Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs

The Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) mouse strains have a 16-fold difference in duration of loss of the righting response (LORR) following administration of a sedative dose of ethanol. Four quantitative trait loci (QTLs) have been mapped in these strains for this trait. Underlying each of these QTLs must be one or more genetic differences (polymorphisms in either gene coding or regulatory regions) influencing ethanol sensitivity. Because prior studies have tended to focus on differences in coding regions, genome-wide expression profiling in cerebellum was used here to identify candidate genes for regulatory region differences in these two strains. Fifteen differentially expressed genes were found that map to the QTL regions and polymorphisms were identified in the promoter regions of four of these genes by direct sequencing of ILS and ISS genomic DNA. Polymorphisms in the promoters of three of these genes, Slc22a4, Rassf2, and Tax1bp3, disrupt putative transcription factor binding sites. Slc22a4 and another candidate, Xrcc5, have human orthologs that map to genomic regions associated with human ethanol sensitivity in genetic linkage studies. These genes represent novel candidates for the LORR phenotype and provide new targets for future studies into the neuronal processes underlying ethanol sensitivity

Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability

Abstract The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient variants have been linked to autism spectrum disorder (ASD) and schizophrenia in human genetic studies. We tested male and female Dlgap1 wild type (WT), heterozygous (HT), and knockout (KO) mice in a battery of behavioral tests: open field, dig, splash, prepulse inhibition, forced swim, nest building, social approach, and sucrose preference. We also used biochemical approaches to examine the role of DLGAP1 in the organization of PSD protein complexes. Dlgap1 KO mice were most notable for disruption of protein interactions in the PSD, and deficits in sociability. Other behavioral measures were largely unaffected. Our data suggest that Dlgap1 knockout leads to PSD disruption and reduced sociability, consistent with reports of DLGAP1 haploinsufficient variants in schizophrenia and ASD

Orbital interactions and chemical reactivity of metal particles and metal surfaces

A review is presented with 101 refs. on chem. bonding to metal surfaces and small metal particles demonstrating the power of symmetry concepts to predict changes in chem. bonding. Ab-initio calcns. of chemisorption to small particles, as well as semiempirical extended Hueckel calcns. applied to the study of the reactivity of metal slabs are reviewed. On small metal particles, classical notions of electron promotion and hybridization are found to apply. The surroundings of a metal atom (ligands in complexes, other metal atoms at surfaces), affect bonding and reactivity through the prehybridization they induce. A factor specific for large particles and surfaces is the required localization of electrons on the atoms involved in the metal surface bond. At the surface, the bond energy is found to relate to the grou8p orbital local d. of states at the Fermi level. The use of this concept is extensively discussed and illustrated for chemisorption of CO and dissocn. of NO on metal surfaces. A discussion is given of the current decompn. schemes of bond energies and related concepts (exchange (Pauli)-repulsion, polarization, charge transfer). The role of non-orthogonality of fragment orbitals and of kinetic and potential energy for Pauli repulsion and (orbital) polarization is analyzed. Numerous examples are discussed to demonstrate the impact of those concepts on chem. bonding theor

An ecological future for weed science to sustain crop production and the environment. A review

Sustainable strategies for managing weeds are critical to meeting agriculture's potential to feed the world's population while conserving the ecosystems and biodiversity on which we depend. The dominant paradigm of weed management in developed countries is currently founded on the two principal tools of herbicides and tillage to remove weeds. However, evidence of negative environmental impacts from both tools is growing, and herbicide resistance is increasingly prevalent. These challenges emerge from a lack of attention to how weeds interact with and are regulated by the agroecosystem as a whole. Novel technological tools proposed for weed control, such as new herbicides, gene editing, and seed destructors, do not address these systemic challenges and thus are unlikely to provide truly sustainable solutions. Combining multiple tools and techniques in an Integrated Weed Management strategy is a step forward, but many integrated strategies still remain overly reliant on too few tools. In contrast, advances in weed ecology are revealing a wealth of options to manage weedsat the agroecosystem levelthat, rather than aiming to eradicate weeds, act to regulate populations to limit their negative impacts while conserving diversity. Here, we review the current state of knowledge in weed ecology and identify how this can be translated into practical weed management. The major points are the following: (1) the diversity and type of crops, management actions and limiting resources can be manipulated to limit weed competitiveness while promoting weed diversity; (2) in contrast to technological tools, ecological approaches to weed management tend to be synergistic with other agroecosystem functions; and (3) there are many existing practices compatible with this approach that could be integrated into current systems, alongside new options to explore. Overall, this review demonstrates that integrating systems-level ecological thinking into agronomic decision-making offers the best route to achieving sustainable weed management

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock.” DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006–2014). The PubMed/Medline/Embase literature (2006–14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. CONCLUSIONS: The major new recommendation in the 2014 update is consideration of institution—specific use of 1) a “recognition bundle” containing a trigger tool for rapid identification of patients with septic shock, 2) a “resuscitation and stabilization bundle” to help adherence to best practice principles, and 3) a “performance bundle” to identify and overcome perceived barriers to the pursuit of best practice principles