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Objectives: To determine the impact of cardiorespiratory fitness (CRF) on physiological and performance outcomes during a 120-m vertical high-rise ascent in firefighters with CRF levels at or above (higher-fit) and below (lower-fit [LF]) the national recommended minimum physical employment standard (VO2max 42.3 mL·kg-1·min-1). Methods: Twenty-eight firefighters completed two high-rise firefighting trials (continuous and discontinuous ascent with predetermined 1-minute rest breaks). Task time, heart rate, ratings of perceived exertion, core body temperature, and thermal comfort were recorded at predetermined elevations. Results: Task time was significantly longer in both trials for the LF group. Ratings of perceived exertion and thermal comfort were also significantly higher in the LF group, with three times more LF firefighters being unable to complete the ascent without sounding their low-air alarm. Conclusions: Higher CRF improves performance and efficiency during stair-climbing in simulated high-rise firefighting tasks. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to determine the physiological effects of breathing apparatus and ascent strategies during a simulated 120-m vertical high-rise firefighting ascent. Methods: Twenty-eight firefighters completed four high-rise firefighting trials wearing standard- or extended-duration breathing apparatus with continuous ascent (SDBA-C/EDBA-C) or with breaks (SDBA-B/EDBA-B). Task time, heart rate, ratings of perceived exertion, core body temperature, and thermal comfort were recorded at predetermined elevations. Results: Task time took significantly longer during the EDBA-C compared with SDBA-C trial. Heart rate (at 40, 80, and 100 m) was significantly lower in trials following breaks compared with the continuous trials. Core body temperature rose by 0.11°C every 10 m of ascent. During the SDBA trials, 89% to 96% of firefighters activated their low air alarm compared with only 7% in EDBA. Conclusions Firefighters should wear EDBA beyond 80 m of ascent and are encouraged to take regular breaks. [ABSTRACT FROM AUTHOR]

The identification of genomic loci that are associated with osteoarthritis (OA) has provided a starting point for understanding how genetic variation activates catabolic processes in the joint. However, genetic variants can only alter gene expression and cellular function when the epigenetic environment is permissive to these effects. In this review, we provide examples of how epigenetic shifts at distinct life stages can alter the risk for OA, which we posit is critical for the proper interpretation of genomewide association studies (GWAS). During development, intensive work on the growth and differentiation factor 5 (GDF5) locus has revealed the importance of tissue-specific enhancer activity in controlling both joint development and the subsequent risk for OA. During homeostasis in adults, underlying genetic risk factors may help establish beneficial or catabolic "set points" that dictate tissue function, with a strong cumulative effect on OA risk. During aging, methylation changes and the reorganization of chromatin can "unmask" the effects of genetic variants. The destructive function of variants that alter aging would only mediate effects after reproductive competence and thus avoid any evolutionary selection pressure, as consistent with larger frameworks of biological aging and its relationship to disease. A similar "unmasking" may occur during OA progression, which is supported by the finding of distinct expression quantitative trait loci (eQTLs) in chondrocytes depending on the degree of tissue degradation. Finally, we propose that massively parallel reporter assays (MPRAs) will be a valuable tool to test the function of putative OA GWAS variants in chondrocytes from different life stages. [ABSTRACT FROM AUTHOR]

To address large gaps in our understanding of the molecular regulation of articular and growth plate cartilage development in humans, we used our directed differentiation approach to generate these distinct cartilage tissues from human embryonic stem cells. The resulting transcriptomic profiles of hESC-derived articular and growth plate chondrocytes were similar to fetal epiphyseal and growth plate chondrocytes, with respect to genes both known and previously unknown to cartilage biology. With the goal to characterize the regulatory landscapes accompanying these respective transcriptomes, we mapped chromatin accessibility in hESC-derived chondrocyte lineages, and mouse embryonic chondrocytes, using ATAC-sequencing. Integration of the expression dataset with the differentially accessible genomic regions revealed lineage-specific gene regulatory networks. We validated functional interactions of two transcription factors (TFs) (RUNX2 in growth plate chondrocytes and RELA in articular chondrocytes) with their predicted genomic targets. The maps we provide thus represent a framework for probing regulatory interactions governing chondrocyte differentiation. This work constitutes a substantial step towards comprehensive and comparative molecular characterizations of distinct chondrogenic lineages and sheds new light on human cartilage development and biology. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the impact of natural selection on human-specific pelvic morphology. Topics explored include the genetic factors which may have contributed to the anatomical changes observed in the human pelvis, comparison between humans, chimpanzees, and gorillas in terms of pelvic morphology, and the epigenomic and transcriptomic features of human pelvic chondrocyte development.

