Nasal tau immunotherapy clears intracellular tau pathology and improves cognitive functions in aged tauopathy mice.

Pathological tau aggregates cause cognitive decline in neurodegenerative tauopathies, including Alzheimer's disease (AD). These aggregates are prevalent within intracellular compartments. Current tau immunotherapies have shown limited efficacy in clearing intracellular tau aggregates and improving cognition in clinical trials.

Macrocyclic Oxindole Peptide Epoxyketones-A Comparative Study of Macrocyclic Inhibitors of the 20S Proteasome.

Peptide macrocycles have recently gained attention as protease inhibitors due to their metabolic stability and specificity. However, the development of peptide macrocycles with improved binding potency has so far been challenging. Here we present macrocyclic peptides derived from the clinically applied proteasome inhibitor carfilzomib with an oxindole group that mimics the natural product TMC-95A.

Upper and Lower Motor Neurons and the Skeletal Muscle: Implication for Amyotrophic Lateral Sclerosis (ALS).

The relationships between motor neurons and the skeletal muscle during development and in pathologic contexts are addressed in this Chapter.We discuss the developmental interplay of muscle and nervous tissue, through neurotrophins and the activation of differentiation and survival pathways. After a brief overview on muscular regulatory factors, we focus on the contribution of muscle to early and late neurodevelopment.

Exploring what progress is being made in the development of health promotion material for vascular dementia: A systematic review of the evidence.

A systematic review conducted by Price and Keady (Journal of Nursing and Healthcare of Chronic Illness, 2, 88 and 2010) demonstrated that there was a dearth of health-promoting literature available for people diagnosed with vascular dementia. The correlation between health behavior and the onset of cardiovascular change that can lead to vascular dementia had demonstrated a need for health education and health-promoting information to be made accessible to vulnerable populations to ameliorate the risk of cognitive decline because of cardiovascular disease. Dementia is a progressive and life-limiting condition and with limited treatment options and a lack of progress in identifying a way to delay onset or even cure the condition.

Heat shock transcription factors demonstrate a distinct mode of interaction with mitotic chromosomes.

A large number of transcription factors have been shown to bind and interact with mitotic chromosomes, which may promote the efficient reactivation of transcriptional programs following cell division. Although the DNA-binding domain (DBD) contributes strongly to TF behavior, the mitotic behaviors of TFs from the same DBD family may vary. To define the mechanisms governing TF behavior during mitosis in mouse embryonic stem cells, we examined two related TFs: Heat Shock Factor 1 and 2 (HSF1 and HSF2).

Mountaintop removal coal mining impacts on structural and functional indicators in Central Appalachian streams.

Mountaintop removal coal mining (MTR) has been a major source of landscape change in the Central Appalachians of the United States (US). Changes in stream hydrology, channel geomorphology and water quality caused by MTR coal mining can lead to severe impairment of stream ecological integrity. The objective of the Clean Water Act (CWA) is to restore and maintain the ecological integrity of the Nation's waters.

HOTAIR beyond repression: In protein degradation, inflammation, DNA damage response, and cell signaling.

Long noncoding RNAs (lncRNAs) are pervasively transcribed from the mammalian genome as transcripts that are usually >200 nucleotides long. LncRNAs generally do not encode proteins but are involved in a variety of physiological processes, principally as epigenetic regulators. HOX transcript antisense intergenic RNA (HOTAIR) is a well-characterized lncRNA that has been implicated in several cancers and in various other diseases.

Emerging Roles of Protease-Activated Receptors (PARs) in the Modulation of Synaptic Transmission and Plasticity.

Protease-activated receptors (PARs) are a class of G protein-coupled receptors (GPCRs) with a unique mechanism of activation, prompted by a proteolytic cleavage in their N-terminal domain that uncovers a tethered ligand, which binds and stimulates the same receptor. PARs subtypes (PAR1-4) have well-documented roles in coagulation, hemostasis, and inflammation, and have been deeply investigated for their function in cellular survival/degeneration, while their roles in the brain in physiological conditions remain less appreciated. Here, we describe PARs' effects in the modulation of neurotransmission and synaptic plasticity.

