Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes.

The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.

Reconstructing Prehistoric African Population Structure.

We assembled genome-wide data from 16 prehistoric Africans. We show that the anciently divergent lineage that comprises the primary ancestry of the southern African San had a wider distribution in the past, contributing approximately two-thirds of the ancestry of Malawi hunter-gatherers ∼8,100-2,500 years ago and approximately one-third of the ancestry of Tanzanian hunter-gatherers ∼1,400 years ago. We document how the spread of farmers from western Africa involved complete replacement of local hunter-gatherers in some regions, and we track the spread of herders by showing that the population of a ∼3,100-year-old pastoralist from Tanzania contributed ancestry to people from northeastern to southern Africa, including a ∼1,200-year-old southern African pastoralist. The deepest diversifications of African lineages were complex, involving either repeated gene flow among geographically disparate groups or a lineage more deeply diverging than that of the San contributing more to some western African populations than to others. We finally leverage ancient genomes to document episodes of natural selection in southern African populations. PAPERCLIP.

The first peoples of the Atacama Desert lived among the trees: A 11,600- to 11,200-year-old grove and congregation site.

In deserts, water has been singled out as the most important factor for choosing where to settle, but trees were likely an important part of the landscape for hunter-gatherers beyond merely constituting an economic resource. Yet, this critical aspect has not been considered archaeologically. Here, we present the results of mapping and radiocarbon dating of a truly unique archaeological record. Over 150 preserved stumps around five Late Pleistocene/Early Holocene archaeological campsites (12,800 to 11,200 cal BP) show that trees were key features in the creation of everyday habitats for the first inhabitants of the Atacama Desert. At two of these sites, QM12 and QM35, the spatial and chronological correlation between trees and hearths reveals that people located their homes under the tree canopy. At residential site QM35, artifact distribution coincides with a grove dated to ~11,600 to 11,200 cal BP. A third residential area (QM32) occurred along the grove margins ~12,000 to 11,200 cal BP. Based on the distinct cultural material of these two camps, we propose that two different groups intermittently shared this rich wetland-grove environment. The tree taxa suggest a preference for the native Schinus molle, a tree scarcely present on the landscape today, over the endemic, nitrogen-fixing Strombocarpa tamarugo, both for toolmaking and firewood and even though the S. tamarugo was locally more abundant. Together with the spatial and chronological coincidence of campsites, hearths, and trees, we propose that people spared the most abundant and resilient species to create their homes, in turn promoting fertility oases amid the Atacama's hyperaridity.

A submerged Stone Age hunting architecture from the Western Baltic Sea.

The Baltic Sea basins, some of which only submerged in the mid-Holocene, preserve Stone Age structures that did not survive on land. Yet, the discovery of these features is challenging and requires cross-disciplinary approaches between archeology and marine geosciences. Here, we combine shipborne and autonomousunderwater vehicle hydroacoustic data with up to a centimeter range resolution, sedimentological samples, and optical images to explore a Stone Age megastructure located in 21 m water depth in the Bay of Mecklenburg, Germany. The structure is made of 1,673 individual stones which are usually less than 1 m in height, placed side by side over a distance of 971 m in a way that argues against a natural origin by glacial transport or ice push ridges. Running adjacent to the sunken shoreline of a paleolake (or bog), whose youngest phase was dated to 9,143 ±36 ka B.P., the stonewall was likely used for hunting the Eurasian reindeer (Rangifer tarandus) during the Younger Dryas or early Pre-Boreal. It was built by hunter-gatherer groups that roamed the region after the retreat of the Weichselian Ice Sheet. Comparable Stone Age megastructures have become known worldwide in recent times but are almost unknown in Europe. The site represents one of the oldest documented man-made hunting structures on Earth, and ranges among the largest known Stone Age structure in Europe. It will become important for understanding subsistence strategies, mobility patterns, and inspire discussions concerning the territorial development in the Western Baltic Sea region.

The impact of farming on prehistoric culinary practices throughout Northern Europe.

