Publications by authors named "Patrick Roberts"

128 Publications

Earliest known human burial in Africa.

Nature 2021 May 5;593(7857):95-100. Epub 2021 May 5.

UMR 5199 CNRS De la Préhistoire à l'Actuel: Culture, Environnement, et Anthropologie (PACEA), Université Bordeaux, Talence, France.

The origin and evolution of hominin mortuary practices are topics of intense interest and debate. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.
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http://dx.doi.org/10.1038/s41586-021-03457-8DOI Listing
May 2021

Exploring the relation between BOLD fMRI and cognitive performance using a computer-based quantitative systems pharmacology model: Applications to the COMTVAL158MET genotype and ketamine.

Eur Neuropsychopharmacol 2021 May 1;50:12-22. Epub 2021 May 1.

In Silico Biosciences, Hugo Geerts, 686 Westwind Dr, Berwyn, PA 19312, United States.

BOLD fMRI is increasingly used mostly in an observational way to probe the effect of genotypes or therapeutic intervention in normal and diseased subjects. We use a mechanism-based quantitative systems pharmacology computer model of a human cortical microcircuit, previously calibrated for the 2-back working memory paradigm, adding established biophysical principles, of glucose metabolism, oxygen consumption, neurovascular effects and the paramagnetic impact on blood oxygen levels to calculate a readout for the voxel-based BOLD fMRI signal. The objective was to study the effect of the Catechol-O-methyl Transferase Val158Met (COMT) genotype on performance and BOLD fMRI. While the simulation suggests that on average virtual COMTVV genotype subjects perform worse, subjects with lower GABA, lower 5-HT and higher 5-HT activation can improve cognitive performance to the level of COMTMM subjects but at the expense of higher BOLD fMRI signal. In a schizophrenia condition, increased NMDA, GABA tone and noise levels, and lower DR activity can improve cognitive outcome with greater BOLD fMRI signal in COMT Val-carriers. We further generate hypotheses about why ketamine in healthy controls increases the BOLD fMRI signal but reduces cognitive performance. These simulations suggest a strong non-linear relationship between BOLD fMRI signal and cognitive performance. When validated, this mechanistic approach can be useful for moving beyond the descriptive nature of BOLD fMRI imaging and supporting the proper interpretation of imaging biomarkers in CNS disorders.
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http://dx.doi.org/10.1016/j.euroneuro.2021.04.001DOI Listing
May 2021

No evidence for widespread island extinctions after Pleistocene hominin arrival.

Proc Natl Acad Sci U S A 2021 May;118(20)

Archaeology and Natural History, College of Asia and the Pacific, The Australian National University, Canberra, ACT 2601, Australia.

The arrival of modern humans into previously unoccupied island ecosystems is closely linked to widespread extinction, and a key reason cited for Pleistocene megafauna extinction is anthropogenic overhunting. A common assumption based on late Holocene records is that humans always negatively impact insular biotas, which requires an extrapolation of recent human behavior and technology into the archaeological past. Hominins have been on islands since at least the early Pleistocene and for at least 50 thousand y (ka). Over such lengthy intervals it is scarcely surprising that significant evolutionary, behavioral, and cultural changes occurred. However, the deep-time link between human arrival and island extinctions has never been explored globally. Here, we examine archaeological and paleontological records of all Pleistocene islands with a documented hominin presence to examine whether humans have always been destructive agents. We show that extinctions at a global level cannot be associated with Pleistocene hominin arrival based on current data and are difficult to disentangle from records of environmental change. It is not until the Holocene that large-scale changes in technology, dispersal, demography, and human behavior visibly affect island ecosystems. The extinction acceleration we are currently experiencing is thus not inherent but rather part of a more recent cultural complex.
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http://dx.doi.org/10.1073/pnas.2023005118DOI Listing
May 2021

Exaptation Traits for Megafaunal Mutualisms as a Factor in Plant Domestication.

Front Plant Sci 2021 24;12:649394. Epub 2021 Mar 24.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Megafaunal extinctions are recurring events that cause evolutionary ripples, as cascades of secondary extinctions and shifting selective pressures reshape ecosystems. Megafaunal browsers and grazers are major ecosystem engineers, they: keep woody vegetation suppressed; are nitrogen cyclers; and serve as seed dispersers. Most angiosperms possess sets of physiological traits that allow for the fixation of mutualisms with megafauna; some of these traits appear to serve as exaptation (preadaptation) features for farming. As an easily recognized example, fleshy fruits are, an exaptation to agriculture, as they evolved to recruit a non-human disperser. We hypothesize that the traits of rapid annual growth, self-compatibility, heavy investment in reproduction, high plasticity (wide reaction norms), and rapid evolvability were part of an adaptive syndrome for megafaunal seed dispersal. We review the evolutionary importance that megafauna had for crop and weed progenitors and discuss possible ramifications of their extinction on: (1) seed dispersal; (2) population dynamics; and (3) habitat loss. Humans replaced some of the ecological services that had been lost as a result of late Quaternary extinctions and drove rapid evolutionary change resulting in domestication.
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http://dx.doi.org/10.3389/fpls.2021.649394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024633PMC
March 2021

Reimagining the relationship between Gondwanan forests and Aboriginal land management in Australia's "Wet Tropics".

iScience 2021 Mar 16;24(3):102190. Epub 2021 Feb 16.

