluence with Pond Brook. Relocation of the river channel eliminated mussels from a 0.5 km stretch in eastern Twinsburg. Furthermore, the impact of effluent from a wastewater treatment plant was minor, at most. Mussel diversity diminished from five to three species commonly found below this facility. A change in river habitat to faster flow, however, provided an alternate explanation for this faunal change. The most striking difference was the replacement of Lasmigona costata, a species usually found in medium and large rivers, by L. compressa, a species common in small streams and headwaters

A Study of the Unionidae of Tinkers Creek, Ohio

We present data on freshwater mussel (Mollusca: Bivalvia: Unionidae) distributions for Tinkers Creek, a small Ohio stream that previously had not been surveyed for its unionid fauna. The distribution of these mussels was mapped against the changing habitat of the stream, with special attention paid to two zones of human manipulation, a wastewater treatment plant and a stretch of the river where the bed was relocated to enable development. At least five unionid species live in Tinkers Creek. These are Pyganodon grandis, Lampsilis radiata luteola, Fusconaiajlava, Lasmigona costata, and Lasmigona compressa. Fresh shells suggested the presence of three others: Strophitus undulatus, Toxolasma parvus, and Alasmidonta marginata. The region of Tinkers Creek where the mussels are most common extends through Twinsburg, Ohio, and upstream to a waterfall just below the confluence with Pond Brook. Relocation of the river channel eliminated mussels from a 0.5 km stretch in eastern Twinsburg. Furthermore, the impact of effluent from a wastewater treatment plant was minor, at most. Mussel diversity diminished from five to three species commonly found below this facility. A change in river habitat to faster flow, however, provided an alternate explanation for this faunal change. The most striking difference was the replacement of Lasmigona costata, a species usually found in medium and large rivers, by L. compressa, a species common in small streams and headwaters

Vascular complications of prosthetic inter-vertebral discs

Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had eroded into the bifurcation of the inferior vena cava and the left common iliac vein. In three cases the aortic bifurcation was also involved. The fibrosis was so severe that dissecting out the arteries and veins to provide access to the relevant disc proved impossible. Formal division of the left common iliac vein and artery with subsequent repair was our solution. Anterior inter-vertebral disc displacement was associated with severe vascular injury. Preventing anterior disc displacement is essential in disc design. In the event of anterior displacement, disc removal should be planned with a Vascular Surgeon

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Phylomemetics—Evolutionary Analysis beyond the Gene

Genes are propagated by error-prone copying, and the resulting variation provides the basis for phylogenetic reconstruction of evolutionary relationships. Horizontal gene transfer may be superimposed on a tree-like evolutionary pattern, with some relationships better depicted as networks. The copying of manuscripts by scribes is very similar to the replication of genes, and phylogenetic inference programs can be used directly for reconstructing the copying history of different versions of a manuscript text. Phylogenetic methods have also been used for some time to analyse the evolution of languages and the development of physical cultural artefacts. These studies can help to answer a range of anthropological questions. We propose the adoption of the term “phylomemetics” for phylogenetic analysis of reproducing non-genetic elements

Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation

IntroductionWe have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor–gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.MethodsMice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study.ResultsWe demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis.DiscussionOur results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients

Presidential Commission on the Supreme Court of the United States Final Report

On April 9, 2021, President Joseph R. Biden, Jr. issued Executive Order 14023 establishing this Commission, to consist of “individuals having experience with and knowledge of the Federal judiciary and the Supreme Court of the United States.” The Order charged the Commission with producing a report for the President that addresses three sets of questions. First, the Report should include “[a]n account of the contemporary commentary and debate about the role and operation of the Supreme Court in our constitutional system and about the functioning of the constitutional process by which the President nominates and, by and with the advice and consent of the Senate, appoints Justices to the Supreme Court.” Second, the Report should consider the “historical background of other periods in the Nation’s history when the Supreme Court’s role and the nominations and advice-and-consent process were subject to critical assessment and prompted proposals for reform.” Third, the Report should provide an analysis of the principal arguments for and against particular proposals to reform the Supreme Court, “including an appraisal of [their] merits and legality,” and should be informed by “a broad spectrum of ideas.” The Report begins by explaining the genesis of today’s Court reform debate, including by identifying developments that gave rise to President Biden’s decision to issue the April 2021 Executive Order, particularly the debates surrounding the most recent nominations. This Introduction emphasizes that the Court’s composition and jurisprudence long have been subjects of public controversy and debate in the nation’s civic life: The Court serves as a crucial guardian of the rule of law and also plays a central role in major social and political conflicts. Its decisions have profound effects on the life of the nation. Though conflict surrounding the processes by which the President nominates and the Senate confirms Justices is not new, it has become more intensely partisan in recent years. The Introduction also articulates three common and interrelated ideas frequently invoked in reform debates and throughout the Chapters of the Report: the importance of protecting or enhancing the Court’s legitimacy; the role of judicial independence in our system of government; and the value of democracy and its relationship to the Supreme Court’s decisionmaking. These important ideas can mean different things to different people. The Introduction discusses the range of meanings ascribed to these terms, with the aim of clarifying how they are deployed in arguments for and against reform

