Many animal species are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and could act as reservoirs; however, transmission in free-living animals has not been documented. White-tailed deer, the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns can transmit the virus. To test the hypothesis that SARS-CoV-2 is circulating in deer, 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through January of 2021 were assayed for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 (33.2%) deer samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, following the November 2020 peak of human cases in Iowa, and coinciding with the onset of winter and the peak deer hunting season, SARS-CoV-2 RNA was detected in 80 of 97 (82.5%) RPLN samples collected over a 7-wk period. Whole genome sequencing of all 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 (n = 51; 54.5%) and B.1.311 (n = 19; 20%) accounting for ∼75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple human-to-deer transmission events followed by subsequent deer-to-deer spread. These discoveries have important implications for the long-term persistence of the SARS-CoV-2 pandemic. Our findings highlight an urgent need for a robust and proactive “One Health” approach to obtain enhanced understanding of the ecology, molecular evolution, and dissemination of SARS-CoV-2.

Individual risk of type 2 diabetes (T2D) is modified by perturbations of adipose mass, distribution and function. To investigate mechanisms responsible, we explored the molecular, cellular, and whole-body effects of T2D-associated alleles near KLF14. We show that KLF14 diabetes-risk alleles act in adipose tissue to reduce KLF14 expression, and modulate, in trans, expression of 385 genes. We demonstrate that, in human cellular studies, reduced KLF14 expression increases pre-adipocyte proliferation but disrupts lipogenesis, and, in mice, adipose-specific deletion of Klf14 partially recapitulates the human phenotype of insulin resistance, dyslipidemia and T2D. We show that KLF14 T2D risk-allele carriers shift body fat from gynoid to abdominal stores, and display a marked increase in adipocyte cell size: these effects on fat distribution, and the T2D-association, are female-specific. Metabolic risk associated with variation at this imprinted locus depends on both the sex of the subject, and of the parent from whom the risk-allele derives.

Of the environmental factors which have an impact on body weight, nutrients are most influential. Within normal limits, hypothalamic and related neuronal populations correct perturbations in energy metabolism, to return the body to its nutritional set-point, either through direct response to nutrients or indirectly via peripheral appetite signals. Excessive intake of certain macronutrients, such as simple carbohydrates and SFA, can lead to obesity and attendant metabolic dysfunction, also reflected in alterations in structural plasticity, and, intriguingly, neurogenesis, in some of these brain regions. Neurogenesis, previously thought to occur only in the embryo, is now known to take place in the adult brain, dependent on numerous stimulating and inhibiting factors, including dietary components. Because of classic associations between neurogenesis and the hippocampus, in learning and cognition, this brain region has also been the focus of attention in the study of links between diet and neurogenesis. Recently, however, a more complete picture of this relationship has been building: not only has the hypothalamus been shown to satisfy the criteria for a neurogenic niche, but appetite-related mediators, including circulating hormones, such as leptin and ghrelin, pro-inflammatory cytokines and the endocannabinoid intracellular messengers, are also being examined for their potential role in mediating neurogenic responses to macronutrients. The present review draws together these observations and investigates whether PUFA may exert their attenuating effects on body weight through the stimulation of adult neurogenesis. Exploration of the effects of nutraceuticals on neurogenic brain regions may encourage the development of new rational therapies in the fight against obesity.Key words: Macronutrients: Adult neurogenesis: High-fat diets: PUFA Maintenance of a healthy body weight and composition is important for the achievement of lifelong health and wellbeing (1) . It occurs through the successful balancing of energy expenditure and energy intake within a normal range, which is controlled by several complex regulatory systems (2) , themselves being governed by the interaction with both internal and external environmental factors. Internal factors include circulating metabolic and hormonal signals, whereas the nutrients that we consume are the most influential external factors. Their effects on body weight depend not only on the amount consumed, but also on their type. Thus, a diet high in carbohydrates and/or fat will encourage weight gain (3) ; however, genetic contribution notwithstanding (4) the nature of that gain -how much adipose tissue accrues and where it is deposited in the body -will depend on whether carbohydrates are simple or complex, and whether fats are saturated or polyunsaturated (5,6) .The current obesity epidemic is thought to be largely attributable to excessive consumption of palatable foods, high in refined (simple) sugars and saturated fats (3) . As part of a complex causation, including re...

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Myelin basic protein (MBP) phosphorylation is a complex regulatory process that modulates the contribution of MBP to the stability of the myelin sheath. Recent research has demonstrated the modulation of MBP phosphorylation by mitogen-activated protein kinase (MAPK) during myelinogenesis and in the demyelinating disease multiple sclerosis. Here we investigated the physiological regulation of MBP phosphorylation by MAPK during neuronal activity in the alveus, the myelinated output fibers of the hippocampus. Using a phosphospecific antibody that recognizes the predominant MAPK phosphorylation site in MBP, Thr 95 , we found that MBP phosphorylation is regulated by high-frequency stimulation but not low-frequency stimulation of the alveus. This change was blocked by application of tetrodotoxin, indicating that action potential propagation in axons is required. It is interesting that the change in MBP phosphorylation was attenuated by the reactive oxygen species scavengers superoxide dismutase and catalase and the nitric oxide synthase inhibitor N-nitro-L-arginine. Removal of extracellular calcium also blocked the changes in MBP phosphorylation. Thus, we propose that during periods of increased neuronal activity, calcium activates axonal nitric oxide synthase, which generates the intercellular messengers nitric oxide and superoxide and regulates the phosphorylation state of MBP by MAPK. Key Words: Myelin basic protein-Mitogen-activated protein kinase-Phosphorylation-Hippocampus-Alveus-Action potential-Reactive oxygen species-Reactive nitrogen species. J. Neurochem. 73, 1090 -1097 (1999).Myelin basic proteins (MBPs) are a family of positively charged proteins that contribute to the formation and compaction of the myelin sheath. In the CNS, MBPs are found in myelinating oligodendrocytes at the major dense line, the cytoplasmic interface of the myelin sheath (Monuki and Lemke, 1995). MBP is absolutely required for formation of myelin and the major dense line, as a large deletion of the MBP gene in the mutant mouse, shiverer, results in an almost complete absence of myelin in the CNS of these mice (Roach et al., 1983). Moreover, increasing the expression of MBP in shiverer mice restores the major dense line and the myelin sheath in a dose-dependent manner (Shine et al., 1992). It is thought that MBP contributes to the formation of myelin by interactions with proteolipid protein (Edwards et al., 1989) in conjunction with its own homophilic interactions (Smith, 1982). Because MBP is highly positively charged and closely apposed to the negative lipid bilayer of myelin, regulation of the charge nature of MBP could alter the compaction and structure of the myelin sheath.One such posttranslational modification that alters the charge properties of MBP is phosphorylation. MBP is an excellent substrate for several protein kinases, including protein kinase C, protein kinase A, calcium/calmodulindependent protein kinase II, and mitogen-activated protein kinase (MAPK) (reviewed by Ulmer, 1988). Phosphorylation decreases th...