Department of Archaeology and History, La Trobe University, Melbourne, Australia.

The "Wet Tropics" of Australia host a unique variety of plant lineages that trace their origins to the super-continent of Gondwanaland. While these "ancient" evolutionary records are rightly emphasized in current management of the region, multidisciplinary research and lobbying by Rainforest Aboriginal Peoples have also demonstrated the significance of the cultural heritage of the "Wet Tropics." Here, we evaluate the existing archeological, paleoenvironmental, and historical evidence to demonstrate the diverse ways in which these forests are globally significant, not only for their ecological heritage but also for their preservation of traces of millennia of anthropogenic activities, including active burning and food tree manipulation. We argue that detailed paleoecological, ethnobotanical, and archeological studies, working within the framework of growing national and world heritage initiatives and active application of traditional knowledge, offer the best opportunities for sustainable management of these unique environments in the face of increasingly catastrophic climate change and bushfires.
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http://dx.doi.org/10.1016/j.isci.2021.102190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921842PMC
March 2021

The Middle to Later Stone Age transition at Panga ya Saidi, in the tropical coastal forest of eastern Africa.

J Hum Evol 2021 Apr 11;153:102954. Epub 2021 Mar 11.

Department of Archaeology, Max Planck Institute for the Science of Human History, Kahlaische Strasse 10, 07745, Jena, Germany; Department of Anthropology, National Museum of Natural History, Smithsonian Institution, 600 Maryland Ave SW, Washington, D.C., USA; School of Social Science, The University of Queensland, Brisbane, QLD, 4072, Australia.

The Middle to Later Stone Age transition is a critical period of human behavioral change that has been variously argued to pertain to the emergence of modern cognition, substantial population growth, and major dispersals of Homo sapiens within and beyond Africa. However, there is little consensus about when the transition occurred, the geographic patterning of its emergence, or even how it is manifested in the stone tool technology that is used to define it. Here, we examine a long sequence of lithic technological change at the cave site of Panga ya Saidi, Kenya, that spans the Middle and Later Stone Age and includes human occupations in each of the last five Marine Isotope Stages. In addition to the stone artifact technology, Panga ya Saidi preserves osseous and shell artifacts, enabling broader considerations of the covariation between different spheres of material culture. Several environmental proxies contextualize the artifactual record of human behavior at Panga ya Saidi. We compare technological change between the Middle and Later Stone Age with on-site paleoenvironmental manifestations of wider climatic fluctuations in the Late Pleistocene. The principal distinguishing feature of Middle from Later Stone Age technology at Panga ya Saidi is the preference for fine-grained stone, coupled with the creation of small flakes (miniaturization). Our review of the Middle to Later Stone Age transition elsewhere in eastern Africa and across the continent suggests that this broader distinction between the two periods is in fact widespread. We suggest that the Later Stone Age represents new short use-life and multicomponent ways of using stone tools, in which edge sharpness was prioritized over durability.
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http://dx.doi.org/10.1016/j.jhevol.2021.102954DOI Listing
April 2021

Re-evaluating Scythian lifeways: Isotopic analysis of diet and mobility in Iron Age Ukraine.

PLoS One 2021 10;16(3):e0245996. Epub 2021 Mar 10.

Max Planck Institute for the Science of Human History, Department of Archaeology, Stable Isotope Group, Jena, Germany.

The Scythians are frequently presented, in popular and academic thought alike, as highly mobile warrior nomads who posed a great economic risk to growing Mediterranean empires from the Iron Age into the Classical period. Archaeological studies provide evidence of first millennium BCE urbanism in the steppe while historical texts reference steppe agriculture, challenging traditional characterizations of Scythians as nomads. However, there have been few direct studies of the diet and mobility of populations living in the Pontic steppe and forest-steppe during the Scythian era. Here, we analyse strontium, oxygen, and carbon isotope data from human tooth enamel samples, as well as nitrogen and carbon isotope data of bone collagen, at several Iron Age sites across Ukraine commonly associated with 'Scythian' era communities. Our multi-isotopic approach demonstrates generally low levels of human mobility in the vicinity of urban locales, where populations engaged in agro-pastoralism focused primarily on millet agriculture. Some individuals show evidence for long-distance mobility, likely associated with significant inter-regional connections. We argue that this pattern supports economic diversity of urban locales and complex trading networks, rather than a homogeneous nomadic population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245996PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946291PMC
March 2021

Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer.

Cancer Chemother Pharmacol 2021 May 17;87(5):689-700. Epub 2021 Feb 17.

G1 Therapeutics, Inc., Research Triangle Park, NC, USA.