To investigate changes in culinary practices associated with the arrival of farming, we analysed the organic residues of over 1,000 pottery vessels from hunter-gatherer-fisher and early agricultural sites across Northern Europe from the Lower Rhine Basin to the Northeastern Baltic. Here, pottery was widely used by hunter-gatherer-fishers prior to the introduction of domesticated animals and plants. Overall, there was surprising continuity in the way that hunter-gatherer-fishers and farmers used pottery. Both aquatic products and wild plants remained prevalent, a pattern repeated consistently across the study area. We argue that the rapid adaptation of farming communities to exploit coastal and lagoonal resources facilitated their northerly expansion, and in some cases, hunting, gathering, and fishing became the most dominant subsistence strategy. Nevertheless, dairy products frequently appear in pottery associated with the earliest farming groups often mixed with wild plants and fish. Interestingly, we also find compelling evidence of dairy products in hunter-gatherer-fisher Ertebølle pottery, which predates the arrival of domesticated animals. We propose that Ertebølle hunter-gatherer-fishers frequently acquired dairy products through exchange with adjacent farming communities prior to the transition. The continuity observed in pottery use across the transition to farming contrasts with the analysis of human remains which shows substantial demographic change through ancient DNA and, in some cases, a reduction in marine consumption through stable isotope analysis. We postulate that farmers acquired the knowledge and skills they needed to succeed from local hunter-gatherer-fishers but without substantial admixture.

An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder due to a mutation in the lysosomal enzyme iduronate-2-sulfatase (IDS) gene. IDS deficiency leads to a progressive, multisystem accumulation of glycosaminoglycans (GAGs) and results in central nervous system (CNS) manifestations in the severe form. We developed up to clinical readiness a new hematopoietic stem cell (HSC) gene therapy approach for MPS II that benefits from a novel highly effective transduction protocol. We first provided proof of concept of efficacy of our approach aimed at enhanced IDS enzyme delivery to the CNS in a murine study of immediate translational value, employing a lentiviral vector (LV) encoding a codon-optimized human IDS cDNA. Then the therapeutic LV was tested for its ability to efficiently and safely transduce bona fide human HSCs in clinically relevant conditions according to a standard vs. a novel protocol that demonstrated superior ability to transduce bona fide long-term repopulating HSCs. Overall, these results provide strong proof of concept for the clinical translation of this approach for the treatment of Hunter syndrome.

Population interconnectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers.

The evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here, we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density are explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also estimate the range of hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by our newly compiled dataset of dated archaeological sites. Finally, we show that genomic estimates of divergence times between CAHG groups match our ecological estimates of periods favoring population splits, and that recoveries of connectivity would have facilitated subsequent gene flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.

A 44-y perspective on the influence of cash on Ju/'hoansi Bushman networks of sharing and gifting.

Money has been portrayed by major theorists as an agent of individualism, an instrument of freedom, a currency that removes personal values attached to things, and a generator of avarice. Regardless, the impact of money varies greatly with the cultural turf of the recipient societies. For traditional subsistence economies based on gifting and sharing, surplus perishable resources foraged from the environment carry low costs to the giver compared with the benefits to the receiver. With cash, costs to the giver are usually the same as benefits to the receiver, making sharing expensive and introducing new choices. Using quantitative data on possessions and expenditures collected over a 44-y period from 1974 to 2018 among the Ju/'hoansi (!Kung) in southern Africa, former hunter-gatherers, we look at how individuals spend monetary income, how a partial monetary economy alters traditional norms and institutions (egalitarianism, gifting, and sharing), and how institutions from the past steer change. Results show that gifting declines as cash is spent to increase the well-being of individual families and that gifting and sharing decrease and networks narrow. The sharing of meals and casual gifting hold fast. Substantial material inequalities develop, even between neighbors, but social, gender, and political equalities persist. A strong tradition for individual autonomy combined with monetary income allows individuals to spend their money as they choose, adapt to modern conditions, and pursue new options. However, new challenges are emerging to develop greater community cooperation and build substantial and sustainable economies in the face of such centrifugal forces.

A close-up view of the Hunter syndrome.

The Lysosomal Storage disease known as Mucopolysaccharidosis type II, is caused by mutations affecting the iduronate-2-sulfatase required for heparan and dermatan sulfate catabolism. The central nervous system (CNS) is mostly and severely affected by the accumulation of both substrates. The complexity of the CNS damage observed in MPS II patients has been limitedly explored. The use of mass spectrometry (MS)-based proteomics tools to identify protein profiles may yield valuable information about the pathological mechanisms of Hunter syndrome. In this further study, we provide a new comparative proteomic analysis of MPS II models by using a pipeline consisting of the identification of native protein complexes positioned selectively by using a specific antibody, coupled with mass spectrometry analysis, allowing us to identify changes involving in a significant number of new biological functions, including a specific brain antioxidant response, a down-regulated autophagic, the suppression of sulfur catabolic process, a prominent liver immune response and the stimulation of phagocytosis among others.

Copper as an Electron Hunter for Enhancing Bi2O2CO3 Electrocatalytic CO2 Conversion to Formate.

Cu-doped Bi2O2CO3 catalyst with copper (Cu) acting an electron hunter for conversion of carbon dioxide into formate is developed. The Cu-Bi2O2CO3 catalyst with hollow microsphere structure extends the duration of CO2 retention on the catalyst, providing a greater number of active sites. It exhibits remarkable performance with conversion efficacy of 98.5% and current density of 800 mA cm-2 across a wide potential window (-0.8 to -1.3 V vs RHE). Density functional theory investigations reveal that the presence of copper (Cu) significantly enhances the charge density at the active sites and influences the local electronic structure of bismuth (Bi), thereby reducing the energy barrier associated with the transformation of *OCHO species into formate.

Bow hunter's syndrome due to an anomalous right vertebral artery origin and contralateral absence: a case report and literature review.

BACKGROUND: Bow Hunter's syndrome (BHS), also known as rotational vertebral artery occlusion (RVAO), is a rare condition characterized by dynamic vertebrobasilar insufficiency due to position-dependent occlusion of the vertebral artery (VA). In the existing literature, most cases of BHS are attributed to osteophytic compression originating from the occipital condyle or within the transverse foramen, often accompanied by anatomical abnormalities of the VA. However, cases presenting solely with VA anomalies in the absence of any cervical vertebral structural abnormality are rare. This case report presents a unique instance of BHS in a 56-year-old male, attributed to the anomalous origin of the right VA and the absence of the left VA, without cervical structural abnormalities. CASE PRESENTATION: The patient exhibited symptoms like episodic dizziness and vertigo, which were exacerbated by rightward head rotation and alleviated upon returning to a neutral position. Diagnostic evaluation, including digital subtraction angiography, revealed that the right VA originated from the right common carotid artery and compression-induced stenosis of the right VA during head rotation. Conservative management, including avoidance of certain head movements and anti-arteriosclerosis medication, led to symptom resolution over a two-year follow-up period. CONCLUSIONS: This report contributes to the understanding of BHS by highlighting a rare vascular anomaly presentation and incorporates a review of 14 similar case reports in the literature describing that an anatomical abnormality of the VA is mainly responsible for the pathology of BHS in the absence of cervical vertebral anomalies, thus emphasizing the need for careful diagnostic and management strategies.

Bilateral Hunter's bow syndrome: a rare case diagnosed by dynamic digital subtraction angiography.

A 27-year-old female patient suffered from recurrent episodes of dizziness, visual rotation, and intermittent right-hand numbness over one month. Symptoms persisted and were triggered by rotating the head to the right or left for more than 10 seconds. Neurological examination showed that the symptoms were most pronounced when the head was rotated over 45 degrees to the right. Dynamic digital subtraction angiography (dDSA) was performed to confirm the diagnosis. Leftward head rotation caused occlusion of the right vertebral artery(VA) . However, the symptoms were mild, owing to sufficient compensation by the right posterior communicating artery (PCA) . Rightward head rotation exceeding 45 degrees resulted in occlusion of the left VA. The resultant symptoms were pronounced due to inadequate compensation of the left PCA. CT angiographic reconstruction showed bilateral vertebral arteries with tortuous loops of vessels at the level of the C2 vertebrae . CT images showed no cleavage between the left VA and the anterior surface of the left C2 transverse foramen. Conservative treatment was recommended considering the patient's young age and limited severity of her symptoms. Bow Hunter's syndrome is a rare neurovascular disorder characterized by dynamic occlusion of the VAs during head rotation, leading to inadequate blood flow to the posterior cerebral circulation. Bow hunter syndrome, where bilateral dynamic occlusion occurs without a discernible dominant side of the VA, is uncommon. The medical community must acknowledge cervical vertigo as a distinct disorder. dDSA remains the gold standard for its diagnosis.

People have shaped most of terrestrial nature for at least 12,000 years.

