Deguelin exerts potent nematocidal activity the mitochondrial respiratory chain.

As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mitoribosomal protein production before inhibiting motility.

An attentional drift diffusion model over binary-attribute choice.

In order to make good decisions, individuals need to identify and properly integrate information about various attributes associated with a choice. Since choices are often complex and made rapidly, they are typically affected by contextual variables that are thought to influence how much attention is paid to different attributes. I propose a modification of the attentional drift-diffusion model, the binary-attribute attentional drift diffusion model (baDDM), which describes the choice process over simple binary-attribute choices and how it is affected by fluctuations in visual attention.

Mio-Pliocene aridity in the south-central Andes associated with Southern Hemisphere cold periods.

Although Earth's climate history is best known through marine records, the corresponding continental climatic conditions drive the evolution of terrestrial life. Continental conditions during the latest Miocene are of particular interest because global faunal turnover is roughly synchronous with a period of global glaciation from ∼6.2-5.

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types.

High-intensity interval training and calorie restriction promote remodeling of glucose and lipid metabolism in diet-induced obesity.

Calorie restriction (CR) decreases adiposity, but the magnitude and defense of weight loss is less than predicted due to reductions in total daily energy expenditure (TEE). The purpose of the current investigation was to determine whether high-intensity interval training (HIIT) would increase markers of sympathetic activation in white adipose tissue (WAT) and rescue CR-mediated reductions in EE to a greater extent than moderate-intensity aerobic exercise training (MIT). Thirty-two 5-wk-old male C57BL/6J mice were placed on ad libitum HFD for 11 wk, followed by randomization to one of four groups ( = 8/group) for an additional 15 wk: ) CON (remain on HFD), ) CR (25% lower energy intake), ) CR + HIIT (25% energy deficit created by 12.

The Composition of Poly(Ethylene Terephthalate) (PET) Surface Precipitates Determined at High Resolving Power by Tandem Mass Spectrometry Imaging.

We present the first demonstration of a general method for the chemical characterization of small surface features at high magnification via simultaneous collection of mass spectrometry (MS) imaging and tandem MS imaging data. High lateral resolution tandem secondary ion MS imaging is employed to determine the composition of surface features on poly(ethylene terephthalate) (PET) that precipitate during heat treatment. The surface features, probed at a lateral resolving power of<200 nm using a surface-sensitive ion beam, are found to be comprised of ethylene terephthalate trimer at a greater abundance than is observed in the surrounding polymer matrix.

Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus.

Background: In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm), one of the most pathogenic parasites of ruminants.

Methods: In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus.

Developmental changes in pharyngeal swallowing acoustics: a comparison of adults and children.

This study examined developmental differences in the acoustics of pharyngeal swallowing. Thirty-one young children (M = 4.5 years) and 29 adults (M = 22.

ToF-SIMS Parallel Imaging MS/MS of Lipid Species in Thin Tissue Sections.

Unambiguous identification of detected species is essential in complex biomedical samples. To date, there are not many mass spectrometry imaging techniques that can provide both high spatial resolution and identification capabilities. A new and patented imaging tandem mass spectrometer, exploiting the unique characteristics of the nanoTOF II (Physical Electronics, USA) TOF-SIMS TRIFT instrument, was developed to address this.

Associations of human skeletal muscle fiber type and insulin sensitivity, blood lipids, and vascular hemodynamics in a cohort of premenopausal women.

Purpose: Cardiometabolic disease remains a leading cause of morbidity and mortality in developed nations. Consequently, identifying and understanding factors associated with underlying pathophysiological processes leading to chronic cardio metabolic conditions is critical. Metabolic health, arterial elasticity, and insulin sensitivity (SI) may impact disease risk, and may be determined in part by myofiber type.

d-Aspartic acid ameliorates painful and neuropsychiatric changes and reduces β-amyloid Aβ peptide in a long lasting model of neuropathic pain.

Depressive symptoms and other neuropsychiatric dysfunctions are common in neurodegenerative disorders, including chronic pain and dementia. A correlation between the β-amyloid protein accumulation and the development of depression has been suggested, however the underlying mechanisms are unknown. d-Aspartate (d-Asp) is a free d-amino acid found in the mammalian brain and involved in neurological and psychiatric processes, such as cognition and affective disorders.

Reduced dose CT with model-based iterative reconstruction compared to standard dose CT of the chest, abdomen, and pelvis in oncology patients: intra-individual comparison study on image quality and lesion conspicuity.

Purpose: To compare image quality and lesion conspicuity of reduced dose (RD) CT with model-based iterative reconstruction (MBIR) compared to standard dose (SD) CT in patients undergoing oncological follow-up imaging.

Methods: Forty-four cancer patients who had a staging SD CT within 12 months were prospectively included to undergo a weight-based RD CT with MBIR. Radiation dose was recorded and tissue attenuation and image noise of four tissue types were measured.

Cognitive functioning, aging, and work: A review and recommendations for research and practice.

