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"Miller, Jennifer M."
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H3K4me2 distinguishes a distinct class of enhancers during the maternal-to-zygotic transition
After egg fertilization, an initially silent embryonic genome is transcriptionally activated during the maternal-to-zygotic transition. In zebrafish, maternal vertebrate pluripotency factors Nanog, Pou5f3 (OCT4 homolog), and Sox19b (SOX2 homolog) (NPS) play essential roles in orchestrating embryonic genome activation, acting as “pioneers” that open condensed chromatin and mediate acquisition of activating histone modifications. However, some embryonic gene transcription still occurs in the absence of these factors, suggesting the existence of other mechanisms regulating genome activation. To identify chromatin signatures of these unknown pathways, we profiled the histone modification landscape of zebrafish embryos using CUT&RUN. Our regulatory map revealed two subclasses of enhancers distinguished by presence or absence of H3K4me2. Enhancers lacking H3K4me2 tend to require NPS factors for de novo activation, while enhancers bearing H3K4me2 are epigenetically bookmarked by DNA hypomethylation to recapitulate gamete activity in the embryo, independent of NPS pioneering. Thus, parallel enhancer activation pathways combine to induce transcriptional reprogramming to pluripotency in the early embryo.
Journal Article
Ostrich eggshell bead diameter in the Holocene: Regional variation with the spread of herding in eastern and southern Africa
Despite their ubiquity in Holocene African archaeological assemblages, ostrich eggshell (OES) beads are rarely studied in detail. An exception is in southern Africa, where there is a proposed relationship between OES bead diameter and the arrival of herding ~2000 years before present. In 1987, Leon Jacobson first observed that beads from forager sites in Namibia tended to be smaller than those associated with herder sites. Studies examining bead size around the Western Cape have generally confirmed Jacobson's findings, though the driving forces of the diameter change remain unknown. Since this time, diameter has become an informal way of distinguishing forager and herder assemblages in southern Africa, but no large-scale studies of OES bead variation have been undertaken. Here we present an expanded analysis of Holocene OES bead diameters from southern, and for the first time, eastern Africa. Results reveal distinct patterns in OES bead size over time, reflecting different local dynamics associated with the spread of herding. In southern Africa, OES diameters display low variability and smaller absolute size through time. While larger beads begin to appear <2000 years ago, most beads in our study remained smaller. In contrast, eastern African OES bead diameters are consistently larger over the last 10,000 years and show no appreciable size change with the introduction of herding. Notably, larger beads thought to be associated with herders in southern Africa fall within the range of eastern African beads, indicating a potential connection between these regions in the Late Holocene consistent with genetic findings. Regional differences in bead size are subtle, on the order of millimeters, yet offer a potentially important line of evidence for investigating the spread of herding in sub-Saharan Africa. In order to understand the meaning of these changes, we encourage additional studies of OES bead assemblages and urge researchers to report individual bead diameters, rather than averages by level.
Journal Article
67,000 years of coastal engagement at Panga ya Saidi, eastern Africa
The antiquity and nature of coastal resource procurement is central to understanding human evolution and adaptations to complex environments. It has become increasingly apparent in global archaeological studies that the timing, characteristics, and trajectories of coastal resource use are highly variable. Within Africa, discussions of these issues have largely been based on the archaeological record from the south and northeast of the continent, with little evidence from eastern coastal areas leaving significant spatial and temporal gaps in our knowledge. Here, we present data from Panga ya Saidi, a limestone cave complex located 15 km from the modern Kenyan coast, which represents the first long-term sequence of coastal engagement from eastern Africa. Rather than attempting to distinguish between coastal resource use and coastal adaptations, we focus on coastal engagement as a means of characterising human relationships with marine environments and resources from this inland location. We use aquatic mollusc data spanning the past 67,000 years to document shifts in the acquisition, transportation, and discard of these materials, to better understand long-term trends in coastal engagement. Our results show pulses of coastal engagement beginning with low-intensity symbolism, and culminating in the consistent low-level transport of marine and freshwater food resources, emphasising a diverse relationship through time. Panga ya Saidi has the oldest stratified evidence of marine engagement in eastern Africa, and is the only site in Africa which documents coastal resources from the Late Pleistocene through the Holocene, highlighting the potential archaeological importance of peri-coastal sites to debates about marine resource relationships.
Journal Article
Cave morphology and human-mediated sediment deposition: Late Pleistocene to Holocene evolution of the cave floor at Panga ya Saidi, coastal Kenya
Panga ya Saidi (PYS), a cave situated in a forested upland near the coast of Kenya, contains an archaeological record that spans at least 78,000 years and is crucial for understanding the evolution of Homo sapiens populations in eastern Africa. Here we report on new systematic excavation, three-dimensional scanning, radiocarbon dating, and geoarchaeological analyses that provide insights on sedimentary dynamics, occupation patterns, and site-formation processes at PYS. Our data show that while unroofed parts of the cave probably contain the deepest stratigraphies, these are likely to be dominated by colluvial influx and yield limited cultural deposits. Sheltered zones near the chamber edges exhibit better stratigraphic integrity and higher artifact densities, with deposits exceeding 5.5 meters in thickness in the main excavation area. In this area, marked shifts in occupation intensity and sediment sources enable us to reconstruct the evolution of the inhabited cave space. Our findings underscore PYS as a key site for understanding human behavior, adaptation, and environmental interactions from the Late Pleistocene to the Holocene, with implications for broader interpretations of the evolution of Homo sapiens populations in eastern Africa.
Journal Article
Quantifying and Tracing Information Cascades in Swarms
We propose a novel, information-theoretic, characterisation of cascades within the spatiotemporal dynamics of swarms, explicitly measuring the extent of collective communications. This is complemented by dynamic tracing of collective memory, as another element of distributed computation, which represents capacity for swarm coherence. The approach deals with both global and local information dynamics, ultimately discovering diverse ways in which an individual's spatial position is related to its information processing role. It also allows us to contrast cascades that propagate conflicting information with waves of coordinated motion. Most importantly, our simulation experiments provide the first direct information-theoretic evidence (verified in a simulation setting) for the long-held conjecture that the information cascades occur in waves rippling through the swarm. Our experiments also exemplify how features of swarm dynamics, such as cascades' wavefronts, can be filtered and predicted. We observed that maximal information transfer tends to follow the stage with maximal collective memory, and principles like this may be generalised in wider biological and social contexts.
Journal Article
CXCR4+ mammary gland macrophageal niche promotes tumor initiating cell activity and immune suppression during tumorigenesis
Tumor-initiating cells (TICs) share features and regulatory pathways with normal stem cells, yet how the stem cell niche contributes to tumorigenesis remains unclear. Here, we identify CXCR4
+
macrophages as a niche population enriched in normal mammary ducts, where they promote the regenerative activity of basal cells in response to luminal cell-derived CXCL12. CXCL12 triggers AKT-mediated stabilization of β-catenin, which induces Wnt ligands and pro-migratory genes, enabling intraductal macrophage infiltration and supporting regenerative activity of basal cells. Notably, these same CXCR4
+
niche macrophages regulate the tumor-initiating activity of various breast cancer subtypes by enhancing TIC survival and tumor-forming capacity, while promoting early immune evasion through regulatory T cell induction. Furthermore, a CXCR4
+
niche macrophage gene signature correlates with poor prognosis in human breast cancer. These findings highlight the pivotal role of the CXCL12-CXCR4 axis in orchestrating interactions between niche macrophages, mammary epithelial cells, and immune cells, thereby establishing a supportive niche for both normal tissue regeneration and mammary tumor initiation.
Mammary gland resident macrophages are known to be crucial components of the mammary stem cell niche. Here, the authors show that CXCR4
+
macrophages form a niche that regulates the tumor-initiating activity of breast cancer cells and induces early immune evasion through the recruitment of regulatory T cells.
Journal Article
Cultural, economic, and settlement shifts over the last 9,000 years at Kakapel Rockshelter, Western Kenya
The spread of food production in sub-Saharan Africa involved multi-directional dispersals of domesticated plant and animal species, often associated with major migrations. The Lake Victoria Basin of eastern Africa was likely an important crossroads in this process, hosting interactions between diverse populations with hunter-gatherer, mobile pastoralist, and farming lifeways in the Holocene. Recent discovery of a large assemblage of ancient domesticated plant remains at Kakapel Rockshelter in the Chelelemuk Hills of Busia County, western Kenya have provided new insights into the timing for when different domesticated crops were adopted within this key region. Here, we expand on the archaeological and cultural context for these findings by reporting results of field excavations, regional surveys, radiocarbon dating, and artifact analyses for deposits recovered from Kakapel Rockshelter dating over the last 9,000 years. Multiple occupational episodes with distinct cultural and technological traits are apparent including Early Holocene foragers, Early Iron Age agropastoralists, and multiple Later Iron Age populations. Agropastoralism first appears here by c. 2400 BP, but it is not until the introduction of sorghum and finger millet after c. 1200 BP in association with arrivals of new groups with Nilotic ancestry that we document the shift to a higher density of sites and longer-term settlement in the region.
Journal Article
Ostrich eggshell beads reveal 50,000-year-old social network in Africa
Humans evolved in a patchwork of semi-connected populations across Africa
1
,
2
; understanding when and how these groups connected is critical to interpreting our present-day biological and cultural diversity. Genetic analyses reveal that eastern and southern African lineages diverged sometime in the Pleistocene epoch, approximately 350–70 thousand years ago (ka)
3
,
4
; however, little is known about the exact timing of these interactions, the cultural context of these exchanges or the mechanisms that drove their separation. Here we compare ostrich eggshell bead variations between eastern and southern Africa to explore population dynamics over the past 50,000 years. We found that ostrich eggshell bead technology probably originated in eastern Africa and spread southward approximately 50–33 ka via a regional network. This connection breaks down approximately 33 ka, with populations remaining isolated until herders entered southern Africa after 2 ka. The timing of this disconnection broadly corresponds with the southward shift of the Intertropical Convergence Zone, which caused periodic flooding of the Zambezi River catchment (an area that connects eastern and southern Africa). This suggests that climate exerted some influence in shaping human social contact. Our study implies a later regional divergence than predicted by genetic analyses, identifies an approximately 3,000-kilometre stylistic connection and offers important new insights into the social dimension of ancient interactions.
By tracing the changing size of ostrich eggshell beads, climate is shown to have an important role in influencing when and where regional African populations interacted.
Journal Article
AMERICA'S ROLE IN THE MAKING OF JAPAN'S ECONOMIC MIRACLE
Japan's remarkable postwar growth spurt in the 1960s would not have been possible without Japan's alliance with the United States. Policy makers, political scientists, economists, historians, and journalists on both sides of the Pacific have made this claim, but no study has yet tested it with modern statistical methods. In this article, we compare the economic growth trajectories of Japan and a statistically constructed “synthetic” Japan, which had a similar profile until the late 1950s but did not experience the consolidation of the US–Japan alliance, a process that began in 1958 and culminated with the signing of a formal defense pact in January 1960. We find that Japan's per capita gross domestic product (GDP) grew much faster than the synthetic Japan's from 1958 to 1968. We substantiate these results with in-depth historical analyses on how the United States facilitated Japan's economic miracle.
Journal Article