Predictors of Comorbid Eating Disorders and Association with Other Obsessive-Compulsive Spectrum Disorders in Trichotillomania

Trichotillomania (TTM) and eating disorders (ED) share many phenomenological similarities, including ritualized compulsive behaviors. Given this, and that comorbid EDs may represent additional functional burden to hair pullers, we sought to identify factors that predict diagnosis of an ED in a TTM population. Subjects included 555 adult females (age range 18–65) with DSM-IV-TR TTM or chronic hair pullers recruited from multiple sites. 7.2% (N = 40) of our TTM subjects met criteria for an ED in their lifetime. In univariable regression analysis, obsessive-compulsive disorder (OCD), Yale-Brown Obsessive Compulsive Scale (Y-BOCS) worst-ever compulsion and total scores, certain obsessive-compulsive spectrum disorders, anxiety disorder, attention-deficit/hyperactivity disorder (ADHD), and substance disorder all met the pre-specified criteria for inclusion in the multivariable analysis. In the final multivariable model, diagnosis of OCD (OR: 5.68, 95% CI: 2.2–15.0) and diagnosis of an additional body-focused repetitive behavior disorder (BFRB) (OR: 2.69, 95% CI: 1.1–6.8) were both associated with increased risk of ED in TTM. Overall, our results provide further support of the relatedness between ED and TTM. This finding highlights the importance of assessing for comorbid OCD and additional BFRBs in those with TTM. Future research is needed to identify additional predictors of comorbid disorders and to better understand the complex relationships between BFRBs, OCD and EDs

Method for in-solution, high-throughput T1 relaxometry using fluorescent nanodiamonds

Fluorescent nanodiamonds (FNDs) have been exploited as sensitive quantum probes for nanoscale chemical and biological sensing applications, with the majority of demonstrations to date relying on the detection of single FNDs. This places significant limits on the measurement time, throughput and statistical significance of a measured result as there is usually marked inhomogeneity within FND samples. Here we have developed a measurement platform that can report the T1 spin relaxation time from a large ensemble of FNDs in solution. We first describe a refined sensing protocol for this modality and then use it to identify the optimal FND size for the detection of paramagnetic targets. Our approach is simple to set up, robust and can be used for rapid material characterisation or a variety of in-situ quantum sensing applications.Comment: 8 pages, 3 figure

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Ebola Virus–Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013-2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms-ophthalmologic and auditory-are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody

Participation in collaborative fisheries research improves the perceptions of recreational anglers towards marine protected areas

Collaborative fisheries research programs engage stakeholders in data collection efforts, often with the benefit of increasing transparency about the status and management of natural resources. These programs are particularly important in marine systems, where management of recreational and commercial fisheries have historically been contentious. One such program is the California Collaborative Fisheries Research Program (CCFRP), which was designed in 2006 to engage recreational anglers in the scientific process and evaluate the efficacy of California’s network of marine protected areas. CCFRP began on the Central Coast of California and expanded statewide in 2017 to include six partner institutions in three regions: Northern, Central, and Southern California. To date, over 2,000 volunteer anglers have participated in the program, with many anglers volunteering for multiple years. However, the impacts of outreach, education, and collaborative research on those anglers at the statewide scale are currently unknown. Thus, the objective of the current study was to survey the statewide pool of volunteer anglers to assess the degree to which participation in CCFRP has influenced angler perceptions of MPAs, fisheries management, and conservation. We received 259 completed surveys out of a pool of 1,386 active anglers, equating to an 18.7% response rate. Participation in CCFRP resulted in a significant, positive impact on anglers’ attitudes towards MPAs in California across all regions. Anglers who participated in six or more CCFRP fishing trips had a more positive perception of MPAs than those who participated in fewer trips. Volunteer anglers across all regions perceived that they caught larger fishes, a higher abundance of fishes, and a greater diversity of species inside MPAs, consistent with the ecological findings of the program. These results highlight the benefits of involving community members in collaborative scientific research. Collaboration between researchers and the broader community increases transparency and trust between stakeholders, and results in greater understanding of natural resource dynamics, ultimately producing better management outcomes

The influence of vector‐borne disease on human history: socio‐ecological mechanisms

Vector-borne diseases (VBDs) are embedded within complex socio-ecological systems. While research has traditionally focused on the direct effects of VBDs on human morbidity and mortality, it is increasingly clear that their impacts are much more pervasive. VBDs are dynamically linked to feedbacks between environmental conditions, vector ecology, disease burden, and societal responses that drive transmission. As a result, VBDs have had profound influence on human history. Mechanisms include: (1) killing or debilitating large numbers of people, with demographic and population-level impacts; (2) differentially affecting populations based on prior history of disease exposure, immunity, and resistance; (3) being weaponised to promote or justify hierarchies of power, colonialism, racism, classism and sexism; (4) catalysing changes in ideas, institutions, infrastructure, technologies and social practices in efforts to control disease outbreaks; and (5) changing human relationships with the land and environment. We use historical and archaeological evidence interpreted through an ecological lens to illustrate how VBDs have shaped society and culture, focusing on case studies from four pertinent VBDs: plague, malaria, yellow fever and trypanosomiasis. By comparing across diseases, time periods and geographies, we highlight the enormous scope and variety of mechanisms by which VBDs have influenced human history

Quantitative Evidence for the Effects of Multiple Drivers on Continental-Scale Amphibian Declines

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed