N-1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism

Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N-1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at similar to 18 h of fasting and being lowest similar to 3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.Peer reviewe

Multidrug-resistant Mycobacterium tuberculosis in HIV-Infected Persons, Peru

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima-Peru and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%)of 965 patients who were HIV-negative or of unknown HIV status (p < 0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB

Identification of effecting proteins by MALDI TOF/TOF mass spectrometry of the root-knot nematode Meloidogyne javanica

La principal problemática del cultivo de vid son los nematodos agalladores de la raíz causan serios problemas en el rendimiento en la mayoría de cultivos en todo el mundo. A través de sus diferentes mecanismos de infección estos nematodos sintetizan y secretan una mezcla de efectores a base de compuestos proteicos que utilizan para penetrar la raíz, migrar y desarrollarse en células gigantes de alimentación radicular en las plantas hospederas. El uso de nuevas herramientas moleculares como la espectrometría de masas MALDI TOF/TOF (Matrix-Assisted Laser Desorption/Ionization - Time-Of-Flight) y la técnica de PCR (Polymerase Chain Reaction) han permitido conocer estas proteínas y genes en diferentes microorganismos. Objetivo: Caracterizar al nematodo agallador de la raíz Meloidogyne javanica mediante la secuenciación del gen ARNr 18S a partir de muestras radiculares infectadas y las proteínas efectoras de juveniles (J2) y adultas (J4) estadio de M. javanica mediante la espectrometría doble masa MALDI TOF/TOF de tipo shotgun proteomics. Metodología: Las raíces infectadas del cultivo de vid fueron colectadas para extraer agallas y J2 frescos de M. javanica, posteriormente se inocularon en plantas de tomate. Se utilizaron J4 de M. javanica para la extracción del ADN genómico y su secuenciamiento a nivel del gen ARNr 18S. Los estadios J2 y J4 de M. javanica, se desinfectaron con hipoclorito de sodio (0,5%) y agua destilada estéril, para la extracción y análisis de proteínas con MALDI-TOF/TOF. Por último, las secuencias obtenidas fueron procesadas con los softwares ProteinPilot™ y Protein BLAST para la identificación de proteínas efectores de M. javanica. Resultados: Se identificó molecularmente, a través de la amplificación por PCR del gen ADNr 18S al nemátodo M. javanica con un porcentaje de identidad de 98% a partir de muestras radiculares infectadas y mediante espectrometría de masas MALDI TOF/TOF, se identificaron secuencias proteicas efectoras tales como: Beta-1,4-endoglucanas y polygalaturonasa, identificadas a partir de J2, y la expansin B2, CLAVATA3/ESR, Pectato lyasa y Chorismato mutasa a partir de J4, involucradas en los diversos procesos de infección. Además, se lograron identificar 49 proteínas no efectoras del nematodo en ambos estadios relacionadas al desarrollo biológico conservado. Implicaciones: Los resultados indican la existencia de proteínas efectoras relacionadas a la formación de agallas de la raíz. Conclusiones: Este estudio confirman que la metodología de espectrometría de doble masa proporciona de una forma rápida y reproducible un perfil proteómico que el nematodo agallador sintetiza para infectar las células radiculares y que puede ser usado en otros tipos de patógenos

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum