Role of RhoA and rho kinase in lysophosphatidic acid-induced endothelial barrier dysfunction.

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Prospecting for new questions: integrating geophysics to define anthropological research objectives and inform excavation strategies at monumental sites

Geophysical data have the potential to significantly contribute to archaeological research projects when effectively integrated with more traditional methods. Although pre-existing archaeological questions about a site may be answered using geophysical methods, beginning an investigation with an extensive geophysical survey can assist in understanding the function and archaeological potential of a site, and may even transform preconceptions about the type and spatial organisation of features that are present. In this way, these prospection tools not only accurately locate and map features to allow recovery of cultural material for identification and dating, we argue that they can go much further, allowing us to prospect for new and appropriate archaeological and anthropological research questions. Such an approach is best realised when geophysical and traditional archaeologists work together to define new objectives and strategies to address them, and by maintaining this collaboration to allow continual feedback between geophysical and archaeological data. A flexible research design is therefore essential in order to allow the methodologies to adapt to the site, the results, and the questions being posed. This methodology is demonstrated through two case studies from mound sites in southeast USA: the transitional Mississippian Washausen site in Illinois; and the Middle Woodland Garden Creek site in North Carolina. In both cases, integrating geophysical methods throughout the archaeological investigations has resulted in multiple phases of generating and addressing new research objectives. Although clearly beneficial at these two mound sites in southeast USA, this interdisciplinary approach has obvious implications well beyond these temporal and geographical areas

Prospecting for new questions: integrating geophysics to define anthropological research objectives and inform excavation strategies at monumental sites

Geophysical data have the potential to significantly contribute to archaeological research projects when effectively integrated with more traditional methods. Although pre-existing archaeological questions about a site may be answered using geophysical methods, beginning an investigation with an extensive geophysical survey can assist in understanding the function and archaeological potential of a site, and may even transform preconceptions about the type and spatial organisation of features that are present. In this way, these prospection tools not only accurately locate and map features to allow recovery of cultural material for identification and dating, we argue that they can go much further, allowing us to prospect for new and appropriate archaeological and anthropological research questions. Such an approach is best realised when geophysical and traditional archaeologists work together to define new objectives and strategies to address them, and by maintaining this collaboration to allow continual feedback between geophysical and archaeological data. A flexible research design is therefore essential in order to allow the methodologies to adapt to the site, the results, and the questions being posed. This methodology is demonstrated through two case studies from mound sites in southeast USA: the transitional Mississippian Washausen site in Illinois; and the Middle Woodland Garden Creek site in North Carolina. In both cases, integrating geophysical methods throughout the archaeological investigations has resulted in multiple phases of generating and addressing new research objectives. Although clearly beneficial at these two mound sites in southeast USA, this interdisciplinary approach has obvious implications well beyond these temporal and geographical areas

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Tidal sedimentary dynamics of the Early Pleistocene Messina Strait (Calabria, southern Italy) based on its modern analogue

The Messina Strait excursion opens a series of geological field trips associated with the 10th International Congress of Tidal Sedimentology (Tidalites), Matera, Italy, 5-7 October 2021. This guide aims at documenting a number of selected outcrops located along the eastern margin of the modern Messina Strait, in order to illustrate the sedimentary dynamics of the Early Pleistocene tide-dominated Messina Strait. Since the Pliocene, this extensional basin separated Sicily from Calabria, forming a wide non-tidal seaway. Successively, this basin turned into a ca. 10-15 km-wide and 40 km-long, tide-dominated strait during the Early Pleistocene, prior to its definitive closure following a Middle Pleistocene phase of tectonic uplift. As for today in its modern analogue, the ancient strait acted as a major conduit for marine water exchanges between the Ionian and the Tyrrhenian seas. Semi-diurnal, reverse bidirectional tidal currents flowed in phase opposition parallel to the strait margins, being subject to tidal amplification due to bathymetric restriction across the shallower strait-centre zone. This oceanographic setting partitioned the strait into specific environments. Nowadays, their sedimentary record is exposed in a series of outcrops across the western (Sicily) and eastern (Calabria) margins of the modern strait. A series of stops along a south-to-north transect covers a total distance of ca. 20 km. Outcrops of the first day show coarse-grained deposits lying adjacent to a block-faulted central horst and transgressively overlain by cross-stratified, mixed bioclastic-siliciclastic arenites. These strata record bypass and residual sedimentation in the strait-centre zone of the ancient system. The second day, large- and medium-scale cross-stratification exhibiting a variety of tidal sedimentary indicators are observed, interpreted as the ancient northern tidal dune field. The third day focuses on one major section representing the north-eastern flank of the ancient strait, where subaqueous canyon-fill strata, mass-wasting deposits and tide-influenced delta front-facies are exposed

