The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many ...sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.
HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by ...persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.
Understanding mechanisms of tree mortality and the
dynamics of associated canopy gaps is relevant for robust estimates of
carbon balance in forests. We combined monthly RGB images acquired from an
...unoccupied aerial vehicle with field surveys to identify gaps in an 18 ha plot
installed in an old-growth central Amazon forest. We measured the size and
shape of gaps and analyzed their temporal variation and correlation with
rainfall over a period of 28 months. We further described associated modes
of tree mortality (i.e., snapping, uprooting and standing dead) and branch
fall and quantified associated losses of biomass. In total, we detected 32
gaps either in the images or field ranging in area from 9 to 835 m2. Relatively small gaps (< 39 m2) opened by branch fall
were the most frequent (11 gaps). Out of 18 gaps for which both field and
image data were available, three could not be detected remotely. Gaps
observed in the field but not captured on the imagery were relatively small
and mainly formed by the fall of branches from live and standing dead trees.
Our data show that ∼ 17 % of the tree-mortality and
branch-fall events only affected the lower canopy and the understory of the
forest and are likely neglected by top-of-the-canopy assessments.
Regardless of the detection method, the size distribution was best described
by a lognormal function for gaps starting from the smallest detected size (9 and 10 m2 for field and imagery data, respectively), and the
Weibull and Power functions for gaps larger than 25 m2. Properly
assessing associated confidence intervals requires larger sample sizes.
Repeated field measurements reveal that gap area does not differ
significantly among modes of tree mortality or branch fall in central Amazon
forests, with the last contributing the least to biomass loss. Predicting
mechanisms of gap formation based on associated area and biomass loss
remains challenging, which highlights the need for larger datasets. The rate
of gap area formation was positively correlated with the frequency of
extreme rainfall events, which may be related to a higher frequency of
storms propagating extreme rain and wind gusts. While remote sensing has proven to be an accurate and precise method for mapping gaps compared to field data (i.e., ground truth), it is important to note that our sample size was relatively small. Therefore, the extrapolation of
these results beyond our study region and landscape shall be made
cautiously. Apart from improving landscape assessments of carbon balance,
regional information on gap dynamics and associated mechanisms of formation
are fundamental to address forest responses to altered disturbance regimes
resulting from climate change.
Clinopyroxene and amphibole are the main mafic minerals in peralkaline granites of the Papanduva Pluton, Morro Redondo Complex, one of the most important granitic occurrences within the Graciosa ...A-type Province, S-SE Brazil. Clinopyroxene is present as three distinct late- to post-magmatic textural generations of aegirine, as well as post-magmatic aegirine–augite. Amphibole is predominantly magmatic ferrorichterite and arfvedsonite, and post-magmatic riebeckite. Major and trace element compositions reveal evolutionary trends characterized by increasing Fe3+ and Na and decreasing Fe2+, Ca, HFSE, and REE contents from core to crystal rims; trace element and REE partitioning is controlled by the composition of the coexisting melts or fluid phases, as well as by crystal chemistry. δ18O values for minerals investigated range from +2.3 to +6.4‰ and correlate both with increasing degrees of alkalinity and quasi-solidus (sub-magmatic) deformation affecting several granites of the Papanduva Pluton. These deformation events played a significant role in the concentration and circulation of residual melts and fluid phases from which amphiboles and clinopyroxenes precipitated. Combined textural, chemical, and O isotope findings suggest that these fluids evolved through more oxidizing (close to the FMQ buffer), alkali- (i.e. peralkaline), fluorine-, and 18O-rich conditions, associated with higher abundances of HFSEs and REEs within a temperature interval between 750 and 700°C (late-magmatic stages) and 400–450°C (post-magmatic stages).
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•Amphibole and clinopyroxene are late- to post-magmatic phases.•Evolution trends are defined by increasing Na and Fe3+ and decreasing Ca and Fe2+.•Composition of coexisting fluids controls the rare-earth element partitioning.•Oxygen isotope ratios positively correlate with increasing rock deformation.•Sub-magmatic deformation influenced the circulation of residual melts and fluids.
A. Cozzoli, J.‐F. Rolland, R. F. Capogrosso, V. T. Sblendorio, V. Longo, S. Simonetti, B. Nico and A. De Luca (2011) Neuropathology and Applied Neurobiology37, 243–256 Evaluation of potential ...synergistic action of a combined treatment with alpha‐methyl‐prednisolone and taurine on the mdx mouse model of Duchene muscular dystrophy
Aims: Glucocorticoids are the sole drugs clinically used in Duchenne muscular dystrophy, in spite of the relevant side effects. Combination of glucocorticoids with synergistic drugs may be one strategy to lower doses and control side effects, meanwhile providing wider control of the complex pathology. This study is a preclinical evaluation of the effect of a combined treatment of α‐methyl‐prednisolone (PDN) with taurine, a safe aminoacid with positive effects on some pathology‐related events. Methods: PDN (1 mg/kg/day i.p.) and taurine (1 g/kg/day orally) were administered either alone or in combination, for 4–8 weeks to male dystrophic mdx mice chronically exercised on a treadmill. Effects were assessed in vivo and ex vivo with a variety of methodological approaches. Results:In vivo, each treatment significantly increased fore limb strength, a marked synergistic effect being observed with the combination PDN + taurine. Ex vivo, PDN + taurine completely restored the mechanical threshold, an electrophysiological index of calcium homeostasis, of extensor digitorum longus myofibres and the benefit was greater than for PDN alone. In parallel, the overactivity of voltage‐independent cation channels in dystrophic myofibres was reduced. No effects were observed on plasma levels of creatine kinase, while lactate dehydrogenase was decreased by taurine and, to a minor extent, by PDN + taurine. A similar histology profile was observed in PDN and PDN + taurine‐treated muscles. PDN + taurine significantly increased taurine level in fast‐twitch muscle and brain, by high‐pressure liquid chromatography analysis. Conclusions: The combination PDN + taurine has additive actions on in vivo and ex vivo functional end points, with less evident advantages on histopathology and biochemical markers of the disease.