This memoir recounts the author’s first meetings with David Soren in Tunis and Rome during the summer of 1970. It also records an influential visit to the Roman apartment of a major artist and collector of Etruscan antiquities, Eugene Berman (1899–1972), that same summer and gives a brief description of the collection, now the property of the Italian State. Finally it shows how that visit helped to set the author on a path that would lead to his career as an Etruscologist. [ABSTRACT FROM AUTHOR]

Abstract: Two original in situ HF techniques of dielectric characterization in two wide bands have been developed in order to estimate the moisture content of soils by complex impedance measurement. These techniques are based on the capacitive effect (1–20MHz) and on the propagation of electromagnetic waves at high frequencies (0.1–4GHz). The two measurement techniques use straight conductors that are inserted into the soil. Specific inversion algorithms were developed to estimate the apparent real permittivity of the soil versus frequency from the complex impedance. The validation of both instruments was made in the laboratory in the presence of dry and wet sands. In situ experiments were also made at high frequencies. These complementary devices should enlarge the range of usual soil moisture measurement techniques. [Copyright &y& Elsevier]

A critical element in China's current economic reform program is the creation of modern corporate governance structures in its corporations. Many of China's largest firms are caught between market incentives and political pressures, creating a situation ripe for managerial inefficiency. This article examines the financial and regulatory structures necessary for an efficient corporate governance system to function in China, and it assesses how these structures currently operate in the economy. The article identifies key failures in fostering modern corporate governance practices, which in turn jeopardize central elements of the government's reform program. The article includes a case study of the governance practices of PetroChina Company Ltd, the internationally listed subsidiary of China National Petroleum Corporation. The success or failure of the government's efforts to create proper governance mechanisms will carry important economic and political ramifications for China. Indeed, the successful implementation of corporate governance reforms may mark the final stages of China's evolution into a market economy. [ABSTRACT FROM AUTHOR]

The article assesses the contribution of mass deacidification treatments in contrast to cold storage treatments on paper stability. Some ideas and deliberations are given how to evaluate the benefit of deacidification method of library and archives preservation in comparison to the benefit of other relevant methods (e.g. cold storage) and to the risks for documents in libraries and archives. Cold storage represents another approach to stabilizing books and documents but its effectiveness comes from slowing down the rate of chemical reactions rather than by preventing the reactions from occurring, which is a merit of deacidification treatments.

The electrical contact resistance at the interface between two materials is often an unknown when modelling certain processes, such as the anodes and cathodes in Hall–He´roult cells or the spot welding of sheet metal. In this paper, a 2D axisymmetric weakly coupled thermo-electro-mechanical finite element methodology built in the commercial code ANSYS is presented. It allows the generation of Joule heat directly at the interface, the precise representation of the contact areas as well as the testing of different contact resistance models. Using existing experimental results of industrial carbon and steel cylinders in contact at different temperatures, a novel phenomenological constitutive law for electrical contact resistance was developed. This experiment was repeated at room temperature with Alcoa-Lauralco carbon and cast iron cylinders, and the 2D finite element model was used to validate and calibrate the constitutive law. An excellent agreement was found between the model predictions and the new experimental data. [Copyright &y& Elsevier]

