Defining paleoclimatic routes and opportunities for hominin dispersals across Iran

Fossil and archaeological evidence indicates that hominin dispersals into Southwest Asia occurred throughout the Pleistocene, including the expansion of Homo sapiens populations out of Africa. While there is evidence for hominin occupations in the Pleistocene in Iran, as evidenced by the presence of Lower to Upper Paleolithic archaeological sites, the extent to which humid periods facilitated population expansions into western Asia has remained unclear. To test the role of humid periods on hominin dispersals here we assess Paleolithic site distributions and paleoenvironmental records across Iran. We developed the first spatially comprehensive, high-resolution paleohydrological model for Iran in order to assess water availability and its influence on hominin dispersals. We highlight environmentally mediated routes which likely played a key role in Late Pleistocene hominin dispersals, including the expansion of H. sapiens and Neanderthals eastwards into Asia. Our combined analyses indicate that, during MIS 5, there were opportunities for hominins to traverse a northern route through the Alborz and Kopet Dagh Mountains and the Dasht-I Kavir desert owing to the presence of activated fresh water sources. We recognize a new southern route along the Zagros Mountains and extending eastwards towards Pakistan and Afghanistan. We find evidence for a potential northern route during MIS 3, which would have permitted hominin movements and species interactions in Southwest Asia. Between humid periods, these interconnections would have waned, isolating populations in the Zagros and Alborz Mountains, where hominins may have continued to have had access to water

Taphonomic and zooarchaeological investigations at the middle Pleistocene site of Ti's al Ghadah, western Nefud Desert, Saudi Arabia

In recent years, the Arabian Peninsula has emerged as a key region for elucidating hominin and faunal evolution and dispersals between Africa and Eurasia. Central to this research is the middle Pleistocene site of Ti's al Ghadah (TAG) which has yielded a diverse and abundant fossil faunal assemblage and the earliest chronometrically dated evidence for hominins in this part of the world. Here, we present the first detailed taphonomic study of the large Unit 5 fossil assemblage from the site. We aim to assess which actor/s were responsible for the accumulation of the assemblage and evaluate evidence that might be consistent with the accumulation of fauna by hominins. We also describe, for the first time, fossils and lithic artefacts from stratigraphic horizons not previously considered, providing taphonomic insights into their accumulation. The taphonomic work shows that the Unit 5 faunal assemblage was accumulated by ambush predators, likely large felids and hominins, in a lake side environment, and that carcasses were subsequently scavenged by more durophagus carnivores such as hyenas and canids. Less can be reliably said regarding the newly described fossil assemblages given their poor preservation and significant wind abrasion, but large carnivores again appear to have played a role, and hominins probably played a role in the accumulation of at least one of these. This study provides the first detail insights into the interplay between hominins, carnivores, and herbivores in Arabia, and suggests that watering holes have been a focus on the Arabian landscape for resources since the middle Pleistocene

Middle-late Quaternary palaeoclimate variability from lake and wetland deposits in the Nefud Desert, Northern Arabia

Records of former lake and wetland development in present day arid/hyper-arid environments provide an important source of information for palaeoclimatic and palaeoenvironmental studies. In Arabia, such records are typically confined to eccentricity-modulated insolation maxima, and are often spatially and temporally discontinuous. Here we present records from a single locality in Northern Arabia of wetter interludes during both global interglacial and glacial conditions, providing a unique opportunity to examine the nature of these events in a common setting. At Jubbah, in the southern Nefud Desert, lake and wetland deposits reveal the repeated formation of a water body within a large endorheic basin over the past ca. 360 kyr. Lake/wetland formation occurred during MIS 11/9, 7, 5, 3 and the early Holocene, assisted by local topographic controls, and spring recharge. Palaeoenvironmental and palaeoecological data reveal the existence of a large still water body formed during either MIS 11 or 9 (ca. 363 ka), and basin wide alluviation followed by lake formation during MIS 7 (ca. 212 ka). During MIS 5e (ca. 130 ka) a large freshwater lake occupied the basin, while during MIS 5a (ca. 80 ka) the basin contained a shallow wetland and freshwater lake complex. Lake/wetland formation also occurred during early MIS 3 (ca. 60 ka), at the Terminal Pleistocene-Holocene transition (ca. 12.5 ka), and the early-middle Holocene (ca. 9–6.5 ka). Phases of lake and wetland development coincided with human occupation of the basin during the Middle Palaeolithic, Epipalaeolithic and Neolithic periods, highlighting the significance of the region for early demographic change