Advances in visualizing transcription factor - DNA interactions.

At the heart of the transcription process is the specific interaction between transcription factors (TFs) and their target DNA sequences. Decades of molecular biology research have led to unprecedented insights into how TFs access the genome to regulate transcription. In the last 20 years, advances in microscopy have enabled scientists to add imaging as a powerful tool in probing two specific aspects of TF-DNA interactions: structure and dynamics.

Protease-activated receptor 1 (PAR1) inhibits synaptic NMDARs in mouse nigral dopaminergic neurons.

Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR), whose activation requires a proteolytic cleavage in the extracellular domain exposing a tethered ligand, which binds to the same receptor thus stimulating Gα-, Gα- and Gα proteins. PAR1, activated by serine proteases and matrix metalloproteases, plays multifaceted roles in neuroinflammation and neurodegeneration, in stroke, brain trauma, Alzheimer's diseases, and Parkinson's disease (PD). Substantia nigra pars compacta (SNpc) is among areas with highest PAR1 expression, but current evidence on its roles herein is restricted to mechanisms controlling dopaminergic (DAergic) neurons survival, with controversial data showing PAR1 either fostering or counteracting degeneration in PD models.

Adsorption Behavior of Organic Molecules: A Study of Benzotriazole on Cu(111) with Spectroscopic and Theoretical Methods.

The adsorption of organic molecules on solid substrates is important to applications in fields such as catalysis, photovoltaics, corrosion inhibition, adhesion, and sensors. The molecular level description of the surface-molecule interaction and of the adsorption structures in these complex systems is crucial to understand their properties and function. Here, we present an investigation of one such system, benzotriazole (BTAH) on single-crystal Cu(111) in vacuum conditions.

The mechanism in junctional failure of thoraco-lumbar fusions. Part II: Analysis of a series of PJK after thoraco-lumbar fusion to determine parameters allowing to predict the risk of junctional breakdown.

Purpose: To identify risk factors, in 12 patients with junctional breakdown (JBD) after thoraco-sacral fusions and to test a software locating maximal bending moment on full spine EOS images.

Methods: Twelve patients underwent long fusions for lumbar degenerative pathologies. Preop EOS images were compared to first postop EOS showing JBD.

The mechanism in junctional failure of thoraco-lumbar fusions. Part I: Biomechanical analysis of mechanisms responsible of vertebral overstress and description of the cervical inclination angle (CIA).

Purpose: The purpose of the study is to describe the biomechanical theory explaining junctional breakdowns in thoraco-lumbar fusions, by taking the example of vertebral compression fractures. Also, a new angle, the cervical inclination angle (CIA), describing the relative position of the head at each vertebral level, is presented.

Methods: For the CIA, the data were collected from 137 asymptomatic subjects of a prospective database, containing clinical and radiologic informations.

Team-Based Interprofessional Competency Training for Dementia Screening and Management.

As many as 50% of people satisfying diagnostic criteria for dementia are undiagnosed. A team-based training program for dementia screening and management was developed targeting four professions (medicine, nursing, pharmacy, social work) whose scope of practice involves dementia care. An interprofessional group of 10 faculty members was trained to facilitate four interactive competency stations on dementia screening, differential diagnoses, dementia management and team care planning, and screening for and managing caregiver stress.

Effect of cytostatic proline rich polypeptide-1 on tumor suppressors of inflammation pathway signaling in chondrosarcoma.

Cytokines produced in the tumour microenvironment exert an important role in cancer pathogenesis and in the inhibition of disease progression. Cancer of the cartilage is termed metastatic chondrosarcoma; however, the signaling events resulting in mesenchymal cell transformation to sarcoma have yet to be fully elucidated. The present study aimed to characterize the cytokine expression profile in the human JJ012 chondrosarcoma cell line, as well as the effect of cytostatic proline-rich polypeptide-1 (PRP-1).