Niuhuang is a commonly used Chinese traditional medicine with immunoregulatory and anti-inflammatory properties. Deoxycholic acid (DCA) is a major active constituent of Niuhuang. The reaction of human leukocytes to chemoattractants is an important part of the host immune response and also plays a crucial role in the development of inflammation. We, therefore, investigated the in vitro effects of DCA on human monocyte and neutrophil responses to classic chemoattractants [fMet-Leu-Phe (fMLP), complement fraction 5a (C5a)], CC chemokine [monocyte chemoattractant protein-1 (MCP-1/CCL2)], and/or CXC chemokines [stromal cell-derived factor-1 (SDF-1α/CXCL12), interleukin-8 (IL-8/CXCL8)]. The results showed that DCA significantly inhibited fMLP-induced monocyte and neutrophil chemotaxis and calcium mobilization, and also blocked the binding of [3H]fMLP and anti-formyl peptide receptor (FPR) monoclonal antibodies (mAb) to the cells. The inhibitory effects of DCA on calcium mobilization and anti-FPR-mAb binding to the receptor could be abrogated by washing DCA out of the cell suspension, suggesting that DCA blocked fMLP receptors via a steric hindrance mechanism, not via receptor internalization. DCA had no significant inhibitory effects on MCP-1-, SDF-1α-, or C5a-induced monocyte function, or C5a- or IL-8-induced neutrophil function. Taken together, our experimental results suggest that blockade of fMLP receptors may contribute to the anti-inflammatory effects of traditional medicine containing DCA. [Copyright &y& Elsevier]

The proximate mechanisms by which physical activity (PA) slows senescence and decreases morbidity and mortality have been extensively documented. However, we lack an ultimate, evolutionary explanation for why lifelong PA, particularly during middle and older age, promotes health. As the growing worldwide epidemic of physical inactivity accelerates the prevalence of noncommunicable diseases among aging populations, integrating evolutionary and biomedical perspectives can foster new insights into how and why lifelong PA helps preserve health and extend lifespans. Building on previous life-history research, we assess the evidence that humans were selected not just to live several decades after they cease reproducing but also to be moderately physically active during those postreproductive years. We next review the longstanding hypothesis that PA promotes health by allocating energy away from potentially harmful overinvestments in fat storage and reproductive tissues and propose the novel hypothesis that PA also stimulates energy allocation toward repair and maintenance processes. We hypothesize that selection in humans for lifelong PA, including during postreproductive years to provision offspring, promoted selection for both energy allocation pathways which synergistically slow senescence and reduce vulnerability to many forms of chronic diseases. As a result, extended human health spans and lifespans are both a cause and an effect of habitual PA, helping explain why lack of lifelong PA in humans can increase disease risk and reduce longevity [ABSTRACT FROM AUTHOR]

During human evolution, the knee adapted to the biomechanical demands of bipedalism by altering chondrocyte developmental programs. This adaptive process was likely not without deleterious consequences to health. Today, osteoarthritis occurs in 250 million people, with risk variants enriched in non-coding sequences near chondrocyte genes, loci that likely became optimized during knee evolution. We explore this relationship by epigenetically profiling joint chondrocytes, revealing ancient selection and recent constraint and drift on knee regulatory elements, which also overlap osteoarthritis variants that contribute to disease heritability by tending to modify constrained functional sequence. We propose a model whereby genetic violations to regulatory constraint, tolerated during knee development, lead to adult pathology. In support, we discover a causal enhancer variant (rs6060369) present in billions of people at a risk locus (GDF5 - UQCC1), showing how it impacts mouse knee-shape and osteoarthritis. Overall, our methods link an evolutionarily novel aspect of human anatomy to its pathogenesis. • Human/mouse long bone chondrocyte ATAC-seq reveals site-specific regulatory elements • Ancient positive and purifying selection shape human knee regulation and morphology • Modern human drift and pleiotropy violate regulatory constraint conferring OA risk • Validation at GDF5 reveals a single regulatory variant impacting both shape and OA Epigenetic profiling of chondrocytes reveals selection and constraint on knee regulatory elements including those overlapping osteoarthritis risk variants, including a functionally verified common enhancer variant sufficient to affect knee shape in mouse. [ABSTRACT FROM AUTHOR]

Over-consumption of fructose in adults and children has been linked to increased risk of non-alcoholic fatty liver disease (NAFLD). Recent studies have highlighted the effect of fructose on liver inflammation, fibrosis, and immune cell activation. However, little work summarizes the direct impact of fructose on macrophage infiltration, phenotype, and function within the liver. We demonstrate that chronic fructose diet decreased Kupffer cell populations while increasing transitioning monocytes. In addition, fructose increased fibrotic gene expression of collagen 1 alpha 1 (Col1a1) and tissue metallopeptidase inhibitor 1 (Timp1) as well as inflammatory gene expression of tumor necrosis factor alpha (Tnfa) and expression of transmembrane glycoprotein NMB (Gpnmb) in liver tissue compared to glucose and control diets. Single cell RNA sequencing (scRNAseq) revealed fructose elevated expression of matrix metallopeptidase 12 (Mmp12), interleukin 1 receptor antagonist (Il1rn), and radical S-adenosyl methionine domain (Rsad2) in liver and hepatic macrophages. In vitro studies using IMKC and J774.1 cells demonstrated decreased viability when exposed to fructose. Additionally, fructose increased Gpnmb, Tnfa, Mmp12, Il1rn, and Rsad2 in unpolarized IMKC. By mass spectrometry, C13 fructose tracing detected fructose metabolites in glycolysis and the pentose phosphate pathway (PPP). Inhibition of the PPP further increased fructose induced Il6, Gpnmb, Mmp12, Il1rn, and Rsad2 in nonpolarized IMKC. Taken together, fructose decreases cell viability while upregulating resolution and anti-inflammatory associated genes in Kupffer cells. [ABSTRACT FROM AUTHOR]

Pollination services are affected by landscape context, farming management and pollinator community structure, all of which impact flower visitation rates, pollen deposition and final production. We studied these processes in Argentina for highbush blueberry crops, which depend on pollinators to produce marketable yields.We studied how land cover and honeybee stocking influence the abundance of wild and managed pollinators in blueberry crops, using structural equation modelling to disentangle the cascading effects through which pollinators contribute to blueberry fruit number, size, nutritional content and overall yield.All pollinator functional groups responded to landscape changes at a spatial scale under 1000 m, and the significance or direction of the effects were modulated by the field‐level deployment of honeybee hives.Fruit diameter increased with pollen deposited, but decreased with honeybee abundance, which, had indirect effects on fruit acidity. Honeybees had a positive effect on the number of fruit produced by the plants and also benefited the overall yield (kg plant−1) through independent effects on both the quality and quantity components of fruit production.Synthesis and applications. Deployment of beehives in blueberry fields can buffer, but not compensate for the negative effects on honeybee abundance produced by surrounding large scale none‐flowering crops. Such compensation would require high‐quality beehives by monitoring their health and strength. The contribution of honeybees to crop production is not equal across production metrics. That is, higher abundance of honeybees increases the number of berries produced but at the cost of smaller and more acidic fruits, potentially reducing their market value. Growers must consider this trade‐off between fruit quantity and quality when actively managing honeybee abundance. [ABSTRACT FROM AUTHOR]