Multidecadal accumulation of anthropogenic and remineralized dissolved inorganic carbon along the Extended Ellett Line in the northeast Atlantic Ocean

Marine carbonate chemistry measurements have been carried out annually since 2009 during UK research cruises along the Extended Ellett Line (EEL), a hydrographic transect in the northeast Atlantic Ocean. The EEL intersects several water masses that are key to the global thermohaline circulation, and therefore the cruises sample a region in which it is critical to monitor secular physical and biogeochemical changes. We have combined results from these EEL cruises with existing quality-controlled observational data syntheses to produce a hydrographic time series for the EEL from 1981 to 2013. This reveals multidecadal increases in dissolved inorganic carbon (DIC) throughout the water column, with a near-surface maximum rate of 1.80 ± 0.45 µmol kg−1 yr−1. Anthropogenic CO2 accumulation was assessed, using simultaneous changes in apparent oxygen utilization (AOU) and total alkalinity (TA) as proxies for the biogeochemical processes that influence DIC. The stable carbon isotope composition of DIC (δ13CDIC) was also determined and used as an independent test of our method. We calculated a volume-integrated anthropogenic CO2 accumulation rate of 2.8 ± 0.4 mg C m−3 yr−1 along the EEL, which is about double the global mean. The anthropogenic CO2 component accounts for only 31 ± 6% of the total DIC increase. The remainder is derived from increased organic matter remineralization, which we attribute to the lateral redistribution of water masses that accompanies subpolar gyre contraction. Output from a general circulation ecosystem model demonstrates that spatiotemporal heterogeneity in the observations has not significantly biased our multidecadal rate of change calculations and indicates that the EEL observations have been tracking distal changes in the surrounding North Atlantic and Nordic Seas

Beyond Never-Never Land: Integrating LiDAR and Geophysical Surveys at the Johnston Site, Pinson Mounds State Archaeological Park, Tennessee, USA

Archaeologists often use near-surface geophysics or LiDAR-derived topographic imagery in their research. However, rarely are the two integrated in a way that offers a robust understanding of the complex historical palimpsests embedded within a social landscape. In this paper we present an integrated aerial and terrestrial remote sensing program at the Johnston Site, part of the larger Pinson Mounds landscape in the American MidSouth. Our work at Johnston was focused on better understanding the history of human landscape use and change so that we can begin to compare the Johnston Site with other large Middle Woodland (200 BC-AD 500) ceremonial centers in the region. Our research allowed us to examine the accuracy of an early map of the Johnston Site made in the early 20th century. However, our integrated remote sensing approach allows us to go well beyond testing the usefulness of the map; it helps identify different uses of the site through time and across space. Our research emphasizes the importance of an integrated remote sensing methodology when examining complex social landscapes of the past and present

Beyond Never-Never Land: Integrating LiDAR and Geophysical Surveys at the Johnston Site, Pinson Mounds State Archaeological Park, Tennessee, USA

Archaeologists often use near-surface geophysics or LiDAR-derived topographic imagery in their research. However, rarely are the two integrated in a way that offers a robust understanding of the complex historical palimpsests embedded within a social landscape. In this paper we present an integrated aerial and terrestrial remote sensing program at the Johnston Site, part of the larger Pinson Mounds landscape in the American MidSouth. Our work at Johnston was focused on better understanding the history of human landscape use and change so that we can begin to compare the Johnston Site with other large Middle Woodland (200 BC-AD 500) ceremonial centers in the region. Our research allowed us to examine the accuracy of an early map of the Johnston Site made in the early 20th century. However, our integrated remote sensing approach allows us to go well beyond testing the usefulness of the map; it helps identify different uses of the site through time and across space. Our research emphasizes the importance of an integrated remote sensing methodology when examining complex social landscapes of the past and present

A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress

Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs. We show that oxaliplatin, unlike cisplatin and carboplatin, does not kill cells through the DNA-damage response. Rather, oxaliplatin kills cells by inducing ribosome biogenesis stress. This difference in drug mechanism explains the distinct clinical implementation of oxaliplatin relative to cisplatin, and it might enable mechanistically informed selection of distinct platinum drugs for distinct malignancies. These data highlight the functional diversity of core components of front-line cancer therapy and the potential benefits of applying a mechanism-based rationale to the use of our current arsenal of anti-cancer drugs