Corticosterone predicts double-brooding in female savannah sparrows (Passerculus sandwichensis).

Given that double-brooding (rearing two broods within a season) can increase annual fecundity, it is unclear why some females in multi-brooded populations rear only one brood per season. The Quality Hypothesis proposes that double-brooded females are high quality and, thus, have sufficient energetic resources available to bear the costs of rearing two broods per season. Glucocorticoids - endocrine hormones that have a critical role in energy regulation - could reflect female quality, and, therefore, also have the potential to indicate whether a female will rear a second brood.

Structure-Based Design of Novel TLR7/8 Agonist Payloads Enabling an Immunomodulatory Conjugate Approach.

Dual activation of the TLR7 and TLR8 pathways leads to the production of type I interferon and proinflammatory cytokines, resulting in efficient antigen presentation by dendritic cells to promote T-cell priming and antitumor immunity. We developed a novel series of TLR7/8 dual agonists with varying ratios of TLR7 and TLR8 activity for use as payloads for an antibody-drug conjugate approach. The agonist-induced production of several cytokines in human whole blood confirmed their functional activity.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

Impact of late rainy season indoor residual spraying on holoendemic malaria transmission: a cohort study in northern Zambia.

Background: Indoor residual spraying (IRS) is a malaria control strategy implemented before the rainy season. Nchelenge District, Zambia is a holoendemic setting where IRS has been conducted since 2008 with little impact on malaria incidence or parasite prevalence. Pre-rainy season IRS may not reduce the post-rainy season peak abundance of the major vector, Anopheles funestus.