Positional Cloning of “Lisch-like”, a Candidate Modifier of Susceptibility to Type 2 Diabetes in Mice

In 404 Lepob/ob F2 progeny of a C57BL/6J (B6) x DBA/2J (DBA) intercross, we mapped a DBA-related quantitative trait locus (QTL) to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, and pancreatic islet histology. The interval was refined to 1.8 Mb in a series of B6.DBA congenic/subcongenic lines also segregating for Lepob. The phenotypes of B6.DBA congenic mice include reduced β-cell replication rates accompanied by reduced β-cell mass, reduced insulin/glucose ratio in blood, reduced glucose tolerance, and persistent mild hypoinsulinemic hyperglycemia. Nucleotide sequence and expression analysis of 14 genes in this interval identified a predicted gene that we have designated “Lisch-like” (Ll) as the most likely candidate. The gene spans 62.7 kb on Chr1qH2.3, encoding a 10-exon, 646–amino acid polypeptide, homologous to Lsr on Chr7qB1 and to Ildr1 on Chr16qB3. The largest isoform of Ll is predicted to be a transmembrane molecule with an immunoglobulin-like extracellular domain and a serine/threonine-rich intracellular domain that contains a 14-3-3 binding domain. Morpholino knockdown of the zebrafish paralog of Ll resulted in a generalized delay in endodermal development in the gut region and dispersion of insulin-positive cells. Mice segregating for an ENU-induced null allele of Ll have phenotypes comparable to the B.D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Antimicrobial Efficacy and Synergy of Metal Ions against Enterococcus faecium, Klebsiella pneumoniae and Acinetobacter baumannii in Planktonic and Biofilm Phenotypes

The effects of metal ion solutions (silver, copper, platinum, gold and palladium) were determined individually and in combination against Enterococcus faecium, Acinetobacter baumannii and Klebsiella pneumoniae. Platinum, gold and palladium showed the greatest antimicrobial efficacy in zone of inhibition (ZoI) assays. When tested in combinations using ZoI assays, gold/platinum, gold/palladium and platinum/palladium were indicative of synergy. Microbial inhibitory concentration demonstrated platinum and gold against Enterococcus faecium, platinum against Klebsiella pneumoniae and platinum and silver against Acinetobacter baumannii were optimal. Minimal bactericidal concentrations determined the greatest bactericidal activity was again platinum gold and palladium against all three bacteria. Fractional Inhibitory Concentration (FIC) studies demonstrated that the silver/platinum combination against Enterococcus faecium, and silver/copper combination against Acinetobacter baumannii demonstrated antimicrobial synergy. Following crystal violet biofilm assays for single metal ion solutions, antimicrobial efficacies were demonstrated for all the metals against all the bacteria Synergistic assays against biofilms demonstrated gold/palladium, gold/platinumand platinum/palladium resulted in the greatest antimicrobial efficacy. Overall, platinum, palladium and gold metal ion solutions in individual use or combination demonstrated the greatest antimicrobial efficacies against planktonic or biofilm bacteria. This work demonstrates the potential for using a range of metal ions, as biocidal formulations against both planktonic or biofilm bacteria

Descentralização, universalidade e eqüidade nas reformas da saúde<A NAME="top"></A> Decentralization, universal access, and equity in health reforms

Este artigo contextualiza as políticas aplicadas ao campo da saúde na década de 1990 a partir de dois eixos contraditórios: o mandato da Constituição Federal de 1988 e da Lei Orgânica da Saúde (LOAS) de 1990; e a onda neoliberal que influenciou as reformas de Estado em toda a América Latina. O texto detalha os percursos e os percalços do setor saúde na implantação de uma agenda de descentralização fundamentada nos princípios constitucionais de universalização, eqüidade e participação cidadã. E conclui que a reforma da saúde, tal como prevista na LOAS, está se realizando com oscilações, avanços e recuos que traduzem ambigüidades, conflitos e contradições em relação às mudanças no papel do Estado brasileiro a partir da década de 1990. Ele perdeu sua capacidade de formular e implementar políticas nacionais de desenvolvimento, centrou-se no ajuste fiscal e está permeado pelas pressões da globalização do capital.<br>This article analyzes Brazilian policies applied to the field of health in the 1990s from two contradictory angles: the mandate of the 1988 Federal Constitution and the 1990 National Health Act (LOAS) on the one hand and the neoliberal wave that influenced public sector reforms throughout Latin America on the other. The paper discusses pathways and obstacles in the health sector during the implementation of a decentralization agenda based on the constitutional principles of universal access, equity, and citizens' participation. It concludes that the health reform provided for under the National Health Act is being achieved with ups and downs that express contradictions related to changes in the role of the Brazilian public sector beginning in the 1990s. The state lost its capacity to formulate and implement national development policies, focused on fiscal adjustment, and is permeated by pressure from globalization of capital