Impacts of adapted dance on mood and physical function among persons living with Alzheimer's disease.

Background: Most individuals living with Alzheimer's disease and related dementias (ADRD) experience one or more neuropsychiatric symptoms, such as agitation which negatively impacts their quality of life. Adapted dance integrates recorded music and movement that is appropriate for people with cognitive limitations. Adapted dance may be an enjoyable activity for persons living with ADRD and may provide psychological and physical benefits.

Exercise-Induced Antisenescence and Autophagy Restoration Mitigate Metabolic Disorder-Induced Cardiac Disruption in Mice.

Introduction: Metabolic disorder promotes premature senescence and poses more severe cardiac dysfunction in females than males. Although endurance exercise (EXE) has been known to confer cardioprotection against metabolic diseases, whether EXE-induced cardioprotection is associated with mitigating senescence in females remains unknown. Thus, the aim of the present study was to examine metabolic disorder-induced cardiac anomalies (cellular senescence, metabolic signaling, and autophagy) using a mouse model of obese/type 2 diabetes induced by a high-fat/high-fructose (HFD/HF) diet.

A spatial study of bladder cancer mortality and incidence in the contiguous US: 2000-2014.

Bladder cancer is a significant health issue across the United States of America (USA). Evidence of unequal distribution of a disease or condition's incidence and mortality would suggest that important geographically-defined variables may play a role. In this study, a spatial cluster analysis of bladder cancer mortality identified significant hot spots in some parts of the USA.

Adhesion, forces and the stability of interfaces.

Weak molecular interactions (WMI) are responsible for processes such as physisorption; they are essential for the structure and stability of interfaces, and for bulk properties of liquids and molecular crystals. The dispersion interaction is one of the four basic interactions types - electrostatics, induction, dispersion and exchange repulsion - of which all WMIs are composed. The fact that each class of basic interactions covers a wide range explains the large variety of WMIs.

Geographic Clusters of Alzheimer's Disease Mortality Rates in the USA: 2008-2012.

Importance: The results identified geographic clusters of high and low Alzheimer's disease (AD)-related mortality across the contiguous United States. These clusters identify specific geographic groupings of counties that allow researchers to narrow the focus to identify some of the biopsychosocial variables contributing to increased or decreased AD mortality.

Objectives: To determine the extent to which geographic clusters exist where AD mortality significantly differs from the national average.

A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project.

Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France.

Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis.

Vancomycin is a key antibiotic used in the treatment of multiple conditions including infections associated with cystic fibrosis and methicillin-resistant Staphylococcus aureus. The present study sought to develop a model based on empirical evidence of optimal vancomycin dose as judged by clinical observations that could accelerate the achievement of desired trough level in children with cystic fibrosis. Transformations of dose and trough were used to arrive at regression models with excellent fit for dose based on weight or age for a target trough.

Dispersion Interactions and the Stability of Amine Dimers.

Weak, intermolecular interactions in amine dimers were studied by using the combination of a dispersionless density functional and a function that describes the dispersion contribution to the interaction energy. The validity of this method was shown by comparison of structural and energetic properties with data obtained with a conventional density functional and the coupled cluster method. The stability of amine dimers was shown to depend on the size, the shape, and the relative orientation of the alkyl substituents, and it was shown that the stabilization energy for large substituents is dominated by dispersion interactions.

Calcineurin proteolysis in astrocytes: Implications for impaired synaptic function.

Mounting evidence suggests that astrocyte activation, found in most forms of neural injury and disease, is linked to the hyperactivation of the protein phosphatase calcineurin. In many tissues and cell types, calcineurin hyperactivity is the direct result of limited proteolysis. However, little is known about the proteolytic status of calcineurin in activated astrocytes.

Phage display for identification of serum biomarkers of traumatic brain injury.

Background: The extent and severity of traumatic brain injuries (TBIs) can be difficult to determine with current diagnostic methods. To address this, there has been increased interest in developing biomarkers to assist in the diagnosis, determination of injury severity, evaluation of recovery and therapeutic efficacy, and prediction of outcomes. Several promising serum TBI biomarkers have been identified using hypothesis-driven approaches, largely examining proteins that are abundant in neurons and non-neural cells in the CNS.

Imaging of hepatocellular carcinoma patient-derived xenografts using ⁸⁹Zr-labeled anti-glypican-3 monoclonal antibody.

Imaging probes for early detection of hepatocellular carcinoma (HCC) are highly desired to overcome current diagnostic limitations which lead to poor prognosis. The membrane protein glypican-3 (GPC3) is a potential molecular target for early HCC detection as it is over-expressed in >50% of HCCs, and is associated with early hepatocarcinogenesis. We synthesized the positron emission tomography (PET) probe (89)Zr-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with (89)Zr, and evaluated its tumor-targeting capacity.

Calpain cleaves methionine aminopeptidase-2 in a rat model of ischemia/reperfusion.

Ischemic stroke results in multiple injurious signals within a cell including dysregulation of calcium homeostasis. Consequently, there is an increase in the enzymatic activity of the calpains, calcium dependent proteases that are thought to contribute to neuronal injury. In addition, cellular stress due to ischemia/reperfusion also triggers a decrease in protein translation through activation of the unfolded protein response (UPR).

Redox regulation of cysteine-dependent enzymes in neurodegeneration.

Evidence of increased oxidative stress has been found in various neurodegenerative diseases and conditions. While it is unclear whether oxidative stress is a cause or effect, protein, lipid, and DNA have all been found to be susceptible to oxidant-induced modifications that alter their function. Results of clinical trials based on the oxidative-stress theory have been mixed, though data continues to indicate that prevention of high levels of oxidative stress is beneficial for health and increases longevity.

Thiol-protease oxidation in age-related neuropathology.

Increased oxidative stress is a hallmark of every major neurodegenerative disease that has been studied. Numerous biomarkers of oxidative stress have been found, indicating that waves of oxidation had, at one time or another, overwhelmed antioxidant defenses, leaving behind a host of oxidized DNA, lipids, and proteins in their path. Although some level of oxidation may be beneficial, perhaps mediated by a hormetic response, the extent and types of oxidation detected in neuropathological states would suggest that oxidative stress contributes to a loss of homeostasis and cellular dysfunction.

Proteolysis of calcineurin is increased in human hippocampus during mild cognitive impairment and is stimulated by oligomeric Abeta in primary cell culture.

Recent reports demonstrate that the activation and interaction of the protease calpain (CP) and the protein phosphatase calcineurin (CN) are elevated in the late stages of Alzheimer's disease (AD). However, the extent to which CPs and CN interact during earlier stages of disease progression remains unknown. Here, we investigated CP and CN protein levels in cytosolic, nuclear, and membrane fractions prepared from human postmortem hippocampal tissue from aged non-demented subjects, and subjects diagnosed with mild cognitive impairment (MCI).

Redox regulation of cysteine-dependent enzymes.

It is well-established that maintenance of the intracellular redox (i.e., reduction-oxidation) state is critical for cell survival and that prolonged or abnormal perturbations toward oxidation result in cell dysfunction.

NMR structural characterization of the penta-peptide calpain inhibitor.

Calpains are ubiquitous intracellular calcium- and thiol-dependent proteases. Their over activation, resulting in the degradation of various substrates, has been implicated in a number of cardiovascular and neurological disorders. Here, we present the first structural characterization of LSEAL penta-peptide, a potent calpain inhibitor, bound to the calmodulin-like domain of calpain.

Protease activity in post-mortem red swamp crayfish (Procambarus clarkii) muscle stored in modified atmosphere packaging.

Protease activity during storage is thought to be an important contributor to decreased shelf life of fresh seafood. To examine this, three batches of red swamp crayfish ( Procambarus clarkii) tails, placed on trays, were packed with a polyvinyl chloride film (aerobic packaging or AP), under vacuum (vacuum packaging or VP), or under a modified atmosphere (MAP: 80% CO 2/10% O 2/10% N 2), and proteolytic activity was measured on days 0, 1, 3, 6, and 10 during storage at 2 degrees C. The crude extract from the crayfish digestive system (gut) did not have an apparent role in muscle proteolysis as negligible proteolytic activity was detected.

Identification and characterization of PEBP as a calpain substrate.

Calpains are calcium- and thiol-dependent proteases whose dysregulation has been implicated in a number of diseases and conditions such as cardiovascular dysfunction, ischemic stroke, and Alzheimer's disease (AD). While the effects of calpain activity are evident, the precise mechanism(s) by which dysregulated calpain activity results in cellular degeneration are less clear. In order to determine the impact of calpain activity, there is a need to identify the range of specific calpain substrates.

Inhibition of calpain-mediated cell death by a novel peptide inhibitor.

Calpains are calcium- and thiol-dependent proteases whose overactivation and degradation of various substrates have been implicated in a number of diseases and conditions such as cardiovascular dysfunction and ischemic stroke. With increasing evidence for calpain's role in cellular damage, the development of calpain inhibitors continues to be an important objective. Previously, we identified a highly specific calcium-dependent, calpain interacting peptide L-S-E-A-L, that showed homology to domains A and C of the only known endogenous inhibitor of calpains, calpastatin.

Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas.

Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, plays a role in cell growth, differentiation, and migration. The objectives of this study were to assess the diagnostic value of GPC3 immunostaining in hepatocellular carcinomas (HCCs) and to analyze its expression profile in preneoplastic lesions. Tissue microarrays were built by sampling 54 HCCs and adjacent liver tissues (21 developing from cirrhosis and 33 from normal liver) and 94 cirrhotic macronodules.

Oxidation of thiol-proteases in the hippocampus of Alzheimer's disease.

The hippocampus of Alzheimer's disease brain has been shown to be highly oxidized compared to age-matched controls. One of the most sensitive targets of oxidation is anionic sulfur which can be found within the active site of members of the cysteine-protease family. Thus, while members of the cysteine-protease family such as the calpains and caspases have been found to be in an active conformation in vulnerable brain regions in AD it is possible that their proteolytic activity is hampered due to the robust oxidative stress found at these locations.

Identification of a novel calpain inhibitor using phage display.

Calpains are calcium- and thiol-dependent proteases that cleave a variety of intracellular substrates. Overactivation of the calpains has been implicated in a number of diseases and conditions such as ischemic stroke indicating a need for the development of calpain inhibitors. A major problem with current calpain inhibitors has been specific targeting to calpain.

Oxidative stress inhibits ionomycin-mediated cell death in cortical neurons.

Thiol-proteases play important roles in many cellular processes, including maintenance of protein homeostasis and execution of cell death. Therefore, determining how this family of enzymes is regulated is critical for our understanding of both physiological and pathological conditions. Because these proteases require a reduced cysteine residue for activity, the cellular redox state plays a crucial role in regulating the activity of thiol proteases.