Cathepsin D overexpression in the nervous system rescues lethality and A42 accumulation of cathepsin D systemic knockout .

The lysosome is responsible for protein and organelle degradation and homeostasis and the cathepsins play a key role in maintaining protein quality control. Cathepsin D (CTSD), is one such lysosomal protease, which when deficient in humans lead to neurolipofuscinosis (NCL) and is important in removing toxic protein aggregates. Prior studies demonstrated that CTSD germ-line knockout-KO (CDKO) resulted in accumulation of protein aggregates, decreased proteasomal activities, and postnatal lethality on Day 26 ± 1.

Evidence-based advice on timing and location of tsetse control measures in Shimba Hills National reserve, Kenya.

Controlling tsetse flies is critical for effective management of African trypanosomiasis in Sub-Saharan Africa. To enhance timely and targeted deployment of tsetse control strategies a better understanding of their temporal dynamics is paramount. A few empirical studies have explained and predicted tsetse numbers across space and time, but the resulting models may not easily scale to other areas.

The effect of a pharmaceutical ghrelin agonist on lifespan in C57BL/6J male mice: A controlled experiment.

Interventions for animal lifespan extension like caloric restriction (CR) have identified physiologic and biochemical pathways related to hunger and energy-sensing status as possible contributors, but mechanisms have not been fully elucidated. Prior studies using ghrelin agonists show greater food intake but no effect on lifespan in rodent models. This experiment in male C57BL/6J mice tested the influence of ghrelin agonism for perceived hunger, in the absence of CR, on longevity.

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation.

RORγt-Expressing Pathogenic CD4 T Cells Cause Brain Inflammation during Chronic Colitis.

Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn's disease and ulcerative colitis patients. However, the mechanism causing neuropathological disorders in inflammatory bowel disease patients remains unknown. Studies have linked the Th17 subset of CD4 T cells to brain diseases associated with neuroinflammation and cognitive impairment, including multiple sclerosis, ischemic brain injury, and Alzheimer's disease.

Satellite-based modelling of potential tsetse (Glossina pallidipes) breeding and foraging sites using teneral and non-teneral fly occurrence data.

Background: African trypanosomiasis, which is mainly transmitted by tsetse flies (Glossina spp.), is a threat to public health and a significant hindrance to animal production. Tools that can reduce tsetse densities and interrupt disease transmission exist, but their large-scale deployment is limited by high implementation costs.

Widespread Doublecortin Expression in the Cerebral Cortex of the .

It has been demonstrated that in adulthood rodents show newly born neurons in the subgranular layer (SGL) of the dentate gyrus (DG), and in the subventricular zone (SVZ). The neurons generated in the SVZ migrate through the rostral migratory stream (RMS) to the olfactory bulb. One of the markers of newly generated neurons is doublecortin (DCX).

Reductive stress promotes protein aggregation and impairs neurogenesis.

Redox homeostasis regulates key cellular signaling in both physiology and pathology. While perturbations result in shifting the redox homeostasis towards oxidative stress are well documented, the influence of reductive stress (RS) in neurodegenerative diseases and its mechanisms are unknown. Here, we postulate that a redox shift towards the reductive arm (through the activation of Nrf2 signaling) will damage neurons and impair neurogenesis.

Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.

PDE4 cyclic nucleotide phosphodiesterases reduce 3', 5' cAMP levels in the CNS and thereby regulate PKA activity and the phosphorylation of CREB, fundamental to depression, cognition, and learning and memory. The PDE4 isoform PDE4D5 interacts with the signaling proteins β-arrestin2 and RACK1, regulators of β-adrenergic and other signal transduction pathways. Mutations in in humans predispose to acrodysostosis, associated with cognitive and behavioral deficits.

DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies.

DOCK3 is a member of the DOCK family of guanine nucleotide exchange factors that regulate cell migration, fusion and viability. Previously, we identified a dysregulated miR-486/DOCK3 signaling cascade in dystrophin-deficient muscle, which resulted in the overexpression of DOCK3; however, little is known about the role of DOCK3 in muscle. Here, we characterize the functional role of DOCK3 in normal and dystrophic skeletal muscle.

Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APP mouse model.

Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological processes, including the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, and neuroinflammation, lead to cognitive impairment at middle and eventually later stages of AD progression. Over the last decade, focused efforts have explored repurposed drug approaches for AD pathophysiological mechanisms.

Mapping suitability for rice production in inland valley landscapes in Benin and Togo using environmental niche modeling.

Inland valleys (IVs) in Africa are important landscapes for rice cultivation and are targeted by national governments to attain self-sufficiency. Yet, there is limited information on the spatial distribution of IVs suitability at the national scale. In the present study, we developed an ensemble model approach to characterize the IVs suitability for rainfed lowland rice using 4 machine learning algorithms based on environmental niche modeling (ENM) with presence-only data and background sample, namely Boosted Regression Tree (BRT), Generalized Linear Model (GLM), Maximum Entropy (MAXNT) and Random Forest (RF).

The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice.

Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease that is caused by the loss of functional dystrophin protein in cardiac and skeletal muscles. DMD patient muscles become weakened, leading to eventual myofiber breakdown and replacement with fibrotic and adipose tissues. Inflammation drives the pathogenic processes through releasing inflammatory cytokines and other factors that promote skeletal muscle degeneration and contributing to the loss of motor function.

Cyclic O exposure synergizes with aging leading to memory impairment in male APOE ε3, but not APOE ε4, targeted replacement mice.

