Acute restraint stress rapidly impacts reproductive neuroendocrinology and downstream gonad function in big brown bats (Eptesicus fuscus).

Animals face unpredictable challenges that require rapid, facultative physiological reactions to support survival but may compromise reproduction. Bats have a long-standing reputation for being highly sensitive to stressors, with sensitivity and resilience varying both within and among species, yet little is known about how stress affects the signaling that regulates reproductive physiology. Here, we provide the first description of the molecular response of the hypothalamic-pituitary-gonadal (HPG) axis of male big brown bats (Eptesicus fuscus) in response to short-term stress using a standardized restraint manipulation.

Immunoreactive distribution of gonadotropin-inhibitory hormone precursor, RFRP, in a temperate bat species (Eptesicus fuscus).

Gonadotropin-inhibitory hormone (GnIH, also known RFRP-3 in mammals) is an important regulator of the hypothalamic-pituitary-gonadal axis and downstream reproductive physiology. Substantial species differences exist in the localization of cell bodies producing RFRP-3 and patterns of fiber immunoreactivity in the brain, raising the question of functional differences. Many temperate bat species exhibit unusual annual reproductive patterns.

Flexibility in an emergency life-history stage: acute food deprivation prevents sickness behaviour but not the immune response.

The emergency life-history stage (ELHS) can be divided into two subcategories that describe distinct, coordinated responses to disease- or non-disease-related physiological challenges. Whether an individual can simultaneously express aspects of both subcategories when faced with multiple challenges is poorly understood. Emergency life-history theory suggests that disease- and non-disease-related responses are coordinated at the level of the whole organism and therefore cannot be expressed simultaneously.

Food access modifies GnIH, but not CRH, cell number in the hypothalamus in a female songbird.

Food deprivation or restriction causes animals to mount a stereotypical behavioral and physiological response that involves overall increases in activity, elevated glucocorticoid production, and (often) inhibition of the reproductive system. Although there is increasing evidence that these responses can differ in their degree or covariation between the sexes, most studies to-date on food restriction/deprivation have focused on male songbirds. We therefore aimed to characterize the behavioral, physiological, and neuroendocrine response to acute food deprivation in a female songbird using a nomadic species, the zebra finch.

Synergistic Myeloma Cell Death via Novel Intracellular Activation of Caspase-10-Dependent Apoptosis by Carfilzomib and Selinexor.

Exportin1 (XPO1; also known as chromosome maintenance region 1, or CRM1) controls nucleo-cytoplasmic transport of most tumor suppressors and is overexpressed in many cancers, including multiple myeloma, functionally impairing tumor suppressive function via target mislocalization. Selective inhibitor of nuclear export (SINE) compounds block XPO1-mediated nuclear escape by disrupting cargo protein binding, leading to retention of tumor suppressors, induction of cancer cell death, and sensitization to other drugs. Combined treatment with the clinical stage SINE compound selinexor and the irreversible proteasome inhibitor (PI) carfilzomib induced synergistic cell death of myeloma cell lines and primary plasma cells derived from relapsing/refractory myeloma patients and completely impaired the growth of myeloma cell line-derived tumors in mice.

Proteomic profiling of naïve multiple myeloma patient plasma cells identifies pathways associated with favourable response to bortezomib-based treatment regimens.

Toward our goal of personalized medicine, we comprehensively profiled pre-treatment malignant plasma cells from multiple myeloma patients and prospectively identified pathways predictive of favourable response to bortezomib-based treatment regimens. We utilized two complementary quantitative proteomics platforms to identify differentially-regulated proteins indicative of at least a very good partial response (VGPR) or complete response/near complete response (CR/nCR) to two treatment regimens containing either bortezomib, liposomal doxorubicin and dexamethasone (VDD), or lenalidomide, bortezomib and dexamethasone (RVD). Our results suggest enrichment of 'universal response' pathways that are common to both treatment regimens and are probable predictors of favourable response to bortezomib, including a subset of endoplasmic reticulum stress pathways.