Periodic Environmental Disturbance Drives Repeated Ecomorphological Diversification in an Adaptive Radiation of Antarctic Fishes.

AbstractThe ecological theory of adaptive radiation has profoundly shaped our conceptualization of the rules that govern diversification. However, while many radiations follow classic early-burst patterns of diversification as they fill ecological space, the longer-term fates of these radiations depend on many factors, such as climatic stability. In systems with periodic disturbances, species-rich clades can contain nested adaptive radiations of subclades with their own distinct diversification histories, and how adaptive radiation theory applies in these cases is less clear. Here, we investigated patterns of ecological and phenotypic diversification within two iterative adaptive radiations of cryonotothenioid fishes in Antarctica's Southern Ocean: crocodile icefishes and notoperches. For both clades, we observe evidence of repeated diversification into disparate regions of trait space between closely related taxa and into overlapping regions of trait space between distantly related taxa. We additionally find little evidence that patterns of ecological divergence are correlated with evolution of morphological disparity, suggesting that these axes of divergence may not be tightly linked. Finally, we reveal evidence of repeated convergence in sympatry that suggests niche complementarity. These findings reflect the dynamic history of Antarctic marine habitats and may guide hypotheses of diversification dynamics in environments characterized by periodic disturbance.

Phylogenomic Species Delimitation Dramatically Reduces Species Diversity in an Antarctic Adaptive Radiation.

Application of genetic data to species delimitation often builds confidence in delimitations previously hypothesized using morphological, ecological, and geographic data and frequently yields recognition of previously undescribed cryptic diversity. However, a recent critique of genomic data-based species delimitation approaches is that they have the potential to conflate population structure with species diversity, resulting in taxonomic oversplitting. The need for an integrative approach to species delimitation, in which molecular, morphological, ecological, and geographic lines of evidence are evaluated together, is becoming increasingly apparent. Here, we integrate phylogenetic, population genetic, and coalescent analyses of genome-wide sequence data with investigation of variation in multiple morphological traits to delimit species within the Antarctic barbeled plunderfishes (Artedidraconidae: Pogonophryne). Pogonophryne currently comprises 29 valid species, most of which are distinguished solely by variation in the ornamentation of the mental barbel that projects from the lower jaw, a structure previously shown to vary widely within a single species. However, our genomic and phenotypic analyses result in a dramatic reduction in the number of distinct species recognized within the clade, providing evidence to support the recognition of no more than six species. We propose to synonymize 24 of the currently recognized species with five species of Pogonophryne. We find genomic and phenotypic evidence for a new species of Pogonophryne from specimens collected in the Ross Sea. Our findings represent a rare example in which the application of molecular data provides evidence of taxonomic oversplitting on the basis of morphology, clearly demonstrating the utility of an integrative species delimitation framework.[ddRADseq; multispecies coalescent; Notothenioidei; SNPs; Southern Ocean.].

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge.

Many molecular machines are built from modular components with well-defined motile capabilities, such as axles and wheels. Hinges are particularly useful, as they provide the minimum flexibility needed for a simple and pronounced conformational change. Compounds with multiple stable conformers are common, but molecular hinges almost exclusively operate via dihedral rotations rather than truly hinge-like clamping mechanisms. An ideal molecular hinge would better reproduce the behavior of hinged devices, such as gates and tweezers, while remaining soluble, scalable, and synthetically versatile. Herein, we describe two isomeric macrocycles with clamp-like open and closed geometries, which crystallize as separate polymorphs but interconvert freely in solution. An unusual one-pot addition cyclization reaction was used to produce the macrocycles on a multigram scale from inexpensive reagents, without supramolecular templating or high-dilution conditions. Using mechanistic information from NMR kinetic studies and at-line mass spectrometry, we developed a semicontinuous flow synthesis with maximum conversions of 85-93% and over 80% selectivity for a single isomer. The macrocycles feature voids that are sterically protected from guests, including reactive species such as fluoride ions, and could therefore serve as chemically inert hinges for adaptive supramolecular receptors and flexible porous materials.

A Replicable Approach to Promoting Best Practices: Translating Cardiovascular Disease Prevention Research.

