Preventing the Establishment of a Wildlife Disease Reservoir: A Case Study of Bovine Tuberculosis in Wild Deer in Minnesota, USA

Bovine tuberculosis (bTB) has been found in 12 cattle operations and 27 free-ranging white-tailed deer (Odocoileus virginianus) in northwestern Minnesota, following the state's most recent outbreak of the disease in 2005 in the northwest part of the state. Both deer and cattle have the same strain of bTB. The Minnesota Board of Animal Health has been leading efforts to eradicate the disease in Minnesota's cattle, which have included the depopulation of all infected herds, a cattle buy-out program, and mandatory fencing of stored feeds. The Minnesota Department of Natural Resources began surveillance efforts in free-ranging white-tailed deer in fall 2005. All bTB-infected deer have been found within a 16 km2 area in direct association with infected cattle farms. Aggressive efforts to reduce deer densities through liberalized hunting and sharpshooting have resulted in a 55% decline in deer densities. Also, recreational feeding of wild deer has been banned. Disease prevalence in deer has decreased from 1.2% in 2005 to an undetectable level in 2010

Managing Bovine Tuberculosis in White-Tailed Deer in Northwestern Minnesota: A 2008 Progress Report

Bovine tuberculosis (TB), first discovered in 2005, has now been found in 12 cattle operations in northwestern Minnesota. To date, all of the infected cattle herds have been depopulated and the Board of Animal Health (BAH) has continued to test cattle herds in the area. The strain has been identified as one that is consistent with Bovine TB found in cattle in the southwestern United States and Mexico. In response to the disease being detected in cattle, the Minnesota Department of Natural Resources (MNDNR) began surveillance efforts in free-ranging white-tailed deer (Odocoileus virginianus) within a 15-mile radius of the infected farms in fall 2005. To date, 25 deer have been found infected with Bovine TB. All infected deer were sampled within a 164mi2 area, called the Bovine TB Core, which is centered in Skime, Minnesota, and encompasses 8 of the previously infected cattle farms. In fall 2008, Minnesota was granted a Split-State Status for Bovine TB by the United States Department of Agriculture (USDA) that resulted in a lessening of testing requirements for cattle in the majority of the state (status level = “Modified Accredited advanced”), with a small area in northwestern Minnesota remaining more restrictive (status level = “Modified Accredited”). Also in 2008, the Minnesota State Legislature passed an initiative that allocated funds to buy-out cattle herds located in the Bovine TB Management Zone, spending $3 million to remove 6,200 cattle from 46 farms by January 2009; resulting in the discovery of the 12th infected cattle herd. The remaining cattle farms in the Bovine TB Management Zone (n = 27) were required to erect deer-exclusion fencing to protect stored forage and winter feeding areas, costing an additional$690,000 in state funds. In November 2008, the MNDNR conducted Bovine TB surveillance of hunter-harvested white-tailed deer within the newly created Modified Accredited Zone, and results indicated that none of the 1,246 deer tested were positive for the disease. This marked the first large scale surveillance effort that failed to detect the disease in hunter-harvested deer since sampling efforts began in 2005. MNDNR also conducted targeted removal operations in the Bovine TB Core Area, using both aerial and ground sharpshooting, during winters 2007, 2008 and 2009. These intensive winter deer removal operations removed a combined total of 2,163 deer and detected 13 (52%) of the TB-positive deer discovered to date. Further, a recreational feeding ban, covering 4,000mi2 in northwestern MN, was instituted in November 2006 to help reduce the risk of deer to deer transmission of the disease and enforcement officers have been working to stop illegal feeding activities. The MNDNR will continue to conduct hunter-harvested surveillance for the next 5 years to monitor infection in the local deer population, and consider the continuation of aggressive management actions (e.g., sharpshooting deer in key locations) to address concerns of deer becoming a potential disease reservoir

