[Abstract unavailable

SUMMARY Overnutrition is associated with chronic inflammation in metabolic tissues; however, whether metabolic inflammation compromises the neural regulatory systems and therefore promotes overnutrition-associated diseases remains unexplored. Our results demonstrate that a mediator of metabolic inflammation, IKKβ/NF-κB, normally remains inactive although enriched in the hypothalamic neurons; however, overnutrition atypically activates hypothalamic IKKβ/NF-κB at least through elevated endoplasmic reticulum stress in the hypothalamus. While forced activation of hypothalamic IKKβ/NF-κB interrupts central insulin/leptin signaling and actions, site- or cell-specific suppression of IKKβ either broadly across the brain, or locally within the mediobasal hypothalamus, or specifically in hypothalamic AGRP neurons significantly protects against obesity and glucose intolerance. The involved molecular mechanisms include the control of IKKβ/NF-κB over SOCS3, a core inhibitor of insulin and leptin signaling. In conclusion, the hypothalamic IKKβ/NF-κB program is a general neural mechanism for energy imbalance underlying obesity; suppressing hypothalamic IKKβ/NF-κB represents a new strategy to combat obesity and related diseases.

Research on bias in peer review examines scholarly communication and funding processes to assess the epistemic and social legitimacy of the mechanisms by which knowledge communities vet and self‐regulate their work. Despite vocal concerns, a closer look at the empirical and methodological limitations of research on bias raises questions about the existence and extent of many hypothesized forms of bias. In addition, the notion of bias is predicated on an implicit ideal that, once articulated, raises questions about the normative implications of research on bias in peer review. This review provides a brief description of the function, history, and scope of peer review; articulates and critiques the conception of bias unifying research on bias in peer review; characterizes and examines the empirical, methodological, and normative claims of bias in peer review research; and assesses possible alternatives to the status quo. We close by identifying ways to expand conceptions and studies of bias to contend with the complexity of social interactions among actors involved directly and indirectly in peer review.

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Hypothalamic neuropeptides play essential roles in regulating energy and body weight balance. Energy imbalance and obesity have been linked to hypothalamic signaling defects in regulating neuropeptide genes; however, it is unknown whether dysregulation of neuropeptide exocytosis could be critically involved. This study discovered that synaptotagmin-4, an atypical modulator of synaptic exocytosis, is expressed most abundantly in oxytocin neurons of the hypothalamus. Synaptotagmin-4 negatively regulates oxytocin exocytosis, and dietary obesity is associated with increased vesicle binding of synaptotagmin-4 and thus enhanced negative regulation of oxytocin release. Overexpressing synaptotagmin-4 in hypothalamic oxytocin neurons and centrally antagonizing oxytocin in mice are similarly obesogenic. Synaptotagmin-4 inhibition prevents against dietary obesity by normalizing oxytocin release and energy balance under chronic nutritional excess. In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases.