CCR5-∆32, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 gene polymorphisms in individuals with HIV-1, HIV/HTLV-1, and HIV/HTLV-2 in São Paulo, Brazil

Background. Chemokine and chemokine-receptor polymorphisms have been associated with protection against HIV infection and delayed progression to AIDS, whereas polymorphisms in IFNλ4 (formerly IL28B) have been associated with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) development. Evolutionary selection against ancestral genes differs among human populations, resulting in varying risks of acquiring and developing viral diseases. Methods. DNA samples from 434 patients infected with HIV-1 and/or co-infected with HTLV-1/-2, and samples from 74 HIV and HTLV non-infected individuals from São Paulo, Brazil, were divided into five groups: HIV-naïve, n=160; HIV-ART, n=180; HIV/HTLV-1, n=53; HIV/HTLV-2, n=41; and control, n=74. These samples were analyzed for CCR5-∆32 deletion, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 single nucleotide polymorphisms using PCR and PCR-RFLP techniques. These polymorphisms' genotype and allele frequencies were calculated and compared among groups using logistic regression analysis. Results. All polymorphism profiles described in the literature were detected in this study. The wild-type genotype predominated in all genes analyzed except for IFNλ4 rs12979860. Statistical differences in allele frequencies among groups were detected in the CCR5 and CCR2 genes, with a high frequency of ∆32 in HIV-naïve vs. HIV-ART (OR 2.45, P=0.037) and a minus mutant allele A (CCR2-64I) in HIV-naïve vs. HIV/HTLV-1 (OR 1.90, P=0.048), HIV-ART vs. HIV/HTLV-1 (OR 2.62, P=0.003), and HIV/ART vs. HIV/HTLV-2 (OR 2.42, P=0.016). Conclusions. The polymorphism profiles detected in the study groups corroborate the profiles described in racial admixed populations. High CCR2-64I mutant allele frequencies were detected in HIV/HTLV-1/-2 co-infected individuals, and CCR5-∆32 showed predictive value for ART initiation

Acompanhamento das tecnologias apícolas adotadas em assentamentos rurais de Corumbá, MS.

A Embrapa Pantanal executa desde março de 2009 um projeto de pesquisa participativa em dois Assentamentos Rurais de Corumbá/MS em parceria com a AAPAN, AGRAER, Fundação Terra do Pantanal e com alguns assentados, com o objetivo de avaliar as tecnologias apícolas adotadas, propor ajustes e inclusões ao sistema produtivo. Diversas revisões foram realizadas nas colônias de abelhas africanizadas (Apis mellifera) em três apiários, sendo constatadas a despadronização e inadequações na qualidade e no acabamento da madeira utilizada na confecção das colmeias, na localização, na mobilidade e na infra-estrutura nos apiários. Uma assentada com a assistência técnica da Embrapa Pantanal substituiu as suas colmeias rústicas pelo modelo padrão e em todos os apiários foram adotados alguns ajustes nas demais restrições identificadas. No entanto, a adoção de outras tecnologias é limitada devido ao restrito acesso dos assentados a financiamentos, insumos e materiais apícolas de qualidade na região.Disponível também em: Cadernos de Agroecologia, V. 5, n.1, 2010

Pulling absorbing and collapsing polymers from a surface

A self-interacting polymer with one end attached to a sticky surface has been studied by means of a flat-histogram stochastic growth algorithm known as FlatPERM. We examined the four-dimensional parameter space of the number of monomers up to 91, self-attraction, surface attraction and force applied to an end of the polymer. Using this powerful algorithm the \emph{complete} parameter space of interactions and force has been considered. Recently it has been conjectured that a hierarchy of states appears at low temperature/poor solvent conditions where a polymer exists in a finite number of layers close to a surface. We find re-entrant behaviour from a stretched phase into these layering phases when an appropriate force is applied to the polymer. We also find that, contrary to what may be expected, the polymer desorbs from the surface when a sufficiently strong critical force is applied and does \emph{not} transcend through either a series of de-layering transitions or monomer-by-monomer transitions.Comment: 4 pages, 4 figure

Extinction law variations and dust excitation in the spiral galaxy NGC 300

We investigate the origin of the strong radial gradient in the ultraviolet-to-infrared ratio in the spiral galaxy NGC 300, and emphasize the importance of local variations in the interstellar medium geometry, concluding that they cannot be neglected with respect to metallicity effects. This analysis is based upon a combination of maps from GALEX and Spitzer, and from the ground (UBVRI, Halpha and Hbeta). We select ionizing stellar clusters associated with HII regions of widely varying morphologies, and derive their fundamental parameters from population synthesis fitting of their spectral energy distributions, measured to eliminate local backgrounds accurately. From these fits, we conclude that the stellar extinction law is highly variable in the line of sight of young clusters of similar ages. In the particular model geometry that we consider most appropriate to the sampled regions, we checked that our findings are not significantly altered by the correct treatment of radiative transfer effects. The variations are systematic in nature: extinction laws of the Milky Way or LMC type are associated with compact HII regions (the compacity being quantified in two different ways), while clusters surrounded by diffuse HII regions follow extinction laws of the 30 Doradus or SMC type. The Calzetti starburst attenuation law, although most often degenerate with the 30 Doradus extinction law, overpredicts ionizing photon fluxes by large amounts. We also find that the extinction law variations are correlated with the column density of dust species emitting in the near- and mid-infrared. Finally, we briefly discuss the nebular to stellar extinction ratios, and the excitation of aromatic band carriers, invalidating their claimed association with cold dust.Comment: accepted for publication in ApJ -- figure 6 abridged her

Search for Gamma Ray Bursts with the Argo-YBJ Detector in Scaler Mode

We report on the search for Gamma Ray Bursts (GRBs) in the energy range 1-100 GeV in coincidence with the prompt emission detected by satellites using the Astrophysical Radiation with Ground-based Observatory at YangBaJing (ARGO-YBJ) air shower detector. Thanks to its mountain location (Yangbajing, Tibet, P.R. China, 4300 m a.s.l.), active surface (about 6700 m**2 of Resistive Plate Chambers), and large field of view (about 2 sr, limited only by the atmospheric absorption), the ARGO-YBJ air shower detector is particularly suitable for the detection of unpredictable and short duration events such as GRBs. The search is carried out using the "single particle technique", i.e. counting all the particles hitting the detector without measurement of the energy and arrival direction of the primary gamma rays. Between 2004 December 17 and 2009 April 7, 81 GRBs detected by satellites occurred within the field of view of ARGO-YBJ (zenith angle < 45 deg). It was possible to examine 62 of these for >1 GeV counterpart in the ARGO-YBJ data finding no statistically significant emission. With a lack of detected spectra in this energy range fluence upper limits are profitable, especially when the redshift is known and the correction for the extragalactic absorption can be considered. The obtained fluence upper limits reach values as low as 10**{-5} erg cm**{-2} in the 1-100 GeV energy region. Besides this individual search for a higher energy counterpart, a statistical study of the stack of all the GRBs both in time and in phase was made, looking for a common feature in the GRB high energy emission. No significant signal has been detected.Comment: accepted for publication in Ap

Precise CRISPR/Cas-mediated gene repair with minimal off-target and unintended on-target mutations in human hematopoietic stem cells

While CRISPR-Cas9 is key for the development of gene therapy, its potential off-target mutations are still a major concern. Here, we establish a "spacer-nick" gene correction approach that combines the Cas9(D10A) nickase with a pair of PAM-out sgRNAs at a distance of 200 to 350 bp. In combination with adeno-associated virus (AAV) serotype 6 template delivery, our approach led to efficient HDR in human hematopoietic stem and progenitor cells (HSPCs including long-term HSCs) and T cells, with minimal NHEJ-mediated on-target mutations. Using spacer-nick, we developed an approach to repair disease-causing mutations occurring in the HBB, ELANE, IL7R, and PRF1 genes. We achieved gene correction efficiencies of 20 to 50% with minimal NHEJ-mediated on-target mutations. On the basis of in-depth off-target assessment, frequent unintended genetic alterations induced by classical CRISPR-Cas9 were significantly reduced or absent in the HSPCs treated with spacer-nick. Thus, the spacer-nick gene correction approach provides improved safety and suitability for gene therapy

Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism

Altres ajuts: acords transformatius de la UABCDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge. The online version contains supplementary material available at 10.1007/s40618-022-01948-7

Structure and dynamics of ring polymers: entanglement effects because of solution density and ring topology

The effects of entanglement in solutions and melts of unknotted ring polymers have been addressed by several theoretical and numerical studies. The system properties have been typically profiled as a function of ring contour length at fixed solution density. Here, we use a different approach to investigate numerically the equilibrium and kinetic properties of solutions of model ring polymers. Specifically, the ring contour length is maintained fixed, while the interplay of inter- and intra-chain entanglement is modulated by varying both solution density (from infinite dilution up to \approx 40 % volume occupancy) and ring topology (by considering unknotted and trefoil-knotted chains). The equilibrium metric properties of rings with either topology are found to be only weakly affected by the increase of solution density. Even at the highest density, the average ring size, shape anisotropy and length of the knotted region differ at most by 40% from those of isolated rings. Conversely, kinetics are strongly affected by the degree of inter-chain entanglement: for both unknots and trefoils the characteristic times of ring size relaxation, reorientation and diffusion change by one order of magnitude across the considered range of concentrations. Yet, significant topology-dependent differences in kinetics are observed only for very dilute solutions (much below the ring overlap threshold). For knotted rings, the slowest kinetic process is found to correspond to the diffusion of the knotted region along the ring backbone.Comment: 17 pages, 11 figure

The First High Redshift Quasar from Pan-STARRS

We present the discovery of the first high redshift (z > 5.7) quasar from the Panoramic Survey Telescope and Rapid Response System 1 (Pan-STARRS1 or PS1). This quasar was initially detected as an i dropoutout in PS1, confirmed photometrically with the SAO Widefield InfraRed Camera (SWIRC) at Arizona's Multiple Mirror Telescope (MMT) and the Gamma-Ray Burst Optical/Near-Infrared Detector (GROND) at the MPG 2.2 m telescope in La Silla. The quasar was verified spectroscopically with the the MMT Spectrograph, Red Channel and the Cassegrain Twin Spectrograph (TWIN) at the Calar Alto 3.5 m telescope. It has a redshift of 5.73, an AB z magnitude of 19.4, a luminosity of 3.8 x 10^47 erg/s and a black hole mass of 6.9 x 10^9 solar masses. It is a Broad Absorption Line quasar with a prominent Ly-beta peak and a very blue continuum spectrum. This quasar is the first result from the PS1 high redshift quasar search that is projected to discover more than a hundred i dropout quasars, and could potentially find more than 10 z dropout (z > 6.8) quasars.Comment: 8 pages, 7 figure

A high stability semiconductor laser system for a 88^{88}Sr-based optical lattice clock

We describe a frequency stabilized diode laser at 698 nm used for high resolution spectroscopy of the 1S0-3P0 strontium clock transition. For the laser stabilization we use state-of-the-art symmetrically suspended optical cavities optimized for very low thermal noise at room temperature. Two-stage frequency stabilization to high finesse optical cavities results in measured laser frequency noise about a factor of three above the cavity thermal noise between 2 Hz and 11 Hz. With this system, we demonstrate high resolution remote spectroscopy on the 88Sr clock transition by transferring the laser output over a phase-noise-compensated 200 m-long fiber link between two separated laboratories. Our dedicated fiber link ensures a transfer of the optical carrier with frequency stability of 7 \cdot 10^{-18} after 100 s integration time, which could enable the observation of the strontium clock transition with an atomic Q of 10^{14}. Furthermore, with an eye towards the development of transportable optical clocks, we investigate how the complete laser system (laser+optics+cavity) can be influenced by environmental disturbances in terms of both short- and long-term frequency stability.Comment: 9 pages, 9 figures, submitted to Appl. Phys.