Homo sapiens reached the higher latitudes of Europe by 45,000 years ago

Iscience

Palaeoproteomic analysis of skeletal proteomes is used to provide taxonomic identifications for an increasing number of archaeological specimens. The success rate depends on a range of taphonomic factors and differences in the extraction protocols employed. By analyzing 12 archaeological bone specimens from two archaeological sites, we demonstrate that reducing digestion duration from 18 to 3 hours has no measurable impact on the obtained taxonomic identifications. Peptide marker recovery, COL1 sequence coverage, or proteome complexity are also not significantly impacted. Although we observe minor differences in sequence coverage and glutamine deamidation, these are not consistent across our dataset. A 6-fold reduction in digestion time reduces electricity consumption, and therefore CO2 emission intensities. We furthermore demonstrate that working in 96-well plates further reduces electricity …

bioRxiv

Biological sex is key information for archaeological and forensic studies, which can be determined by proteomics. However, lack of a standardised approach for fast and accurate sex identification currently limits the reach of proteomics applications. Here, we introduce a streamlined mass spectrometry (MS)-based workflow for determination of biological sex using human dental enamel. Our approach builds on a minimally invasive sampling strategy by acid etching, a rapid online liquid chromatography (LC) gradient coupled to high-resolution parallel reaction monitoring assay allowing for a throughput of 200 samples-per-day with high quantitative performance enabling confident identification of both males and females. Additionally, we have developed a streamlined data analysis pipeline and integrated it into an R-Shiny interface for ease-of-use. The method was first developed and optimised using modern teeth and then validated in an independent set of deciduous teeth of known sex. Finally, the assay was successfully applied to archaeological material, enabling the analysis of over 300 individuals. We demonstrate unprecedented performance and scalability, speeding up MS analysis by tenfold compared to conventional proteomics-based sex identification methods. This work paves the way for large-scale archaeological or forensic studies enabling the investigation of entire populations rather than focusing on individual high-profile specimens.

Scientific Reports

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10−8) association of the rs117011822 variant, on chromosome 11, of rs7208524 …

Cancer Research

ACR-368 (prexasertib) is a clinically advanced CHK1/2 inhibitor which has demonstrated durable activity across a proportion of patients with advanced solid tumors. Genomic biomarkers have proven unsuccessful in predicting response to ACR-368, limiting its clinical success. Using AP3, we previously developed a response-predictive proteomics-based test for ACR-368 (ACR-368 OncoSignature) for the identification of patients sensitive to ACR-368 monotherapy treatment as demonstrated in blinded preclinical studies. A Phase 2 clinical trial is ongoing where patients are treated with ACR-368 monotherapy based on OncoSignature-predicted sensitivity (NCT05548296). Here, we demonstrate the utility of AP3 for the identification of a key druggable resistance mechanism to ACR-368 and how to overcome that with low dose gemcitabine (gem), providing OncoSignature negative patients with a new potential …

The spread of Homo sapiens into new habitats across Eurasia~ 45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species’ history.‘Transitional’technocomplexes, such as the Lincombian–Ranisian–Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to~ 45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning~ 12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold …

bioRxiv

Identification of the taxonomic origin of bone tools is an important, but often complicated, component of studying past societies. The species used for bone tool production provide insight into what species were exploited, potentially how, and for what purpose. Additionally, the choice of species may have important implications for the place of the tool within the larger toolkit. However, the taxonomic identification of bone tools is often unsuccessful based on morphology. Here we apply three palaeoproteomic techniques, ZooMS, SPIN and a targeted database search to narrow down the taxonomic identification of an unusually large Bronze Age bone tool from Heiloo, the Netherlands, to the North Atlantic right whale (Eubalaena glacialis). Additionally, the tool was investigated for use-wear, which showed that it was likely used for the processing of plant fibres. The assignment of the tool as whale bone adds support to the exploitation of whales by coastal Bronze Age populations, not just for meat, as previously suggested, but also for bone as a resource for tool production. We know of no other parallel of a bone tool such as this in terms of size, use, hafting, and taxonomic identity.

Open Research Europe

Background Data-dependent, bottom-up proteomics is widely used for identifying proteins and peptides. However, one key challenge is that 70% of fragment ion spectra consistently fail to be assigned by conventional database searching. This ‘dark matter’ of bottom-up proteomics seems to affect fields where non-model organisms, low-abundance proteins, non-tryptic peptides, and complex modifications may be present. While palaeoproteomics may appear as a niche field, understanding and reporting unidentified ancient spectra require collaborative innovation in bioinformatics strategies. This may advance the analysis of complex datasets. Methods 14.97 million high-impact ancient spectra published in Nature and Science portfolios were mined from public repositories. Identification rates, defined as the proportion of assigned fragment ion spectra, were collected as part of deposited database search outputs or parsed using open-source python packages. Results and Conclusions We report that typically 94% of the published ancient spectra remain unidentified. This phenomenon may be caused by multiple factors, notably the limitations of database searching and the selection of user-defined reference data with advanced modification patterns. These ‘spectra without stories’ highlight the need for widespread data sharing to facilitate methodological development and minimise the loss of often irreplaceable ancient materials. Testing and validating alternative search strategies, such as open searching and de novo sequencing, may also improve overall identification rates. Hence, lessons learnt in palaeoproteomics may …

Journal of the American Society for Mass Spectrometry

To improve the coverage in bottom-up proteomics, S-aminoethylation of cysteine residues (AE-Cys) was carried out with 2-bromoethylamine, followed by cleavage with lysyl endopeptidase (Lys-C) or Lys-C/trypsin. A model study with bovine serum albumin showed that the C-terminal side of AE-Cys was successfully cleaved by Lys-C. The frequency of side reactions at amino acids other than Cys was less than that in the case of carbamidomethylation of Cys with iodoacetamide. Proteomic analysis of A549 cell extracts in the data-dependent acquisition mode after AE-Cys modification afforded a greater number of identified protein groups, especially membrane proteins. In addition, label-free quantification of proteins in mouse nonsmall cell lung cancer (NSCLC) tissue in the data-independent acquisition mode after AE-Cys modification showed improved NSCLC pathway coverage and greater reproducibility …

Eur Eat Disord Rev

Conclusions: Results suggest that a traumatic event history may hinder treatment success and that PTSD may be more influential than the trauma exposure itself.

bioRxiv

Proteins are the primary targets of almost all small molecule drugs. However, even the most selectively designed drugs can potentially target several unknown proteins. Identification of potential drug targets can facilitate design of new drugs and repurposing of existing ones. Current state-of-the-art proteomics methodologies enable screening of thousands of proteins against a limited number of drug molecules. Here we report the development of a label-free quantitative proteomics approach that enables proteome-wide screening of small organic molecules in a scalable, reproducible, and rapid manner by streamlining the proteome integral solubility alteration (PISA) assay. We used rat organs ex-vivo to determine organ specific targets of medical drugs and enzyme inhibitors to identify novel drug targets for common drugs such as Ibuprofen. Finally, global drug profiling revealed overarching trends of how small molecules affect the proteome through either direct or indirect protein interactions.

nature communications

Mass spectrometry (MS)-based proteomics workflows typically involve complex, multi-step processes, presenting challenges with sample losses, reproducibility, requiring substantial time and financial investments, and specialized skills. Here we introduce One-Tip, a proteomics methodology that seamlessly integrates efficient, one-pot sample preparation with precise, narrow-window data-independent acquisition (nDIA) analysis. One-Tip substantially simplifies sample processing, enabling the reproducible identification of >9000 proteins from ~1000 HeLa cells. The versatility of One-Tip is highlighted by nDIA identification of ~6000 proteins in single cells from early mouse embryos. Additionally, the study incorporates the Uno Single Cell Dispenser™, demonstrating the capability of One-Tip in single-cell proteomics with >3000 proteins identified per HeLa cell. We also extend One-Tip workflow to analysis of …

The cerebrospinal fluid (CSF) proteome could offer important insights into central nervous system (CNS) malignancies. To advance proteomic research in pediatric CNS cancer, the current study aims to (1) evaluate past mass spectrometry-based workflows and (2) synthesize previous CSF proteomic data, focusing on both qualitative summaries and quantitative re-analysis. In our analysis of 11 studies investigating the CSF proteome in pediatric patients with acute lymphoblastic leukemia (ALL) or primary brain tumors, we observed significant methodological variability. This variability negatively affects comparative analysis of the included studies, as per GRADE criteria for quality of evidence. The qualitative summaries covered 161 patients and 134 non-tumor controls, while the application of validation cohort varied among the studies. The quantitative re-analysis comprised 15 B-ALL vs 6 “healthy” controls and 15 medulloblastoma patients vs 22 non-tumor controls. Certain CSF proteins were identified as potential indicators of specific malignancies or stages of neurotoxicity during chemotherapy, yet definitive conclusions were impeded by inconsistent data. There were no proteins with statistically significant differences when comparing cases versus controls that were corroborated across studies where quantitative reanalysis was feasible. From a gene ontology enrichment, we observed that age disparities between unmatched case and controls may mislead to protein correlations more indicative of age-related CNS developmental stages rather than neuro-oncological disease. Despite efforts to batch correct (HarmonizR) and impute missing …

Scientific Reports

Placing the origin of an undeciphered script in time is crucial to understanding the invention of writing in human history. Rapa Nui, also known as Easter Island, developed a script, now engraved on fewer than 30 wooden objects, which is still undeciphered. Its origins are also obscure. Central to this issue is whether the script was invented before European travelers reached the island in the eighteenth century AD. Hence direct radiocarbon dating of the wood plays a fundamental role. Until now, only two tablets were directly dated, placing them in the nineteenth c. AD, which does not solve the question of independent invention. Here we radiocarbon-dated four Rongorongo tablets preserved in Rome, Italy. One specimen yielded a unique and secure mid-fifteenth c. date, while the others fall within the nineteenth c. AD. Our results suggest that the use of the script could be placed to a horizon that predates the arrival of …

Journal of Archaeological Science

The highly fragmented nature of Palaeolithic faunal assemblages is a regular limitation in archaeozoological analyses as it prevents a precise taxonomic identification following comparative anatomy criteria. In this paper, we integrate Zooarchaeology by Mass Spectrometry (ZooMS) analysis of unidentifiable bone fragments within archaeozoological and taphonomic data to overcome this limitation and disentangle the subsistence strategies of Solutrean and Magdalenian human groups of the La Viña rock shelter (northern Iberia). The ZooMS results are consistent with the archaeozoological data showing preferential exploitation of red deer complemented by horses and caprids, whereas large bovids and reindeer are a minor component. This study also reveals significant species variability in classifying unidentifiable bones to mammal-size classes. The combination of biomolecular methods and traditional …

Journal of Proteome Research

Protein arginine methylations are important post-translational modifications (PTMs) in eukaryotes, regulating many biological processes. However, traditional collision-based mass spectrometry methods inevitably cause neutral losses of methylarginines, preventing the deep mining of biologically important sites. Herein we developed an optimized mass spectrometry workflow based on electron-transfer dissociation (ETD) with supplemental activation for proteomic profiling of arginine methylation in human cells. Using symmetric dimethylarginine (sDMA) as an example, we show that the ETD-based optimized workflow significantly improved the identification and site localization of sDMA. Quantitative proteomics identified 138 novel sDMA sites as potential PRMT5 substrates in HeLa cells. Further biochemical studies on SERBP1, a newly identified PRMT5 substrate, confirmed the coexistence of sDMA and asymmetric …

The spread of Homo sapiens into new habitats across Eurasia~ 45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species’ history.‘Transitional’technocomplexes, such as the Lincombian–Ranisian–Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to~ 45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning~ 12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold …

Authorea Preprints

The common vole is a temperate rodent widespread across Europe. Phylogeographic studies of its extant populations suggested the Last Glacial Maximum (LGM) as one of the main drivers of the species’ population history. However, analyses based solely on extant genetic diversity may not recover the full complexity of Late Pleistocene population dynamics. To reconstruct the population history of the common vole through the Last Glacial Period, we analysed a 4.2 kb-long fragment of mitochondrial DNA of 148 ancient and 51 modern specimens, sampled from across Europe, and covering the last 60 thousand years (ka). We estimate the time to the most recent common ancestor of Last Glacial common vole lineages to 90 ka ago and the diversification of the main extant lineages to between 55 and 40 ka ago, substantially earlier than previously estimated. Our data suggests multiple lineage turnovers in Europe at the end of Marine Isotope Stage (MIS) 3 and around the Pleistocene/Holocene transition. Conversely, data from the Western Carpathians suggest continuity throughout the LGM. This further suggests that climate amelioration during MIS 2 had little impact on common voles and that the main driver of population dynamics was the reduction of open habitats during the interstadial periods.

In temperate and subtropical regions, ancient proteins are reported to survive up to about 2 million years, far beyond the known limits of ancient DNA preservation in the same areas. Accordingly, their amino acid sequences currently represent the only source of genetic information available to pursue phylogenetic inference involving species that went extinct too long ago to be amenable for ancient DNA analysis. Here we present a complete workflow, including sample preparation, mass spectrometric data acquisition and computational analysis, to recover and interpret million-year-old dental enamel protein sequences. During sample preparation, the proteolytic digestion step, usually an integral part of conventional bottom-up proteomics, is omitted to increase the recovery of the randomly degraded peptides spontaneously generated by extensive diagenetic hydrolysis of ancient proteins over geological time …

Nature

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes, and molecular mechanisms that are often specific to cell type,. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10−8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster …

Nature

Author Correction: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion Author Correction: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion Nature. 2024 Feb 9. doi: 10.1038/s41586-024-07164-y. Online ahead of print. Authors Yu-Hwa Huang 1 , Chen Zhu # 2 , Yasuyuki Kondo # 1 , Ana C Anderson 2 , Amit Gandhi 1 , Andrew Russell 3 , Stephanie K Dougan 4 , Britt-Sabina Petersen 5 , Espen Melum 1 6 , Thomas Pertel 2 , Kiera L Clayton 7 , Monika Raab 8 , Qiang Chen 9 , Nicole Beauchemin 10 , Paul J Yazaki 11 , Michal Pyzik 1 , Mario A Ostrowski 7 12 , Jonathan N Glickman 13 , Christopher E Rudd 8 , Hidde L Ploegh 4 , Andre Franke 5 , Gregory A Petsko 3 , Vijay K Kuchroo 2 , Richard S Blumberg 14 Affiliations 1 Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, 02115, Massachusetts, USA. 2 …

Nature

화학공학소재연구정보센터(CHERIC) | 연구정보 | 문헌DB | 학술지 검색 화학공학소재연구정보 센터 홈 로그인 로그아웃 연락처 사이트맵 센터 센터소개 회원가입/정보수정 뉴스 공지사항 연구 동향 학회참관기 우수연구자소개 취업정보 연구정보 문헌DB KDB Compound Search 전문연구 정보 동영상 심포지움 자료 연구성과보고서 저널정보 논문 작성법 참고문헌DB 분석기기DB 화학 공정DB PSPDB 연구자지식지도 상태도정보 교육정보 사이버강의-학부 사이버강의-대학원 실무 강좌 강의자료 링크 교육자료 링크 사이버실험실 물성측정실험 매뉴얼 커뮤니티 공학포럼 카페 신진연구자인터뷰 리소스 특허정보 술어DB 관련법령 자격증정보 성과소개서 연구보고서 문헌DB 학술지 검색 학술대회 발표논문집 최신 국내 저널 최신 리뷰페이퍼 KDB Periodic Table of Elements Unit Conversion Universal Constants Pure Component Properties Binary Vapor-Liquid Equil. Data Calculation Modules Research Articles Citing KDB Compound Search …

Nature

EconPapers: Why it was right to reject the Anthropocene as a geological epoch EconPapers Economics at your fingertips EconPapers Home About EconPapers Working Papers Journal Articles Books and Chapters Software Components Authors JEL codes New Economics Papers Advanced Search EconPapers FAQ Archive maintainers FAQ Cookies at EconPapers Format for printing The RePEc blog The RePEc plagiarism page Why it was right to reject the Anthropocene as a geological epoch Mark Maslin (), Matthew Edgeworth, Erle C. Ellis and Philip L. Gibbard Nature, 2024, vol. 629, issue 8010, 41-41 Abstract: Letter to the Editor Keywords: Geology; Environmental sciences; Climate change; Sustainability (search for similar items in EconPapers) Date: 2024 References: Add references at CitEc Citations: Downloads: (external link) https://www.nature.com/articles/d41586-024-01268-1 Abstract (text/html) Access to …

Nature

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations, , , , – in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite …

Nature

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods,. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome,. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins, –. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes. This 15-fold increase in genus-level sampling relative to comparable nuclear studies provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating …

Nature

Van der Waals encapsulation of two-dimensional materials in hexagonal boron nitride (hBN) stacks is a promising way to create ultrahigh-performance electronic devices 1, 2, 3, 4. However, contemporary approaches for achieving van der Waals encapsulation, which involve artificial layer stacking using mechanical transfer techniques, are difficult to control, prone to contamination and unscalable. Here we report the transfer-free direct growth of high-quality graphene nanoribbons (GNRs) in hBN stacks. The as-grown embedded GNRs exhibit highly desirable features being ultralong (up to 0.25 mm), ultranarrow (< 5 nm) and homochiral with zigzag edges. Our atomistic simulations show that the mechanism underlying the embedded growth involves ultralow GNR friction when sliding between AA′-stacked hBN layers. Using the grown structures, we demonstrate the transfer-free fabrication of embedded GNR field …

Nature

Scientific evidence regularly guides policy decisions, with behavioural science increasingly part of this process. In April 2020, an influential paper proposed 19 policy recommendations (‘claims’) detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to …

Nature

Topology, – and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a ‘hybrid’ topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a …

Nature

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian–Ranisian–Jerzmanowician (LRJ), which has been described in northwestern and central Europe5–8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated …

Nature

The glymphatic movement of fluid through the brain removes metabolic waste, , –. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease, , –. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings …

Nature

Western Eurasia witnessed several large-scale human migrations during the Holocene, , , –. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness …

Nature

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis,, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn’s disease. Several of these compounds and …

Nature

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival …

Nature

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples,. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic …

Nature

Myeloid cells are known to suppress antitumour immunity. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells …

Nature

EconPapers: Urban trees: how to maximize their benefits for humans and the environment EconPapers Economics at your fingertips EconPapers Home About EconPapers Working Papers Journal Articles Books and Chapters Software Components Authors JEL codes New Economics Papers Advanced Search EconPapers FAQ Archive maintainers FAQ Cookies at EconPapers Format for printing The RePEc blog The RePEc plagiarism page Urban trees: how to maximize their benefits for humans and the environment Lina Tang (), Guofan Shao and Peter M. Groffman Nature, 2024, vol. 626, issue 7998, 261-261 Abstract: Letter to the Editor Keywords: Policy; Sustainability; Environmental sciences (search for similar items in EconPapers) Date: 2024 References: Add references at CitEc Citations: Track citations by RSS feed Downloads: (external link) https://www.nature.com/articles/d41586-024-00300-8 Abstract (text/…

Nature

Crop production is a large source of atmospheric ammonia (NH 3), which poses risks to air quality, human health and ecosystems 1, 2, 3, 4, 5. However, estimating global NH 3 emissions from croplands is subject to uncertainties because of data limitations, thereby limiting the accurate identification of mitigation options and efficacy 4, 5. Here we develop a machine learning model for generating crop-specific and spatially explicit NH 3 emission factors globally (5-arcmin resolution) based on a compiled dataset of field observations. We show that global NH 3 emissions from rice, wheat and maize fields in 2018 were 4.3±1.0 Tg N yr− 1, lower than previous estimates that did not fully consider fertilizer management practices 6, 7, 8, 9. Furthermore, spatially optimizing fertilizer management, as guided by the machine learning model, has the potential to reduce the NH 3 emissions by about 38%(1.6±0.4 Tg N yr− 1 …

Nature

Understanding the formation and stabilization mechanisms of soil organic carbon (SOC) is important for managing land carbon (C) and mitigating climate change. Tao et al. 1 reported that microbial C use efficiency (CUE) is the primary determinant of global SOC storage and that the relative impact of plant C inputs on SOC is minor. Although soil microbes undoubtedly play an important role in SOC cycling, we are concerned about the robustness of the approach taken by Tao et al. 1. The potential biases in their analyses may lead to misleading, model-dependent results.An important piece of evidence in support of an empirical relationship between CUE and SOC stems from a meta-analysis based on 132 paired CUE and SOC measurements. Tao et al. 1 applied a linear mixed-effects model to this dataset that included CUE, mean annual temperature (MAT), soil depth and random effects and explained 55% of the …

Nature

Western Eurasia witnessed several large-scale human migrations during the Holocene, , , –. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness …