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209 result(s) for "Lorenzo, Juan R."
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A fast-evolving human NPAS3 enhancer gained reporter expression in the developing forebrain of transgenic mice
The developmental brain gene NPAS3 stands out as a hot spot in human evolution because it contains the largest number of human-specific, fast-evolving, conserved, non-coding elements. In this paper we studied 2xHAR142, one of these elements that is located in the fifth intron of NPAS3. Using transgenic mice, we show that the mouse and chimp 2xHAR142 orthologues behave as transcriptional enhancers driving expression of the reporter gene lacZ to a similar NPAS3 expression subdomain in the mouse central nervous system. Interestingly, the human 2xHAR142 orthologue drives lacZ expression to an extended expression pattern in the nervous system. Thus, molecular evolution of 2xHAR142 provides the first documented example of human-specific heterotopy in the forebrain promoted by a transcriptional enhancer and suggests that it may have contributed to assemble the unique properties of the human brain.
A fast-evolving human NPAS3 enhancer gained reporter expression in the developing forebrain of transgenic mice
The developmental brain gene NPAS3 stands out as a hot spot in human evolution because it contains the largest number of human-specific, fast-evolving, conserved, non-coding elements. In this paper we studied 2xHAR142, one of these elements that is located in the fifth intron of NPAS3. Using transgenic mice, we show that the mouse and chimp 2xHAR142 orthologues behave as transcriptional enhancers driving expression of the reporter gene lacZ to a similar NPAS3 expression subdomain in the mouse central nervous system. Interestingly, the human 2xHAR142 orthologue drives lacZ expression to an extended expression pattern in the nervous system. Thus, molecular evolution of 2xHAR142 provides the first documented example of human-specific heterotopy in the forebrain promoted by a transcriptional enhancer and suggests that it may have contributed to assemble the unique properties of the human brain.
Response of vegetation to drought time-scales across global land biomes
We evaluated the response of the Earth land biomes to drought by correlating a drought index with three global indicators of vegetation activity and growth: vegetation indices from satellite imagery, tree-ring growth series, and Aboveground Net Primary Production (ANPP) records. Arid and humid biomes are both affected by drought, and we suggest that the persistence of the water deficit (i.e., the drought time-scale) could be playing a key role in determining the sensitivity of land biomes to drought. We found that arid biomes respond to drought at short time-scales; that is, there is a rapid vegetation reaction as soon as water deficits below normal conditions occur. This may be due to the fact that plant species of arid regions have mechanisms allowing them to rapidly adapt to changing water availability. Humid biomes also respond to drought at short time-scales, but in this case the physiological mechanisms likely differ from those operating in arid biomes, as plants usually have a poor adaptability to water shortage. On the contrary, semiarid and subhumid biomes respond to drought at long time-scales, probably because plants are able to withstand water deficits, but they lack the rapid response of arid biomes to drought. These results are consistent among three vegetation parameters analyzed and across different land biomes, showing that the response of vegetation to drought depends on characteristic drought time-scales for each biome. Understanding the dominant time-scales at which drought most influences vegetation might help assessing the resistance and resilience of vegetation and improving our knowledge of vegetation vulnerability to climate change.
Evidence of increasing drought severity caused by temperature rise in southern Europe
We use high quality climate data from ground meteorological stations in the Iberian Peninsula (IP) and robust drought indices to confirm that drought severity has increased in the past five decades, as a consequence of greater atmospheric evaporative demand resulting from temperature rise. Increased drought severity is independent of the model used to quantify the reference evapotranspiration. We have also focused on drought impacts to drought-sensitive systems, such as river discharge, by analyzing streamflow data for 287 rivers in the IP, and found that hydrological drought frequency and severity have also increased in the past five decades in natural, regulated and highly regulated basins. Recent positive trend in the atmospheric water demand has had a direct influence on the temporal evolution of streamflows, clearly identified during the warm season, in which higher evapotranspiration rates are recorded. This pattern of increase in evaporative demand and greater drought severity is probably applicable to other semiarid regions of the world, including other Mediterranean areas, the Sahel, southern Australia and South Africa, and can be expected to increasingly compromise water supplies and cause political, social and economic tensions among regions in the near future.
Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome facilitate tRNA translocation
An 11.7‐Å‐resolution cryo‐EM map of the yeast 80S·eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges. Sordarin positions domain III of eEF2 so that it can interact with the sarcin–ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation explains the inhibitory action of sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state. A ratchet‐like subunit rearrangement (RSR) occurs in the 80S·eEF2·sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes. A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction.
Inconsistent response of taxonomic groups to space and environment in mediterranean and tropical pond metacommunities
The metacommunity concept provides a theoretical framework that aims at explaining organism distributions by a combination of environmental filtering, dispersal, and drift. However, few works have attempted a multitaxon approach and even fewer have compared two distant biogeographical regions using the same methodology. We tested the expectation that temperate (mediterranean-climate) pond metacommunities would be more influenced by environmental and spatial processes than tropical ones, because of stronger environmental gradients and a greater isolation of waterbodies. However, the pattern should be different among groups of organisms depending on their dispersal abilities. We surveyed 30 tropical and 32 mediterranean temporary ponds from Costa Rica and Spain, respectively, and obtained data on 49 environmental variables. We characterized the biological communities of bacteria and archaea (from the water column and the sediments), phytoplankton, zooplankton, benthic invertebrates, amphibians and birds, and estimated the relative role of space and environment on metacommunity organization for each group and region, by means of variation partitioning using generalized additive models. Purely environmental effects were important in both tropical and mediterranean ponds, but stronger in the latter, probably due to their larger limnological heterogeneity. Spatially correlated environment and pure spatial effects were greater in the tropics, related to higher climatic heterogeneity and dispersal processes (e.g., restriction, surplus) acting at different scales. The variability between taxonomic groups in the contribution of spatial and environmental factors to metacommunity variation was very wide, but higher in active, compared with passive, dispersers. Higher environmental effects were observed in mediterranean passive dispersers, and higher spatial effects in tropical passive dispersers. The unexplained variation was larger in the tropical setting, suggesting a higher role for stochastic processes, unmeasured environmental factors, or biotic interactions in the tropics, although this difference affected some actively dispersing groups (insects and birds) more than passive dispersers. These results, despite our limitations in comparing only two regions, provide support, for a wide variety of aquatic organisms, for the classic view of stronger abiotic niche constraints in temperate areas compared with the tropics. The heterogeneous response of taxonomic groups between regions also points to a stronger influence of regional context than organism adaptations on metacommunity organization.
Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition
Two phase 2 trials assessed the efficacy and safety of intravenous infusions of a broadly neutralizing antibody, VRCO1, to prevent HIV-1 infection. VRC01 did not cause adverse events and did not prevent overall HIV-1 acquisition significantly more effectively than placebo. In secondary analyses, VRC01 prevented transmission of VRC01-sensitive HIV-1 isolates.
Diagnostic Approach to Unexplained Cardiac Arrest (from the FIVI-Gen Study)
Unexplained cardiac arrest (UCA) can be caused by low-penetrance genetic disorders. The aim of this cross-sectional study is to assess the usefulness of a new diagnostic protocol: Thirty-five patients were recruited from 9 Spanish centers. Electrocardiogram, echocardiogram, and coronary catheterization were used to rule out electrical or structural heart disease in all subjects. Patients underwent pharmacologic tests with epinephrine and flecainide, followed by assessment of family members using electrocardiogram and echocardiogram, and next-generation genetic sequencing to analyze 126 genes if all the other test results were negative. A firm diagnosis of channelopathy required phenotypic proof of the condition in unmasking tests, the presence of a pathogenic variant consistent with the phenotype observed, and/or co-segregation of the mutation found in a family member's phenotype. A firm diagnosis was made in 18 cases. The diagnoses were 7 Brugada syndrome, 5 catecholaminergic polymorphic ventricular tachycardia, 3 long QT syndrome, 2 early repolarization syndrome, and 1 short QT syndrome. Pharmacologic testing was the most frequent method of diagnosis. In 5 cases, the diagnosis was made based on positive genetic testing without phenotypic alterations. In conclusion, this sequential diagnostic protocol allows diagnoses to be made in approximately half of the UCA cases. These diagnoses are low clinical penetrance channelopathies. If interpreted carefully, genetic tests can be a useful tool for diagnosing UCA without a phenotype.
Homogenization and Assessment of Observed Near-Surface Wind Speed Trends over Spain and Portugal, 1961–2011
Near-surface wind speed trends recorded at 67 land-based stations across Spain and Portugal for 1961–2011, also focusing on the 1979–2008 subperiod, were analyzed. Wind speed series were subjected to quality control, reconstruction, and homogenization using a novel procedure that incorporated the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5)-simulated series as reference. The resultant series show a slight downward trend for both 1961–2011 (−0.016 m s−1decade−1) and 1979–2008 (−0.010 m s−1decade−1). However, differences between seasons with declining values in winter and spring, and increasing trends in summer and autumn, were observed. Even though wind stilling affected 77.8% of the stations in winter and 66.7% in spring, only roughly 40% of the declining trends were statistically significant at thep< 0.10 level. On the contrary, increasing trends appeared in 51.9% of the stations in summer and 57.4% in autumn, with also around 40% of the positive trends statistically significant at thep< 0.10 level. In this article, the authors also investigated (i) the possible impact of three atmospheric indices on the observed trends and (ii) the role played by the urbanization growth in the observed decline. An accurate homogenization and assessment of the long-term trends of wind speed is crucial for many fields such as wind energy (e.g., power generation) and agriculture–hydrology (e.g., evaporative demand).