The Long Shadow of Senescence: Age Impacts Survival and Territory Defense in Loons

Senescence, increased mortality that occurs among animals of advanced age, impacts behavior and ecology in many avian species. We investigated actuarial, reproductive, and behavioral senescence using capture, marking, and resighting data from a 26-year study of common loons (Gavia immer). Territorial residents of both sexes exhibited high annual survival (0.94) until their mid 20s, at which point survival fell to 0.76 and 0.77 in males and females, respectively. Sexual symmetry in actuarial senescence is somewhat surprising in this species, because males make a substantially greater investment in territory defense and chick-rearing and because males engage in lethal contests for territory ownership. Survival of displaced breeders (0.80) was lower than that of territorial residents in both young and old individuals. Old males and females also experienced slightly higher annual probability of eviction (0.16 for males; 0.17 for females) than prime-aged breeders (0.13 for both sexes), indicating senescence in territory defense. Prime-aged males reclaimed territories at a high rate (0.49), in contrast to females of the same age (0.33). However, old males resettled with success (0.35) similar to old females (0.31), suggesting that males decline in competitive ability as they age. Nonetheless males, but not females, showed an apparent increase in breeding success over the entire lifetime, a possible indication that very old males make a terminal investment in reproductive output at the cost of survival

Desacetyl-α-melanocyte stimulating hormone and α-melanocyte stimulating hormone are required to regulate energy balance.

OBJECTIVE: Regulation of energy balance depends on pro-opiomelanocortin (POMC)-derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating hormone (α-MSH) is the predicted natural POMC-derived peptide that regulates energy balance. Desacetyl-α-MSH, the precursor for α-MSH, is present in brain and blood. Desacetyl-α-MSH is considered to be unimportant for regulating energy balance despite being more potent (compared with α-MSH) at activating the appetite-regulating MC4R in vitro. Thus, the physiological role for desacetyl-α-MSH is still unclear. METHODS: We created a novel mouse model to determine whether desacetyl-α-MSH plays a role in regulating energy balance. We engineered a knock in targeted QKQR mutation in the POMC protein cleavage site that blocks the production of both desacetyl-α-MSH and α-MSH from adrenocorticotropin (ACTH1-39). RESULTS: The mutant ACTH1-39 (ACTHQKQR) functions similar to native ACTH1-39 (ACTHKKRR) at the melanocortin 2 receptor (MC2R) in vivo and MC4R in vitro. Male and female homozygous mutant ACTH1-39 (Pomctm1/tm1) mice develop the characteristic melanocortin obesity phenotype. Replacement of either desacetyl-α-MSH or α-MSH over 14 days into Pomctm1/tm1 mouse brain significantly reverses excess body weight and fat mass gained compared to wild type (WT) (Pomcwt/wt) mice. Here, we identify both desacetyl-α-MSH and α-MSH peptides as regulators of energy balance and highlight a previously unappreciated physiological role for desacetyl-α-MSH. CONCLUSIONS: Based on these data we propose that there is potential to exploit the naturally occurring POMC-derived peptides to treat obesity but this relies on first understanding the specific function(s) for desacetyl-α-MSH and α-MSH

Influence of Polymorphism on the Electronic Structure of Ga2O3

The search for new wide band gap materials is intensifying to satisfy the need for more advanced and energy efficient power electronic devices. Ga$_2$O$_3$ has emerged as an alternative to SiC and GaN, sparking a renewed interest in its fundamental properties beyond the main $\beta$-phase. Here, three polymorphs of Ga$_2$O$_3$, $\alpha$, $\beta$ and $\varepsilon$, are investigated using X-ray diffraction, X-ray photoelectron and absorption spectroscopy, and ab initio theoretical approaches to gain insights into their structure - electronic structure relationships. Valence and conduction electronic structure as well as semi-core and core states are probed, providing a complete picture of the influence of local coordination environments on the electronic structure. State-of-the-art electronic structure theory, including all-electron density functional theory and many-body perturbation theory, provide detailed understanding of the spectroscopic results. The calculated spectra provide very accurate descriptions of all experimental spectra and additionally illuminate the origin of observed spectral features. This work provides a strong basis for the exploration of the Ga$_2$O$_3$ polymorphs as materials at the heart of future electronic device generations.Comment: Updated manuscript version after peer revie

Roster of soldiers, sailors, and marines of the war of 1812, the Mexican war, and the war of the rebellion residing in Nebraska, June 1, 1895.

I. United States government.--II. Executive officers of the state and territories.--II. Elections and statistics.--IV. Nebraska members of Congress.--V. Roster (p. [143]-538)Mode of access: Internet

Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study.

IntroductionEGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations.MethodsPatients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed.ResultsA total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5-12.9 mo) overall and 10.7 months (95% CI: 3.2-18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%-48.1%) overall and 41.2% (95% CI: 18.4%-67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations.ConclusionsOsimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR-activating mutation