A Practice Improvement Education Program Using a Mentored Approach to Improve Nursing Facility Depression Care-Preliminary Data.

Depression is common in nursing facility residents. Depression data obtained using the Minimum Data Set (MDS) 3.0 offer opportunities for improving diagnostic accuracy and care quality.

Preparing the workforce for healthy aging programs: the Skills for Healthy Aging Resources and Programs (SHARP) model.

Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop and test a model community college career technical education program, Skills for Healthy Aging Resources and Programs (SHARP), for undergraduate college students, current personnel in aging service and community organizations, and others interested in retraining.

The Israel Diabetes and Cognitive Decline (IDCD) study: Design and baseline characteristics.

Background: Type 2 diabetes (T2D) is associated with increased risk of dementia. The prospective longitudinal Israel Diabetes and Cognitive Decline study aims at identifying T2D-related characteristics associated with cognitive decline.

Methods: Subjects are population-based T2D 65+, initially cognitively intact.

The interactive effects of PTSD, emotion regulation, and anger management strategies on female-perpetrated IPV.

Research supports a relationship between posttraumatic stress disorder (PTSD) symptoms and intimate partner violence (IPV) perpetration, and theory implicates emotion regulation and anger management skills as probable moderators to that relationship (Chemtob, Novaco, Hamada, Gross, & Smith, 1997). However, no study has investigated these interactive relationships with female-perpetrated physical IPV. Therefore, this study examined the interactive effects of PTSD symptoms, emotion regulation, and anger management skills on female-perpetrated physical IPV.

Addressing patient alcohol use: a view from general practice.

Introduction: General practitioners (GPs) have the potential to promote alcohol harm minimisation via discussion of alcohol use with patients, but knowledge of GPs' current practice and attitudes on this matter is limited. Our aim was to assess GPs' current practice and attitudes towards discussing alcohol use with their patients.

Methods: This qualitative study involved semi-structured, face-to-face interviews with 19 GPs by a group of medical students in primary care practices in Wellington, New Zealand.

California Geriatric Education Center logic model: an evaluation and communication tool.

A logic model is a communications tool that graphically represents a program's resources, activities, priority target audiences for change, and the anticipated outcomes. This article describes the logic model development process undertaken by the California Geriatric Education Center in spring 2008. The CGEC is one of 48 Geriatric Education Centers across the nation, funded by the U.

Selective adhesion and mineral deposition by osteoblasts on carbon nanofiber patterns.

In an effort to develop better orthopedic implants, osteoblast (bone-forming cells) adhesion was determined on microscale patterns (30 microm lines) of carbon nanofibers placed on polymer substrates. Patterns of carbon nanofibers (CNFs) on a model polymer (polycarbonate urethane [PCU]) were developed using an imprinting method that placed CNFs in selected regions. Results showed the selective adhesion and alignment of osteoblasts on CNF patterns placed on PCU.

Increased osteoblast functions on theta + delta nanofiber alumina.

Nanophase materials, or materials with grain sizes less than 100 nm in at least one direction, are promising materials for various implant applications since our tissues are composed of nanometer components (i.e., proteins and/or inorganics).

Nanometer surface roughness increases select osteoblast adhesion on carbon nanofiber compacts.

Carbon nanofibers have exceptional theoretical mechanical properties (such as low weight-to-strength ratios) that, along with possessing nanoscale fiber dimensions similar to crystalline hydroxyapatite found in bone, suggest strong possibilities for use as an orthopedic/dental implant material. To determine, for the first time, cytocompatibility properties pertinent for bone prosthetic applications, osteoblast (bone-forming cells), fibroblast (cells contributing to callus formation and fibrous encapsulation events that result in implant loosening), chondrocyte (cartilage-forming cells), and smooth muscle cell (for comparison purposes) adhesion were determined on carbon nanofibers in the present in vitro study. Results provided evidence that, compared to conventional carbon fibers, nanometer dimension carbon fibers promoted select osteoblast adhesion.