Archaeological and paleoecological evidence shows that by 10,000 BCE, all human societies employed varying degrees of ecologically transformative land use practices, including burning, hunting, species propagation, domestication, cultivation, and others that have left long-term legacies across the terrestrial biosphere. Yet, a lingering paradigm among natural scientists, conservationists, and policymakers is that human transformation of terrestrial nature is mostly recent and inherently destructive. Here, we use the most up-to-date, spatially explicit global reconstruction of historical human populations and land use to show that this paradigm is likely wrong. Even 12,000 y ago, nearly three quarters of Earth's land was inhabited and therefore shaped by human societies, including more than 95% of temperate and 90% of tropical woodlands. Lands now characterized as "natural," "intact," and "wild" generally exhibit long histories of use, as do protected areas and Indigenous lands, and current global patterns of vertebrate species richness and key biodiversity areas are more strongly associated with past patterns of land use than with present ones in regional landscapes now characterized as natural. The current biodiversity crisis can seldom be explained by the loss of uninhabited wildlands, resulting instead from the appropriation, colonization, and intensifying use of the biodiverse cultural landscapes long shaped and sustained by prior societies. Recognizing this deep cultural connection with biodiversity will therefore be essential to resolve the crisis.

Voiceprint Fault Diagnosis of Converter Transformer under Load Influence Based on Multi-Strategy Improved Mel-Frequency Spectrum Coefficient and Temporal Convolutional Network.

In order to address the challenges of low recognition accuracy and the difficulty in effective diagnosis in traditional converter transformer voiceprint fault diagnosis, a novel method is proposed in this article. This approach takes account of the impact of load factors, utilizes a multi-strategy improved Mel-Frequency Spectrum Coefficient (MFCC) for voiceprint signal feature extraction, and combines it with a temporal convolutional network for fault diagnosis. Firstly, it improves the hunter-prey optimizer (HPO) as a parameter optimization algorithm and adopts IHPO combined with variational mode decomposition (VMD) to achieve denoising of voiceprint signals. Secondly, the preprocessed voiceprint signal is combined with Mel filters through the Stockwell transform. To adapt to the stationary characteristics of the voiceprint signal, the processed features undergo further mid-temporal processing, ultimately resulting in the implementation of a multi-strategy improved MFCC for voiceprint signal feature extraction. Simultaneously, load signal segmentation is introduced for the diagnostic intervals, forming a joint feature vector. Finally, by using the Mish activation function to improve the temporal convolutional network, the IHPO-ITCN is proposed to adaptively optimize the size of convolutional kernels and the number of hidden layers and construct a transformer fault diagnosis model. By constructing multiple sets of comparison tests through specific examples and comparing them with the traditional voiceprint diagnostic model, our results show that the model proposed in this paper has a fault recognition accuracy as high as 99%. The recognition accuracy was significantly improved and the training speed also shows superior performance, which can be effectively used in the field of multiple fault diagnosis of converter transformers.

Reconsidering the link between past material culture and cognition in light of contemporary hunter-gatherer material use.

Many have interpreted symbolic material culture in the deep past as evidencing the origins sophisticated, modern cognition. Scholars from across the behavioural and cognitive sciences, including linguists, psychologists, philosophers, neuroscientists, primatologists, archaeologists and paleoanthropologists have used such artefacts to assess the capacities of extinct human species, and to set benchmarks, milestones or otherwise chart the course of human cognitive evolution. To better calibrate our expectations, the present paper instead explores the material culture of three contemporary African forager groups. Results show that, while these groups are unequivocally behaviourally modern, they would leave scant long-lasting evidence of symbolic behaviour. Artefact-sets are typically small, perhaps as consequence of residential mobility. When excluding traded materials, few artefacts have components with moderate-strong taphonomic signatures. Present analyses show that artefact function influences preservation probability, such that utilitarian tools for the processing of materials and the preparation of food are disproportionately likely to contain archaeologically traceable components. There are substantial differences in material-use between populations, which create important population-level variation preservation probability independent of cognitive differences. I discuss the factors - cultural, ecological and practical - that influence material choice. In so doing, I highlight the difficulties of using past material culture as an evolutionary or cognitive yardstick.

The first maternal genetic study of hunter-gatherers from Vietnam.