Public, private and personal: Qualitative research on policymakers' opinions on smokefree interventions to protect children in 'private' spaces

<p>Abstract</p> <p>Background</p> <p>Governments use law to constrain aspects of private activities for purposes of protecting health and social wellbeing. Policymakers have a range of perceptions and beliefs about what is public or private. An understanding of the possible drivers of policymaker decisions about where government can or should intervene for health is important, as one way to better guide appropriate policy formation. Our aim was to identify obstacles to, and opportunities for, government smokefree regulation of private and public spaces to protect children. In particular, to seek policymaker opinions on the regulation of smoking in homes, cars and public parks and playgrounds in a country with incomplete smokefree laws (New Zealand).</p> <p>Methods</p> <p>Case study, using structured interviews to ask policymakers (62 politicians and senior officials) about their opinions on new smokefree legislation for public and private places. Supplementary data was obtained from the Factiva media database, on the views of New Zealand local authority councillors about policies for smokefree outdoor public places.</p> <p>Results</p> <p>Overall, interviewees thought that government regulation of smoking in private places was impractical and unwise. However, there were some differences on what <it>was </it>defined as 'private', particularly for cars. Even in public parks, smoking was seen by some as a 'personal' decision, and unlikely to be amenable to regulation. Most participants believed that educative, supportive and community-based measures were better and more practical means of reducing smoking in private places, compared to regulation.</p> <p>Conclusions</p> <p>The constrained view of the role of regulation of smoking in public and private domains may be in keeping with current political discourse in New Zealand and similar Anglo-American countries. Policy and advocacy options to promote additional smokefree measures include providing a better voice for childrens' views, increasing information to policymakers about the harms to children from secondhand smoke and the example of adult smoking, and changing the culture for smoking around children.</p

Demonstration of the innate electrophilicity of 4-(3-(benzyloxy)phenyl)-2-(ethylsulfinyl)-6trifluoromethyl)pyrimidine (BETP), a small molecule positive allosteric modulator of the glucagon-like peptide-1. Drug Metab. Dispos

ABSTRACT 4-(3-(Benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP) represents a novel small-molecule activator of the glucagonlike peptide-1 receptor (GLP-1R), and exhibits glucose-dependent insulin secretion in rats following i.v. (but not oral) administration. To explore the quantitative pharmacology associated with GLP-1R agonism in preclinical species, the in vivo pharmacokinetics of BETP were examined in rats after i.v. and oral dosing. Failure to detect BETP in circulation after oral administration of a 10-mg/kg dose in rats was consistent with the lack of an insulinotropic effect of orally administered BETP in this species. Likewise, systemic concentrations of BETP in the rat upon i.v. administration (1 mg/kg) were minimal (and sporadic). In vitro incubations in bovine serum albumin, plasma, and liver microsomes from rodents and humans indicated a facile degradation of BETP. Failure to detect metabolites in plasma and liver microsomal incubations in the absence of NADP was suggestive of a covalent interaction between BETP and a protein amino acid residue(s) in these matrices. Incubations of BETP with glutathione (GSH) in buffer revealed a rapid nucleophilic displacement of the ethylsulfoxide functionality by GSH to yield adduct M1, which indicated that BETP was intrinsically electrophilic. The structure of M1 was unambiguously identified by comparison of its chromatographic and mass spectral properties with an authentic standard. The GSH conjugate of BETP was also characterized in NADPH-and GSH-supplemented liver microsomes and in plasma samples from the pharmacokinetic studies. Unlike BETP, M1 was inactive as an allosteric modulator of the GLP-1R