Multiple pathological mechanisms contribute to hippocampal damage in the experimental autoimmune encephalomyelitis model of multiple sclerosis.

Emotional and cognitive deficits and associated hippocampal damage observed in multiple sclerosis (MS) are now recognized as primary disease manifestations. However, the pathological substrate of these dysfunctions is unclear. In the experimental autoimmune encephalomyelitis (EAE) MS model, impaired hippocampal-dependent functions are concomitant with severe microglial reactivity and neurodegeneration, but reports vary with respect to evidence of lymphocytic infiltration, raising questions as to the nature of the underlying neurodegenerative mechanisms.

The relationship between pectoral fin ray stiffness and swimming behavior in Labridae: insights into design, performance and ecology.

The functional capabilities of flexible, propulsive appendages are directly influenced by their mechanical properties. The fins of fishes have undergone extraordinary evolutionary diversification in structure and function, which raises questions of how fin mechanics relate to swimming behavior. In the fish family Labridae, pectoral fin swimming behavior ranges from rowing to flapping.

Development and evaluation of a new diffusive gradients in thin-films technique for measuring organotin compounds in coastal sediment pore water.

Organotins present a toxicological risk to biota in the aquatic environment. Understanding the behaviour of these compounds in sediment is challenging, with sophisticated analytical techniques required for their measurement. We investigated the use of silica-bound sorbents for diffusive gradients in thin-films (DGT) adsorption gels to pre-concentrate five organotins (monobutlytin (MBT), dibutyltin (DBT), tributyltin (TBT), diphenyltin (DPhT), triphenyltin (TPhT)) found frequently in coastal sediment.

Acute Administration of the Nonpathogenic, Saprophytic Bacterium, Mycobacterium vaccae, Induces Activation of Serotonergic Neurons in the Dorsal Raphe Nucleus and Antidepressant-Like Behavior in Association with Mild Hypothermia.

Peripheral immune activation can have profound physiologic and behavioral effects. One mechanism through which immune activation may affect physiology and behavior is through actions on brainstem neuromodulatory systems, such as serotonergic systems. To test this hypothesis, in Experiment 1, adult male BALB/c mice were implanted with telemetric recording devices and then immunized with Mycobacterium vaccae NCTC 11659 (0.

Isolation of polymorphic microsatellite loci in the New Zealand endemic sand-binder, (Cyperaceae).

Premise Of The Study: (Cyperaceae) is a declining sand-binding sedge of ecological and cultural importance. Microsatellite primers were developed in to investigate how population genetic structure is related to the pronounced morphological, physiological, and ecological variation observed in this species.

Methods And Results: A 454 shotgun-sequencing approach was used to generate 157,274 raw sequence reads, 536 of which contained microsatellites.

Using Linkage Maps as a Tool To Determine Patterns of Chromosome Synteny in the Genus .

Next generation sequencing techniques have revolutionized the collection of genome and transcriptome data from nonmodel organisms. This manuscript details the application of restriction site-associated DNA sequencing (RADseq) to generate a marker-dense genetic map for Brook Trout (). The consensus map was constructed from three full-sib families totaling 176 F individuals.

Using RNA-seq to determine patterns of sex-bias in gene expression in the brain of the sex-role reversed Gulf Pipefish (Syngnathus scovelli).

Sex-bias in gene expression is a widespread mechanism for controlling the development of phenotypes that differ between males and females. Most studies on sex-bias in gene expression have focused on species that exhibit traditional sex-roles (male-male competition and female parental care). By contrast the Syngnathid fishes (sea horses, pipefish, and sea dragons) are a group of organisms where many species exhibit male brooding and sex-role reversal (female-female competition for mates and paternal parental care), and little is known about how patterns of sex-bias in gene expression vary in species with sex-role reversal.

Inactivity Is Nycthemeral, Endogenously Generated, Homeostatically Regulated, and Melatonin Modulated in a Free-Living Platyhelminth Flatworm.

Introduction: Sleep either appeared once early in the evolution of animals, or at multiple instances over evolutionary time. Understanding whether sleep is a diagnostic trait for members of the kingdom Animalia has important implications for our understanding of the evolution of sleep and sleep functions. Unfortunately, knowledge on the phylogenetic breadth of sleep is restricted to vertebrates, a few arthropods and molluscs, and one species of nematode.

Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib).

Aberrant activation of signaling through the RAS-RAF-MEK-ERK (MAPK) pathway is implicated in numerous cancers, making it an attractive therapeutic target. Although BRAF and MEK-targeted combination therapy has demonstrated significant benefit beyond single-agent options, the majority of patients develop resistance and disease progression after approximately 12 months. Reactivation of ERK signaling is a common driver of resistance in this setting.

Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care.

Background: Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited.

Aims: To assess the yield of IBD from FC testing in primary care.

Methods: Retrospective review of hospital records to assess the outcome following FC testing in primary care.

AHR and CYP1A expression link historical contamination events to modern day developmental effects in the American alligator.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that initiates a transcriptional pathway responsible for the expression of CYP1A subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of activating the AHR, and while dioxin and PCB inputs into the environment have been dramatically curbed following strict regulatory efforts in the United States, they persist in the environment and exposures remain relevant today. Little is known regarding the effects that long-term chronic exposures to dioxin or dioxin-like compounds might have on the development and subsequent health of offspring from exposed individuals, nor is much known regarding AHR expression in reptilians.

Chronic work stress and decreased vagal tone impairs decision making and reaction time in jockeys.

