Post-partum longissimus dorsi muscle loss, but not back fat, is associated with resumption of postpartum ovarian activity in dairy cattle

The objectives of this observational cohort study were to assess the effect of body condition score change, back fat depth change, and muscle diameter change on the time to commencement of luteal activity and first estrus in commercial pedigree Holstein cows. One hundred and 40 of 200 commercial pedigree Holstein cows were enrolled in one dairy herd in Somerset, United Kingdom, over 52 weeks in 2021-22. The herd used 4 automatic milking machines with in-line progesterone measurement capability to determine commencement of luteal activity and time to first estrus. Cows were followed until at least 60 d postpartum and milk progesterone measured daily starting from 10 DIM. Body condition scoring and ultrasound measurements of back fat depth and Longissimus dorsi muscle diameter were performed on cows twice: within 7 d of both calving and 60 DIM. Other explanatory variables assessed included parity, 60-d and 305-d milk yield, and subclinical ketosis (β-hydroxybutryate (βHB) ≥ 1.2mmol/L). Occurrence of clinical disease 8 mm was associated with the longest times to luteal activity and first estrus. In addition to being affected by muscle loss, commencement of luteal activity was delayed by subclinical ketosis, clinical disease, and failure to gain body condition to 60 DIM. Cows that had a BCS loss of 0.25 or more between calving and 60 DIM were at least 52 ± 22% less likely to have commenced luteal activity compared with those that gained BCS. Interestingly, cows that had no change in body condition score commenced luteal activity later than those that gained body condition score. Muscle loss was associated with time to first estrus irrespective of clinical disease status. Cows that lost > 8 mm of muscle diameter showed estrus behavior later than cows that lost 1.5 to 5 mm. In conclusion, our findings indicate that extensive muscle loss postpartum was associated with a delayed start to luteal activity and first estrus irrespective of body condition change, clinical disease, and subclinical ketosis. Marginal muscle loss and a gain in body condition, however, were associated with an earlier start to luteal activity and first estrus

Report of a Joint Cancer Research UK/Medical Research Council workshop on cancer cachexia research at the Royal College of Physicians, Tuesday, 2 December 2003

A joint workshop held by Cancer Research UK and the Medical Research Council aimed to stimulate interest in further research into the area of cancer cachexia. The workshop was divided into four sessions: an overview of cancer cachexia, potential mechanisms involved and methodologies that might be used to understand cachexia, and also the experience of cachexia from other disease areas. The workshop identified a need to develop a multimodal therapeutic approach to cancer cachexia and a need to undertake more multidisciplinary research

Human-animal interactions and machine-animal interactions in animals under human care: a summary of stakeholder and researcher perceptions and future directions

Animals under human care are exposed to a potentially large range of both familiar and unfamiliar humans. Human-animal interactions vary across settings, and individuals, with the nature of the interaction being affected by a suite of different intrinsic and extrinsic factors. These interactions can be described as positive, negative or neutral. Across some industries, there has been a move towards the development of technologies to support or replace human interaction with animals. Whilst this has many benefits, there can also be challenges associated with increased technology use. A day-long Animal Welfare Research Network workshop was hosted at Harper Adams University, UK, with the aim of bringing together stakeholders and researchers (n = 38) from the companion, farm and zoo animal fields, to discuss benefits, challenges and limitations of human-animal interactions and machine-animal interactions for animals under human care and create a list of future research priorities. The workshop consisted of four talks from experts within these areas, followed by break-out room discussions. This work is the outcome of that workshop. The key recommendations are that approaches to advancing the scientific discipline of machine-animal interactions in animals under human care should focus on: (1) interdisciplinary collaboration; (2) development of validated methods; (3) incorporation of an animal-centred perspective; (4) a focus on promotion of positive animal welfare states (not just avoidance of negative states); and (5) an exploration of ways that machines can support a reduction in the exposure of animals to negative human-animal interactions to reduce negative, and increase positive, experiences for animals

Protein kinase A regulatory subunit distribution in medulloblastoma

<p>Abstract</p> <p>Background</p> <p>Previous studies showed a differential distribution of the four regulatory subunits of cAMP-dependent protein kinases inside the brain, that changed in rodent gliomas: therefore, the distribution of these proteins inside the brain can give information on the functional state of the cells. Our goal was to examine human brain tumors to provide evidence for a differential distribution of protein kinase A in different tumors.</p> <p>Methods</p> <p>The distribution of detergent insoluble regulatory (R1 and R2) and catalytic subunits of cAMP dependent kinases was examined in pediatric brain tumors by immunohistochemistry and fluorescent cAMP analogues binding.</p> <p>Results</p> <p>R2 is organized in large single dots in medulloblastomas, while it has a different appearance in other tumors. Fluorescent cAMP labelling was observed only in medulloblastoma.</p> <p>Conclusions</p> <p>A different distribution of cAMP dependent protein kinases has been observed in medulloblastoma.</p

Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity

Background: The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).Methods: Female patients (n = 15) and controls (n = 15) performed a cardiopulmonary exercise test (CPET) by cycling at a continuously increased work rate till maximal exertion. The CPET was repeated 24 h later. Before the tests, blood was taken for the isolation of peripheral blood mononuclear cells (PBMC), which were processed in a special way to preserve their oxidative phosphorylation, which was tested later in the presence of ADP and phosphate in permeabilized cells with glutamate, malate and malonate plus or minus the complex I inhibitor rotenone, and succinate with rotenone plus or minus the complex II inhibitor malonate in order to measure the ATP production via Complex I and II, respectively. Plasma CK was determined as a surrogate measure of a decreased oxidative phosphorylation in muscle, since the previous finding that in a group of patients with external ophthalmoplegia the oxygen consumption by isolated muscle mitochondria correlated negatively with plasma creatine kinase, 24 h after exercise.Results: At both exercise tests the patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients. In the past this was also found in patients with defects in the mitochondrial oxidative phosphorylation. However the oxidative phosphorylation in PBMC was similar in CFS/ME patients and controls. The plasma creatine kinase levels before and 24 h after exercise were low in patients and controls, suggesting normality of the muscular mitochondrial oxidative phosphorylation.Conclusion: The decrease in mitochondrial ATP synthesis in the CFS/ME patients is not caused by a defect in the enzyme complexes catalyzing oxidative phosphorylation, but in another factor

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral Sclerosis

BACKGROUND: Widespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS) has been described in neuropathological studies. The presence of cortical atrophy in conventional and scientific neuroimaging has been a matter of debate. In studies using computertomography, positron emission tomography, proton magnetic resonance spectroscopy and conventional T2-weighted and proton-weighted images, results have been variable. Recent morphometric studies by magnetic resonance imaging have produced conflicting results regarding the extent of grey and white matter involvement in ALS patients. METHODS: The authors used optimized voxel-based morphometry as an unbiased whole brain approach to detect differences between regional grey and white matter volumes. Seventeen patients with a diagnosis of ALS according to El-Escorial criteria and seventeen age-matched controls received a high resolution anatomical T1 scan. RESULTS: In ALS patients regional grey matter volume (GMV) reductions were found in the pre- and postcentral gyrus bilaterally which extended to premotor, parietal and frontal regions bilaterally compared with controls (p < 0.05, corrected for the entire volume). The revised ALS functional rating scale showed a positive correlation with GMV reduction of the right medial frontal gyrus corresponding to the dorsolateral prefrontal cortex. No significant differences were found for white matter volumes or when grey and white matter density images were investigated. There were no further correlations with clinical variables found. CONCLUSION: In ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent feature of the disease. Supporting the concept of ALS being a multisytem disorder, our study provides further evidence for extramotor involvement which is widespread. The lack of correlation with common clinical variables probably reflects the fact that heterogeneous disease processes underlie ALS. The discrepancy within all published morphometric studies in ALS so far may be related to differences in patient cohorts and several methodological factors of the data analysis process. Longitudinal studies are required to further clarify the time course and distribution of grey and white matter pathology during the course of ALS

Upregulation of P2Y2 receptors by retinoids in normal human epidermal keratinocytes

Retinoids, vitamin A derivatives, are important regulators of the growth and differentiation of skin cells. Although retinoids are therapeutically used for several skin ailments, little is known about their effects on P2 receptors, known to be involved in various functions in the skin. DNA array analysis showed that treatment of normal human epidermal keratinocytes (NHEKs) with all-trans-retinoic acid (ATRA), an agonist to RAR (retinoic acid receptor), enhanced the expression of mRNA for the P2Y2 receptor, a metabotropic P2 receptor that is known to be involved in the proliferation of the epidermis. The expression of other P2 receptors in NHEKs was not affected by ATRA. ATRA increased the mRNA for the P2Y2 receptor in a concentration-dependent fashion (1 nM to 1 μM). Am80, a synthesized agonist to RAR, showed a similar enhancement, whereas 9-cis-retinoic acid (9-cisRA), an agonist to RXR (retinoid X receptor), enhanced P2Y2 gene expression to a lesser extent. Ca2+ imaging analysis showed that ATRA also increased the function of P2Y2 receptors in NHEKs. Retinoids are known to enhance the turnover of the epidermis by increasing both proliferation and terminal differentiation. The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs. Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs. This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling