Open models for removal data

Individuals of protected species, such as amphibians and reptiles, often need to be removed from sites before development commences. Usually, the population is considered to be closed. All individuals are assumed to i) be present and available for detection at the start of the study period and ii) remain at the site until the end of the study, unless they are detected. However, the assumption of population closure is not always valid. We present new removal models which allow for population renewal through birth and/or immigration, and population depletion through sampling as well as through death/emigration. When appropriate, productivity may be estimated and a Bayesian approach allows the estimation of the probability of total population depletion. We demonstrate the performance of the models using data on common lizards, Zootoca vivipara, and great crested newts, Triturus cristatus

Basement membrane ligands initiate distinct signalling networks to direct cell shape

Cells have evolved mechanisms to sense the composition of their adhesive microenvironment. Although much is known about general mechanisms employed by adhesion receptors to relay signals between the extracellular environment and the cytoskeleton, the nuances of ligand-specific signalling remain undefined. Here, we investigated how glomerular podocytes, and four other basement membrane-associated cell types, respond morphologically to different basement membrane ligands. We defined the composition of the respective adhesion complexes using mass spectrometry-based proteomics. On type IV collagen, all epithelial cell types adopted a round morphology, with a single lamellipodium and large adhesion complexes rich in actin-binding proteins. On laminin (511 or 521), all cell types attached to a similar degree but were polygonal in shape with small adhesion complexes enriched in endocytic and microtubule-binding proteins. Consistent with their distinctive morphologies, cells on type IV collagen exhibited high Rac1 activity, while those on laminin had elevated PKCα. Perturbation of PKCα was able to interchange morphology consistent with a key role for this pathway in matrix ligand-specific signalling. Therefore, this study defines the switchable basement membrane adhesome and highlights two key signalling pathways within the systems that determine distinct cell morphologies. Proteomic data are availableviaProteomeXchange with identifier PXD017913

Biomass and Productivity of Thalassia testudinum in Estuaries of the Florida Panhandle

Thalassia testudinum often dominates seagrass meadows of the Florida panhandle but few measurements of productivity, biomass, density, turnover or leaf area index in this region have been made. We targeted 5 estuaries located at similar latitudes, 30⁰ ± 0.3⁰N: Big Lagoon, Santa Rosa Sound, St. Andrew Bay, St. Joseph Bay, and St. George Sound. This study was one component of a collaborative partnership of state and local researchers examining factors preventing recovery in panhandle estuarine areas that had historically contained seagrass in the 1940s and 1950s. Measurements were made twice in 2016, once in June and then again in summer or fall, except in Santa Rosa Sound where measurements were made 3 times. In the estuaries sampled for the second time in July or August, aboveground productivity was greater than in June. St. Joseph Bay had the highest aboveground productivity (4.3 g/m2/d) and 1—sided leaf area index (4.2) while St. George Sound had the lowest values (0.41 g/m2/d and 1.0). Principal component analysis suggested that St. Andrew Bay, Big Lagoon and Santa Rosa Sound were the most similar, with higher values for shoot densities and leaf turnover and lower salinities and watershed:water ratios. St. Joseph Bay had high aboveground productivity and salinity, and low turbidity. St. George Sound had low aboveground productivity, high total suspended solids and the highest watershed:water ratio. These baseline productivity estimates will be useful to assess the success of restoration efforts targeting seagrasses in the Florida panhandle and evaluate impacts of climate change on seagrasses

Global analysis reveals the complexity of the human glomerular extracellular matrix.

The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.National Institutes of Health (U.S.) (Grant R01 EB006365-06)Brain Science Foundation (Private Grant 106708

RNA-based therapies in inherited retinal diseases

Inherited retinal diseases (IRDs) are a genetically and phenotypically heterogeneous group of genetic eye disorders. There are more than 300 disease entities, and together this group of disorders affects millions of people globally and is a frequent cause of blindness or low-vision certification. However, each type is rare or ultra-rare. Characteristically, the impaired vision in IRDs is due to retinal photoreceptor dysfunction and loss resulting from mutation in a gene that codes for a retinal protein. Historically, IRDs have been considered incurable and individuals living with these blinding conditions could be offered only supportive care. However, the treatment landscape for IRDs is beginning to evolve. Progress is being made, driven by improvements in understanding of genotype-phenotype relationships, through advances in molecular genetic testing and retinal imaging. Alongside this expanding knowledge of IRDs, the current era of precision medicine is fueling a growth in targeted therapies. This has resulted in the first treatment for an IRD being approved. Several other therapies are currently in development in the IRD space, including RNA-based therapies, gene-based therapies (such as augmentation therapy and gene editing), cell therapy, visual prosthetics, and optogenetics. RNA-based therapies are a novel approach within precision medicine that have demonstrated success, particularly in rare diseases. Three antisense oligonucleotides (AONs) are currently in development for the treatment of specific IRD subtypes. These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials

Barriers and facilitators influencing the sustainment of health behaviour interventions in schools and childcare services: a systematic review