The inverse relationship between acute stress and decision-making is well documented, but few studies have investigated the impact of chronic stress. Jockeys work exhaustive schedules and have extremely dangerous occupations, with safe performance requiring quick reaction time and accurate decision-making. We used the effort reward imbalance (ERI) occupational stress model to assess the relationship of work stress with indices of stress physiology and decision-making and reaction time.

A Systematic Review and Meta-analysis of the Effort-Reward Imbalance Model of Workplace Stress and Hypothalamic-Pituitary-Adrenal Axis Measures of Stress.

Objective: The association between effort-reward imbalance (ERI) and various health outcomes has been well documented over the past 20 years, but the mechanisms responsible for this association remain unclear. The present meta-analysis assessed the associations of ERI and overcommitment (OC) in the workplace with hypothalamic-pituitary-adrenal (HPA) axis measures.

Methods: Electronic databases were searched with the phrase "effort*reward*imbalance," which yielded 319 studies leading to 56 full-text studies being screened.

Whole-body hyperthermia and a subthreshold dose of citalopram act synergistically to induce antidepressant-like behavioral responses in adolescent rats.

Background: Open and randomized, double blind, placebo-controlled clinical trials have demonstrated clinical efficacy of infrared whole-body hyperthermia in treatment of major depressive disorder (MDD). Demonstration of antidepressant-like behavioral effects of whole-body hyperthermia in preclinical rodent models would provide further support for the clinical use of infrared whole-body hyperthermia for the treatment of MDD, and would provide additional opportunities to explore underlying mechanisms.

Methods: Adolescent male Wistar rats were habituated daily for 7days to an incubator (23°C, 15min), then exposed, 24h later, to an 85-min period of whole-body hyperthermia (37°C) or control conditions (23°C), with or without pretreatment with a subthreshold dose of the selective serotonin reuptake inhibitor, citalopram (5mg/kg, s.

Rational design of peptide derivatives for inhibition of MyD88-mediated toll-like receptor signaling in human peripheral blood mononuclear cells and epithelial cells exposed to Francisella tularensis.

Small molecules were developed to attenuate proinflammatory cytokines resulting from activation of MyD88-mediated toll-like receptor (TLR) signaling by Francisella tularensis. Fifty-three tripeptide derivatives were synthesized to mimic a key BB-loop region involved in toll-like/interleukin-1 receptor recognition (TIR) domain interactions. Compounds were tested for inhibition of TNF-α, IFN-γ, IL-6, and IL-1β in human peripheral blood mononuclear cells (PBMCs) and primary human bronchial epithelial cells exposed to LPS extracts from F.

The Rising Tide of Antimicrobial Resistance in Aquaculture: Sources, Sinks and Solutions.

As the human population increases there is an increasing reliance on aquaculture to supply a safe, reliable, and economic supply of food. Although food production is essential for a healthy population, an increasing threat to global human health is antimicrobial resistance. Extensive antibiotic resistant strains are now being detected; the spread of these strains could greatly reduce medical treatment options available and increase deaths from previously curable infections.

Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials.

Background: Opioid-induced constipation is a frequent side-effect of opioid treatment, and standard interventions have limited or inconsistent efficacy. This study assessed the efficacy and safety of naldemedine, a peripherally acting μ-opioid receptor antagonist, for the treatment of opioid-induced constipation in patients with chronic non-cancer pain.

Methods: We report two double-blind, randomised, placebo-controlled trials in adults with chronic non-cancer pain and opioid-induced constipation.

Mechanosensation is evolutionarily tuned to locomotor mechanics.

The biomechanics of animal limbs has evolved to meet the functional demands for movement associated with different behaviors and environments. Effective movement relies not only on limb mechanics but also on appropriate mechanosensory feedback. By comparing sensory ability and mechanics within a phylogenetic framework, we show that peripheral mechanosensation has evolved with limb biomechanics, evolutionarily tuning the neuromechanical system to its functional demands.

Homology-Directed Recombination for Enhanced Engineering of Chimeric Antigen Receptor T Cells.

Gene editing by homology-directed recombination (HDR) can be used to couple delivery of a therapeutic gene cassette with targeted genomic modifications to generate engineered human T cells with clinically useful profiles. Here, we explore the functionality of therapeutic cassettes delivered by these means and test the flexibility of this approach to clinically relevant alleles. Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR) T cells could be used to treat patients with HIV-associated B cell malignancies.

Exploration of US men's professional sport organization concussion policies.

Concussion policies are increasingly being developed and adopted among professional sports organizations. We sought to compare the policies of the National Hockey League (NHL), the National Basketball Association (NBA), the National Football League (NFL), and Major League Baseball (MLB). Our objective was to summarize each policy and evaluate the extent to which each policy is organization-specific and/or consistent with medical guidelines.

Local Spinal Cord Circuits and Bilateral Mauthner Cell Activity Function Together to Drive Alternative Startle Behaviors.

The reticulospinal Mauthner cells (M-cells) of the startle circuit have been considered to be dedicated to one basic motor output and the C-type startle response in fish. The neural circuit underlying the C-start, a startle behavior in which the fish forms a "C"-shaped body bend has been described in depth in goldfish and zebrafish [1, 2] and is thought to occur in other species [3, 4]. However, previous research has shown that some species can perform a second type of startle called the S-start [5-7].

Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids.

Background: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids.

Methods: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study.

Engineering HIV-Resistant, Anti-HIV Chimeric Antigen Receptor T Cells.

The treatment or cure of HIV infection by cell and gene therapy has been a goal for decades. Recent advances in both gene editing and chimeric antigen receptor (CAR) technology have created new therapeutic possibilities for a variety of diseases. Broadly neutralizing monoclonal antibodies (bNAbs) with specificity for the HIV envelope glycoprotein provide a promising means of targeting HIV-infected cells.