Monoaminergic Neuropathology in Alzheimer's disease

Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138.Peer reviewedPostprin

An Investigation into the Perceptions of Veterinarians towards Perioperative Pain Management in Calves

While veterinarians are instrumental to the welfare of calves (Bos taurus), limited knowledge exists concerning veterinary perceptions towards perioperative pain management in calves. As a part of a larger, nationwide study investigating the perceptions of veterinarians towards calf welfare, the current work sought to quantify veterinary perceptions towards perioperative pain management, including barriers to its use, and investigate demographic influences affecting those perceptions. An electronic mixed-methods survey was completed by 104 veterinarians registered with the Veterinary Council of New Zealand. The current work revealed that most veterinarians considered a multimodal approach as the most effective method for ameliorating perioperative pain in calves, rejected the practice of differential treatment based on developmental age, and perceived that postprocedural pain persists beyond 24 h for the majority of procedures included in the survey. Despite this, veterinarians identified certain barriers that may inhibit the provision of pain mitigation on-farm, including costs, inadequate recognition of pain, and ingrained farming practices. Certain demographic effects were found to influence perceptions towards perioperative pain management, including gender, the number of years since graduation, and species emphasis. Nevertheless, the current work demonstrated considerable support among veterinarians to improve pain management protocols during routine husbandry procedures. The asymmetries that exist between the current minimum provisions of perioperative pain management and veterinary perspectives suggest that substantive improvements are necessary in order to reconcile New Zealand’s existing regulatory regime with developments in scientific knowledge

ALTERATIONS IN THE GLUTAMATERGIC SYSTEM AND THEIR ASSOCIATIONS WITH CLINICAL AND NEUROPATHOLOGICAL FEATURES OF NEURODEGENERATIVE DISEASES

Ph.DDOCTOR OF PHILOSOPH

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases

Mutations in NR2E3, a gene encoding an orphan nuclear transcription factor, cause two retinal dystrophies with a distinct phenotype, but the precise role of NR2E3 in rod and cone transcriptional networks remains unclear. To dissect NR2E3 function, we performed scRNA-seq in the retinas of wildtype and two different Nr2e3 mouse models that show phenotypes similar to patients carrying NR2E3 mutations. Our results reveal that rod and cone populations are not homogeneous and can be separated into different sub-classes. We identify a previously unreported cone pathway that generates hybrid cones co-expressing both cone- and rod-related genes. In mutant retinas, this hybrid cone subpopulation is more abundant and includes a subpopulation of rods transitioning towards a cone cell fate. Hybrid photoreceptors with high misexpression of cone- and rod-related genes are prone to regulated necrosis. Overall, our results shed light on the role of NR2E3 in modulating photoreceptor differentiation towards cone and rod fates and explain how different mutations in NR2E3 lead to distinct visual disorders in humans

Animal board invited review: Animal source foods in healthy, sustainable, and ethical diets – An argument against drastic limitation of livestock in the food system

Animal source foods are evolutionarily appropriate foods for humans. It is therefore remarkable that they are now presented by some as unhealthy, unsustainable, and unethical, particularly in the urban West. The benefits of consuming them are nonetheless substantial, as they offer a wide spectrum of nutrients that are needed for cell and tissue development, function, and survival. They play a role in proper physical and cognitive development of infants, children, and adolescents, and help promote maintenance of physical function with ageing. While high-red meat consumption in the West is associated with several forms of chronic disease, these associations remain uncertain in other cultural contexts or when consumption is part of wholesome diets. Besides health concerns, there is also widespread anxiety about the environmental impacts of animal source foods. Although several production methods are detrimental (intensive cropping for feed, overgrazing, deforestation, water pollution, etc.) and require substantial mitigation, damaging impacts are not intrinsic to animal husbandry. When well-managed, livestock farming contributes to ecosystem management and soil health, while delivering high-quality foodstuffs through the upcycling of resources that are otherwise non-suitable for food production, making use of marginal land and inedible materials (forage, by-products, etc.), integrating livestock and crop farming where possible has the potential to benefit plant food production through enhanced nutrient recycling, while minimising external input needs such as fertilisers and pesticides. Moreover, the impacts on land use, water wastage, and greenhouse gas emissions are highly contextual, and their estimation is often erroneous due to a reductionist use of metrics. Similarly, whether animal husbandry is ethical or not depends on practical specificities, not on the fact that animals are involved. Such discussions also need to factor in that animal husbandry plays an important role in culture, societal well-being, food security, and the provision of livelihoods. We seize this opportunity to argue for less preconceived assumptions about alleged effects of animal source foods on the health of the planet and the humans and animals involved, for less top-down planning based on isolated metrics or (Western) technocratic perspectives, and for more holistic and circumstantial approaches to the food system.Peer reviewe

Running during pregnancy mitigates Alzheimer-linke neurovascular dysfunction in mouse offspring

Körperliche Aktivität verbessert sowohl die Funktion des Gehirns von Gesunden als auch von Personen, die an der Alzheimer-Krankheit erkrankt sind. Bisher gab es jedoch nur wenige Untersuchungen, die sich mit dem Effekt von mütterlicher Aktivität auf die Gehirnfunktion der Nachkommen beschäftigt haben und wenn beschränkten sich diese auf gesunde Individuen. Vorarbeiten konnten zeigen, dass mütterliches Laufen während der Schwangerschaft die Amyloidpathologie der Nachkommen im Alzheimer-Mausmodell signifikant verringert. In dieser Arbeit wurde darauf aufbauend der Einfluss pränataler physischer Aktivität auf die neurovaskuläre Dysfunktion im Tiermodell der Alzheimer-Erkrankung untersucht, als mögliche Erklärung dieses Effekts. Hierbei wurde die mütterliche Stimulation durch freiwilliges Laufen im Laufrad während der Schwangerschaft im Gegensatz zur Standardhaltung gewährleistet. Nach 5-monatiger Standardhaltung der Transgenen und Wildtyp-Mäuse wurden die Gehirne der Nachkommen untersucht. Dabei zeigt sich eine Verbesserung der neurovaskulären Funktion der transgenen Tiere durch veränderte Expression der Amyloid-β-Transporter und eine gesteigerte Angiogenese. Der Amyloid-β-Efflux Transporter Multidrug Resistance Protein 1 (MDR1) ist nach mütterlichem Laufen hochreguliert, während der Aβ-Influx Transporter Receptor for advanced glycation enproducts (RAGE) herabreguliert ist. Low-density lipoprotein receptor-related preotein 1 (LRP1), ein weiterer Amyloid-β-Efflux Transporter, zeigt sich unverändert. Jedoch konnte die transkriptionelle Herabregulation eines LRP1-Inhibitors festgestellt werden. Daraus lässt sich schlussfolgern, dass der positive Effekt mütterlichen Laufens auf die Amyloidpathologie der Nachkommen durch eine Veränderung der neurovaskulären Funktion mitverursacht ist. Einen möglichen Übertragungsweg stellen epigenetische Veränderungen der Nachkommen dar. Die Übertragbarkeit dieser Ergebnisse auf den Menschen unterliegt der eingeschränkten Vergleichbarkeit vom Tiermodell der Alzheimer-Krankheit und der humanen Alzheimer-Erkrankung. Dennoch können diese experimentellen Daten zeigen, dass körperliches Training nicht nur auf das Individuum selbst sondern auch auf die nachfolgende Generation positive Effekte ausüben und damit der Entstehung einer neurodegenerativen Erkankung präventiv entgegenwirken kann.Physical activity protects brain function in healthy individuals and those with Alzheimer’s disease (AD). Evidence for beneficial effects of parental exercise on the health status of their progeny is sparse and limited to nondiseased individuals. Previous research show that maternal running interferes with offspring’s AD-like pathology. This work sought to decipher the underlying mechanisms in TgCRND8 mice. Maternal stimulation was provided by voluntary wheel running vs. standard housing during pregnancy. Following 5 month of standard housing of transgenic and wild-type offspring, their brains were examined for neurovascular dysfunction. Running during pregnancy improved the neurovascular function by orchestrating different Amyloid-Beta transporters and increasing angiogenesis. One possible explanation are epigenetic changes of the progeny

