Bovine Mastitis Resistance: Novel Quantitative Trait Loci and the Role of Bovine Mammary Epithelial Cells

Bovine mastitis, or inflammation of the mammary gland, has substantial economic and animal welfare implications. A genetic basis for mastitis resistance traits is recognized and can be used to guide selective breeding programs. The discovery of regions of the genome associated with mastitis resistance, and knowledge of the underlying molecular mechanisms responsible, can facilitate development of efficient mastitis control and therapeutic strategies. The objectives of this dissertation research were to identify sites of genetic variation associated with mastitis resistance, and to define the contributions of the milk-secreting epithelial cells to mammary gland immune responses and mastitis resistance. Twenty seven regions of the bovine genome potentially involved in mastitis resistance were identified in Holstein dairy cattle. Additionally, this research demonstrates a role of bovine mammary epithelial cells in mastitis resistance, and provides guidance for the use of an in vitro model for mastitis studies. Primary bovine mammary epithelial cells from mastitis-resistant cows have differential expression of 42 inflammatory genes compared with cells from mastitis-susceptible cows, highlighting the importance of epithelial cells in mastitis resistance. Bovine mammary epithelial cells display both similarities and differences in pro-inflammatory gene expression compared to fibroblasts, and their expression of inflammatory genes is influenced by administration of the enzyme phospholipase A2. The growth potential of milk-derived bovine mammary epithelial cells in vitro can be extended, facilitating their use in mastitis studies, by transfection with a viral protein. Collectively, this research contributes to current knowledge on bovine mastitis resistance and in vitro models

Genetic sequencing using 16s rRNA for pathogen identification in retropharyngeal lymph nodes from wild elk

Cervical region lymph nodes collected by hunters from 43 wild hunter-harvested elk (Cervus elaphus) in Utah were submitted to the Utah Veterinary Diagnostic Laboratory during fall 2009. We evaluated these lymph nodes as specimens for identification of bacterial pathogens using 16S rRNA genetic sequencing. Thirty-seven bacterial species were identified; each was found in 2 to 30 individual elk. Many common ruminant livestock pathogens were identified in elk; pathogens previously reported in elk were Pasteurella multocida and Streptococcus spp. Cervical region lymph nodes harvested from wild ruminants appear to be acceptable samples for genetic sequencing of bacteria

Cognitive impairment, dementia and quality of life.

Peer reviewe

Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice

Mast Cell Diseases in Practice and Research:Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

Syringomyelia in an Adult American Paint Horse

Syringomyelia is a form of myelodysplasia defined by the formation of one or more fluid-filled cavities within the spinal cord that do not communicate with the central canal. The defect may be congenital or acquired. Clinical signs correlate to the segment of spinal cord affected and include pain, paresis, proprioceptive deficits, alterations in sensation, scoliosis, and autonomic dysfunction. This report describes the clinical and pathologic changes in a case of acquired syringomyelia in a 10-year-old American Paint Horse mare. The horse had a six-week history of progressive proprioceptive deficits in all four limbs, bilateral pelvic limb ataxia, and muscle fasciculations that were unresponsive to treatment with stall rest, phenylbutazone, and dexamethasone. Syringomyelia was diagnosed postmortem within cervical, thoracic, and lumbar spinal cord segments. Acquired syringomyelia should be considered among differential diagnoses in adult horses displaying progressive neurologic deficits

ONLINE REVIEWS AS MARKETING PLACEBO? FIRST INSIGHTS FROM NEURO-IS UTILISING FNIRS

In the digital era, costumers often peruse online reviews prior to purchasing a product or a service. These online reviews may not only influence purchase intentions, but also unintentionally shape the expectations that form later customer experiences with the product – a phenomenon defined as ‘marketing placebo effect’. Against this background this research aims to investigate a potential placebo effect of online reviews on a behavioural and neural level. While recording neural activity via functional near-infrared spectroscopy (fNIRS), participants consumed a product after reading a well- or poorlyfitting online review of the product. The results indicate that well-fitting online reviews increased the liking of the product compared to poorly-fitting online reviews, and by doing so, constitute a placebo effect. In parallel, they induce increased neural activity in regions that are associated in neuroscientific literature with processing social information (i.e. medial PFC). In contrast, poorly-fitting online reviews increased activity in regions related to conflict resolution (i.e. lateral PFC). These results demonstrate that online reviews make for an effective placebo, influencing customer experiences on both, the behavioural and the neural level

A response time selection algorithm for more accurate crowds

A convenient and effective approach to extract accurate information from groups is to apply the majority rule. Simply put, what most people believe to be a question’s answer often proves to be correct. However, the majority rule has a glaring weakness: in environments where most people are likely to answer a question incorrectly (e.g., extremely difficult questions), the majority answer will typically be incorrect. We address this problem by introducing a simple selection algorithm based on people’s response times that selects more accurate answers - particularly in environments where the majority fails to identify a question's true answer. We propose that, instead of following the majority answer of the entire group for these types of questions, one should follow the majority answer of a smaller selection of group members who took their time to answer the question. With over 10.000 participants responding to 140 general-knowledge questions of various degrees of difficulty (relying on publicly accessible data and data from a laboratory study), we demonstrate that the majority answer of a small crowd of slow-responding individuals is indeed more accurate for such questions than the majority answer of a much larger crowd, or a small crowd of fast-responding individuals. These findings demonstrate how a simple and observable cue of response time can be used as a powerful arbiter of accuracy in environments where most people’s answers are incorrect