OBJECTIVE: Significant delays in translating health care-related research into public health programs and medical practice mean that people may not get the best care when they need it. Regarding cardiovascular disease, translation delays can mean lives may be unnecessarily lost each year. To facilitate the translation of knowledge to action, we created a Best Practices Guide for Cardiovascular Disease Prevention Programs. DESIGN: Using the Rapid Synthesis Translation Process and the Best Practices Framework as guiding frameworks, we collected and rated research evidence for hypertension control and cholesterol management strategies. After identifying best practices, we gathered information about programs that were implementing the practices and about resources useful for implementation. Research evidence and supplementary information were consolidated in an informational resource and published online. Web metrics were collected and analyzed to measure use and reach of the guide. RESULTS: The Best Practices Guide was released in January 2018 and included background information and resources on 8 best practice strategies. It was published as an online resource, publicly accessible from the Centers for Disease Control and Prevention Web site in 2 different formats. Web metrics show that in the first year after publication, there were 25 589 Web page views and 2467 downloads. A query of partner use of the guide indicated that it was often shared in partners' own resources, newsletters, and online material. CONCLUSION: In following a systematic approach to creating the Best Practices Guide and documenting the steps taken in its development, we offer a replicable approach for translating research on health care practices into a resource to facilitate implementation. The success of this approach is attributed to 3 key factors: using a prescribed and documented approach to evidence translation, working closely with stakeholders throughout the process, and prioritizing the content design and accessibility of the final product.

Timing of State and Territorial COVID-19 Stay-at-Home Orders and Changes in Population Movement - United States, March 1-May 31, 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is thought to spread from person to person primarily by the respiratory route and mainly through close contact (1). Community mitigation strategies can lower the risk for disease transmission by limiting or preventing person-to-person interactions (2). U.S. states and territories began implementing various community mitigation policies in March 2020. One widely implemented strategy was the issuance of orders requiring persons to stay home, resulting in decreased population movement in some jurisdictions (3). Each state or territory has authority to enact its own laws and policies to protect the public's health, and jurisdictions varied widely in the type and timing of orders issued related to stay-at-home requirements. To identify the broader impact of these stay-at-home orders, using publicly accessible, anonymized location data from mobile devices, CDC and the Georgia Tech Research Institute analyzed changes in population movement relative to stay-at-home orders issued during March 1-May 31, 2020, by all 50 states, the District of Columbia, and five U.S. territories.* During this period, 42 states and territories issued mandatory stay-at-home orders. When counties subject to mandatory state- and territory-issued stay-at-home orders were stratified along rural-urban categories, movement decreased significantly relative to the preorder baseline in all strata. Mandatory stay-at-home orders can help reduce activities associated with the spread of COVID-19, including population movement and close person-to-person contact outside the household.

Translating Workforce Development Policy Interventions for Community Health Workers: Application of a Policy Research Continuum.

CONTEXT: There is a need for knowledge translation to advance health equity in the prevention and control of cardiovascular disease and type 2 diabetes. One recommended strategy is engaging community health workers (CHWs) to have a central role in related interventions. Despite strong evidence of effectiveness for CHWs, there is limited information examining the impact of state CHW policy interventions. This article describes the application of a policy research continuum to enhance knowledge translation of CHW workforce development policy in the United States. METHODS: During 2016-2019, a team of public health researchers and practitioners applied the policy research continuum, a multiphased systematic assessment approach that incorporates legal epidemiology to enhance knowledge translation of CHW workforce development policy interventions in the United States. The continuum consists of 5 discrete, yet interconnected, phases including early evidence assessments, policy surveillance, implementation studies, policy ratings, and impact studies. RESULTS: Application of the first 3 phases of the continuum demonstrated (1) how CHW workforce development policy interventions are linked to strong evidence bases, (2) whether existing state CHW laws are evidence-informed, and (3) how different state approaches were implemented. DISCUSSION: As a knowledge translation tool, the continuum enhances dissemination of timely, useful information to inform decision making and supports the effective implementation and scale-up of science-based policy interventions. When fully implemented, it assists public health practitioners in examining the utility of different policy intervention approaches, the effects of adaptation, and the linkages between policy interventions and more distal public health outcomes.

Inducing Social Self-Sorting in Organic Cages To Tune The Shape of The Internal Cavity.

Many interesting target guest molecules have low symmetry, yet most methods for synthesising hosts result in highly symmetrical capsules. Methods of generating lower symmetry pores are thus required to maximise the binding affinity in host-guest complexes. Herein, we use mixtures of tetraaldehyde building blocks with cyclohexanediamine to access low-symmetry imine cages. Whether a low-energy cage is isolated can be correctly predicted from the thermodynamic preference observed in computational models. The stability of the observed structures depends on the geometrical match of the aldehyde building blocks. One bent aldehyde stands out as unable to assemble into high-symmetry cages-and the same aldehyde generates low-symmetry socially self-sorted cages when combined with a linear aldehyde. We exploit this finding to synthesise a family of low-symmetry cages containing heteroatoms, illustrating that pores of varying geometries and surface chemistries may be reliably accessed through computational prediction and self-sorting.

Bromelain-based enzymatic debridement of e-cigarette burns: a single unit experience.

OBJECTIVE: It is widely accepted that the early debridement of burns improves outcome. There is increasing evidence that enzymatic debridement is an effective technique for removal of full-thickness and deep-dermal burns, reducing blood loss and often the need for autologous skin grafting by avoiding over excision of the burn. We aim to highlight the potential use of this form of debridement as an alternative to surgical management in patients with electronic cigarette (e-cigarette)-associated flame burn injuries. METHODS: This case series presents the use of Nexobrid (MediWound Ltd, Israel), a non-surgical, bromelain-based enzymatic debridement technique, in patients with deep partial-thickness burns (range: 1-3% total body surface area), avoiding the need for autologous skin grafting. RESULTS: Burn wounds in two patients healed within 14 days without complications or the need for further surgical intervention. Another patient required further dressings after discharge but failed to attend follow-up appointments. These results are comparable with those reported by others using conservative management of e-cigarette burns. CONCLUSION: The authors wish to raise awareness of the potential for a combination of thermal and chemical burns related to e-cigarette explosions. Chemical burns should be excluded by pH testing of the burn wound. From our experience, small e-cigarette-associated flame burns can be considered for management with enzymatic debridement.

Phylogenetic analysis of Antarctic notothenioids illuminates the utility of RADseq for resolving Cenozoic adaptive radiations.

Notothenioids are a clade of ∼120 species of marine fishes distributed in extreme southern hemisphere temperate near-shore habitats and in the Southern Ocean surrounding Antarctica. Over the past 25 years, molecular and morphological approaches have redefined hypotheses of relationships among notothenioid lineages as well as their relationships among major lineages of percomorph teleosts. These phylogenies provide a basis for investigation of mechanisms of evolutionary diversification within the clade and have enhanced our understanding of the notothenioid adaptive radiation. Despite extensive efforts, there remain several questions concerning the phylogeny of notothenioids. In this study, we deploy DNA sequences of ∼100,000 loci obtained using RADseq to investigate the phylogenetic relationships of notothenioids and to assess the utility of RADseq loci for lineages that exhibit divergence times ranging from the Paleogene to the Quaternary. The notothenioid phylogenies inferred from the RADseq loci provide unparalleled resolution and node support for several long-standing problems including, (1) relationships among species of Trematomus, (2) resolution of Indonotothenia cyanobrancha as the sister lineage of Trematomus, (3) the deep paraphyly of Nototheniidae, (4) the paraphyly of Lepidonotothen s.l., (5) paraphyly of Artedidraco, and 6) the monophyly of the Bathydraconidae. Assessment of site rates demonstrates that RADseq loci are similar to mtDNA protein coding genes and exhibit peak phylogenetic informativeness at the time interval during which the major Antarctic notothenioid lineages originated and diversified. In addition to providing a well-resolved phylogenetic hypothesis for notothenioids, our analyses quantify the predicted utility of RADseq loci for Cenozoic phylogenetic inferences.

Investigating the effect of supramolecular gel phase crystallization on gel nucleation.

