Summary Newborn mice emit signals that promote parenting from mothers and fathers, but trigger aggressive responses from virgin males. Although pup-directed attacks by males require vomeronasal function, the specific infant cues that elicit this behavior are unknown. We developed a behavioral paradigm based on reconstituted pup cues and showed that discrete infant morphological features combined with salivary chemosignals elicit robust male aggression. Seven vomeronasal receptors were identified based on infant-mediated activity, and the involvement of two receptors, Vmn2r65, and Vmn2r88, in infant-directed aggression was demonstrated by genetic deletion. Using the activation of these receptors as readouts for biochemical fractionation, we isolated two pheromonal compounds, the submandibular gland protein C and hemoglobins. Unexpectedly, none of the identified vomeronasal receptors and associated cues were specific to pups. Thus, infant-mediated aggression by virgin males relies on the recognition of pup’s physical traits in addition to parental and infant chemical cues.

Despite recent advances, the efficacy of androgen/androgen receptor (AR)-targeted therapy remains  limited for many patients with metastatic prostate cancer. This is in part because prostate cancers adaptively switch to the androgen/AR-independent pathway for survival and growth, thereby conferring therapy resistance. Tumor hypoxia is considered as a major cause of treatment resistance. However, the exact mechanism is largely unclear. Here we report that chronic-androgen deprivation therapy (ADT) in the condition of hypoxia induces adaptive androgen/AR-independence, and therefore confers resistance to androgen/AR-targeted therapy, e.g., enzalutamide. Mechanistically, this is mediated by glucose-6-phosphate isomerase (GPI), which is transcriptionally repressed by AR in hypoxia, but restored and increased by AR inhibition. In turn, GPI maintains glucose metabolism and energy homeostasis in hypoxia by redirecting the glucose flux from androgen/AR-dependent pentose phosphate pathway (PPP) to hypoxia-induced glycolysis pathway, thereby reducing the growth inhibitory effect of enzalutamide. Inhibiting GPI overcomes the therapy resistance in hypoxia in vitro and increases enzalutamide efficacy in vivo.

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Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent abscesses in the groin and flexural areas. HS is associated with a wide range of comorbidities that complicate the disease course. Although these comorbidities have been well-described, it remains unclear how these comorbidities co-associate and whether comorbidity profiles affect disease trajectory. In addition, it is unknown how comorbidity associations are modulated by race and gender. In this comprehensive analysis of 77 million patients in a large U.S. population-based cohort, we examine co-association patterns among HS comorbidities and identify clinically relevant phenotypic subtypes within HS. We demonstrate that these subtypes not only differ among races, but also influence clinical outcomes as measured by HS-related emergency department (ED) visits and cellulitis. Taken together, our findings provide key insights that elucidate the unique disease trajectories experienced by HS patients, and equip clinicians with a novel framework for risk stratification and improved targeted care in HS.

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Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid cells. Nature 1982; 299:65-7. 2 Kim YH, Tavallaee M, Sundram U et al. Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and S ezary syndrome with variable CD30 expression level: a multi-institution collaborative project. J Clin Oncol 2015; 33:3750-8. 3 Mah evas T, Ram-Wolff C, Battistella M et al. Dramatic response to brentuximab vedotin in a refractory nontransformed CD30mycosis fungoides allowing allogeneic stem cell transplantation and longterm complete remission.

The original version of this Article contained errors in Fig. 7. In panels e and f, the graph titles incorrectly read 'LNCaP-AdtNs' and 'LAPC4-AdtNs', respectively. These errors have now been corrected in both the PDF and HTML versions of the Article.

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