Prevalence of movement asymmetries in high-performing riding horses perceived as free from lameness and riders' perception of horse sidedness.

A high proportion of horses in training, perceived as free from lameness by their owner, exhibit vertical movement asymmetries. These types of asymmetries are sensitive measures of lameness, but their specificity as indicators of orthopaedic pathology or locomotor function remains unclear. Equine athletes performing at a high level could be assumed to exhibit a higher degree of movement symmetry compared with the general horse population, but this has not been confirmed.

Perceived sidedness and correlation to vertical movement asymmetries in young warmblood horses.

The prevalence of vertical asymmetries is high in "owner-sound" warmblood riding horses, however the origin of these asymmetries is unknown. This study investigated correlations between vertical asymmetries and motor laterality. Young warmblood riding horses (N = 65), perceived as free from lameness were evaluated on three visits, each comprising objective gait analysis (inertial measurement units system) and a rider questionnaire on perceived sidedness of the horse.

Serum nerve growth factor in horses with osteoarthritis-associated lameness.

Background: Nerve growth factor (NGF) is a neurotrophin that is increased in osteoarthritic joints of horses. In humans, NGF has been associated with pain, and both synovial and serum NGF concentrations are increased in osteoarthritic patients. Studies in humans also have shown that serum NGF concentration can increase with stress.

Prevalence of vertical movement asymmetries at trot in Standardbred and Swedish Warmblood foals.

Many horses, just before and during their athletic career, show vertical movement asymmetries, to the same degree as clinically lame horses. It is unknown whether these asymmetries are caused by pain or have alternative explanations, such as inherent biological variation. In the latter case, movement asymmetries would be expected to be present at a very young age.

INTERPROFESSIONAL ROLES AND COLLABORATIONS TO ADDRESS COVID-19 PANDEMIC CHALLENGES IN NURSING HOMES.

Nursing home experts and informatics nurses collaborated to develop guidelines for nursing homes that revealed partnership principles in action during the COVID-19 pandemic. This article describes efforts to define interprofessional nursing home staff roles within the partnership-based COVID-19 Response Guideline, and to examine changes in nursing practice compared to the pre-pandemic practice of nurses. The qualitative process of identification of nursing home staff roles revealed the extensive scope of interprofessional partnership needed to respond to the pandemic.

Reduced affinity of calcium sensing-receptor heterodimers and reduced mutant homodimer trafficking combine to impair function in a model of familial hypocalciuric hypercalcemia type 1.

Heterozygous loss-of-function mutation of the calcium sensing-receptor (CaSR), causes familial hypocalciuric hypercalcemia type 1 (FHH1), a typically benign condition characterized by mild hypercalcemia. In contrast, homozygous mutation of this dimer-forming G-protein coupled receptor manifests as the lethal neonatal severe hyperparathyroidism (NSHPT). To investigate the mechanisms by which CaSR mutations lead to these distinct disease states, we engineered wild-type (WT) and an exon 5-deficient disease-causing mutation, and transfected expression constructs into human embryonic kidney (HEK) cells.

Towards Machine Recognition of Facial Expressions of Pain in Horses.

Automated recognition of human facial expressions of pain and emotions is to a certain degree a solved problem, using approaches based on computer vision and machine learning. However, the application of such methods to horses has proven difficult. Major barriers are the lack of sufficiently large, annotated databases for horses and difficulties in obtaining correct classifications of pain because horses are non-verbal.

Effect of transportation and social isolation on facial expressions of healthy horses.

Horses have the ability to generate a remarkable repertoire of facial expressions, some of which have been linked to the affective component of pain. This study describes the facial expressions in healthy horses free of pain before and during transportation and social isolation, which are putatively stressful but ordinary management procedures. Transportation was performed in 28 horses by subjecting them to short-term road transport in a horse trailer.

Local Anesthetic Systemic Toxicity Complicating Thyroid Biopsy.