In the present study, molecular detection of human adenoviruses (HAdV) and enteroviruses (EV) was performed in surface water samples collected from beaches Ipanema and Lami, located on the shores of ...Lake Guaíba, city of Porto Alegre, RS, southern Brazil. Furthermore, water safety was evaluated by counting thermotolerant coliforms (TC), following local government regulations. A total of 36 samples were collected monthly from six different sites along the beaches. Viral genomes were found in 30 (83.3%) samples. The higher detection rate was observed for HAdV (77.8%), followed by EV (22.2%). Although low concentrations of TC have been found, the occurrence of viral genomes in water samples was frequent and may pose a potential risk of infection for people bathing in these beaches.
Homogeneous dispersion of carbon nanotubes (CNTs) in polymers has significantly improved their processing and application as nanomaterials. Generally, CNTs tend to agglomerate due to their high ...aspect ratios and strong van der Waals interaction. Surface functionalization appears to be a solution to this problem. This study presents a controlled dispersion of carbon nanotubes in polyethylene through surface modification using a mixture of concentrated acid and octadecylamine (ODA). CNTs were characterized by Fourier transform infrared, Raman and X-ray photoelectron spectroscopy, and transmission electron microscopy. The results confirmed that carboxyl and alkane groups were successfully introduced on CNT surfaces. The acid- and amine-functionalized carbon nanotubes were dispersed in four solvents with different polarities (water, ethanol, acetone, and xylene) to correlate the degree of dispersion of CNT with their polarity. The results showed that CNT dispersion stability strongly depends on solvent and carbon nanotube polarities after the functionalization step. The nanohardness and tensile tests showed that the addition of CNTs, especially the functionalized with ODA, leaded the polymer harder, increasing its Young’s modulus and tensile strength. However, its toughness and deformation capacity were reduced. The potential applications of CNT-based polymer nanocomposites broaden considerably due to the surface engineering of carbon nanotubes.
Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to ...lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.
Antiretroviral therapy (ART) effectively inhibits HIV-1 replication but is not curative due to the persistence of a latent viral reservoir in resting CD4
+
T cells. This reservoir is a major barrier ...to cure. Sequencing studies have revealed that the population of proviruses persisting in ART-treated individuals is dominated by defective proviruses that cannot give rise to viral rebound due to fatal defects including large deletions and APOBEC3-mediated hypermutation. Near full genome sequencing (nFGS) of individual proviruses is used in reservoir assays to provide an estimate of the fraction of proviruses that are intact. nFGS methods rely on a long-distance outer PCR capturing most (~9 kb) of the genome, followed by nested inner PCRs. The outer PCR is carried out at limit dilution, and interpretation of the results is based on the assumption that all proviruses are quantitatively captured. Here, we evaluate nFGS methods using the intact proviral DNA assay (IPDA), a multiplex digital droplet PCR assay that quantitates intact and defective proviruses with single molecule sensitivity using only short, highly efficient amplicons. We analyzed proviral templates of known sequence to avoid the additional complication of sequence polymorphism. With the IPDA, we quantitated molecular yields at each step of nFGS methods. We demonstrate that nFGS methods are inefficient and miss ~70% of full-length proviruses due to amplification failure at the initial outer PCR step. In contrast, proviruses with large internal deletions encompassing 70% of the genome can be quantitatively amplified under the same conditions. Accurate measurement of the latent reservoir of HIV-1 is essential for evaluating the efficacy of cure strategies, and the bias against full length proviruses in nFGS methods must be considered.
Accurate characterization of tropical moist forest changes is needed to support conservation policies and to quantify their contribution to global carbon fluxes more effectively. We document, at ...pantropical scale, the extent and changes (degradation, deforestation, and recovery) of these forests over the past three decades. We estimate that 17% of tropical moist forests have disappeared since 1990 with a remaining area of 1071 million hectares in 2019, from which 10% are degraded. Our study underlines the importance of the degradation process in these ecosystems, in particular, as a precursor of deforestation, and in the recent increase in tropical moist forest disturbances (natural and anthropogenic degradation or deforestation). Without a reduction of the present disturbance rates, undisturbed forests will disappear entirely in large tropical humid regions by 2050. Our study suggests that reinforcing actions are needed to prevent the initial degradation that leads to forest clearance in 45% of the cases.
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