Background: The ongoing COVID-19 pandemic has spread across 188 countries and claimed over 300,000 lives so far. Despite strong public health messaging and strict community restrictions in Canada, misconceptions and high-risk behaviours such as mass public gatherings have contributed to its spread across the country. Local data on the knowledge, attitudes, and practices from high-case areas could inform public health messaging during the current unprecedented pandemic. Study Objective: To collate and describe the knowledge, attitudes, and practices of highly affected Canadian communities related to the COVID-19 pandemic and to evaluate factors associated with risky behaviours in order to inform public health policies and communication. Methods and Study Design: Information on COVID-19 knowledge, attitudes, and practices was collected via online convenience sampling from 1,593 Canadians between 6 to 26 April, 2020. The high outbreak provinces of Alberta and Ontario were targeted. Findings: While knowledge of COVID-19 transmission and prevention was high (mean knowledge score of 10.5/12 (88%)), a significant minority of respondents (32%) expressed at least one attitude resistant to public messaging that could hamper containment efforts: visiting crowded places other than grocery stores or pharmacies, close encounters with non-household members, and intention not to isolate if having mild flu symptoms, or known COVID-19 exposure. Factors associated with these risky behaviours included low COVID-19 knowledge (OR 1.2 (95% CI 1.1-1.3), p=0.0057), feeling not worried (OR 2.9 (95% CI 2.2-3.9), p<0.001), and feeling uninformed about the pandemic (OR 1.6 (95% CI 1.1-2.3), p=0.030). Respondents reported high acceptance of a potential vaccine (93%) and endorsed a wide-spread vaccination strategy (81%). Interpretation: Low levels of knowledge and worry regarding COVID-19 may be key contributors to resistance against public health messaging. A potential vaccine, if made available to the general public, would likely be widely accepted. [ABSTRACT FROM AUTHOR]

South Carolina coastal and inland wetlands are continentally important to resident, migrating, and wintering dabbling ducks (Anatini), diving and sea ducks (Aythini, Mergini, Oxyurini), pelagic waterbirds (Anhingidae, Laridae, Pelicanidae, and Phalcrocoracidae), and wading birds (Ardeidaie, Ciconiidae, Threskiornithidae). Our goal was to model wetland selection of these waterbird guilds in South Carolina during autumn–winter to determine habitat preferences and guide wetland conservation and restoration amid sea‐level rise and other coastal pressures. We conducted aerial surveys and recorded waterbird occurrence and relative abundance in winters 2017–2019. We modeled waterbird–habitat relationships relative to managed and unmanaged coastal and inland wetlands, legally protected conservation lands (e.g. federal, state, and private easements), and habitat diversity. Waterbirds selected a variety of wetlands emphasizing the importance of wetland diversity within habitat complexes. However, only managed tidal impoundments (MTIs) and protected conservation lands were selected across all waterbird guilds. Results suggest these are contemporary keystone habitats for promoting wintering waterbird abundance and diversity in South Carolina and other South Atlantic coastal regions. To compensate for future coastal wetland loss while facilitating the current and future needs of migrating and wintering waterbirds, we recommend: (1) identification and continued management of MTIs resilient to sea‐level rise; (2) strategic planning and partnerships for land acquisition and legal protections inland; and (3) land protection networks between extant coastal and inland sites designated for future construction and emigration of decommissioned MTIs. Stakeholder and partner engagement is paramount to prioritize resource allocation for the restoration, construction, and decommissioning of coastal and inland wetlands. [ABSTRACT FROM AUTHOR]

Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus' impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

Motivation: Spatially clustered mutations within specific regions of protein structure are thought to result from strong positive selection for altered protein functions and are a common feature of oncoproteins in cancer. Although previous studies have used spatial substitution clustering to identify positive selection between pairs of proteins, the ability of this approach to identify functional shifts in protein phylogenies has not been explored. Results: We implemented a previous measure of spatial substitution clustering (the P3D statistic) and extended it to detect spatially clustered substitutions at specific branches of phylogenetic trees. We then applied the analysis to 423 690 phylogenetic branches from 9261 vertebrate protein families, and examined its ability to detect historical shifts in protein function. Our analysis identi- fied 19 607 lineages from 5362 protein families in which substitutions were spatially clustered on protein structures at P3D<0.01. Spatially clustered substitutions were overrepresented among ligand-binding residues and were significantly enriched among particular protein families and functions including C2H2 transcription factors and protein kinases. A small but significant proportion of branches with spatially clustered substitution also were under positive selection according to the branch-site test. Lastly, exploration of the top-scoring candidates revealed historical substitution events in vertebrate protein families that have generated new functions and protein interactions, including ancient adaptations in SLC7A2, PTEN, and SNAP25. Ultimately, our work shows that lineage-specific, spatially clustered substitutions are a useful feature for identifying functional shifts in protein families, and reveal new candidates for future experimental study. [ABSTRACT FROM AUTHOR]