Purpose: Trilaciclib is a first-in-class CDK4/6 inhibitor that transiently arrests hematopoietic stem and progenitor cells (HSPCs) in the G1 phase of the cell cycle to preserve them from chemotherapy-induced damage (myelopreservation). We report integrated analyses of preclinical and clinical data that informed selection of the recommended Phase II dose (RP2D) used in trilaciclib trials in extensive-stage small cell lung cancer (ES-SCLC).

Methods: A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model developed from preclinical data guided selection of an optimal dose for G1 bone marrow arrest in a first-in-human Phase I study (G1T28-1-01). PK, PD, safety, and efficacy data from G1T28-1-01 and two Phase Ib/IIa studies (G1T28-02/-03) in ES-SCLC were analyzed to support RP2D selection.

Results: Model simulation of bone marrow arrest based on preclinical data predicted that a ≥ 192 mg/m dose would induce a 40-50% decrease in total bone marrow proliferation in humans and almost 100% cell cycle arrest of cycling HSPCs. Consistent with this model, analysis of bone marrow aspirates in healthy volunteers after trilaciclib 192 mg/m administration demonstrated almost 100% G1 arrest in HSPCs and 40% decrease in total bone marrow proliferation, with minimal toxicity. G1T28-02/-03 reported similar PK parameters with trilaciclib 200 mg/m but slightly lower exposures than expected compared with healthy volunteers; consequently, 240 and 280 mg/m doses were also tested to match healthy volunteer exposures. Based on PK and relevant safety data, 240 mg/m was selected as the RP2D, which was also favored by myelopreservation endpoints in G1T28-02/-03.

Conclusion: Integrated PK/PD, safety, and efficacy data support 240 mg/m as the RP2D for trilaciclib. CLINICALTRIALS.

Gov Identifiers: NCT02243150; NCT02499770; NCT02514447.
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http://dx.doi.org/10.1007/s00280-021-04239-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026479PMC
May 2021

Ancient proteins provide evidence of dairy consumption in eastern Africa.

Nat Commun 2021 01 27;12(1):632. Epub 2021 Jan 27.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Consuming the milk of other species is a unique adaptation of Homo sapiens, with implications for health, birth spacing and evolution. Key questions nonetheless remain regarding the origins of dairying and its relationship to the genetically-determined ability to drink milk into adulthood through lactase persistence (LP). As a major centre of LP diversity, Africa is of significant interest to the evolution of dairying. Here we report proteomic evidence for milk consumption in ancient Africa. Using liquid chromatography tandem mass spectrometry (LC-MS/MS) we identify dairy proteins in human dental calculus from northeastern Africa, directly demonstrating milk consumption at least six millennia ago. Our findings indicate that pastoralist groups were drinking milk as soon as herding spread into eastern Africa, at a time when the genetic adaptation for milk digestion was absent or rare. Our study links LP status in specific ancient individuals with direct evidence for their consumption of dairy products.
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http://dx.doi.org/10.1038/s41467-020-20682-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841170PMC
January 2021

Pandanus nutshell generates a palaeoprecipitation record for human occupation at Madjedbebe, northern Australia.

Nat Ecol Evol 2021 03 25;5(3):295-303. Epub 2021 Jan 25.

School of Social Science, The University of Queensland, Brisbane, Queensland, Australia.

Little is known about the Pleistocene climatic context of northern Australia at the time of early human settlement. Here we generate a palaeoprecipitation proxy using stable carbon isotope analysis of modern and archaeological pandanus nutshell from Madjedbebe, Australia's oldest known archaeological site. We document fluctuations in precipitation over the last 65,000 years and identify periods of lower precipitation during the penultimate and last glacial stages, Marine Isotope Stages 4 and 2. However, the lowest effective annual precipitation is recorded at the present time. Periods of lower precipitation, including the earliest phase of occupation, correspond with peaks in exotic stone raw materials and artefact discard at the site. This pattern is interpreted as suggesting increased group mobility and intensified use of the region during drier periods.
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http://dx.doi.org/10.1038/s41559-020-01379-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929916PMC
March 2021

'Emptying Forests?' Conservation Implications of Past Human-Primate Interactions.

Trends Ecol Evol 2021 04 8;36(4):345-359. Epub 2021 Jan 8.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany. Electronic address:

Non-human primates are among the most vulnerable tropical animals to extinction and ~50% of primate species are endangered. Human hunting is considered a major cause of increasingly 'empty forests', yet archaeological data remains under-utilised in testing this assertion over the longer-term. Zooarchaeological datasets allow investigation of human exploitation of primates and the reconstruction of extinction, extirpation, and translocation processes. We evaluate the application and limitations of data from zooarchaeological studies spanning the past 45 000 years in South and Southeast Asia in guiding primate conservation efforts. We highlight that environmental change was the primary threat to many South and Southeast Asian non-human primate populations during much of the Holocene, foreshadowing human-induced land-use and environmental change as major threats of the 21st century.
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http://dx.doi.org/10.1016/j.tree.2020.12.004DOI Listing
April 2021

Earliest Olduvai hominins exploited unstable environments ~ 2 million years ago.

