An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models

The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates a signaling mechanism used by tumor cells to suppress apoptosis can protect healthy cells from the harmful effects of radiation. We studied CBLB502, a polypeptide drug derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR5) and activates nuclear factor-kappaB signaling. A single injection of CBLB502 before lethal total-body irradiation protected mice from both gastrointestinal and hematopoietic acute radiation syndromes and resulted in improved survival. CBLB502 injected after irradiation also enhanced survival, but at lower radiation doses. It is noteworthy that the drug did not decrease tumor radiosensitivity in mouse models. CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.     

Solvent tuning of electrochemical potentials in the active sites of HiPIP versus ferredoxin

A persistent puzzle in the field of biological electron transfer is the conserved iron-sulfur cluster motif in both high potential iron-sulfur protein (HiPIP) and ferredoxin (Fd) active sites. Despite this structural similarity, HiPIPs react oxidatively at physiological potentials, whereas Fds are reduced. Sulfur K-edge x-ray absorption spectroscopy uncovers the substantial influence of hydration on this variation in reactivity. Fe-S covalency is much lower in natively hydrated Fd active sites than in HiPIPs but increases upon water removal; similarly, HiPIP covalency decreases when unfolding exposes an otherwise hydrophobically shielded active site to water. Studies on model compounds and accompanying density functional theory calculations support a correlation of Fe-S covalency with ease of oxidation and therefore suggest that hydration accounts for most of the difference between Fd and HiPIP reduction potentials.     

Asphericity in supernova explosions from late-time spectroscopy

Core-collapse supernovae (CC-SNe) are the explosions that announce the death of massive stars. Some CC-SNe are linked to long-duration gamma-ray bursts (GRBs) and are highly aspherical. One important question is to what extent asphericity is common to all CC-SNe. Here we present late-time spectra for a number of CC-SNe from stripped-envelope stars and use them to explore any asphericity generated in the inner part of the exploding star, near the site of collapse. A range of oxygen emission-line profiles is observed, including a high incidence of double-peaked profiles, a distinct signature of an aspherical explosion. Our results suggest that all CC-SNe from stripped-envelope stars are aspherical explosions and that SNe accompanied by GRBs exhibit the highest degree of asphericity.     

A melanocortin 1 receptor allele suggests varying pigmentation among Neanderthals

The melanocortin 1 receptor (MC1R) regulates pigmentation in humans and other vertebrates. Variants of MC1R with reduced function are associated with pale skin color and red hair in humans of primarily European origin. We amplified and sequenced a fragment of the MC1R gene (mc1r) from two Neanderthal remains. Both specimens have a mutation that was not found in approximately 3700 modern humans analyzed. Functional analyses show that this variant reduces MC1R activity to a level that alters hair and/or skin pigmentation in humans. The impaired activity of this variant suggests that Neanderthals varied in pigmentation levels, potentially on the scale observed in modern humans. Our data suggest that inactive MC1R variants evolved independently in both modern humans and Neanderthals.     

The effect of dietary supplementation with globin and spray-dried porcine plasma on performance,digestibility and histomorphological traits in broiler chickens

This study evaluated the effects of globin and spray-dried porcine plasma (SDPP) on growth performance, digestibility, nitrogen retention, energy retention efficiency (ERE) and intestinal morphology of broiler chickens. A total of 336-day-old male broiler chickens were reared from 1 to 40 days of age and fed 3 diets (8 replicates/diet, 14 birds/replicate) during 3 feeding phases: starter (1–12 days), grower (12–25 days) and finisher (25–40 days). Isonitrogenous diets were formulated by replacing gluten protein isolate contained in the control diet (C diet) with 2% (starter) or 1% (grower and finisher) spray-dried porcine plasma in the plasma diet (SDPP diet). The globin diet (G diet) was obtained by adding globin on the top of C diet at a dose of 0.08% for the whole rearing period. Total tract apparent digestibility (aD), nitrogen retention and ERE were assessed during the three growing phases. At 12  and 40 days of age, one bird per pen was slaughtered to sample gut, liver, spleen and bursa of Fabricius for histomorphological investigations. The SDPP diet increased body weights of chickens at 12 (+60 g; p < .001), 25 (+101 g; p < .001) and 40 days (+130 g; p = .018) of age compared to C and G diets. Also SDPP improved crude protein aD (+9.7%) and ERE (+12.3%) during the starter phase (p < .001). Dietary globin and SDPP inclusion did not affect either the gut morphology or the histopathological findings in birds at 12 and 40 days of age, despite a numerical (+6.90% and +7.40% respectively) villus height improvement in the SDPP group. Overall, these results confirm that dietary supplementation with SDPP and, to a lesser extent, with globin can improve growth performance and dietary protein and energy utilization in broiler chickens without effect on gut functionality.     

Prey depletion caused by overfishing and the decline of marine megafauna in eastern Ionian Sea coastal waters (central Mediterranean)

Surveys primarily aimed at determining dolphin encounter rates were conducted from small inflatable craft in eastern Ionian Sea coastal waters between 1997 and 2004. During 633 surveys totalling 21,276 km of effort, observations of cetaceans and other marine species spotted in a study area of 480 km² were systematically recorded. Common dolphin encounter rates declined 25-fold across the study period, steadily decreasing from 2.18 encounters/100 km in 1997 to 0.09 encounters/100 km in 2004. Encounter rates of tuna also declined significantly. Swordfish encounter rates dropped from 1.03 encounters/100 km in 1997 to 0-0.12 in 1998-2004. Encounter rates of bottlenose dolphins did not show significant trends. The decline of high-order marine predators feeding on epipelagic prey was consistent with the hypothesis of prey depletion, likely resulting from intensive exploitation of local fish stocks, particularly anchovies and sardines. The catholic feeding habits and opportunistic behaviour of bottlenose dolphins may allow them to withstand the effects of overfishing at their present low density.