Retention of xenon in quartz and Earth's missing xenon

The reactivity of xenon with terrestrial oxides was investigated by in situ synchrotron x-ray diffraction. At high temperature (T > 500 kelvin), some silicon was reduced, and the pressure stability of quartz was expanded, attesting to the substitution of some xenon for silicon. When the quartz was quenched, xenon diffused out and only a few weight percent remained trapped in samples. These results show that xenon can be covalently bonded to oxygen in quartz in the lower continental crust, providing an answer to the missing xenon problem; synthesis paths of rare gas compounds are also opened.     

The global circulation of seasonal influenza A (H3N2) viruses

Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.     

Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD

Acting as a signal, hydrogen peroxide circumvents antioxidant defense by overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of Prxs containing Cys-SO(2)H, thus reestablishing the antioxidant firewall. Sestrins contain a predicted redox-active domain homologous to AhpD, the enzyme catalyzing the reduction of a bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine triphosphate-dependent reduction of overoxidized PrxI in vitro, indicating that unlike AhpD, which is a disulfide reductase, sestrins are cysteine sulfinyl reductases. As modulators of peroxide signaling and antioxidant defense, sestrins constitute potential therapeutic targets.     

Massive horizontal gene transfer in bdelloid rotifers

Horizontal gene transfer in metazoans has been documented in only a few species and is usually associated with endosymbiosis or parasitism. By contrast, in bdelloid rotifers we found many genes that appear to have originated in bacteria, fungi, and plants, concentrated in telomeric regions along with diverse mobile genetic elements. Bdelloid proximal gene-rich regions, however, appeared to lack foreign genes, thereby resembling those of model metazoan organisms. Some of the foreign genes were defective, whereas others were intact and transcribed; some of the latter contained functional spliceosomal introns. One such gene, apparently of bacterial origin, was overexpressed in Escherichia coli and yielded an active enzyme. The capture and functional assimilation of exogenous genes may represent an important force in bdelloid evolution.     

Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity

Long-term memory is thought to be mediated by protein synthesis-dependent, late-phase long-term potentiation (L-LTP). Two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in this process, but their relationship is unclear. Here we report that tPA, by activating the extracellular protease plasmin, converts the precursor proBDNF to the mature BDNF (mBDNF), and that such conversion is critical for L-LTP expression in mouse hippocampus. Moreover, application of mBDNF is sufficient to rescue L-LTP when protein synthesis is inhibited, which suggests that mBDNF is a key protein synthesis product for L-LTP expression.     

Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition

Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.     

A dog model to study ovary, ovarian ligament and visceral pain

Objective A dog model was developed to study visceral pain by stimulating the ovarian ligament. Study design Prospective experimental trial. Animals Twelve 1‐year old female hound dogs weighing 25.7 ± 3.6 kg. Methods Dogs were anesthetized with sevoflurane. The right ovary was accessed via laparoscopy. A suture was placed around the ovarian ligament and exteriorized through the abdominal wall for stimulation. The noxious stimulus consisted of pulling the ovary and ovarian ligament with a force transducer. The response to noxious stimulation was determined using the anesthetic minimum alveolar concentration requirement (MAC) for sevoflurane. The ovarian MAC was compared to the standardized somatic noxious stimulation tail clamp MAC. The results are depicted as mean ± SD and corrected to sea‐level. Results The stimulus–response curve during ovarian stimulation in three dogs was hyperbolic and best represented by a three‐parameter logistic growth curve model. The curve plateaued at 7.12 ± 4.19 N. From the stimulus‐response curve, we chose 6.61 N to test the consistency and repeatability of the model in nine dogs. The ovarian stimulation MAC for sevoflurane in these dogs was 2.16 ± 0.46%. The ovarian stimulation confidence interval and limits are comparable to the results from tail stimulation MAC. The tail stimulation MACs before and after laparoscopy surgery were not different (1.86 ± 0.28% and 1.77 ± 0.38% respectively; p > 0.05) but lower when compared to the ovarian MAC (p < 0.01). The dogs recovered from anesthesia without complications. Conclusions and clinical relevance The ovarian stimulation model is an adequate and repeatable means of producing visceral stimulation to determine MAC. The model may provide a humane mechanism to study the effectiveness of analgesics for acute ovarian pain.     

Transition From Sagebrush Steppe to Annual Grass (Bromus tectorum): Influence on Belowground Carbon and Nitrogen

Vegetation changes associated with climate shifts and anthropogenic disturbance have major impacts on biogeochemical cycling. Much of the interior western United States currently is dominated by sagebrush (Artemisia tridentata Nutt.) ecosystems. At low to intermediate elevations, sagebrush ecosystems increasingly are influenced by cheatgrass (Bromus tectorum L.) invasion. Little currently is known about the distribution of belowground organic carbon (OC) on these changing landscapes, how annual grass invasion affects OC pools, or the role that nitrogen (N) plays in carbon (C) retention. As part of a Joint Fire Sciences-funded project called the Sagebrush Treatment Evaluation Project (SageSTEP), we quantified the depth distribution of soil OC and N at seven sites experiencing cheatgrass invasion. We sampled plots that retained sagebrush, but represented a continuum of cheatgrass invasion into the understory. Eighty-four soil cores were taken using a mechanically driven diamond-tipped core drill to a depth of 90 cm, or until bedrock or a restrictive layer was encountered. Samples were taken in 15-cm increments, and soil, rocks, and roots were analyzed for OC and total N. We determined that cheatgrass influences the vertical distribution of OC and N within the soil profile and might result in decreased soil OC content below 60  cm. We also found that OC and total N associated with coarse fragments accounted for at least 10% of belowground pools. This emphasizes the need for researchers to quantify nutrients in deep soil horizons and coarse fragments.     

Endotoxin Concentrations Measured by a Chromogenic Assay in Portal and Peripheral Venous Blood in Ten Dogs With Portosystemic Shunts

A chromogenic Limulus amebocyte lysate assay was used to measure portal and peripheral venous endotoxin concentrations in ten medically managed dogs undergoing surgery for correction of a single extrahepatic portosystemic shunt. In all dogs, both peripheral and portal venous blood samples were obtained at the time of surgical manipulation of the anomalous vessel. In six dogs, peripheral venous samples were obtained an average of 8.0 months after surgery. Five physically normal dogs without biochemical or histologic evidence of liver disease served as controls. Data analysis failed to demonstrate significant differences in peripheral and portal venous endotoxin concentrations between the control and study groups. Postoperatively five of six dogs showed a measurable reduction in peripheral venous endotoxin concentration over intraoperatively obtained values, but the differences were not statistically significant (P = 0.06). Based on results of this study it was concluded that systemic endotoxemia was not present in dogs with a single extrahepatic portosystemic shunt that were medically stable prior to surgery.