The etiology of late-onset Alzheimer's disease is unknown. Recent epidemiological studies suggest that exposure to high levels of ozone (O) may be a risk factor for late-onset Alzheimer's disease. Nonetheless, whether and how O exposure contributes to AD development remains to be determined.

Climate and land use changes will degrade the distribution of Rhododendrons in China.

Biodiversity loss and variation in species responses to climate and land use change have been found across broad taxonomic groups. However, whether species from the same taxonomic group with distinct geographical ranges will respond differently is poorly understood. The aim of this study is to predict the potential impacts of future climate and land use change on the distribution of narrow- and wide-ranging Rhododendron species, and estimate their relative contribution in China.

A Small Molecule Inhibitor of Plasminogen Activator Inhibitor-1 Reduces Brain Amyloid-β Load and Improves Memory in an Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a major cause of dementia in the elderly with no effective treatment. Accumulation of amyloid-β peptide (Aβ) in the brain is a pathological hallmark of AD and is believed to be a central disease-causing and disease-promoting event. In a previous study, we showed that deletion of plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissue type and urokinase type plasminogen activators (tPA and uPA), significantly reduced brain Aβ load in APP/PS1 mice, an animal model of familial AD.

Behavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's disease.

Disruption of circadian rhythms is commonly reported in individuals with Alzheimer's disease (AD). Neurons in the primary circadian pacemaker, the suprachiasmatic nucleus (SCN), exhibit daily rhythms in spontaneous neuronal activity which are important for maintaining circadian behavioral rhythms. Disruption of SCN neuronal activity has been reported in animal models of other neurodegenerative disorders; however, the effect of AD on SCN neurophysiology remains unknown.

Inhibition of amyloid Aβ aggregation by high pressures or specific d-enantiomeric peptides.

Pressure can shift the polymer-monomer equilibrium of Aβ, increasing pressure first leads to a release of Aβ-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high pressure NMR spectroscopy, differences of partial molar volumes ΔV0 and compressibility factors Δβ' of polymerization were determined at different temperatures. The d-enantiomeric peptides RD2 and RD2D3 bind to monomeric Aβ with affinities substantially higher than those determined for fibril formation.

Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B action in hippocampus.

Background: PDE4 cyclic nucleotide phosphodiesterases regulate 3', 5' cAMP abundance in the CNS and thereby regulate PKA activity and phosphorylation of CREB, which has been implicated in learning and memory, depression and other functions. The PDE4 isoform PDE4B1 also interacts with the DISC1 protein, implicated in neural development and behavioral disorders. The cellular functions of PDE4B1 have been investigated extensively, but its function(s) in the intact organism remained unexplored.

The Aβ oligomer eliminating D-enantiomeric peptide RD2 improves cognition without changing plaque pathology.

While amyloid-β protein (Aβ) aggregation into insoluble plaques is one of the pathological hallmarks of Alzheimer's disease (AD), soluble oligomeric Aβ has been hypothesized to be responsible for synapse damage, neurodegeneration, learning, and memory deficits in AD. Here, we investigate the in vitro and in vivo efficacy of the D-enantiomeric peptide RD2, a rationally designed derivative of the previously described lead compound D3, which has been developed to efficiently eliminate toxic Aβ42 oligomers as a promising treatment strategy for AD. Besides the detailed in vitro characterization of RD2, we also report the results of a treatment study of APP/PS1 mice with RD2.

Ecology of West Nile virus across four European countries: empirical modelling of the Culex pipiens abundance dynamics as a function of weather.

Background: Culex pipiens is the major vector of West Nile virus in Europe, and is causing frequent outbreaks throughout the southern part of the continent. Proper empirical modelling of the population dynamics of this species can help in understanding West Nile virus epidemiology, optimizing vector surveillance and mosquito control efforts. But modelling results may differ from place to place.

Optimization of d-Peptides for Aβ Monomer Binding Specificity Enhances Their Potential to Eliminate Toxic Aβ Oligomers.

Amyloid-beta (Aβ) oligomers are thought to be causative for the development and progression of Alzheimer's disease (AD). Starting from the Aβ oligomer eliminating d-enantiomeric peptide D3, we developed and applied a two-step procedure based on peptide microarrays to identify D3 derivatives with increased binding affinity and specificity for monomeric Aβ(1-42) to further enhance the Aβ oligomer elimination efficacy. Out of more than 1000 D3 derivatives, we selected seven novel d-peptides, named ANK1 to ANK7, and characterized them in more detail in vitro.

Vitamin A and retinoic acid combination attenuates neonatal hyperoxia-induced neurobehavioral impairment in adult mice.

Preterm infants exposed to supra-physiological levels of oxygen often have poor executive and memory function associated with reductions in hippocampal volume later in life. We recently showed that adult mice exposed to neonatal hyperoxia have deficits in spatial navigation and increased exploratory behavior associated with hippocampal shrinkage. Retinoids attenuate hyperoxia-induced lung injury in animal models and reduce neonatal chronic lung disease in preterm infants.

Retinal changes in the Tg-SwDI mouse model of Alzheimer's disease.

Alzheimer's disease (AD), a debilitating neurodegenerative illness, is characterized by neuronal cell loss, mental deficits, and abnormalities in several neurotransmitter and protein systems. AD is also associated with visual disturbances, but their causes remain unidentified. We hypothesize that the visual disturbances stem from retinal changes, particularly changes in the retinal cholinergic system, and that the etiology in the retina parallels the etiology in the rest of the brain.