The current limitation of ancient DNA data from Vietnam led to the controversy surrounding the prehistory of people in this region. The combination of high heat and humidity damaged ancient bones that challenged the study of human evolution, especially when using DNA as study materials. So far, only 4 k years of history have been recorded despite the 65 k years of history of anatomically modern human occupations in Vietnam. Here we report, to our knowledge, the oldest mitogenomes of two hunter-gatherers from Vietnam. We extracted DNA from the femurs of two individuals aged 6.2 k cal BP from the Con Co Ngua (CCN) site in Thanh Hoa, Vietnam. This archeological site is the largest cemetery of the hunter-gatherer population in Southeast Asia (SEA) that was discovered, but their genetics have not been explored until the present. We indicated that the CCN haplotype belongs to a rare haplogroup that was not detected in any present-day Vietnamese individuals. Further matrilineal analysis on CCN mitogenomes showed a close relationship with ancient farmers and present-day populations in SEA. The mitogenomes of hunter-gatherers from Vietnam debate the "two layers" model of peopling history in SEA and provide an alternative solution for studying challenging ancient human samples from Vietnam.

Evidence and recommendation for mucopolysaccharidosis type II newborn screening in the United States.

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.

Positional proteomics: is the technology ready to study clinical cohorts?

INTRODUCTION: Positional proteomics provides proteome-wide information on protein termini and their modifications, uniquely enabling unambiguous identification of site-specific, limited proteolysis. Such proteolytic cleavage irreversibly modifies protein sequences resulting in new proteoforms with distinct protease-generated neo-N and C-termini and altered localization and activity. Misregulated proteolysis is implicated in a wide variety of human diseases. Protein termini, therefore, constitute a huge, largely unexplored source of specific analytes that provides a deep view into the functional proteome and a treasure trove for biomarkers. AREAS COVERED: We briefly review principal approaches to define protein termini and discuss recent advances in method development. We further highlight the potential of positional proteomics to identify and trace specific proteoforms, with a focus on proteolytic processes altered in disease. Lastly, we discuss current challenges and potential for applying positional proteomics in biomarker and pre-clinical research. EXPERT OPINION: Recent developments in positional proteomics have provided significant advances in sensitivity and throughput. In-depth analysis of proteolytic processes in clinical cohorts thus appears feasible in the near future. We argue that this will provide insights into the functional state of the proteome and offer new opportunities to utilize proteolytic processes altered or targeted in disease as specific diagnostic, prognostic and companion biomarkers.

Newborn screening for mucopolysaccharidosis type II: Lessons learned.

We describe our experience with population-based newborn screening for mucopolysaccharidosis type II (MPS II) in 586,323 infants by measurement of iduronate-2-sulfatase activity in dried blood spots between December 12, 2017 and April 30, 2022. A total of 76 infants were referred for diagnostic testing, 0.01% of the screened population. Of these, eight cases of MPS II were diagnosed for an incidence of 1 in 73,290. At least four of the eight cases detected had an attenuated phenotype. In addition, cascade testing revealed a diagnosis in four extended family members. Fifty-three cases of pseudodeficiency were also identified, for an incidence of 1 in 11,062. Our data suggest that MPS II may be more common than previously recognized with a higher prevalence of attenuated cases.

Generation and characterization of an immunodeficient mouse model of mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an inherited X-linked recessive disease caused by deficiency of iduronate-2-sulfatase (IDS), resulting in the accumulation of the glycosaminoglycans (GAG) heparan and dermatan sulfates. Mouse models of MPS II have been used in several reports to study disease pathology and to conduct preclinical studies for current and next generation therapies. Here, we report the generation and characterization of an immunodeficient mouse model of MPS II, where CRISPR/Cas9 was employed to knock out a portion of the murine IDS gene on the NOD/SCID/Il2rγ (NSG) immunodeficient background. IDS-/- NSG mice lacked detectable IDS activity in plasma and all analyzed tissues and exhibited elevated levels of GAGs in those same tissues and in the urine. Histopathology revealed vacuolized cells in both the periphery and CNS of NSG-MPS II mice. This model recapitulates skeletal disease manifestations, such as increased zygomatic arch diameter and decreased femur length. Neurocognitive deficits in spatial memory and learning were also observed in the NSG-MPS II model. We anticipate that this new immunodeficient model will be appropriate for preclinical studies involving xenotransplantation of human cell products intended for the treatment of MPS II.