Background Sustainment has been defined as the sustained use or delivery of an intervention in practice following cessation of external implementation support. This review aimed to identify and synthesise factors (barriers and facilitators) that influence the sustainment of interventions (policies, practices, or programmes) in schools and childcare services that address the leading risk factors of chronic disease. Methods Seven electronic databases and relevant reference lists were searched for articles, of any design, published in English, from inception to March 2020. Articles were included if they qualitatively and/or quantitatively reported on school or childcare stakeholders’ (including teachers, principals, administrators, or managers) perceived barriers or facilitators to the sustainment of interventions addressing poor diet/nutrition, physical inactivity, obesity, tobacco smoking, or harmful alcohol use. Two independent reviewers screened texts, and extracted and coded data guided by the Integrated Sustainability Framework, an existing multi-level sustainability-specific framework that assesses factors of sustainment. Results Of the 13,158 articles identified, 31 articles met the inclusion criteria (8 quantitative, 12 qualitative, 10 mixed-methods, and 1 summary article). Overall, 29 articles were undertaken in schools (elementary n=17, middle n=3, secondary n=4, or a combination n=5) and two in childcare settings. The main health behaviours targeted included physical activity (n=9), diet (n=3), both diet and physical activity (n=15), and smoking (n=4), either independently (n=1) or combined with other health behaviours (n=3). Findings suggest that the majority of the 59 barriers and 74 facilitators identified to impact on intervention sustainment were similar across school and childcare settings. Factors predominantly relating to the ‘inner contextual factors’ of the organisation including: availability of facilities or equipment, continued executive or leadership support present, and team cohesion, support, or teamwork were perceived by stakeholders as influential to intervention sustainment. Conclusions Identifying strategies to improve the sustainment of health behaviour interventions in these settings requires a comprehensive understanding of factors that may impede or promote their ongoing delivery. This review identified multi-level factors that can be addressed by strategies to improve the sustainment of such interventions, and suggests how future research might address gaps in the evidence base. Trial registration This review was prospectively registered on PROSPERO: CRD42020127869 , Jan. 2020

Identity centrality and psychosocial functioning : a person-centered approach

There has been increased recognition that identity operates within several “components” and that not every component is likely to be equally central to one’s sense of self. The aim of the current study was to determine the extent to which identity components (i.e., personal, relational, collective, and public) are differentially central to emerging adults’ identity. We used a two-step cluster analytic procedure to identify distinct clusters and determine how these configurations might differ in relation to psychosocial functioning (i.e., well-being, externalizing and internalizing symptoms, illicit drug use, risky sex, and impaired driving). The sample consisted of 8,309 college students (72.8% female; M age = 19.94 years, 18–29, SD = 2.01) from 30 U.S. colleges and universities. Analyses identified six unique clusters based on the centrality of the four identity components. The findings indicated that a more well-rounded identity was associated with the most favorable psychosocial functioning. Results are discussed in terms of important directions for identity research and practical implications

Meaning in life in emerging adulthood: a person-oriented approach

The present study investigated naturally occurring profiles based on two dimensions of meaning in life: Presence of Meaning and Search for Meaning. Cluster analysis was used to examine meaning-in-life profiles, and subsequent analyses identified different patterns in psychosocial functioning for each profile. A sample of 8,492 American emerging adults (72.5% women) from 30 colleges and universities completed measures on meaning in life, and positive and negative psychosocial functioning. Results provided support for five meaningful yet distinguishable profiles. A strong generalizability of the cluster solution was found across age, and partial generalizability was found across gender and ethnicity. Furthermore, the five profiles showed specific patterns in relation to positive and negative psychosocial functioning. Specifically, respondents with profiles high on Presence of Meaning showed the most adaptive psychosocial functioning, whereas respondents with profiles where meaning was largely absent showed maladaptive psychosocial functioning. The present study provided additional evidence for prior research concerning the complex relationship between Presence of Meaning and Search for Meaning, and their relation with psychosocial functioning. Our results offer a partial clarification of the nature of the Search for Meaning process by distinguishing between adaptive and maladaptive searching for meaning in life

Antimicrobial Susceptibility of Vibrio vulnificus and Vibrio parahaemolyticus Recovered from Recreational and Commercial Areas of Chesapeake Bay and Maryland Coastal Bays

Vibrio vulnificus and V. parahaemolyticus in the estuarine-marine environment are of human health significance and may be increasing in pathogenicity and abundance. Vibrio illness originating from dermal contact with Vibrio laden waters or through ingestion of seafood originating from such waters can cause deleterious health effects, particularly if the strains involved are resistant to clinically important antibiotics. The purpose of this study was to evaluate antimicrobial susceptibility among these pathogens. Surface-water samples were collected from three sites of recreational and commercial importance from July to September 2009. Samples were plated onto species-specific media and resulting V. vulnificus and V. parahaemolyticus strains were confirmed using polymerase chain reaction assays and tested for antimicrobial susceptibility using the Sensititre® microbroth dilution system. Descriptive statistics, Friedman two-way Analysis of Variance (ANOVA) and Kruskal-Wallis one-way ANOVA were used to analyze the data. Vibrio vulnificus (n = 120) and V. parahaemolyticus (n = 77) were isolated from all sampling sites. Most isolates were susceptible to antibiotics recommended for treating Vibrio infections, although the majority of isolates expressed intermediate resistance to chloramphenicol (78% of V. vulnificus, 96% of V. parahaemolyticus). Vibrio parahaemolyticus also demonstrated resistance to penicillin (68%). Sampling location or month did not significantly impact V. parahaemolyticus resistance patterns, but V. vulnificus isolates from St. Martin's River had lower overall intermediate resistance than that of the other two sampling sites during the month of July (p = 0.0166). Antibiotics recommended to treat adult Vibrio infections were effective in suppressing bacterial growth, while some antibiotics recommended for pediatric treatment were not effective against some of the recovered isolates. To our knowledge, these are the first antimicrobial susceptibility data of V. vulnificus and V. parahaemolyticus recovered from the Chesapeake Bay. These data can serve as a baseline against which future studies can be compared to evaluate whether susceptibilities change over time