Nat Commun 2021 01 7;12(1). Epub 2021 Jan 7.

Max Planck Institute for the Science of Human History, Jena, Germany.

Rapid environmental change is a catalyst for human evolution, driving dietary innovations, habitat diversification, and dispersal. However, there is a dearth of information to assess hominin adaptions to changing physiography during key evolutionary stages such as the early Pleistocene. Here we report a multiproxy dataset from Ewass Oldupa, in the Western Plio-Pleistocene rift basin of Olduvai Gorge (now Oldupai), Tanzania, to address this lacuna and offer an ecological perspective on human adaptability two million years ago. Oldupai's earliest hominins sequentially inhabited the floodplains of sinuous channels, then river-influenced contexts, which now comprises the oldest palaeolake setting documented regionally. Early Oldowan tools reveal a homogenous technology to utilise diverse, rapidly changing environments that ranged from fern meadows to woodland mosaics, naturally burned landscapes, to lakeside woodland/palm groves as well as hyper-xeric steppes. Hominins periodically used emerging landscapes and disturbance biomes multiple times over 235,000 years, thus predating by more than 180,000 years the earliest known hominins and Oldowan industries from the Eastern side of the basin.
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http://dx.doi.org/10.1038/s41467-020-20176-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791053PMC
January 2021

Investigating the role of matrix habitat use in determining avian area-sensitivity.

Ecol Evol 2020 Dec 13;10(23):12792-12800. Epub 2020 Nov 13.

U.S. Forest Service Northern Research Station University of Massachusetts Amherst MA USA.

The absence of some species from small habitat patches has long posed a challenge for conservationists, yet the underlying mechanisms that cause this "area-sensitivity" remain poorly understood. Capacity of a species to extend their activities into the surrounding matrix habitat represents one potential determinant of area-sensitivity. Species may be able to occupy smaller patches if they can utilize matrix habitat beyond patch boundaries, whereas area-sensitive species may be restricted to larger patches due to their inability to utilize the surrounding matrix. We investigated the potential role of matrix utilization in determining area-sensitivity by mapping the movements of two shrubland-obligate passerines with contrasting patch area requirements in shrub-dominated forest openings ranging in area by nearly an order of magnitude. Our findings were consistent with our predictions; the less area-sensitive chestnut-sided warbler () exhibited greater use of matrix habitat than the highly area-sensitive prairie warbler (). Furthermore, chestnut-sided warblers that occupied smaller openings used mature forest more than conspecifics in larger patches, yet forest use by prairie warblers was unrelated to opening size. Chestnut-sided warblers foraged as frequently in mature forest as within shrubland, whereas prairie warblers foraged significantly more in openings compared to forest. The findings of this study suggest that the ability or inclination of a species to utilize surrounding matrix habitat explains at least some of the observed variation in area-sensitivity in songbirds and potentially other taxa.
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http://dx.doi.org/10.1002/ece3.6810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713974PMC
December 2020

Isotopic and microbotanical insights into Iron Age agricultural reliance in the Central African rainforest.

Commun Biol 2020 Oct 27;3(1):619. Epub 2020 Oct 27.

Department of Archaeology, Max Planck Institute for the Science of Human History, Kahlaische Straße 10, 07745, Jena, Germany.

The emergence of agriculture in Central Africa has previously been associated with the migration of Bantu-speaking populations during an anthropogenic or climate-driven 'opening' of the rainforest. However, such models are based on assumptions of environmental requirements of key crops (e.g. Pennisetum glaucum) and direct insights into human dietary reliance remain absent. Here, we utilise stable isotope analysis (δC, δN, δO) of human and animal remains and charred food remains, as well as plant microparticles from dental calculus, to assess the importance of incoming crops in the Congo Basin. Our data, spanning the early Iron Age to recent history, reveals variation in the adoption of cereals, with a persistent focus on forest and freshwater resources in some areas. These data provide new dietary evidence and document the longevity of mosaic subsistence strategies in the region.
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http://dx.doi.org/10.1038/s42003-020-01324-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591565PMC
October 2020

Environmental drivers of megafauna and hominin extinction in Southeast Asia.

Nature 2020 10 7;586(7829):402-406. Epub 2020 Oct 7.

Max Planck Institute for the Science of Human History, Jena, Germany.

Southeast Asia has emerged as an important region for understanding hominin and mammalian migrations and extinctions. High-profile discoveries have shown that Southeast Asia has been home to at least five members of the genus Homo. Considerable turnover in Pleistocene megafauna has previously been linked with these hominins or with climate change, although the region is often left out of discussions of megafauna extinctions. In the traditional hominin evolutionary core of Africa, attempts to establish the environmental context of hominin evolution and its association with faunal changes have long been informed by stable isotope methodologies. However, such studies have largely been neglected in Southeast Asia. Here we present a large-scale dataset of stable isotope data for Southeast Asian mammals that spans the Quaternary period. Our results demonstrate that the forests of the Early Pleistocene had given way to savannahs by the Middle Pleistocene, which led to the spread of grazers and extinction of browsers-although geochronological limitations mean that not all samples can be resolved to glacial or interglacial periods. Savannahs retreated by the Late Pleistocene and had completely disappeared by the Holocene epoch, when they were replaced by highly stratified closed-canopy rainforest. This resulted in the ascendency of rainforest-adapted species as well as Homo sapiens-which has a unique adaptive plasticity among hominins-at the expense of savannah and woodland specialists, including Homo erectus. At present, megafauna are restricted to rainforests and are severely threatened by anthropogenic deforestation.
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http://dx.doi.org/10.1038/s41586-020-2810-yDOI Listing
October 2020

CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy.

J Immunother Cancer 2020 10;8(2)

Research and Development, G1 Therapeutics, Inc, Research Triangle Park, North Carolina, USA.

Background: Combination treatment with chemotherapy and immune checkpoint inhibitors (ICIs) has demonstrated meaningful clinical benefit to patients. However, chemotherapy-induced damage to the immune system can potentially diminish the efficacy of chemotherapy/ICI combinations. Trilaciclib, a highly potent, selective and reversible cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor in development to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy, has demonstrated proof of concept in recent clinical trials. Furthermore, CDK4/6 inhibition has been shown to augment T-cell activation and antitumor immunity in preclinical settings. Therefore, addition of trilaciclib has the potential to further enhance the efficacy of chemotherapy and ICI combinations.

Methods: In murine syngeneic tumor models, a schedule of 3 weekly doses of trilaciclib was combined with chemotherapy/ICI regimens to assess the effect of transient CDK4/6 inhibition on antitumor response and intratumor T-cell proliferation and function. Peripheral T-cell status was also analyzed in patients with small cell lung cancer (SCLC) treated with chemotherapy with or without trilaciclib to gain insights into the effect of transient exposure of trilaciclib on T-cell activation.

Results: Preclinically, the addition of trilaciclib to chemotherapy/ICI regimens enhanced antitumor response and overall survival compared with chemotherapy and ICI combinations alone. This effect is associated with the modulation of the proliferation and composition of T-cell subsets in the tumor microenvironment and increased effector function. Transient exposure of trilaciclib in patients with SCLC during chemotherapy treatment both preserved and increased peripheral lymphocyte counts and enhanced T-cell activation, suggesting that trilaciclib not only preserved but also enhanced immune system function.

Conclusions: Transient CDK4/6 inhibition by trilaciclib was sufficient to enhance and prolong the duration of the antitumor response by chemotherapy/ICI combinations, suggesting a role for the transient cell cycle arrest of tumor immune infiltrates in remodeling the tumor microenvironment. These results provide a rationale for combining trilaciclib with chemotherapy/ICI regimens to improve antitumor efficacy in patients with cancer.
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http://dx.doi.org/10.1136/jitc-2020-000847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534680PMC
October 2020

Human footprints provide snapshot of last interglacial ecology in the Arabian interior.

Sci Adv 2020 Sep 18;6(38). Epub 2020 Sep 18.

Department of Archaeology, Max Planck Institute for the Science of Human History, Kahlaische Strasse 10, D-07743 Jena, Germany.

The nature of human dispersals out of Africa has remained elusive because of the poor resolution of paleoecological data in direct association with remains of the earliest non-African people. Here, we report hominin and non-hominin mammalian tracks from an ancient lake deposit in the Arabian Peninsula, dated within the last interglacial. The findings, it is argued, likely represent the oldest securely dated evidence for in Arabia. The paleoecological evidence indicates a well-watered semi-arid grassland setting during human movements into the Nefud Desert of Saudi Arabia. We conclude that visitation to the lake was transient, likely serving as a place to drink and to forage, and that late Pleistocene human and mammalian migrations and landscape use patterns in Arabia were inexorably linked.
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http://dx.doi.org/10.1126/sciadv.aba8940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500939PMC
September 2020

Leaf Wax Lipid Extraction for Archaeological Applications.

