A bioinformatic pipeline for identifying informative SNP panels for parentage assignment from RADseq data.

The development of high-throughput sequencing technologies is dramatically increasing the use of single nucleotide polymorphisms (SNPs) across the field of genetics, but most parentage studies of wild populations still rely on microsatellites. We developed a bioinformatic pipeline for identifying SNP panels that are informative for parentage analysis from restriction site-associated DNA sequencing (RADseq) data. This pipeline includes options for analysis with or without a reference genome, and provides methods to maximize genotyping accuracy and select sets of unlinked loci that have high statistical power.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC.

Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening.

Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates from the National Health Interview Survey, and select issues related to cancer screening. In this 2018 update, we also summarize the new American Cancer Society colorectal cancer screening guideline and include a clarification in the language of the 2013 lung cancer screening guideline. CA Cancer J Clin 2018;68:297-316.

Pharmacological characterization of potent and selective NaV1.7 inhibitors engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V.

Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area of vigorous pursuit. In an effort to identify more potent leads compared to our previously reported GpTx-1 peptide series, electrophysiology screening of fractionated tarantula venom discovered the NaV1.

1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of Na1.7 inhibition.

Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit Na1.7 and demonstrate high levels of selectivity over other Na isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity.

Activity of bromodomain protein inhibitors/binders against asexual-stage Plasmodium falciparum parasites.

Bromodomain-containing proteins (BDPs) are involved in the regulation of eukaryotic gene expression. Compounds that bind and/or inhibit BDPs are of interest as tools to better understand epigenetic regulation, and as possible drug leads for different diseases, including malaria. In this study, we assessed the activity of 42 compounds demonstrated or predicted (using virtual screening of a pharmacophore model) to bind/inhibit eukaryotic BDPs for activity against Plasmodium falciparum malaria parasites.

High-Performance WSe Phototransistors with 2D/2D Ohmic Contacts.

We report high-performance WSe phototransistors with two-dimensional (2D) contacts formed between degenerately p-doped WSe and undoped WSe channel. A photoresponsivity of ∼600 mA/W with a high external quantum efficiency up to 100% and a fast response time (both rise and decay times) shorter than 8 μs have been achieved concurrently. More importantly, our WSe phototransistor exhibits a high specific detectivity (∼10 Jones) in vacuum, comparable or higher than commercial Si- and InGaAs-based photodetectors.

Measuring on the go: Response to Morra, Panesi, Traverso, and Usai.

Morra, Panesi, Traverso, and Usai's (Journal of Experimental Child Psychology, 2017, Vol. 167, pp. 246-258) effort to clarify theoretical models and nomenclature confusion surrounding young children's executive functions development is laudable and important.

BASELINE CORTICOSTERONE, HEMATOLOGY, AND BIOCHEMISTRY RESULTS AND CORRELATIONS TO REPRODUCTIVE SUCCESS IN NESTING LOGGERHEAD SEA TURTLES ( CARETTA CARETTA).

Characterizing the health status and reproductive success of wild populations of sea turtles can be difficult; however, obtaining data to do this can provide important insight into the stability and long-term success of a population. This study examined the use of baseline corticosterone to assess reproductive success of a population of nesting loggerhead sea turtles ( Caretta caretta) on Jekyll Island, Georgia and investigated hematological and biochemical trends in this population. A total of 37 nesting loggerhead sea turtles was sampled for this study.

Rapid loss of group 1 innate lymphoid cells during blood stage infection.

Objectives: Innate lymphoid cells (ILCs) share many characteristics with CD4 T cells, and group 1 ILCs share a requirement for T-bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs during infection.

Methods: We quantified group 1 ILCs in peripheral blood collected from subjects infected with with 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of AS-infected mice.

Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

Background: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM).

Methods: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency.

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets.

Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes , and .

Background: Germline pathogenic variants in / are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of / mutation carriers.

Associations of physical activity with anxiety symptoms and status: results from The Irish longitudinal study on ageing.

Aims: Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland.

When are they old enough to drink? Outcomes of an Australian social marketing intervention targeting alcohol initiation.