Androgen receptor immunoreactivity in forebrain axons and dendrites in the rat

As members of the steroid receptor superfamily, androgen receptors (ARs) have been traditionally identified as transcription factors. In the presence of ligand, ARs reside in the nucleus, where, upon ligand binding, the receptors dimerize and bind to specific response elements in the promoter region of hormone-responsive genes. However, in this report, we describe the discovery that ARs are also present in axons and dendrites within the mammalian central nervous system. AR expression in axons was identified in the rat brain at the light microscopic level using two different antibodies directed against the N terminus of the AR protein and nickel intensified 3′-3′-diaminobenzidine, and also using fluorescence methods and confocal microscopy. This distribution was confirmed at the ultrastructural level. In addition, AR immunoreactivity was identified in small dendrites at the ultrastructural level. AR-immunoreactive axons were observed primarily in the cerebral cortex and were rare in regions where nuclear AR expression is abundant. The observation that ARs are present in axons and dendrites highlights the possibility that androgens play an important and novel extranuclear role in neuronal function.Peer Reviewe

Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta

Estradiol regulates serotonin 1A(5-HT1A) receptor signaling. Since desensitization of 5-HT1A receptors may be an underlying mechanism by which selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is important to determine which estrogen receptors are capable of desensitizating 5-HT1A receptor function. We previously demonstrated that selective activation of the estrogen receptor, GPR30, desensitizes 5-HT1A receptor signaling in rat hypothalamic paraventricular nucleus(PVN). However, since estrogen receptor beta(ERβ), is highly expressed in the PVN, we investigated the role of ERβ in estradiol-induced desensitization of 5-HT1A receptor signaling. We first showed that a selective ERβ agonist, diarylpropionitrile(DPN) has a 100-fold lower binding affinity than estradiol for GPR30. Administration of DPN did not desensitize 5-HT1A receptor signaling in rat PVN as demonstrated by agonist-stimulated hormone release. Second, we used a recombinant adenovirus containing ERβ siRNAs to decrease ERβ expression in the PVN. Reductions in ERβ did not alter the estradiol-induced desensitization of 5-HT1A receptor signaling in oxytocin cells. In contrast, in animals with reduced ERβ, estradiol administration, instead of producing desensitization, augmented the ACTH response to a 5-HT1A agonist. Combined with the results from the DPN treatment experiments, desensitization of 5-HT1A receptor signaling does not appear to be mediated by ERβ in oxytocin cells, but that ERβ, together with GPR30, may play a complex role in central regulation of 5-HT1A-mediated ACTH release. Determining the mechanisms by which estrogens induce desensitization may aid in the development of better treatments for mood disorders

Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP

The androgen receptor (AR) has a central role in development and maintenance of the male reproductive system and in the etiology of prostate cancer. The transcription factor Pax6 has recently been reported to act as a repressor of AR and to be hypermethylated in prostate cancer cells. SPBP is a transcriptional regulator that previously has been shown to enhance the activity of Pax6. In this study we have identified SPBP to act as a transcriptional coactivator of AR. We also show that Pax6 inhibits SPBP-mediated enhancement of AR activity on the AR target gene probasin promoter, a repression that was partly reversed by increased expression of SPBP. Enhanced expression of Pax6 reduced the amount of SPBP associated with the probasin promoter when assayed by ChIP in HeLa cells. We mapped the interaction between both AR and SPBP, and AR and Pax6 to the DNA-binding domains of the involved proteins. Further binding studies revealed that Pax6 and SPBP compete for binding to AR. These results suggest that Pax6 represses AR activity by displacing and/or inhibiting recruitment of coactivators to AR target promoters. Understanding the mechanism for inhibition of AR coactivators can give rise to molecular targeted drugs for treatment of prostate cancer

Sex Differences in the Brain: A Whole Body Perspective

Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other organs when considering neural sex differences is that we are likely to miss the fact that some brain sex differences develop to compensate for differences in the internal environment (i.e., because male and female brains operate in different bodies, sex differences are required to make output/function more similar in the two sexes). We also consider evidence that sex differences in sensory systems cause male and female brains to perceive different information about the world; the two sexes are also perceived by the world differently and therefore exposed to differences in experience via treatment by others. Although the topic of sex differences in the brain is often seen as much more emotionally charged than studies of sex differences in other organs, the dichotomy is largely false. By putting the brain firmly back in the body, sex differences in the brain are predictable and can be more completely understood

Managing Bovine Tuberculosis in White-Tailed Deer in Northwestern Minnesota: A 2007 Progress Report

Bovine tuberculosis (TB), first discovered in 2005, has now been found in 11 cattle operations in northwestern Minnesota. To date, all of the infected cattle herds have been depopulated and the Board of Animal Health (BAH) has continued an investigation of herds in the area as well as conducted a statewide surveillance effort. The strain has been identified as one that is consistent with bovine TB found in cattle in the southwestern United States and Mexico. In November 2007, the Minnesota Department of Natural Resources (MNDNR) conducted bovine TB surveillance of hunter-harvested white-tailed deer (Odocoileus virginianus) within a 15-mile radius of the infected farms. Results indicated that 5 of the 1,085 deer tested positive for bovine TB; estimated disease prevalence of 0.46% (SE=0.2%). All infected deer were harvested within 5 miles of Skime, Minnesota, which is in close proximity to 7 of the infected livestock operations. In response to additional deer found infected with bovine TB since 2005, the MNDNR also conducted a targeted deer removal operation during winter 2007, using sharpshooters from the United States Department of Agriculture (USDA) Wildlife Services. An additional 488 deer were removed through this project, yielding 6 more cases of infected deer. Further, a recreational feeding ban, covering 4,000 mi2 in northwestern MN, was instituted in November 2006 to help reduce the risk of deer to deer transmission of the disease and enforcement officers have been working to stop illegal feeding activities. Also, in 2006, the Minnesota State Legislature passed an initiative that allocated $54,000 to deer-proof fencing materials for livestock producers within 5 miles of a previously infected farm; MNDNR erected 15 fences on 11 cattle premises during summer 2007. The findings of additional infection in cattle herds as well as the deer has resulted in the downgrading of Minnesota’s bovine TB status to “modified accredited”, which has increasing testing requirement for cattle statewide. The MNDNR will continue to conduct hunter-harvested surveillance in fall 2008 to monitor infection in the local deer population, and consider the continuation of aggressive management actions (e.g., sharpshooting deer in key locations) to address concerns of deer becoming a potential disease reservoir

Neuroprotection by estradiol

This review highlights recent evidence from clinical and basic science studies supporting a role for estrogen in neuroprotection. Accumulated clinical evidence suggests that estrogen exposure decreases the risk and delays the onset and progression of Alzheimer's disease and schizophrenia, and may also enhance recovery from traumatic neurological injury such as stroke. Recent basic science studies show that not only does exogenous estradiol decrease the response to various forms of insult, but the brain itself upregulates both estrogen synthesis and estrogen receptor expression at sites of injury. Thus, our view of the role of estrogen in neural function must be broadened to include not only its function in neuroendocrine regulation and reproductive behaviors, but also to include a direct protective role in response to degenerative disease or injury. Estrogen may play this protective role through several routes. Key among these are estrogen dependent alterations in cell survival, axonal sprouting, regenerative responses, enhanced synaptic transmission and enhanced neurogenesis. Some of the mechanisms underlying these effects are independent of the classically defined nuclear estrogen receptors and involve unidentified membrane receptors, direct modulation of neurotransmitter receptor function, or the known anti-oxidant activities of estrogen. Other neuroprotective effects of estrogen do depend on the classical nuclear estrogen receptor, through which estrogen alters expression of estrogen responsive genes that play a role in apoptosis, axonal regeneration, or general trophic support. Yet another possibility is that estrogen receptors in the membrane or cytoplasm alter phosphorylation cascades through direct interactions with protein kinases or that estrogen receptor signaling may converge with signaling by other trophic molecules to confer resistance to injury. Although there is clear evidence that estradiol exposure can be deleterious to some neuronal populations, the potential clinical benefits of estrogen treatment for enhancing cognitive function may outweigh the associated central and peripheral risks. Exciting and important avenues for future investigation into the protective effects of estrogen include the optimal ligand and doses that can be used clinically to confer benefit without undue risk, modulation of neurotrophin and neurotrophin receptor expression, interaction of estrogen with regulated cofactors and coactivators that couple estrogen receptors to basal transcriptional machinery, interactions of estrogen with other survival and regeneration promoting factors, potential estrogenic effects on neuronal replenishment, and modulation of phenotypic choices by neural stem cells. Copyright (C) 2001 Elsevier Science Ltd.Peer Reviewe