Supramolecular gel phase crystallization offers a new strategy for drug polymorph screening and discovery. In this method, the crystallization outcome depends on the interaction between solute and gel fibre. While supramolecular gels have shown success in producing new polymorphs and crystals with novel morphologies, role of the gel and nature of gel-solute interaction remains largely unexplored. The present study aims to provide a comprehensive picture of the structural evolution of a supramolecular gel produced from a bis(urea) based gelator (G) in the presence of a polymorphic drug carbamazepine (CBZ). The structural aspects of the gel have been assessed by single crystal X-ray analysis, X-ray powder diffraction (XRPD) and solid state NMR spectroscopy. Small Angle Neutron Scattering (SANS) has been used to follow the changes in gel structure in the presence of CBZ. Visual evidence from morphological study and structural evolution observed at a macroscopic level from rheological measurements, shows good agreement with the SANS results. The concentration of the gelator and the relative proportion of G to CBZ were found to be crucial factors in determining the competitive nucleation events involving gelation and crystallization. At a critical G to CBZ ratio the effect of CBZ on gel structure was maximum and fiber bundling in the gel was found to be critically affected. This study offers important information about how the interplay of gelator assembly and gel-solute interactions can fine-tune the nucleation events in a supramolecular gel phase crystallization.

Pilomatrixoma: A Comprehensive Review of the Literature.

INTRODUCTION: Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a superficial benign skin tumor that arises from hair follicle matrix cells. Although pilomatrixomas are well-recognized lesions, clinically they are frequently misdiagnosed as other skin conditions. By reviewing all the literature over the past 10 years, the aims of this article are to analyze the cause, clinical presentation, management, and outcome of pilomatrixoma among children and adults to gain a more complete understanding of this lesion in today's clinical context. METHODS: A MEDLINE and EMBASE search was conducted from January 2005 to February 2015 using a combination of the terms: "child," "childhood," "adult," and keywords: "pilomatrixoma," "pilomatricoma," and "calcifying epithelioma of Malherbe." A total of 150 articles were reviewed. RESULTS: The lesions occurred most commonly in the first and second decades (mean age 16 years and 7 months). The commonest presentation was of an asymptomatic, firm, slowly growing, mobile nodule. Only 16% were accurately diagnosed on clinical examination. Imaging in the form of ultrasound, computed tomography, and magnetic resonance imaging has been reported. Pathological diagnosis was achieved through incision, punch, and shave biopsies. Pathological findings are discussed and summarized in this review. CONCLUSION: Pilomatrixomas are thought to arise from mutation in the Wnt pathway and has been linked to several genetic conditions. It is commonly misdiagnosed preoperatively; however, with better awareness of the lesion, it can be appropriately treated while avoiding unnecessary diagnostic tests. Complete surgical excision with clear margins is almost always curative.

Gels with sense: supramolecular materials that respond to heat, light and sound.

Advances in the field of supramolecular chemistry have made it possible, in many situations, to reliably engineer soft materials to address a specific technological problem. Particularly exciting are "smart" gels that undergo reversible physical changes on exposure to remote, non-invasive environmental stimuli. This review explores the development of gels which are transformed by heat, light and ultrasound, as well as other mechanical inputs, applied voltages and magnetic fields. Focusing on small-molecule gelators, but with reference to organic polymers and metal-organic systems, we examine how the structures of gelator assemblies influence the physical and chemical mechanisms leading to thermo-, photo- and mechano-switchable behaviour. In addition, we evaluate how the unique and versatile properties of smart materials may be exploited in a wide range of applications, including catalysis, crystal growth, ion sensing, drug delivery, data storage and biomaterial replacement.

Ancient climate change, antifreeze, and the evolutionary diversification of Antarctic fishes.

