The Antarctic Peninsula is one of three regions of the planet that have experienced the highest rates of climate warming over recent decades. Based on a comprehensive large-scale resurvey, allowing ...comparison of new (2009) and historical data (1960s), we show that the two native Antarctic vascular plant species have exhibited significant increases in number of occupied sites and percent cover since the 1960s: Deschampsia antarctica increasing in coverage by 191 % and in number of sites by 104 %. Colobanthus quitensis increasing in coverage by 208 % and number of sites by 35 %. These changes likely occurred in response to increases of 1.2 °C in summer air temperature over the same time period. Both species exhibited changes with elevation due to the interaction of multiple drivers (climatic factors and animal disturbance), producing heterogeneity of responses across an elevation gradient. Below an elevation of 20 m fur seal activity exerted negative impacts. Between 20 and 60 m, both plant species underwent considerable increases in the number of sites and percent cover, likely influenced by both climate warming and nutrient input from seals. Above an elevation threshold of 60 m the maximum elevation of the sites occupied decreased for both species, perhaps as a consequence of physical disturbance at higher elevations due to the permafrost conditions and/or the snow cover thickness and persistence. Understanding the role of disturbance drivers for vegetation change in cold regions may become a research priority to enable improved forecasting of biological responses and feedbacks of climate warming on ecosystems in these globally influential regions.
Muscle thickness (MT) measured by ultrasound has been used to estimate cross‐sectional area (measured by CT and MRI) at a single time point. We tested whether MT could be used as a valid marker of ...MRI determined muscle anatomical cross‐sectional area (ACSA) and volume changes following resistance training (RT). Nine healthy, young, male volunteers (24 ± 2 y.o., BMI 24.1 ± 2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSAmid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post‐training were assessed by Student's paired t test. The relationships between MRI and ultrasound measurements were tested by Pearson's correlation. After RT, MT increased by 7.5 ± 6.1% (P < .001), ACSAmid by 5.2 ± 5% (P < .001), and VOL by 5.0 ± 6.9% (P < .05) (values: means ± SD). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r = .82, P < .001 and r = .73, P < .001, respectively), and between MT and VOL (r = .76, P < .001 and r = .73, P < .001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r = .69, P < .01), but not % change in VOL (r = .33, P > .05). These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.
The paper presents a methodological approach, called “BOttom-up Harmonized Energy-Environmental Models for Europe” (BOHEEME), that combines bottom-up modeling, energy dynamic simulation, and life ...cycle assessment for evaluating and comparing the energy and environmental effects of different renovation strategies of the residential EU building stocks, from micro to the macro level. The study defines 672 building models representative of the residential EU-28 building stocks built before 2010, called archetypes, and the improvement of their envelope, applying different insulation materials from a traditional one to bio-based materials and studying their environmental effects via LCA. The results show that the only improvement of the vertical envelope could reduce the environmental impacts on the residential sector operation of about 6–19% in all the environmental impact categories accounted. Moreover, it could reduce in 2050 about 20% of the CO2eq emission due to the heating and cooling demand and about 13% of the climate change impacts connected to the EU residential energy consumption. The approach and the models proposed could be used for future improvement strategies of all the European residential building stocks, allowing stakeholders, policy-makers, and agencies for identifying the best renovation action.
Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region ...(MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.
Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate ...repertoires in each individual of >1012 antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few—likely one—ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.
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•VRC01-class antibodies from six donors exhibit remarkably similar HIV-1 recognition•NGS sequencing of six donors with VRC01-class antibodies reveals genetic requirements•Restricted gene usage for VRC01-class antibodies indicates single ancestor B cell•Elicitation of VRC01-class antibodies is reproducible
Key points
Vascular function and arterial stiffness are important markers of cardiovascular health and cardiovascular co‐morbidity.
Transitional phases of hypoemia and hypermia, with consequent ...fluctuations in shear rate, occuring during repetitive passive stretching adminstration (passive stretching training) may constitute an effective stimulus to induce an amelioration in vascular function, arterial stiffness and vascular remodelling by improving central and local blood flow control mechanisms.
Vascular function, arterial stiffness and vascular remodelling were evaluated before and after 12 weeks of passive stretching training and after 6 weeks from training cessation, in the femoral, popliteal (treated with stretching), and brachial arteries (untreated) of both sides.
