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Radiocarbon dating of the earliest occupational phases at the Cooper’s Ferry site in western Idaho indicates that people repeatedly occupied the Columbia River basin, starting between 16,560 and 15,280 calibrated years before the present (cal yr B.P.). Artifacts from these early occupations indicate the use of unfluted stemmed projectile point technologies before the appearance of the Clovis Paleoindian tradition and support early cultural connections with northeastern Asian Upper Paleolithic archaeological traditions. The Cooper’s Ferry site was initially occupied during a time that predates the opening of an ice-free corridor (≤14,800 cal yr B.P.), which supports the hypothesis that initial human migration into the Americas occurred via a Pacific coastal route.

The discovery of an artifact cache containing Western Stemmed Tradition (WST) projectile points in a clearly defined pit feature at the Cooper’s Ferry site offers a unique perspective on early lithic technology and logistical organization in western North America. A description and analysis of the cache feature reveals several new insights, including: a rocky cairn capped the surface of the pit feature; some of the artifacts were made from cryptocrystalline silicates found 16 km away; debitage analysis, including aggregate and attribute based measures, identified two distinct lithic reduction stages present in the cache; new radiocarbon assays suggest that the cache is probably not early Holocene in age and may date to associated age estimates of 11,410–11,370 radiocarbon years before present (B.P.). Unlike Clovis caches, the Pit Feature A2 cache at Cooper’s Ferry appears to be a generalized toolkit that was probably placed at the site for future use. If the 11,410–11,370 radiocarbon years B.P. assays date the creation of the Pit Feature A2 cache, then its creators were probably not pioneers in the lower Salmon River canyon but possessed local knowledge about the landscape and raw material sources; these patterns suggest greater time depth for WST foragers.

Geoarchaeological research on the southern coast of Oregon brought to light archaeological evidence of early human occupation in the late Pleistocene. Indian Sands (35CU67) lies on a highly eroded deflated headland on the Oregon coast where previous surveys had found and dated surficial cultural materials as early as 8250 b.p. (uncalibrated radiocarbon years). Prior to excavation of Indian Sands, sediment and stratigraphic analysis, along with radiocarbon and thermoluminescence dates, established the existence of late Pleistocene deposits. The excavations confirmed the presence of buried cultural deposits containing lithic artifacts, charcoal, and fire-cracked rock. Dispersed charcoal from the floor of an artifact-bearing level was dated to 10,430 b.p., more than 200014C years older than any other Oregon coastal site.

Geoarchaeological research on the southern coast of Oregon brought to light archaeological evidence of early human occupation in the late Pleistocene. Indian Sands (35CU67) lies on a highly eroded deflated headland on the Oregon coast where previous surveys had found and dated surficial cultural materials as early as 8250 b.p. (uncalibrated radiocarbon years). Prior to excavation of Indian Sands, sediment and stratigraphic analysis, along with radiocarbon and thermoluminescence dates, established the existence of late Pleistocene deposits. The excavations confirmed the presence of buried cultural deposits containing lithic artifacts, charcoal, and fire-cracked rock. Dispersed charcoal from the floor of an artifactbearing level was dated to 10,430 b.p., more than 2000 l4 C years older than any other Oregon coastal site.

Fusobacterium nucleatum ( Fn ), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals 1 , is enriched in human colorectal cancer (CRC) tumours 2 – 5 . High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis 5 – 8 . Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis ( Fna ). However, genomic analyses reveal that Fna , considered a single subspecies, is instead composed of two distinct clades ( Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter- Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche. A study reveals that Fusobacterium nucleatum subspecies animalis  is bifurcated into two distinct clades, and shows that only one of these dominates the colorectal cancer niche, probably through increased colonization of the human gastrointestinal tract.

Graft-versus-host disease (GVHD) is a serious complication of otherwise curative allogeneic haematopoietic stem cell transplants. Chronic GVHD induces pathological changes in peripheral organs as well as the brain and is a frequent cause of late morbidity and death after bone-marrow transplantation. In the periphery, bone-marrow-derived macrophages are key drivers of pathology, but recent evidence suggests that these cells also infiltrate into cGVHD-affected brains. Microglia are also persistently activated in the cGVHD-affected brain. To understand the involvement of these myeloid cell populations in the development and/or progression of cGVHD pathology, we here utilized the blood–brain-barrier permeable colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (pexidartinib) at varying doses to pharmacologically deplete both cell types. We demonstrate that PLX3397 treatment during the development of cGVHD (i.e., 30 days post-transplant) improves disease symptoms, reducing both the clinical scores and histopathology of multiple cGVHD target organs, including the sequestration of T cells in cGVHD-affected skin tissue. Cognitive impairments associated with cGVHD and neuroinflammation were also attenuated by PLX3397 treatment. PLX3397 treatment prior to the onset of cGVHD (i.e., immediately post-transplant) did not change in clinical scores or histopathology. Overall, our data demonstrate significant benefits of using PLX3397 for the treatment of cGVHD and associated organ pathologies in both the periphery and brain, highlighting the therapeutic potential of pexidartinib for this condition. Key points PLX3397 treatment during the progression phase of chronic graft-versus-host disease (cGVHD) attenuates pathology in multiple organ systems and reduces T-cell infiltration into the skin. PLX3397 treatment during cGVHD progression attenuates microglia/macrophage reactivity and major histocompatibility complex class II (MHCII) expression in the brain. PLX3397 treatment during cGVHD progression alleviates cognitive impairment.

Researchers must be able to generate experimentally testable hypotheses from sequencing-based observational microbiome experiments to discover the mechanisms underlying the influence of gut microbes on human health. We describe geneshot , a novel bioinformatics tool for identifying testable hypotheses based on gene-level metagenomic analysis of WGS microbiome data. By applying geneshot to two independent previously published cohorts, we identify microbial genomic islands consistently associated with response to immune checkpoint inhibitor (ICI)-based cancer treatment in culturable type strains. The identified genomic islands are within operons involved in type II secretion, TonB-dependent transport, and bacteriophage growth.

Big data abound in microbiology, but the workflows designed to enable researchers to interpret data can constrain the biological questions that can be asked. Five years after anvi’o was first published, this community-led multi-omics platform is maturing into an open software ecosystem that reduces constraints in ‘omics data analyses.