Introduction And Aims: This paper reports on the evaluation of an Australian whole-of-community social marketing intervention targeting social norms, which aimed to reduce inflated perceptions of the prevalence of underage drinking and increase the age at which alcohol initiation is considered acceptable.

Design And Methods: A community-wide intervention was delivered in a single community over a period of 2 years, targeting adolescents, parents and community members. Pre-and post-intervention computer-assisted telephone interview surveys were conducted in the intervention and a matched comparison (control) community.

Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

The essential role of the Y chromosome in male sex determination has largely overshadowed the possibility that it may exert other biologic roles. Here, we show that Y-chromosome lineage is a strong determinant of perivascular and renal T-cell infiltration in the stroke-prone spontaneously hypertensive rat, which, in turn, may influence vascular function and blood pressure (BP). We also show, for the first time to our knowledge, that augmented perivascular T-cell levels can directly instigate vascular dysfunction, and that the production of reactive oxygen species that stimulate cyclo-oxygenase underlies this.

Time to change focus? Transitioning from higher neonatal to higher stillbirth mortality in São Paulo State, Brazil.

Background: Differential trends in mortality suggest that stillbirths may dominate neonatal mortality in the medium to long run. Brazil has made major efforts to improve data collection on health indicators at granular geographic levels, and provides an ideal environment to test this hypothesis. Our goals were to examine levels and trends in stillbirths and neonatal deaths and the extent to which the mortality burden caused by stillbirths dominates neonatal mortality at the municipality- and state-level.

Grasp Performance of a Soft Synergy-Based Prosthetic Hand: A Pilot Study.

Current prosthetic hands are frequently rejected in part due to limited functionality and versatility. We assessed the feasibility of a novel prosthetic hand, the SoftHand Pro (SHP), whose design combines soft robotics and hand postural synergies. Able-bodied subjects ( ) tracked cursor motion by opening and closing the SHP and performed a grasp-lift-hold-release (GLHR) task with a sensorized cylindrical object of variable weight.

Using ricelands to provide temporary shorebird habitat during migration.

To help mitigate large wetland losses in California, The Nature Conservancy launched a dynamic conservation incentive program to create temporary wetland habitats in harvested and fallow rice fields for shorebirds migrating along the Pacific Flyway. Farmers were invited to participate in a reverse auction bidding process and winning bids were selected based on their cost and potential to provide high quality shorebird habitat. This was done in 2014 and 2015, for separate enrollment periods that overlapped with spring and fall migration, both before and after the traditional post-harvest flooding period.

Vascular dysfunction in the stroke-prone spontaneously hypertensive rat is dependent on constrictor prostanoid activity and Y chromosome lineage.

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here, we show that vascular dysfunction in the SHRSP is attributable to differential cyclooxygenase (COX) activity with nitric oxide (NO) levels playing a less significant role.

Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1.

Three new isocyanoditerpenes (5-7) have been characterized from Australian specimens of the nudibranch Phyllidiella pustulosa. The planar structure and (3R,6S,7R) absolute configuration of pustulosaisonitrile-1 were deduced by spectroscopic analyses at 900 MHz informed by molecular modeling, DFT calculations, and computational NMR chemical shift predictions and by comparison of experimental electronic circular dichroism (ECD) data with TDDFT-ECD calculations for the truncated model compound 8. A catalyst-controlled enantio- and diastereoselective total synthesis of the two most likely diastereomeric candidates for the structure of 5 solidified its (3R,6S,7R,10S,11R,14R) absolute configuration.

Model-Informed Drug Development for Malaria Therapeutics.

Malaria is a critical public health problem resulting in substantial morbidity and mortality, particularly in developing countries. Owing to the development of resistance toward current therapies, novel approaches to accelerate the development efforts of new malaria therapeutics are urgently needed. There have been significant advancements in the development of in vitro and in vivo experiments that generate data used to inform decisions about the potential merit of new compounds.

Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

Context: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare.

Objective: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series.

Essential Medications for Patients With Suspected or Confirmed Ebola Virus Disease in Resource-Limited Environments.

Background: In 2014, the U.S. Public Health Service (USPHS) Commissioned Corps deployed to Monrovia, Liberia, to operate a 25-bed Ebola treatment unit (ETU) constructed by the U.