After passive stretching training, vascular function and arterial remodelling improved, and arterial stiffness decreased in all the arteries, suggesting modifications of both central and local blood flow control mechanisms. Passive stretching‐induced improvements related to central mechanisms seemed to have a short duration, as they returned to pre‐training baseline within 6 weeks from training cessation, whereas those more related to a local mechanism persisted in the follow‐up.
Acute passive stretching (PS) effects on blood flow (Q̇), shear rate (Ẏ), and vascular function in the feeding arteries of the stretched muscle have been extensively investigated; however, few data are available on vascular adjustments induced by long‐term PS training. We investigated the effects of PS training on vascular function and stiffness of the involved (femoral and popliteal) and uninvolved (brachial) arteries. Our hypothesis was that PS‐induced changes in Q̇ and Ẏ would improve central and local mechanisms of Q̇ control. Thirty‐nine participants were randomly assigned to bilateral PS (n = 14), monolateral PS (n = 13) or no PS training (n = 12). Vascular function was measured before and after 12 weeks of knee extensor and plantar flexor muscles’ PS training by single passive limb movement and flow‐mediated dilatation (FMD). Central (carotid‐femoral artery PWV, PWVCF) and peripheral (carotid‐radial artery PWV, PWVCR) arterial stiffness was measured by pulse‐wave velocity (PWV), together with systolic (SBP) and diastolic (DBP) blood pressure. After PS training, increases of 30%, 25% and 8% (P < 0.05) in femoral ΔQ̇, popliteal and brachial artery FMD%, respectively, occurred in both PS training groups. A decrease in PWVCF, PWVCR, SBP and DBP (−25%, −17%, −4% and −8%, respectively; P < 0.05) was noted. No changes occurred in controls. Vascular function improved and arterial stiffness reduced in the arteries involved and uninvolved with PS training, suggesting modifications in both central and local Q̇ control mechanisms. PS‐induced improvements had a short duration in some of vascular function parameters, as they returned to baseline within 6 weeks of PS training cessation.
Key points
Vascular function and arterial stiffness are important markers of cardiovascular health and cardiovascular co‐morbidity.
Transitional phases of hypoemia and hypermia, with consequent fluctuations in shear rate, occuring during repetitive passive stretching adminstration (passive stretching training) may constitute an effective stimulus to induce an amelioration in vascular function, arterial stiffness and vascular remodelling by improving central and local blood flow control mechanisms.
Vascular function, arterial stiffness and vascular remodelling were evaluated before and after 12 weeks of passive stretching training and after 6 weeks from training cessation, in the femoral, popliteal (treated with stretching), and brachial arteries (untreated) of both sides.
After passive stretching training, vascular function and arterial remodelling improved, and arterial stiffness decreased in all the arteries, suggesting modifications of both central and local blood flow control mechanisms. Passive stretching‐induced improvements related to central mechanisms seemed to have a short duration, as they returned to pre‐training baseline within 6 weeks from training cessation, whereas those more related to a local mechanism persisted in the follow‐up.
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of ...HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
MicroRNAs are predicted to regulate almost equal to30% of all human genes by targeting sequences in their 3' UTR. Polymorphisms in 3' UTR of several genes have been reported to affect gene ...expression, but the mechanism is not fully understood. Here, we demonstrate that 829Crightward arrowT, a naturally occurring SNP, near the miR-24 binding site in the 3' UTR of human dihydrofolate reductase (DHFR) affects DHFR expression by interfering with miR-24 function, resulting in DHFR overexpression and methotrexate resistance. miR-24 has a conserved binding site in DHFR 3' UTR. DHFR with WT and 3' UTR containing the 829Crightward arrowT mutation were expressed in DG44 cells that lack DHFR. Overexpression of miR-24 in cells with WT DHFR resulted in down-regulation of DHFR protein, whereas no effect on DHFR protein expression was observed in the mutant 3' UTR-expressing cells. Inhibition of endogenous miR-24 with a specific inhibitor led to up-regulation of DHFR in WT and not in mutant cells. Cells with the mutant 3' UTR had a 2-fold increase in DHFR mRNA half-life, expressed higher DHFR mRNA and DHFR protein, and were 4-fold more resistant to methotrexate as compared with WT cells. SNP-829Crightward arrowT, therefore, leads to a decrease in microRNA binding leading to overexpression of its target and results in resistance to methotrexate. We demonstrate that a naturally occurring miRSNP (a SNP located at or near a microRNA binding site in 3' UTR of the target gene or in a microRNA) is associated with enzyme overproduction and drug resistance.