Pego do Diabo (Loures, Portugal): Dating the Emergence of Anatomical Modernity in Westernmost Eurasia

Neandertals and the Middle Paleolithic persisted in the Iberian Peninsula south of the Ebro drainage system for several millennia beyond their assimilation/replacement elsewhere in Europe. As only modern humans are associated with the later stages of the Aurignacian, the duration of this persistence pattern can be assessed via the dating of diagnostic occurrences of such stages

Towards the Secondary Bar: Gas Morphology and Dynamics in NGC 4303

The bulk of the molecular line emission in the double barred galaxy NGC4303 as observed in its CO(1-0) line with the OVRO mm-interferometer comes from two straight gas lanes which run north-south along the leading sides of the large-scale primary bar. Inside a radius of ~ 400 pc the molecular gas forms a spiral pattern which, for the northern arm, can be traced to the nucleus. Comparison of the OVRO and archival HST data with dynamical models of gas flow in the inner kiloparsec of single- and double-barred galaxies shows that the observed global properties of the molecular gas are in agreement with models for the gas flow in a strong, large-scale bar, and the two-arm spiral structure seen in CO in the inner kiloparsec can already be explained by a density wave initiated by the potential of that bar. Only a weak correlation between the molecular gas distribution and the extinction seen in the HST V-H map is found in the inner 400 pc of NGC4303: The innermost part of one arm of the nuclear CO spiral correlates with a weak dust filament in the color map, while the overall dust distribution follows a ring or single-arm spiral pattern well correlated with the UV continuum. This complicated nuclear geometry of the stellar and gaseous components allows for two scenarios: (A) A self-gravitating m=1 mode is present forming the spiral structure seen in the UV continuum. In this case the gas kinematics would be unaffected by the small (~ 4'') inner bar. (B) The UV continuum traces a complete ring which is heavily extincted north of the nucleus. Such a ring forms in hydrodynamic models of double bars, but the models cannot account for the UV emission observed on the leading side of the inner bar. (abridged)Comment: 47 pages, 14 figures, accepted for publication in Ap

Cova de les Malladetes (Valencia, Spain). New insights about the Early Upper Palaeolithic in the Mediterranean Basin of the Iberian Peninsula

New excavations carried out at Cova de les Malladetes confirm and improve previous information on the archaeological sequence of this site. A total of 29 new dates allow to specify the chronology of the Aurignacian (levels XIVA-XII) and Gravettian (levels XI-VII). Furthermore, concerning the results obtained during the 1970 excavation, three new levels were identified: level XIVB, which represents a short temporal human occupation hiatus, and levels XV and XVI with some hearths and anthropic evidence, although the lithic material does not permit a cultural attribution. This paper presents data obtained from the analysis of archaeobotanical, micro and macrofaunal assemblages and lithic and osseous industry. Results are relevant concerning the paleoclimatic and paleoenvironmental characterisation of the Early Upper Palaeolithic, as well as for assessing the human occupation patterns during the Gravettian and Aurignacian. Moreover, we evaluate the chronological implications of the basal levels (XIVB, XV and XVI), drawing attention to the absence of an important temporal gap between this phase and the start of the Early Upper Palaeolithic at the site. Finally, our new data extend the information provided by other sites in the Spanish Mediterranean region, allowing a more defined characterisation of the Early Upper Palaeolithic, especially regarding the Evolved Aurignacian chronology and its techno-typological structure, with the presence of Roc-de-Combe subtype Dufour bladelets

Effect of Pathway-Specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-Related Biomarkers Among Asymptomatic Individuals

BACKGROUND: Genetic scores for late-onset Alzheimer's disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier in the lifespan. OBJECTIVE: In this study, we leveraged longitudinal data from the Wisconsin Registry for Alzheimer's Prevention and explored changing patterns in cognition and biomarkers at various age points along six biological pathways. METHODS: PRS and p-PRSs with and without APOE were constructed separately based on the significant SNPs associated with LOAD in a recent genome-wide association study meta-analysis and compared to APOE alone. We used a linear mixed-effects model to assess the association between PRS/p-PRSs and cognitive trajectories among 1,175 individuals. We also applied the model to the outcomes of cerebrospinal fluid biomarkers in a subset. Replication analyses were performed in an independent sample. RESULTS: We found p-PRSs and the overall PRS can predict preclinical changes in cognition and biomarkers. The effects of PRS/p-PRSs on rate of change in cognition, amyloid-β, and tau outcomes are dependent on age and appear earlier in the lifespan when APOE is included in these risk scores compared to when APOE is excluded. CONCLUSION: In addition to APOE, the p-PRSs can predict age-dependent changes in amyloid-β, tau, and cognition. Once validated, they could be used to identify individuals with an elevated genetic risk of accumulating amyloid-β and tau, long before the onset of clinical symptoms

Some comments on the high energy emission from regions of star formation beyond the galaxy

Regions that currently are or have been subject to a strong process of star formation are good candidates to be intense gamma-ray and neutrino emitters. They may even perhaps be sites where ultra high energy cosmic rays are produced. Outside the Galaxy, the more powerful sites of star formation are found within very active galaxies such as starbursts (SGs) and Luminous or Ultra-Luminous Infrared Galaxies (LIRGs or ULIRGs). Some general characteristic of these objects are herein reviewed from the point of view of their possible status as high energy emitters. Revised estimations of the high energy gamma-ray yield of Arp 220 are presented.Comment: 17 pages, 6 figures. Solicited Brief Review prepared for Modern Physics Letters

Carboxyhemoglobin predicts oxygenator performance and imminent oxygenator change in extracorporeal membrane oxygenation

Background The continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid–base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change. Results Out of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO$_{2}$ (estimate for log(COHb): − 2.176 [95% CI − 2.927, − 1.427], p < 0.0001) and with a shorter time to oxygenator change (estimate for log(COHb): − 67.895 [95% CI − 74.209, − 61.542] hours, p < 0.0001). COHb was predictive of oxygenator change within 6 h (estimate for log(COHb): 5.027 [95% CI 1.670, 15.126], p = 0.004). Conclusion COHb correlates with oxygenator performance and can be predictive of imminent oxygenator change. Therefore, longitudinal measurements of COHb in clinical routine might be a cheap and more granular candidate for ECMO surveillance that should be further analyzed in a controlled prospective trial design

Radiocarbon re-dating of contact-era Iroquoian history in northeastern North America

A time frame for late Iroquoian prehistory is firmly established on the basis of the presence/absence of European trade goods and other archeological indicators. However, independent dating evidence is lacking. We use 86 radiocarbon measurements to test and (re)define existing chronological understanding. Warminster, often associated with Cahiagué visited by S. de Champlain in 1615–1616 CE, yields a compatible radiocarbon-based age. However, a well-known late prehistoric site sequence in southern Ontario, Draper-Spang-Mantle, usually dated ~1450–1550, yields much later radiocarbon-based dates of ~1530–1615. The revised time frame dramatically rewrites 16th-century contact-era history in this region. Key processes of violent conflict, community coalescence, and the introduction of European goods all happened much later and more rapidly than previously assumed. Our results suggest the need to reconsider current understandings of contact-era dynamics across northeastern North America

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides

Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.