In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. We further show through brain PET scans of monkeys injected with radiolabeled recombinant human LCN2 (rh-LCN2) and autoradiography in baboon, macaque, and human brain sections, that LCN2 crosses the blood-brain barrier and localizes to the hypothalamus in primates. In addition, daily treatment of lean monkeys with rh-LCN2 decreases food intake by 21%, without overt side effects. These studies demonstrate the biology of LCN2 as a satiety factor and indicator and anorexigenic signal in primates. Failure to stimulate postprandial LCN2 in individuals with obesity may contribute to metabolic dysregulation, suggesting that LCN2 may be a novel target for obesity treatment.Understanding how genes and experience work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated mice and robustly responsive to sex-specific semiochemicals. Sex-combined housing led to an attenuation of the dimorphic representations. Single-cell sequencing analysis revealed an axis of activity-dependent gene expression amongst a subset of the dimorphic OSN populations. Finally, the pro-apoptotic gene Baxwas necessary to generate the dimorphic representations. Altogether, our results suggest a role of experience and activity in influencing homeostatic mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.It is known that research into human genes is heavily skewed towards genes that have been widely studied for decades, including many genes that were being studied before the productive phase of the Human Genome Project. This means that the genes most frequently investigated by the research community tend to be only marginally more important to human physiology and disease than a random selection of genes. Based on an analysis of 10,395 research publications about SARS-CoV-2 that mention at least one human gene, we report here that the COVID-19 literature up to mid-October 2020 follows a similar pattern. This means that a large number of host genes that have been implicated in SARS-CoV-2 infection by four genome-wide studies remain unstudied. While quantifying the consequences of this neglect is not possible, they could be significant.
  Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy, as well as hypocretin deficiency. Cataplexy (the loss of voluntary postural muscle tone, often in response to emotional stimuli) is one of the most disabling features and is associated with significant social impairment and risk of injury. Cataplexy is usually alleviated by antidepressants sodium oxybate and pitolisant. In this case report, we describe three patients with severe, drug-resistant cataplexy who experienced a dramatic improvement when treated with tropatepine, an anticholinergic muscarinic antagonist (commonly used to prevent neuroleptic-induced parkinsonism) after the usual treatments had failed. The single side effect was mild mouth dryness. In addition to providing a new therapeutic option for resistant cataplexy, this benefit supports a role of cholinergic muscarinic transmission in rapid eye movement sleep atonia.
 Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy, as well as hypocretin deficiency. Cataplexy (the loss of voluntary postural muscle tone, often in response to emotional stimuli) is one of the most disabling features and is associated with significant social impairment and risk of injury. Cataplexy is usually alleviated by antidepressants sodium oxybate and pitolisant. In this case report, we describe three patients with severe, drug-resistant cataplexy who experienced a dramatic improvement when treated with tropatepine, an anticholinergic muscarinic antagonist (commonly used to prevent neuroleptic-induced parkinsonism) after the usual treatments had failed.  https://www.selleckchem.com/products/cinchocaine.html  The single side effect was mild mouth dryness. In addition to providing a new therapeutic option for resistant cataplexy, this benefit supports a role of cholinergic muscarinic transmission in rapid eye movement sleep atonia.
  Freezing of gait (FOG) severely impairs life quality of Parkinson disease (PD) patients. The relationship between sleep disturbance and FOG in PD remains unclear, so in this study, we aimed to investigate that relationship.
 
  First, we assessed clinical characteristics of freezers and nonfreezers among PD patients. Next, we assessed clinical characteristics of PD patients with different PDSS1 scores (score on first item of Parkinson's Disease Sleep Scale). Finally, we prospectively followed a cohort of nonfreezers from a baseline clinical visit and to a maximum of 18 months and performed a Cox regression analysis to further investigate the relationship between PDSS1 score and FOG in PD.
 
  A total of 163 participants with PD were included in the baseline analysis. The freezers had significantly worse sleep compared with the nonfreezers. The proportion of freezers in the patients with low PDSS1 score (PDSS1 < 6) was significantly higher than that in the patients with high PDSS1 score (PDSS1 ≥ 6). A total of 52 nonfreezers were prospectively followed. During a maximum 18-month follow-up, FOG incidence (73%) in the PDSS1 < 6 group was significantly higher than that (24%) in the PDSS1 ≥ 6 group (P = .008). Low PDSS1 score (hazard ratio = 4.23, 95% CI 1.64-10.92, P = .003) and high levodopa equivalent daily dose (hazard ratio = 4.18, 95% CI 1.62-10.75, P = .003) were significantly associated with an increased hazard of FOG.
 
  Our study indicated that low PDSS1 score may be a risk indicator for the development of FOG and provided important insights into potential targets for the prevention/delay of FOG in PD.
 Our study indicated that low PDSS1 score may be a risk indicator for the development of FOG and provided important insights into potential targets for the prevention/delay of FOG in PD.