Temperature pervasively impacts the phenotypes and distributions of organisms. These thermal effects generate strong selective pressures on behaviour, physiology, and life history when environmental ...temperatures vary over space and time. Despite this fact, progress toward a quantitative theory of thermal adaptation has lagged behind empirical descriptions of patterns and processes. This book draws on current evolutionary paradigms (optimization, quantitative genetics, and genetic algorithms) to establish a theory of thermal adaptation. It initially focuses on simple models that describe the evolution of thermosensitivity, thermoregulation, or acclimation. Later chapters focus on more complex models describing the coadaptation of traits or the coevolution of species. Throughout the book, various lines of evidence are used to question the major assumptions of these models. Furthermore, the predictions of these models are confronted with experimental and comparative data. Empirical examples represent a wide range of taxa, including bacteria, plants, fungi, and animals. The result is a synthesis of theoretical and empirical studies of thermal biology that offers insights about evolutionary processes.
The messenger RNA (mRNA)-based vaccines BNT162b2 and mRNA-1273 are more than 90% effective against coronavirus disease 2019 (Covid-19). However, their comparative effectiveness for a range of ...outcomes across diverse populations is unknown.
We emulated a target trial using the electronic health records of U.S. veterans who received a first dose of the BNT162b2 or mRNA-1273 vaccine between January 4 and May 14, 2021, during a period marked by predominance of the SARS-CoV-2 B.1.1.7 (alpha) variant. We matched recipients of each vaccine in a 1:1 ratio according to their risk factors. Outcomes included documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, symptomatic Covid-19, hospitalization for Covid-19, admission to an intensive care unit (ICU) for Covid-19, and death from Covid-19. We estimated risks using the Kaplan-Meier estimator. To assess the influence of the B.1.617.2 (delta) variant, we emulated a second target trial that involved veterans vaccinated between July 1 and September 20, 2021.
Each vaccine group included 219,842 persons. Over 24 weeks of follow-up in a period marked by alpha-variant predominance, the estimated risk of documented infection was 5.75 events per 1000 persons (95% confidence interval CI, 5.39 to 6.23) in the BNT162b2 group and 4.52 events per 1000 persons (95% CI, 4.17 to 4.84) in the mRNA-1273 group. The excess number of events per 1000 persons for BNT162b2 as compared with mRNA-1273 was 1.23 (95% CI, 0.72 to 1.81) for documented infection, 0.44 (95% CI, 0.25 to 0.70) for symptomatic Covid-19, 0.55 (95% CI, 0.36 to 0.83) for hospitalization for Covid-19, 0.10 (95% CI, 0.00 to 0.26) for ICU admission for Covid-19, and 0.02 (95% CI, -0.06 to 0.12) for death from Covid-19. The corresponding excess risk (BNT162b2 vs. mRNA-1273) of documented infection over 12 weeks of follow-up in a period marked by delta-variant predominance was 6.54 events per 1000 persons (95% CI, -2.58 to 11.82).
The 24-week risk of Covid-19 outcomes was low after vaccination with mRNA-1273 or BNT162b2, although risks were lower with mRNA-1273 than with BNT162b2. This pattern was consistent across periods marked by alpha- and delta-variant predominance. (Funded by the Department of Veterans Affairs and others.).
This book is intended for use by natural resource managers and scientists, and students in the fields of natural resource management, ecology, and conservation biology, who are confronted with ...complex and difficult decision making problems. The book takes readers through the process of developing a structured approach to decision making, by firstly deconstructing decisions into component parts, which are each fully analyzed and then reassembled to form a working decision model. The book integrates common-sense ideas about problem definitions, such as the need for decisions to be driven by explicit objectives, with sophisticated approaches for modeling decision influence and incorporating feedback from monitoring programs into decision making via adaptive management. Numerous worked examples are provided for illustration, along with detailed case studies illustrating the authors’ experience in applying structured approaches. There is also a series of detailed technical appendices. An accompanying website provides computer code and data used in the worked examples.Additional resources for this book can be found at:www.wiley.com/go/conroy/naturalresourcemanagement.
Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from ...6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.
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•Malawian mothers with undernourished infants have decreased milk oligosaccharides•Sialylated milk sugars promote growth of animals colonized with infant microbiota•Growth promotion does not occur with provision of inulin or in germ-free mice•Sialylated oligosaccharides impact liver, muscle, and brain metabolism
Two preclinical models for infant undernutrition establish a link between consumption of sialylated milk oligosaccharides, the gut microbiota, and healthy growth.