There is a larger proportion and number of older adults in the labor force than ever before. Furthermore, older adults in the workforce are working until later ages. Although a great deal of research has examined physical health and well-being of working older adults, less research has focused on cognitive functioning.

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

Background: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.

Methods: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells).

Catching fire and spreading it: A glimpse into displayed entrepreneurial passion in crowdfunding campaigns.

Crowdfunding is an emerging phenomenon that enables entrepreneurs to solicit financial contributions for new projects from mass audiences. Drawing on the elaboration likelihood model of persuasion and emotional contagion theory, the authors examined the importance of displayed entrepreneurial passion when seeking resources in a crowdfunding context. They proposed that entrepreneurs' displayed passion in the introductory video for a crowdfunding project increases viewers' experienced enthusiasm about the project (i.

Why intensity is not a bad word: Optimizing health status at any age.

Age-related declines in health and function make locomotion increasingly difficult leading to reductions in non-exercise activity thermogenesis (NEAT), skeletal muscle size and strength, and increased adiposity. Exercise is an important strategy to attenuate loss of function through the life cycle. Despite claims to the contrary, high-intensity exercise is important for the prevention of obesity and sarcopenia with advancing age.

Gas chromatography-mass spectrometry analysis of effects of dietary fish oil on total fatty acid composition in mouse skin.

Altering the fatty acid (FA) composition in the skin by dietary fish oil could provide therapeutic benefits. Although it has been shown that fish oil supplementation enhances EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) abundance in the skin, comprehensive skin FA profiling is needed. We established a gas chromatography-mass spectrometry method, which allows precise quantification of FA profile using small (<24 mm for mice and <12 mm for humans) skin specimens that can be readily obtained from live mice and humans.

The structure and function of an RNA polymerase interaction domain in the PcrA/UvrD helicase.

The PcrA/UvrD helicase functions in multiple pathways that promote bacterial genome stability including the suppression of conflicts between replication and transcription and facilitating the repair of transcribed DNA. The reported ability of PcrA/UvrD to bind and backtrack RNA polymerase (1,2) might be relevant to these functions, but the structural basis for this activity is poorly understood. In this work, we define a minimal RNA polymerase interaction domain in PcrA, and report its crystal structure at 1.

Investigating the antiplasmodial activity of primary sulfonamide compounds identified in open source malaria data.

In the past decade there has been a significant reduction in deaths due to malaria, in part due to the success of the gold standard antimalarial treatment - artemisinin combination therapies (ACTs). However the potential threat of ACT failure and the lack of a broadly effective malaria vaccine are driving efforts to discover new chemical entities (NCEs) to target this disease. The primary sulfonamide (PS) moiety is a component of several clinical drugs, including those for treatment of kidney disease, glaucoma and epilepsy, however this chemotype has not yet been exploited for malaria.

Persistence and biodegradation of oil at the ocean floor following Deepwater Horizon.

The 2010 Deepwater Horizon disaster introduced an unprecedented discharge of oil into the deep Gulf of Mexico. Considerable uncertainty has persisted regarding the oil's fate and effects in the deep ocean. In this work we assess the compound-specific rates of biodegradation for 125 aliphatic, aromatic, and biomarker petroleum hydrocarbons that settled to the deep ocean floor following release from the damaged Macondo Well.

Deletion of the Mouse Homolog of Disrupts Discrete Forms of Hippocampal-Dependent Memory and Neurogenesis within the Dentate Gyrus.

L-type voltage-gated calcium channels (LVGCCs) have been implicated in various forms of learning, memory, and synaptic plasticity. Within the hippocampus, the LVGCC subtype, Ca1.2 is prominently expressed throughout the dentate gyrus.

Development and Evaluation of the Tigriopus Course-Based Undergraduate Research Experience: Impacts on Students' Content Knowledge, Attitudes, and Motivation in a Majors Introductory Biology Course.

Within the past decade, course-based undergraduate research experiences (CUREs) have emerged as a viable mechanism to enhance novices' development of scientific reasoning and process skills in the science, technology, engineering, and mathematics disciplines. Recent evidence within the bioeducation literature suggests that student engagement in such experiences not only increases their appreciation for and interest in scientific research but also enhances their ability to "think like a scientist." Despite these critical outcomes, few studies have objectively explored CURE versus non-CURE students' development of content knowledge, attitudes, and motivation in the discipline, particularly among nonvolunteer samples.

Separate Primary Melanomas of the Bulbar Conjunctiva and Eyelid Skin: Clinical Implications of Multiple Primary Melanomas.

Purpose: We report a patient with previous in situ melanoma of the forehead skin who was referred for treatment of a bulbar conjunctival melanoma and a separate superficially invasive melanoma of the eyelid skin, and we offer a review of the biological and clinical implications of patients who have multiple primary melanomas.

Methods: This article offers a clinicopathological correlation with a review of the relevant literature.

Results: An 80-year-old white man was referred for evaluation of a suspicious conjunctival tumor and a lower-eyelid lesion.