BACKGROUND: We developed the Tobacco Prevention Toolkit (Toolkit) to enhance the impact of school‐based tobacco education. This study describes the process of developing the Toolkit, its contents, and reach. METHODS: Qualitative community‐based participatory research (CBPR), including focus group discussions (N = 152) and working groups with parents, educators, researchers, and youth (N = 87) were used to develop the Toolkit and design its implementation. Toolkit reach was assessed through number of trained educators using the Toolkit, estimated number of youth recipients of the Toolkit resources, and using Google Analytics for online engagement. RESULTS: The Toolkit is a free, online resource aimed at preventing tobacco use by middle and high school students. Toolkit content addresses varied forms of tobacco including electronic cigarettes, hookah, smokeless tobacco, and cigarettes; addiction; and positive youth development; and is available in multiple interactive formats such as real‐time quizzes, factsheets, activities, and presentations. The Toolkit is mainly delivered by trained educators, who adapt its content and duration to tailor their drug prevention teaching to student needs. As of April 2020, when data for this paper were collected, 4,750 educators have reached an estimated 1.3 million youth. The Toolkit website has 186,116 users and 802,602 page views, growing steadily since 2016. As of August 2021, additional students have been reached, for now a total of 1.85 million students reached. CONCLUSION: The Toolkit resources are evidence‐based, comprehensive, responsive, interactive, easily accessible, and flexible. Applying CBPR was instrumental in developing the Toolkit and expanding its reach. [ABSTRACT FROM AUTHOR]

Questions: Given the growing abundance and dominance of domestic herbivores in savannah ecosystems, can trees maintain plant herbaceous standing biomass under increasing herbivore pressure? Are there differences in the capacity of leguminous and non‐leguminous trees in sustaining understory herbaceous biomass? And finally, to what extent does plant community composition underneath trees modulate the effects of herbivore assemblage and abundance on herbaceous biomass? Location: Pasturelands and protected areas along the borders of the Serengeti National Park, Tanzania, East Africa. Method: Monthly herbaceous biomass was monitored non‐destructively using a calibrated pasture disc. Measurements were taken within a network of paired exclosures and open plots, underneath large leguminous and non‐leguminous tree canopies and outside canopies. Herbivore community assemblage compositions and abundances were characterised using monthly dung counts, and herbaceous plant community composition was surveyed annually every wet season over two years. Results: Overall, we found that trees promote herbaceous standing biomass, particularly in the presence of moderate herbivory rather than under herbivore exclusion. Greater herbivore abundance and livestock dominance reduced herbaceous plant biomass, but trees, particularly leguminous trees, limited these negative effects. This capacity for trees to limit the effect of herbivores was related to herbaceous plant species composition. Understory plant communities that were compositionally typical of protected areas sustained the highest plant biomass when found in pasturelands with high herbivore pressure. Conclusion: Our findings give greater credence to the importance of preserving large trees in savannah landscapes increasingly dominated by high abundances of livestock. Moreover, our results highlight that park managers and pastoralists need to maintain the specialist herbaceous understory community beneath trees in order to benefit from facilitative tree–understory interactions. [ABSTRACT FROM AUTHOR]

GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. To uncover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology, are enriched at height GWAS loci, particularly near differentially expressed growth plate genes, and enriched for binding motifs of transcription factors with roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at CHSY1, we identified a candidate causal variant (rs9920291) overlapping an open chromatin region. Reporter assays demonstrated that rs9920291 shows allelic regulatory activity, and CRISPR/Cas9 targeting of human chondrocytes demonstrates that the region regulates CHSY1 expression. Thus, integrating biologically relevant epigenetic information (here, from growth plates) with genetic association results can identify biological mechanisms important for human growth. [ABSTRACT FROM AUTHOR]