Pollinator monitoring more than pays for itself

1. Resilient pollination services depend on sufficient abundance of pollinating insects over time. Currently, however, most knowledge about the status and trends of pollinators is based on changes in pollinator species richness and distribution only. 2. Systematic, long‐term monitoring of pollinators is urgently needed to provide baseline information on their status, to identify the drivers of declines and to inform suitable response measures. 3. Power analysis was used to determine the number of sites required to detect a 30% change in pollinator populations over 10 years. We then evaluated the full economic costs of implementing four national monitoring schemes in the UK: (a) professional pollinator monitoring, (b) professional pollination service monitoring, (c) volunteer collected pan traps and (d) volunteer focal floral observations. These costs were compared to (a) the costs of implementing separate, expert‐designed research and monitoring networks and (b) the economic benefits of pollination services threatened by pollinator loss. 4. Estimated scheme costs ranged from £6,159/year for a 75‐site volunteer focal flower observation scheme to £2.7 M/year for an 800‐site professional pollination service monitoring network. The estimated research costs saved using the site network as research infrastructure range from £1.46–4.17 M/year. The economic value of UK crop yield lost following a 30% decline in pollinators was estimated at ~£188 M/year. 5. Synthesis and applications. We evaluated the full costs of running pollinator monitoring schemes against the economic benefits to research and society they provide. The annual costs of monitoring are <0.02% of the economic value of pollination services that would be lost after a 30% decline in pollination services. Furthermore, by providing high‐quality scientific data, monitoring schemes would save at least £1.5 on data collection per £1 spent. Our findings demonstrate that long‐term systematic monitoring can be a cost‐effective tool for both answering key research questions and setting action points for policymakers. Careful consideration must be given to scheme design, the logistics of national‐scale implementation and resulting data quality when selecting the most appropriate combination of surveyors, methods and site networks to deliver a successful scheme

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

Paleolithic occupation of arid Central Asia in the Middle Pleistocene

Central Asia is positioned at a crossroads linking several zones important to hominin dispersal during the Middle Pleistocene. However, the scarcity of stratified and dated archaeological material and paleoclimate records makes it difficult to understand dispersal and occupation dynamics during this time period, especially in arid zones. Here we compile and analyze paleoclimatic and archaeological data from Pleistocene Central Asia, including examination of a new layer-counted speleothem-based multiproxy record of hydrological changes in southern Uzbekistan at the end of MIS 11. Our findings indicate that Lower Palaeolithic sites in the steppe, semi-arid, and desert zones of Central Asia may have served as key areas for the dispersal of hominins into Eurasia during the Middle Pleistocene. In agreement with previous studies, we find that bifaces occur across these zones at higher latitudes and in lower altitudes relative to the other Paleolithic assemblages. We argue that arid Central Asia would have been intermittently habitable during the Middle Pleistocene when long warm interglacial phases coincided with periods when the Caspian Sea was experiencing consistently high water levels, resulting in greater moisture availability and more temperate conditions in otherwise arid regions. During periodic intervals in the Middle Pleistocene, the local environment of arid Central Asia was likely a favorable habitat for paleolithic hominins and was frequented by Lower Paleolithic toolmakers producing bifaces

Homo sapiens in Arabia by 85,000 years ago.

Understanding the timing and character of the expansion of Homo sapiens out of Africa is critical for inferring the colonization and admixture processes that underpin global population history. It has been argued that dispersal out of Africa had an early phase, particularly ~130-90 thousand years ago (ka), that reached only the East Mediterranean Levant, and a later phase, ~60-50 ka, that extended across the diverse environments of Eurasia to Sahul. However, recent findings from East Asia and Sahul challenge this model. Here we show that H. sapiens was in the Arabian Peninsula before 85 ka. We describe the Al Wusta-1 (AW-1) intermediate phalanx from the site of Al Wusta in the Nefud desert, Saudi Arabia. AW-1 is the oldest directly dated fossil of our species outside Africa and the Levant. The palaeoenvironmental context of Al Wusta demonstrates that H. sapiens using Middle Palaeolithic stone tools dispersed into Arabia during a phase of increased precipitation driven by orbital forcing, in association with a primarily African fauna. A Bayesian model incorporating independent chronometric age estimates indicates a chronology for Al Wusta of ~95-86 ka, which we correlate with a humid episode in the later part of Marine Isotope Stage 5 known from various regional records. Al Wusta shows that early dispersals were more spatially and temporally extensive than previously thought. Early H. sapiens dispersals out of Africa were not limited to winter rainfall-fed Levantine Mediterranean woodlands immediately adjacent to Africa, but extended deep into the semi-arid grasslands of Arabia, facilitated by periods of enhanced monsoonal rainfall

Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes

DNA methylation predicts age and provides insight into exceptional longevity of bats

This work was supported by a Paul G. Allen Frontiers Group grant to S.H., the University of Maryland, College of Computer, Mathematical and Natural Sciences to G.S.W., an Irish Research Council Consolidator Laureate Award to E.C.T., a UKRI Future Leaders Fellowship (MR/T021985/1) to S.C.V. and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to P.A.F. S.C.V. and P.D. were supported by a Max Planck Research Group awarded to S.C.V. by the Max Planck Gesellschaft, and S.C.V. and E.Z.L. were supported by a Human Frontiers Science Program Grant (RGP0058/2016) awarded to S.C.V. L.J.G. was supported by an NSERC PGS-D scholarship.Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.Publisher PDFPeer reviewe