Bay Crews (sodabrown3)

Sleep physiology is briefly reviewed before turning to behavioral and neural evidence from young females linking 17β-estradiol to sleep-wake cycle maintenance. Implications of menopause-associated 17β-estradiol loss is also reviewed before discussing how ovarian hormones may support the memory-promoting effects of sleep, and why menopause may exacerbate pathological aging via effects on sleep. While still in its infancy, this research area offers a new sex-based perspective on aging research, with a focus on a modifiable risk factor for pathological aging. Gonadotroph tumors represent approximatively one-third of anterior pituitary tumors, but despite their frequency, no medical treatment is currently recommended for them. This would be greatly needed because following surgery, which is the first-line treatment, a significant percentage of gonadotroph tumors regrow. We performed PubMed searches in March 2020 using the term "gonadotroph" in combination with 36 different keywords related to dopamine type 2 receptor agonists, somatostatin receptor (SST) ligands, temozolomide, peptide receptor radionuclide therapy (PRRT), immunotherapy, vascular endothelial growth factor receptor (VEGFR)-targeted therapy, mammalian target of rapamycin (mTOR) inhibitors, and tyrosine kinase inhibitors. Articles resulting from these searches, as well as relevant references cited by these articles were reviewed. SST2 analogs have demonstrated only very limited antitumor effect, while high-dose cabergoline has been more effective in preventing tumor regrowth, but still in only a gonadotroph tumors, management that should be discussed within multidisciplinary teams.T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Motivated by our previous finding that intron retention (IR) could lead to transcript instability, in this study, we performed BruChase-Seq to experimentally monitor the expression dynamics of nascent transcripts in resting and activated CD4+ T cells. PEG300 nmr Computational modeling was then applied to quantify the stability of spliced and intron-retained transcripts on a genome-wide scale. Beyond substantiating that intron-retained transcripts were considerably less stable than spliced transcripts, we found a global stabilization of spliced mRNAs upon T cell activation, although the stability of intron-retained transcripts remained relatively constant. In addition, we identified that La-related protein 4 (LARP4), an RNA-binding protein (RBP) known to enhance mRNA stability, was involved in T cell activation-dependent mRNA stabilization. Knocking out Larp4 in mice destabilized Nfκb1 mRNAs and reduced secretion of interleukin-2 (IL2) and interferon-gamma (IFNγ), two factors critical for T cell proliferation and function. We propose that coordination between splicing regulation and mRNA stability may provide a novel paradigm to control spatiotemporal gene expression during T cell activation.In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point was met, with an sCR rate of 60% after 8 cycles. Depth of response improved over time. On intent-to-treat (ITT), the sCR rate reached 76%. The rate of minimal residual disease (MRD) negativity using modified ITT was 70% according to next-generation sequencing ( less then 10-5 sensitivity). After median fol