The overdiagnosis of thyroid malignancies may be contributing to the increased incidence of these cancers with a relatively stable mortality rate. We present the case of a man with known malignancies, who underwent biopsy of a suspicious thyroid nodule. This procedure was complicated by local anesthetic systemic toxicity (LAST).

Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus.

Objective: Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes.

Research Design And Methods: We identified 2,435 patients with diabetes who underwent interferon-free and ribavirin-free DAA-based antiviral treatment for HCV in the national Veterans Affairs health care system.

Nicotinamide adenine dinucleotide-induced multimerization of the co-repressor CtBP1 relies on a switching tryptophan.

The transcriptional co-repressor C-terminal binding protein (CtBP) interacts with a number of repressor proteins and chromatin modifying enzymes. How the biochemical properties including binding of dinucleotide, oligomerization, and dehydrogenase domains of CtBP1 direct the assembly of a functional co-repressor to influence gene expression is not well understood. In the current study we demonstrate that CtBP1 assembles into a tetramer in a NAD(H)-dependent manner, proceeding through a dimeric intermediate.

On how to increase safety innovations.

In this action research study, we show by several cases that a synthetic innovation style in combination with an entrepreneurial culture might increase innovations for safety. Rational decisions and early product specifications were replaced by a natural selection of ideas in an acting reality to have the most fitted ideas among the actors. The forthcoming ideas actually ruled the development of the process and the business set-up like in an entrepreneurial culture.

The PARP inhibitor PJ34 causes a PARP1-independent, p21 dependent mitotic arrest.

Poly(ADP)-ribose polymerase (PARP) inhibitors modify the enzymatic activity of PARP1/2. When certain PARP inhibitors are used either alone or in combination with DNA damage agents they may cause a G2/M mitotic arrest and/or apoptosis in a susceptible genetic context. PARP1 interacts with the cell cycle checkpoint proteins Ataxia Telangectasia Mutated (ATM) and ATM and Rad3-related (ATR) and therefore may influence growth arrest cascades.

C-terminal binding protein and poly(ADP)ribose polymerase 1 contribute to repression of the p21(waf1/cip1) promoter.

Transcriptional repression by the C-terminal binding protein (CtBP) is proposed to require nicotinamide adenine dinucleotide dehydrogenase (NAD(H). Previous studies have implicated CtBP in transcriptional repression of the p21(waf1/cip1) gene. Similarly, the NAD-dependent poly(adenosine diphosphate)ribose polymerase 1 (PARP1) may affect p21 expression via its NAD-dependent enzymatic activity; we therefore asked if PARP1 and CtBP were functionally linked in regulating p21 transcription.

A non-isotopic in vitro assay for histone acetylation.

We describe a simple, robust, and relatively inexpensive non-radioactive in vitro assay for measuring histone acetyl-transferase activity. The assay takes advantage of easy to purify recombinant E. coli-derived fusion proteins containing the NH(2)-terminal tails of histones H3 and H4 linked to epitope-tagged maltose-binding protein (MBP), and immunoblotting with antibodies specific to acetylated H3 and H4.

Acetylation of cAMP-responsive element-binding protein (CREB) by CREB-binding protein enhances CREB-dependent transcription.

The coactivator function of cAMP-responsive element-binding protein (CREB)-binding protein (CBP) is partly caused by its histone acetyltransferase activity. However, it has become increasingly clear that CBP acetylates both histones and non-histone proteins, many of which are transcription factors. Here we investigate the role of CBP acetylase activity in CREB-mediated gene expression.

A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span.

Control of chromosome structure is important in the regulation of gene expression, recombination, DNA repair, and chromosome stability. In a two-hybrid screen for proteins that interact with the Drosophila CREB-binding protein (dCBP), a known histone acetyltransferase and transcriptional coactivator, we identified the Drosophila homolog of a yeast chromatin regulator, Sir2. In yeast, Sir2 silences genes via an intrinsic NAD(+)-dependent histone deacetylase activity.

Acetylation of the adenovirus-transforming protein E1A determines nuclear localization by disrupting association with importin-alpha.

Posttranslational modifications may alter the biochemical functions of a protein by modifying associations with other macromolecules, allosterically altering intrinsic catalytic activities, or determining subcellular localization. The adenovirus-transforming protein E1A is acetylated by its cellular targets, the co-activators CREB-binding protein, p300, and p300/CREB-binding protein-associated factor in vitro and also in vivo at a single lysine residue (Lys(239)) within a multifunctional carboxyl-terminal domain necessary for both nuclear localization and interaction with the transcriptional co-repressor carboxyl-terminal binding protein (CtBP). In contrast to a previous report, we demonstrate that acetylation of Lys(239) does not disrupt CtBP binding and that 12 S E1A-mediated repression of CREB-binding protein-dependent transcription does not require recruitment of CtBP.

Altered processing of pro-orphanin FQ/nociceptin and pro-opiomelanocortin-derived peptides in the brains of mice expressing defective prohormone convertase 2.

The bioactivity of neuropeptides can be regulated by a variety of post-translational modifications, including proteolytic processing. Here, gene-targeted mice producing defective prohormone convertase 2 (PC2) were used to examine the post-translational processing of two neuroendocrine prohormones, pro-opiomelanocortin (POMC) and pro-orphanin FQ (pOFQ)/nociceptin (N), in the brain. Reversed-phase HPLC and gel-exclusion chromatography were combined with specific radioimmunoassays to analyze the processing patterns of these two prohormones in the hypothalamus and the amygdala.

The coactivator CBP stimulates human T-cell lymphotrophic virus type I Tax transactivation in vitro.

Tax interacts with the cellular cyclic AMP-responsive element binding protein (CREB) and facilitates the binding of the coactivator CREB binding protein (CBP), forming a multimeric complex on the cyclic AMP-responsive element (CRE)-like sites in the human T-cell lymphotrophic virus type I (HTLV-I) promoter. The trimeric complex is believed to recruit additional regulatory proteins to the HTLV-I long terminal repeat, but there has been no direct evidence that CBP is required for Tax-mediated transactivation. We present evidence that Tax and CBP activate transcription from the HTLV-I 21 base pair repeats on naked DNA templates.

The human T-cell leukemia virus-1 transcriptional activator Tax enhances cAMP-responsive element-binding protein (CREB) binding activity through interactions with the DNA minor groove.

Tax-1, the transcriptional activation protein of human T-cell leukemia virus-1, increases transcription from the human T-cell leukemia virus-1 long terminal repeat and specific cellular promoters through interactions with cellular DNA-binding proteins. The Tax response elements (TxREs) of the long terminal repeat resemble cAMP response elements (CREs), the target of cAMP-responsive element-binding protein (CREB). CREB binds the TxRE with reduced affinity; however, the interaction is specifically enhanced by Tax.

Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms.

We have previously proposed that cAMP-responsive element-binding protein (CREB) activity is stimulated by human T-cell lymphotropic virus-1 (HTLV-1) Tax through two mechanisms that are differentially dependent upon CREB phosphorylation. We have tested this model by examining how Tax affects transcriptional activation mediated by the cAMP-responsive element (CRE) modulator (CREM). The CREM proteins are highly homologous to CREB, particularly in their DNA-binding domains and the kinase-inducible domain (KID), a region that interacts with the coactivator CREB-binding protein (CBP) in a phosphorylation-dependent manner.

Fluorescence polarization analysis of protein-DNA and protein-protein interactions.

Fluorescence polarization is a powerful technique for characterizing macromolecular associations and can provide equilibrium determinations of protein-DNA and protein-protein interactions. This technique is particularly useful (and better suited than electrophoretic methods) to study low affinity protein-protein interactions. In this review, we have outlined the principles underlying the use of fluorescence polarization to study the assembly of higher order complexes that bind to the CRE.