The Southern Ocean around Antarctica is among the most rapidly warming regions on Earth, but has experienced episodic climate change during the past 40 million years. It remains unclear how ancient periods of climate change have shaped Antarctic biodiversity. The origin of antifreeze glycoproteins (AFGPs) in Antarctic notothenioid fishes has become a classic example of how the evolution of a key innovation in response to climate change can drive adaptive radiation. By using a time-calibrated molecular phylogeny of notothenioids and reconstructed paleoclimate, we demonstrate that the origin of AFGP occurred between 42 and 22 Ma, which includes a period of global cooling approximately 35 Ma. However, the most species-rich lineages diversified and evolved significant ecological differences at least 10 million years after the origin of AFGPs, during a second cooling event in the Late Miocene (11.6-5.3 Ma). This pattern indicates that AFGP was not the sole trigger of the notothenioid adaptive radiation. Instead, the bulk of the species richness and ecological diversity originated during the Late Miocene and into the Early Pliocene, a time coincident with the origin of polar conditions and increased ice activity in the Southern Ocean. Our results challenge the current understanding of the evolution of Antarctic notothenioids suggesting that the ecological opportunity that underlies this adaptive radiation is not linked to a single trait, but rather to a combination of freeze avoidance offered by AFGPs and subsequent exploitation of new habitats and open niches created by increased glacial and ice sheet activity.

Tobacco use among middle and high school students--United States, 2013.

Tobacco use is the leading preventable cause of disease and death in the United States, and nearly all tobacco use begins during youth and young adulthood. Among U.S. youths, cigarette smoking has declined in recent years; however, the use of some other tobacco products has increased, and nearly half of tobacco users use two or more tobacco products. CDC analyzed data from the 2013 National Youth Tobacco Survey to determine the prevalence of ever (at least once) and current (at least 1 day in the past 30 days) use of one or more of 10 tobacco products (cigarettes, cigars, hookahs, smokeless tobacco, electronic cigarettes [e-cigarettes], pipes, snus, bidis, kreteks, and dissolvable tobacco) among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2013, 22.9% of high school students reported current use of any tobacco product, and 12.6% reported current use of two or more tobacco products; current use of combustible products (i.e., cigarettes, cigars, pipes, bidis, kreteks, and/or hookahs) was substantially greater (20.7%) than use of other types of tobacco. Also, 46.0% of high school students reported having ever tried a tobacco product, and 31.4% reported ever trying two or more tobacco products. Among middle school students, 3.1% reported current use of cigars, and 2.9% reported current use of cigarettes, with non-Hispanic black students more than twice as likely to report current use of cigars than cigarettes. Monitoring the prevalence of the use of all available tobacco products, including new and emerging products, is critical to support effective population-based interventions to prevent and reduce tobacco use among youths as part of comprehensive tobacco prevention and control programs.

Deville rebooted - practical N2O5 synthesis.

Dinitrogen pentoxide (N2O5), the anhydride of nitric acid, was synthesised by Henri Étienne Sainte-Claire Deville in Paris in 1849 using silver nitrate and chlorine gas. Herein, we revisit, optimise, and modify Deville's method using photocatalysis to enable a safe, clean, practical, and reproducible alternative for N2O5 synthesis in quantitative yields. Moreover, it is predicted that the modifications can accommodate an industrial scale-up, but the silver chloride generated must be recycled.

Scrolling in Supramolecular Gels: A Designer's Guide.

Gelation by small molecules is a topic of enormous importance in catalysis, nanomaterials, drug delivery, and pharmaceutical crystallization. The mechanism by which gelators self-organize into a fibrous gel network is poorly understood. Herein, we describe the crystal structures and gelation properties of a library of bis(urea) compounds and show, via molecular dynamics simulations, how gelator aggregation progresses from a continuous pattern of supramolecular motifs to a homogeneous fiber network. Our model suggests that lamellae with asymmetric surfaces scroll into uniform unbranched fibrils, while sheets with symmetric surfaces undergo stacking to form crystals. The self-assembly of asymmetric lamellae is associated with specific molecular features, such as the presence of narrow and flexible end groups with high packing densities, and likely represents a general mechanism for the formation of small-molecule gels.

6-hydroxydopamine affects multiple pathways to induce cytotoxicity in differentiated LUHMES dopaminergic neurons.