Background Our primary objective was to demonstrate the utility and feasibility of the intraoperative assessment of colon and rectal perfusion using fluorescence angiography (FA) during left-sided ...colectomy and anterior resection. Anastomotic leak (AL) after colorectal resection increases morbidity, mortality, and, in cancer cases, recurrence rates. Inadequate perfusion may contribute to AL. The PINPOINT Endoscopic Fluorescence Imaging System allows for intraoperative assessment of anastomotic perfusion. Study Design This is a prospective, multicenter, open-label, clinical trial that assessed the feasibility and utility of FA for intraoperative perfusion assessment during left-sided colectomy and anterior resection at 11 centers in the United States. Results A total of 147 patients were enrolled, of whom 139 were eligible for analysis. Diverticulitis (44%), rectal cancer (25%), and colon cancer (21%) were the most prevalent indications for surgery. The mean level of anastomosis was 10 ± 4 cm from the anal verge. Splenic-flexure mobilization was performed in 81% and high ligation of the inferior mesenteric artery in 61.9% of patients. There was a 99% success rate for FA, and FA changed surgical plans in 11 (8%) patients, with the majority of changes occurring at the time of transection of the proximal margin (7%). Overall morbidity rates were 17%. The anastomotic leak rate was 1.4% (n = 2). There were no anastomotic leaks in the 11 patients who had a change in surgical plan based on intraoperative perfusion assessment with FA. Conclusions PINPOINT is a safe and feasible tool for intraoperative assessment of tissue perfusion during colorectal resection. There were no anastomotic leaks in patients in whom the anastomosis was revised based on inadequate perfusion with FA.
We review the empirical phylogenetic literature on plant diversification, highlighting challenges in separating the effects of speciation and extinction, in specifying diversification mechanisms, and ...in making convincing arguments. In recent discussions of context dependence, key opportunities and landscapes, and indirect effects and lag times, we see a distinct shift away from single-point/single-cause ‘key innovation’ hypotheses toward more nuanced explanations involving multiple interacting causal agents assembled step-wise through a tree. To help crystalize this emerging perspective we introduce the term ‘synnovation’ (a hybrid of ‘synergy’ and ‘innovation’) for an interacting combination of traits with a particular consequence (‘key synnovation’ in the case of increased diversification rate), and the term ‘confluence’ for the sequential coming together of a set of traits (innovations and synnovations), environmental changes, and geographic movements along the branches of a phylogenetic tree. We illustrate these concepts using the radiation of Bromeliaceae. We also highlight the generality of these ideas by considering how rate heterogeneity associated with a confluence relates to the existence of particularly species-poor lineages, or ‘depauperons.’ Many challenges are posed by this re-purposed research framework, including difficulties associated with partial taxon sampling, uncertainty in divergence time estimation, and extinction.
Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at ...multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established.
Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal ...replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
In this deeply researched prequel to his 2006 study Rough Justice: Lynching and American Society, 1874-1947, Michael J. Pfeifer analyzes the foundations of lynching in American social history. ...Scrutinizing the vigilante movements and lynching violence that occurred in the middle decades of the nineteenth century on the Southern, Midwestern, and far Western frontiers, The Roots of Rough Justice: Origins of American Lynching offers new insights into collective violence in the pre-Civil War era. _x000B__x000B_Pfeifer examines the antecedents of American lynching in an early modern Anglo-European folk and legal heritage. He addresses the transformation of ideas and practices of social ordering, law, and collective violence in the American colonies, the early American Republic, and especially the decades before and immediately after the American Civil War. His trenchant and concise analysis anchors the first book to consider the crucial emergence of the practice of lynching slaves in antebellum America. Pfeifer also leads the way in analyzing the history of American lynching in a global context, from the early modern British Atlantic to the legal status of collective violence in contemporary Latin America and sub-Saharan Africa. _x000B__x000B_Seamlessly melding source material with apt historical examples, The Roots of Rough Justice tackles the emergence not only of the rhetoric surrounding lynching, but of its practice and ideology. Arguing that the origins of lynching cannot be restricted to any particular region, Pfeifer shows how the national and transatlantic context is essential for understanding how whites used mob violence to enforce the racial and class hierarchies across the United States.
Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between ...typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.
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•Mice harboring human ASD, but not TD, microbiomes exhibit ASD-like behaviors•ASD and TD microbiota produce differential metabolome profiles in mice•Extensive alternative splicing of risk genes in brains of mice with ASD microbiota•BTBR mice treated with 5AV or taurine improved repetitive and social behaviors
Repetitive and social behavioral abnormalities in mice with microbiomes from patients with autism spectrum disorder can be corrected by the administration of specific metabolites.
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