Curr Protoc Plant Biol 2020 09;5(3):e20114

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Plant wax lipid molecules, chiefly normal (n-) alkanes and n-alkanoic acids, are frequently used as proxies for understanding paleoenvironmental and paleoclimatic change. These are regularly analyzed from marine and lake sediments and even more frequently in archaeological contexts, enabling the reconstruction of past environments in direct association with records of past human behavior. Carbon and hydrogen isotope measurements of these compounds are used to trace plant type and water-use efficiency, relative paleotemperature, precipitation, evapotranspiration of leaf and soil moisture, and other physiological and ecological parameters. Plant wax lipids have great potential for answering questions related to human-environment interactions, being for the most part chemically inert and easily recoverable in terrestrial sediments, including those dating back millions of years. The growing use of this technique, and comparison of such data with other paleoenvironmental proxies such as pollen and phytolith analysis and soil carbonate and tooth enamel isotope records, make it essential to establish consistent, best-practice protocols for extracting n-alkanes and n-alkanoic acids from archaeological sediments to provide comparable information for interpreting past climatic, ecosystem, and hydrological changes and their interaction with human societies. © 2020 The Authors. Basic Protocol 1: Total lipid extraction Support Protocol 1: Weighing the total lipid extract Support Protocol 2: Cleaning the PSE extraction cells Alternate Protocol 1: Soxhlet total lipid extraction Alternate Protocol 2: Ultrasonic total lipid extraction Basic Protocol 2: Separation of lipids by aminopropyl column chromatography Basic Protocol 3: Separation of lipids by silver-nitrate-infused silica gel column chromatography Support Protocol 3: Preparation of silica gel infused with 10% silver nitrate Basic Protocol 4: Methylation of n-alkanoic acids Basic Protocol 5: Gas chromatography mass spectrometry (GC-MS) Basic Protocol 6: Gas chromatography isotope ratio mass spectrometry (GC-IRMS).
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http://dx.doi.org/10.1002/cppb.20114DOI Listing
September 2020

Bows and arrows and complex symbolic displays 48,000 years ago in the South Asian tropics.

Sci Adv 2020 Jun 12;6(24):eaba3831. Epub 2020 Jun 12.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Archaeologists contend that it was our aptitude for symbolic, technological, and social behaviors that was central to rapidly expanding across the majority of Earth's continents during the Late Pleistocene. This expansion included movement into extreme environments and appears to have resulted in the displacement of numerous archaic human populations across the Old World. Tropical rainforests are thought to have been particularly challenging and, until recently, impenetrable by early . Here, we describe evidence for bow-and-arrow hunting toolkits alongside a complex symbolic repertoire from 48,000 years before present at the Sri Lankan site of Fa-Hien Lena-the earliest bow-and-arrow technology outside of Africa. As one of the oldest rainforest sites outside of Africa, this exceptional assemblage provides the first detailed insights into how our species met the extreme adaptive challenges that were encountered in Asia during global expansion.
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http://dx.doi.org/10.1126/sciadv.aba3831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292635PMC
June 2020

Ancient genomes reveal complex patterns of population movement, interaction, and replacement in sub-Saharan Africa.

Sci Adv 2020 Jun 12;6(24):eaaz0183. Epub 2020 Jun 12.

Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena, Germany.

Africa hosts the greatest human genetic diversity globally, but legacies of ancient population interactions and dispersals across the continent remain understudied. Here, we report genome-wide data from 20 ancient sub-Saharan African individuals, including the first reported ancient DNA from the DRC, Uganda, and Botswana. These data demonstrate the contraction of diverse, once contiguous hunter-gatherer populations, and suggest the resistance to interaction with incoming pastoralists of delayed-return foragers in aquatic environments. We refine models for the spread of food producers into eastern and southern Africa, demonstrating more complex trajectories of admixture than previously suggested. In Botswana, we show that Bantu ancestry post-dates admixture between pastoralists and foragers, suggesting an earlier spread of pastoralism than farming to southern Africa. Our findings demonstrate how processes of migration and admixture have markedly reshaped the genetic map of sub-Saharan Africa in the past few millennia and highlight the utility of combined archaeological and archaeogenetic approaches.
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http://dx.doi.org/10.1126/sciadv.aaz0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292641PMC
June 2020

Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows.

Mol Cancer Ther 2020 08 16;19(8):1575-1588. Epub 2020 Jun 16.

Center for Personalized Medicine, Roswell Park Cancer Institute, Buffalo, New York.

Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have been hypothesized to antagonize the antitumor effects of cytotoxic chemotherapy in tumors that are CDK4/6 dependent. However, there are multiple preclinical studies that illustrate potent cooperation between CDK4/6i and chemotherapy. Furthermore, the combination of CDK4/6i and chemotherapy is being tested in clinical trials to both enhance antitumor efficacy and limit toxicity. Exploitation of the noncanonical effects of CDK4/6i could also provide an impetus for future studies in combination with chemotherapy. Thus, while seemingly mutually exclusive mechanisms are at play, the combination of CDK4/6 inhibition and chemotherapy could exemplify rational medicine.
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http://dx.doi.org/10.1158/1535-7163.MCT-18-1161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473501PMC
August 2020

Paleolithic to Bronze Age Siberians Reveal Connections with First Americans and across Eurasia.

Cell 2020 06 20;181(6):1232-1245.e20. Epub 2020 May 20.

Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena 07745, Germany. Electronic address:

Modern humans have inhabited the Lake Baikal region since the Upper Paleolithic, though the precise history of its peoples over this long time span is still largely unknown. Here, we report genome-wide data from 19 Upper Paleolithic to Early Bronze Age individuals from this Siberian region. An Upper Paleolithic genome shows a direct link with the First Americans by sharing the admixed ancestry that gave rise to all non-Arctic Native Americans. We also demonstrate the formation of Early Neolithic and Bronze Age Baikal populations as the result of prolonged admixture throughout the eighth to sixth millennium BP. Moreover, we detect genetic interactions with western Eurasian steppe populations and reconstruct Yersinia pestis genomes from two Early Bronze Age individuals without western Eurasian ancestry. Overall, our study demonstrates the most deeply divergent connection between Upper Paleolithic Siberians and the First Americans and reveals human and pathogen mobility across Eurasia during the Bronze Age.
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http://dx.doi.org/10.1016/j.cell.2020.04.037DOI Listing
June 2020

A multi-isotope, multi-tissue study of colonial origins and diet in New Zealand.

Am J Phys Anthropol 2020 08 18;172(4):605-620. Epub 2020 May 18.

Department of Earth Sciences, Durham University, Durham, UK.

Objectives: Colonial period New Zealand was lauded as a land of plenty, where colonists could improve their station in life and secure a future for their families. Our understanding of colonial experience, however, is often shaped by historical records which communicate a state-sponsored version of history. This study aims to reconstruct the lives of settlers using isotopic evidence from the colonial skeletons themselves.

Materials And Methods: We use skeletal remains from recently excavated colonial sites in Otago (South Island, New Zealand) to illustrate the information that can be gleaned from the isotopic analysis of individuals. We use Sr/ Sr to identify European settlers, and δ C and δ N from collagen and hair keratin, as well as dental enamel carbonate δ C to trace dietary change over their life-courses.

Results: Strontium isotope analysis shows that all adults in our sample are non-local. Dietary isotopes show that while most individuals had relatively consistent childhood diet, one individual with more rural origins likely had seasonal use of resources during childhood. While some members of the population seem to have increased their meat intake in the new colony most do not have clear evidence for this.

Discussion: We show the diversity of human experience in first-generation New Zealanders both prior to emigration and in the new colony. Despite colonial propaganda claiming that circumstances in New Zealand were improved for all settlers, we have little evidence for this, aside from among individuals of potentially high status.
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http://dx.doi.org/10.1002/ajpa.24077DOI Listing
August 2020

Cannibalism makes invasive comb jelly, Mnemiopsis leidyi, resilient to unfavourable conditions.

Commun Biol 2020 05 7;3(1):212. Epub 2020 May 7.

Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745, Jena, Germany.

The proliferation of invasive marine species is often explained by a lack of predators and opportunistic life history traits. For the invasive comb jelly Mnemiopsis leidyi, it has remained unclear how this now widely distributed species is able to overcome long periods of low food availability, particularly in their northernmost exotic habitats in Eurasia. Based on both field and laboratory evidence, we show that adult comb jellies in the western Baltic Sea continue building up their nutrient reserves after emptying the prey field through a shift to cannibalizing their own larvae. We argue, that by creating massive late summer blooms, the population can efficiently empty the prey field, outcompete intraguild competitors, and use the bloom events to build nutrient reserves for critical periods of prey scarcity. Our finding that cannibalism makes a species with typical opportunistic traits more resilient to environmental fluctuations is important for devising more effective conservation strategies.
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http://dx.doi.org/10.1038/s42003-020-0940-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205609PMC
May 2020

Origin and Health Status of First-Generation Africans from Early Colonial Mexico.

Curr Biol 2020 06 30;30(11):2078-2091.e11. Epub 2020 Apr 30.

Department of Archaeogenetics (DAG), Max-Planck Institute for the Science of Human History (MPI-SHH), Kahlaische Str. 10, 07745 Jena, Germany. Electronic address:

The forced relocation of several thousand Africans during Mexico's historic period has so far been documented mostly through archival sources, which provide only sparse detail on their origins and lived experience. Here, we employ a bioarchaeological approach to explore the life history of three 16 century Africans from a mass burial at the San José de los Naturales Royal Hospital in Mexico City. Our approach draws together ancient genomic data, osteological analysis, strontium isotope data from tooth enamel, δC and δN isotope data from dentine, and ethnohistorical information to reveal unprecedented detail on their origins and health. Analyses of skeletal features, radiogenic isotopes, and genetic data from uniparental, genome-wide, and human leukocyte antigen (HLA) markers are consistent with a Sub-Saharan African origin for all three individuals. Complete genomes of Treponema pallidum sub. pertenue (causative agent of yaws) and hepatitis B virus (HBV) recovered from these individuals provide insight into their health as related to infectious disease. Phylogenetic analysis of both pathogens reveals their close relationship to strains circulating in current West African populations, lending support to their origins in this region. The further relationship between the treponemal genome retrieved and a treponemal genome previously typed in an individual from Colonial Mexico highlights the role of the transatlantic slave trade in the introduction and dissemination of pathogens into the New World. Putting together all lines of evidence, we were able to create a biological portrait of three individuals whose life stories have long been silenced by disreputable historical events.
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http://dx.doi.org/10.1016/j.cub.2020.04.002DOI Listing
June 2020

Isotopic evidence for initial coastal colonization and subsequent diversification in the human occupation of Wallacea.

Nat Commun 2020 04 29;11(1):2068. Epub 2020 Apr 29.

School of Culture, History and Language, College of Asia and the Pacific, The Australian National University, Canberra, ACT, 2600, Australia.

The resource-poor, isolated islands of Wallacea have been considered a major adaptive obstacle for hominins expanding into Australasia. Archaeological evidence has hinted that coastal adaptations in Homo sapiens enabled rapid island dispersal and settlement; however, there has been no means to directly test this proposition. Here, we apply stable carbon and oxygen isotope analysis to human and faunal tooth enamel from six Late Pleistocene to Holocene archaeological sites across Wallacea. The results demonstrate that the earliest human forager found in the region c. 42,000 years ago made significant use of coastal resources prior to subsequent niche diversification shown for later individuals. We argue that our data provides clear insights into the huge adaptive flexibility of our species, including its ability to specialize in the use of varied environments, particularly in comparison to other hominin species known from Island Southeast Asia.
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http://dx.doi.org/10.1038/s41467-020-15969-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190613PMC
April 2020

Economic Diversification Supported the Growth of Mongolia's Nomadic Empires.

Sci Rep 2020 03 3;10(1):3916. Epub 2020 Mar 3.

Max Planck Institute for the Science of Human History, Department of Archaeology, Jena, Germany.

Populations in Mongolia from the late second millennium B.C.E. through the Mongol Empire are traditionally assumed, by archaeologists and historians, to have maintained a highly specialized horse-facilitated form of mobile pastoralism. Until recently, a dearth of direct evidence for prehistoric human diet and subsistence economies in Mongolia has rendered systematic testing of this view impossible. Here, we present stable carbon and nitrogen isotope measurements of human bone collagen, and stable carbon isotope analysis of human enamel bioapatite, from 137 well-dated ancient Mongolian individuals spanning the period c. 4400 B.C.E. to 1300 C.E. Our results demonstrate an increase in consumption of C plants beginning at c. 800 B.C.E., almost certainly indicative of millet consumption, an interpretation supported by archaeological evidence. The escalating scale of millet consumption on the eastern Eurasian steppe over time, and an expansion of isotopic niche widths, indicate that historic Mongolian empires were supported by a diversification of economic strategies rather than uniform, specialized pastoralism.
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http://dx.doi.org/10.1038/s41598-020-60194-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054399PMC
March 2020

Tropical Trees as Time Capsules of Anthropogenic Activity.

Trends Plant Sci 2020 04 6;25(4):369-380. Epub 2020 Feb 6.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany; Department of Archaeology, University of Queensland, St Lucia QLD, 4072, Brisbane, Australia.

After the ice caps, tropical forests are globally the most threatened terrestrial environments. Modern trees are not just witnesses to growing contemporary threats but also legacies of past human activity. Here, we review the use of dendrochronology, radiocarbon analysis, stable isotope analysis, and DNA analysis to examine ancient tree management. These methods exploit the fact that living trees record information on environmental and anthropogenic selective forces during their own and past generations of growth, making trees living archaeological 'sites'. The applicability of these methods across prehistoric, historic, and industrial periods means they have the potential to detect evolving anthropogenic threats and can be used to set conservation priorities in rapidly vanishing environments.
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http://dx.doi.org/10.1016/j.tplants.2019.12.010DOI Listing
April 2020

Pathologic Factors Affecting Colorectal Cancer Survival in a Jamaican Population-the UHWI Experience.

J Racial Ethn Health Disparities 2020 06 25;7(3):413-420. Epub 2019 Nov 25.

Department of Pathology, University of the West Indies (Mona Campus), Mona, Jamaica.

Objective: Colorectal carcinoma (CRC) is the third most common cancer and a leading cause of cancer-related deaths in Jamaica. Globally, CRC mortality rates have been decreasing in developed countries; however, CRC mortality rates are trending upwards in low-income or developing countries. Our objectives are to estimate the overall 5-year survival and to determine the pathologic factors associated with overall survival of colorectal adenocarcinoma after surgery at the University Hospital of the West Indies (UHWI).

Methods: Retrospective, observational (cross-sectional) study on CRC patients. We summarized and analyzed demographic, clinical data, histopathological data, and survival rates. Single predictor Cox regression models were used to establish associations between survival and specified clinicopathological characteristics.

Results: A total of 217 patients who underwent operative resection of colorectal adenocarcinoma from January 2004 to December 2013. Median survival time post-therapeutic intervention was 48 months. Late stage at diagnosis, positive circumferential resection margins, neural and vascular invasion, as well as three or more nodal metastases were all associated with statistically significant worsened outcome.

Conclusions: Despite surgical quality meeting USA standards, CRC survival rates in Jamaica are 13% lower than survival of CRC in non-Hispanic Blacks in the USA. The survival trends found by our study support the application of international indices for CRC prognostication to Jamaican patients.
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http://dx.doi.org/10.1007/s40615-019-00669-7DOI Listing
June 2020