The debilitating effects of Parkinson's disease (PD) progress over time and are pathophysiologically characterized by the formation of Lewy bodies due to the accumulation of α-synuclein aggregates resulting in the death of dopaminergic neurons. In the present study, we determined cell death pathways activated by acute exposure to 6-hydroxydopamine (6-OHDA) in differentiated LUHMES cells empirically followed by a 24 h toxin free interval, henceforth termed as washout/recovery period. Acute 6-OHDA exposure led to morphological changes in LUHMES cells and resulted in significant loss of neurite length and neurite thickness. Generation of reactive oxygen species and loss of mitochondrial membrane potential in the neuronal processes were persistent even after the recovery period. Our results show that 6-OHDA exposure leads to significant reduction in expression of mitochondrial OXPHOS complexes I, II, and IV and activation of caspase mediated apoptotic cell death cascade as observed by enhanced protein expression of cleaved-PARP-1 and cleaved-Caspase-3. Immunofluorescence microscopy approach confirmed that cell death occurs independent of the AIF translocation to the nucleus. Our experimental model, led to a ∼5-fold lower α-synuclein monomer expression and, interestingly, resulted in loss of protein ubiquitination in whole cell lysates. Altogether, this work provides evidence of multiple pathways targeted by 6-OHDA in differentiated LUHMES cells and expands research avenues for addressing the knowledge gap regarding the effect of 6-OHDA in the ubiquitin proteasome system for PD therapies.

Pyrite footprinting of RNA.

In RNA, function follows form. Mapping the surface of RNA molecules with chemical and enzymatic probes has revealed invaluable information about structure and folding. Hydroxyl radicals ((·)OH) map the surface of nucleic acids by cutting the backbone where it is accessible to solvent. Recent studies showed that a microfluidic chip containing pyrite (FeS(2)) can produce sufficient (·)OH to footprint DNA. The 49-nt Diels-Alder RNA enzyme catalyzes the C-C bond formation between a diene and a dienophile. A crystal structure, molecular dynamics simulation and atomic mutagenesis studies suggest that nucleotides of an asymmetric bulge participate in the dynamic architecture of the ribozyme's active center. Of note is that residue U42 directly interacts with the product in the crystallized RNA/product complex. Here, we use powdered pyrite held in a commercially available cartridge to footprint the Diels-Alderase ribozyme with single nucleotide resolution. Residues C39 to U42 are more reactive to (·)OH than predicted by the solvent accessibility calculated from the crystal structure suggesting that this loop is dynamic in solution. The loop's flexibility may contribute to substrate recruitment and product release. Our implementation of pyrite-mediated (·)OH footprinting is a readily accessible approach to gleaning information about the architecture of small RNA molecules.

Pharmacist Interventions for Medication Adherence: Community Guide Economic Reviews for Cardiovascular Disease.

INTRODUCTION: Adherence to medications for cardiovascular disease and its risk factors is less than optimal, although greater adherence to medication has been shown to reduce the risk factors for cardiovascular disease. This paper examines the economics of tailored pharmacy interventions to improve medication adherence for cardiovascular disease prevention and management. METHODS: Literature from inception of databases to May 2019 was searched, yielding 29 studies for cardiovascular disease prevention and 9 studies for cardiovascular disease management. Analyses were done from June 2019 through May 2020. All monetary values are in 2019 U.S. dollars. RESULTS: The median intervention cost per patient per year was $246 for cardiovascular disease prevention and $292 for cardiovascular disease management. The median change in healthcare cost per person per year due to the intervention was -$355 for cardiovascular disease prevention and -$2,430 for cardiovascular disease management. The median total cost per person per year was -$89 for cardiovascular disease prevention, with a median return on investment of 0.01. The median total cost per person per year for cardiovascular disease management was -$1,080, with a median return on investment of 7.52, and 6 of 7 estimates indicating reduced healthcare cost averted exceeded intervention cost. For cardiovascular disease prevention, the median cost per quality-adjusted life year gained was $11,298. There were no cost effectiveness studies for cardiovascular disease management. DISCUSSION: The evidence shows that tailored pharmacy-based interventions to improve medication adherence are cost effective for cardiovascular disease prevention. For cardiovascular disease management, healthcare cost averted exceeds the cost of implementation for a favorable return on investment from a healthcare systems perspective.