Blunt trauma associated with increased cardiovascular morbidity

Cardiovascular diseases and trauma are two major public health issues. Evidence from numerous clinical case reports suggests that trauma may lead to various cardiovascular disorders, such as acute myocardial infarction, cardiac valve disorders and arrhythmias. Various mechanisms of such associations have been suggested; however, no population based studies have been conducted. Population-based studies are important in that they reduce the potential for selection bias and confounding, both of which may limit the interpretation of case reports. In addition, population based studies which include control groups provide quantitative estimates of association. We hypothesize that trauma is significantly associated with increased risk for certain cardiovascular disorders. To examine this issue, we conducted a cross-sectional analysis of the association between certain types of trauma (i.e. blunt cardiac injury (BCI), blunt thoracic injury, blunt abdominal/ pelvic trauma) and certain cardiac disorders (cardiac valve insufficiency and acute myocardial infarction) based on a large database of all hospital discharges from 19 states during a one-year period. We also conducted a matched case-control study of the association between blunt cardiac and thoracic injury and cardiac arrhythmias. Both the exposure (trauma) and the disease (cardiovascular disorders) were identified based on ICD-9-CM codes. Various confounding factors have been identified through the database. Unadjusted, multivariate logistic and the conditional adjusted multivariable regression analyses were performed. Independent of potential confounding factors, discharge for BCI was associated with a 12-fold increased risk for tricuspid valve insufficiency, incompetence, regurgitation or stenosis and a 3.4-fold increased risk for aortic valve insufficiency, incompetence, regurgitation or stenosis. Independent of confounding factors and coronary arteriography status, direct trauma to the heart was associated with a 3-fold increased risk for acute myocardial infarction in persons 46 years or older. When the diagnosis of acute myocardial infarction was confirmed by coronary arteriography, BCI was associated with a 5-fold risk elevation among patients 46 years and older and a 44-fold elevation among patients 45 years and younger. Abdominal or pelvic trauma, irrespective of confounding factors and coronary arteriography status, was associated with a 70% increase in the risk of acute myocardial infarction among patients 45 years and younger and a 3-fold increase among patients 46 years and older. We also found that after adjusting for potential confounders, patients 45 years and younger diagnosed with BCI had 13-fold increase in the risk of cardiac arrhythmia.This research has public health significance because it represents one of very few attempts to look at the association between two major health issues - namely trauma and cardiovascular disorders at such a large population based level. With the findings that several types of traumatic injury (such as thoracic, cardiac, abdominal and pelvic) are associated with an increased risk of specific cardiovascular disorders - namely - cardiac valve insufficiency, acute myocardial infarction and cardiac arrhythmias, it appears that trauma may play an important and heretofore largely unrecognized role in a portion of the national burden of cardiovascular morbidity and mortality

Microgravity science and applications bibliography, 1990 revision

This edition of the Microgravity Science and Applications (MSA) Bibliography is a compilation of government reports, contractor reports, conference proceedings, and journal articles dealing with flight experiments utilizing a low gravity environment to elucidate and control various processes, or with ground based activities that provide supporting research. It encompasses literature published but not cited in the 1989 Revision and that literature which has been published in the past year. Subdivisions of the bibliography include: electronic materials; metals, alloys, and composites; fluids, interfaces, and transport; glasses and ceramics; biotechnology; combustion science; and experimental technology, facilities, and instrumentation. Also included are publications from the European, Soviet, and Japanese programs

Centennial Bibliography On The History Of American Sociology

THE CENTENNIAL BIBLIOGRAPHY ON THE HISTORY OF AMERICAN SOCIOLOGY is intended as an inclusive clearinghouse for sources, studies, and other references that illuminate the origins and subsequent development of the sociological enterprise in the United States of America.2 As such, this bibliography is necessarily provisional and is envisioned as an on-going project to which further citations may be added as they are discovered and as new works are published. Due to the enormous scope of the project, and the short time frame within which the initial compilation was completed, countless useful and insightful references have been unintentionally omitted. Some portions of the citations are currently more comprehensive than others. Gaps, holes, and inexplicable lapses are the sole responsibility of the compiler, for which he not so much apologetic as he is determined to repair them. The assistance of each reader of this bibliography is earnestly enlisted to supply additional references with which they are familiar. Likewise, the current bibliography undoubtedly contains bibliographic errors due in part to the sheer impracticality of physically checking each and every item referenced herein. Again, the assistance of bibliographically astute readers is heartily enlisted to correct such errors. Readers wishing to report errors or to nominate additional candidates for inclusion in future updates of this bibliography are warmly invited to communicate corrections or recommendations together with brief explanations and complete bibliographic particulars via email to: [email protected]