A White Paper on keV sterile neutrino Dark Matter

We present a comprehensive review of keV-scale sterile neutrino Dark Matter, collecting views and insights from all disciplines involved—cosmology, astrophysics, nuclear, and particle physics—in each case viewed from both theoretical and experimental/observational perspectives. After reviewing the role of active neutrinos in particle physics, astrophysics, and cosmology, we focus on sterile neutrinos in the context of the Dark Matter puzzle. Here, we first review the physics motivation for sterile neutrino Dark Matter, based on challenges and tensions in purely cold Dark Matter scenarios. We then round out the discussion by critically summarizing all known constraints on sterile neutrino Dark Matter arising from astrophysical observations, laboratory experiments, and theoretical considerations. In this context, we provide a balanced discourse on the possibly positive signal from X-ray observations. Another focus of the paper concerns the construction of particle physics models, aiming to explain how sterile neutrinos of keV-scale masses could arise in concrete settings beyond the Standard Model of elementary particle physics. The paper ends with an extensive review of current and future astrophysical and laboratory searches, highlighting new ideas and their experimental challenges, as well as future perspectives for the discovery of sterile neutrinos

Aberrant expression of agouti signaling protein (ASIP) as a cause of monogenic severe childhood obesity.

Here we report a heterozygous tandem duplication at the ASIP (agouti signaling protein) gene locus causing ubiquitous, ectopic ASIP expression in a female patient with extreme childhood obesity. The mutation places ASIP under control of the ubiquitously active itchy E3 ubiquitin protein ligase promoter, driving the generation of ASIP in patient-derived native and induced pluripotent stem cells for all germ layers and hypothalamic-like neurons. The patient’s phenotype of early-onset obesity, overgrowth, red hair and hyperinsulinemia is concordant with that of mutant mice ubiquitously expressing the homolog nonagouti. ASIP represses melanocyte-stimulating hormone-mediated activation as a melanocortin receptor antagonist, which might affect eating behavior, energy expenditure, adipocyte differentiation and pigmentation, as observed in the index patient. As the type of mutation escapes standard genetic screening algorithms, we rescreened the Leipzig Childhood Obesity cohort of 1,745 patients and identified four additional patients with the identical mutation, ectopic ASIP expression and a similar phenotype. Taken together, our data indicate that ubiquitous ectopic ASIP expression is likely a monogenic cause of human obesity