Search

Heart failure is the common final pathway of several cardiovascular conditions and a major cause of morbidity and mortality worldwide. Aberrant activation of the adaptive immune system in response to myocardial necrosis has recently been implicated in the development of heart failure. The ß‐adrenergic agonist isoproterenol hydrochloride is used for its cardiac effects in a variety of different dosing regimens with high doses causing acute cardiomyocyte necrosis. To assess whether isoproterenol‐induced cardiomyocyte necrosis triggers an adaptive immune response against the heart, we treated C57BL/6J mice with a single intraperitoneal injection of isoproterenol. We confirmed tissue damage reminiscent of human type 2 myocardial infarction. This is followed by an adaptive immune response targeting the heart as demonstrated by the activation of T cells, the presence of anti‐heart auto‐antibodies in the serum as late as 12 weeks after initial challenge and IgG deposition in the myocardium. All of these are hallmark signs of an established autoimmune response. Adoptive transfer of splenocytes from isoproterenol‐treated mice induces left ventricular dilation and impairs cardiac function in healthy recipients. In summary, a single administration of a high dose of isoproterenol is a suitable high‐throughput model for future studies of the pathological mechanisms of anti‐heart autoimmunity and to test potential immunomodulatory therapeutic approaches. [ABSTRACT FROM AUTHOR]

The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS). Cdkn1c encodes a potent negative regulator of fetal growth that also regulates placental development, consistent with a proposed role for CDKN1C in these complex childhood growth disorders. Here, we report that a mouse modelling the rare microduplications present in some SRS patients exhibited phenotypes including low birth weight with relative head sparing, neonatal hypoglycemia, absence of catch-up growth and significantly reduced adiposity as adults, all defining features of SRS. Further investigation revealed the presence of substantially more brown adipose tissue in very young mice, of both the classical or canonical type exemplified by interscapular-type brown fat depot in mice (iBAT) and a second type of non-classic BAT that develops postnatally within white adipose tissue (WAT), genetically attributable to a double dose of Cdkn1c in vivo and ex-vivo. Conversely, loss-of-function of Cdkn1c resulted in the complete developmental failure of the brown adipocyte lineage with a loss of markers of both brown adipose fate and function. We further show that Cdkn1c is required for post-transcriptional accumulation of the brown fat determinant PR domain containing 16 (PRDM16) and that CDKN1C and PRDM16 co-localise to the nucleus of rare label-retaining cell within iBAT. This study reveals a key requirement for Cdkn1c in the early development of the brown adipose lineages. Importantly, active BAT consumes high amounts of energy to generate body heat, providing a valid explanation for the persistence of thinness in our model and supporting a major role for elevated CDKN1C in SRS. [ABSTRACT FROM AUTHOR]

Light exerts widespread effects on physiology and behaviour. As well as the widely-appreciated role of light in vision, light also plays a critical role in many non-visual responses, including regulating circadian rhythms, sleep, pupil constriction, heart rate, hormone release and learning and memory. In mammals, responses to light are all mediated via retinal photoreceptors, including the classical rods and cones involved in vision as well as the recently identified melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs). Understanding the effects of light on the laboratory mouse therefore depends upon an appreciation of the physiology of these retinal photoreceptors, including their differing sens itivities to absolute light levels and wavelengths. The signals from these photoreceptors are often integrated, with different responses involving distinct retinal projections, making generalisations challenging. Furthermore, many commonly used laboratory mouse strains carry mutations that affect visual or non-visual physiology, ranging from inherited retinal degeneration to genetic differences in sleep and circadian rhythms. Here we provide an overview of the visual and non-visual systems before discussing practical considerations for the use of light for researchers and animal facility staff working with laboratory mice., (Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.)

Veterinarians have unique skills and abilities that could be useful in preparing for and responding to disasters and emergencies. However, veterinarians are often absent from emergency preparedness planning and exercises, and little is known about veterinarians' perceptions of emergency preparedness. A focus group was conducted among veterinarians to explore issues such as previous emergency-preparedness education, types of training needed, barriers to participation in training, and future steps to overcome identified barriers. Focus-group participants reported that they had had little to no emergency-preparedness training and had no clear understanding of what their specific role should be in an emergency. Participants also reported several barriers to participation in training and expressed significant concerns about their ability to respond in an emergency. The concerns reported include limited knowledge of zoonotic diseases, confusion about providing care for animals displaced during natural disasters, and poor relationships with other health professions. In order to respond to disasters, veterinarians require training tailored to their concerns and needs. Furthermore, partnerships between veterinarians and health care workers need to be further developed and strengthened.

Natural zoonotic outbreaks can cause widespread devastation, and several zoonoses can be transmitted as agents of bioterrorism. Although veterinarians can be vital in controlling the transmission of zoonotic diseases, many lack knowledge about their roles in emergency response and about zoonoses. A training session titled "Prevention of Zoonotic Disease Transmission" was provided for New York veterinarians. The training was evaluated using pre-training, post-training, and follow-up surveys, which measured increase in and retention of knowledge. Seventy-five (75) veterinary professionals participated in the training, and 91% responded on pre- and post-training surveys. The percentage of respondents who correctly answered the objective knowledge questions increased from pre-training to post-training. Furthermore, follow-up surveys demonstrated that participants were able to retain much of the information from the training session. Very little research has been found that evaluates a similar training event. As knowledge increases, additional training conferences could benefit veterinarians and supplement this research. The results of the pre-training, post-training, and follow-up surveys indicate that veterinary professionals' knowledge of zoonoses can be significantly improved after receiving training; participants found the training to be useful and requested additional training, indicating that veterinary professionals have a desire to learn about emergency preparedness topics.