Tufas indicate prolonged periods of water availability linked to human occupation in the southern Kalahari.

Detailed, well-dated palaeoclimate and archaeological records are critical for understanding the impact of environmental change on human evolution. Ga-Mohana Hill, in the southern Kalahari, South Africa, preserves a Pleistocene archaeological sequence. Relict tufas at the site are evidence of past flowing streams, waterfalls, and shallow pools. Here, we use laser ablation screening to target material suitable for uranium-thorium dating. We obtained 33 ages covering the last 110 thousand years (ka) and identify five tufa formation episodes at 114-100 ka, 73-48 ka, 44-32 ka, 15-6 ka, and ~3 ka. Three tufa episodes are coincident with the archaeological units at Ga-Mohana Hill dating to ~105 ka, ~31 ka, and ~15 ka. Based on our data and the coincidence of dated layers from other local records, we argue that in the southern Kalahari, from ~240 ka to ~71 ka wet phases and human occupation are coupled, but by ~20 ka during the Last Glacial Maximum (LGM), they are decoupled.

Inhibition of arginase modulates T-cell response in the tumor microenvironment of lung carcinoma.

Immunotherapy has demonstrated significant activity in a broad range of cancer types, but still the majority of patients receiving it do not maintain durable therapeutic responses. Amino acid metabolism has been proposed to be involved in the regulation of immune response. Here, we investigated in detail the role of arginase 1 (Arg1) in the modulation of antitumor immune response against poorly immunogenic Lewis lung carcinoma. We observed that tumor progression is associated with an incremental increase in the number of Arg1+ myeloid cells that accumulate in the tumor microenvironment and cause systemic depletion of ʟ-arginine. In advanced tumors, the systemic concentrations of ʟ-arginine are decreased to levels that impair the proliferation of antigen-specific T-cells. Systemic or myeloid-specific Arg1 deletion improves antigen-induced proliferation of adoptively transferred T-cells and leads to inhibition of tumor growth. Arginase inhibitor was demonstrated to modestly inhibit tumor growth when used alone, and to potentiate antitumor effects of anti-PD-1 monoclonal antibodies and STING agonist. The effectiveness of the combination immunotherapy was insufficient to induce complete antitumor responses, but was significantly better than treatment with the checkpoint inhibitor alone. Together, these results indicate that arginase inhibition alone is of modest therapeutic benefit in poorly immunogenic tumors; however, in combination with other treatment strategies it may significantly improve survival outcomes.

Accurate dating of stalagmites from low seasonal contrast tropical Pacific climate using Sr 2D maps, fabrics and annual hydrological cycles.

Tropical Pacific stalagmites are commonly affected by dating uncertainties because of their low U concentration and/or elevated initial 230Th content. This poses problems in establishing reliable trends and periodicities for droughts and pluvial episodes in a region vulnerable to climate change. Here we constrain the chronology of a Cook Islands stalagmite using synchrotron µXRF two-dimensional mapping of Sr concentrations coupled with growth laminae optical imaging constrained by in situ monitoring. Unidimensional LA-ICP-MS-generated Mg, Sr, Ba and Na variability series were anchored to the 2D Sr and optical maps. The annual hydrological significance of Mg, Sr, Ba and Na was tested by principal component analysis, which revealed that Mg and Na are related to dry-season, wind-transported marine aerosols, similar to the host-rock derived Sr and Ba signatures. Trace element annual banding was then used to generate a calendar-year master chronology with a dating uncertainty maximum of ± 15 years over 336 years. Our approach demonstrates that accurate chronologies and coupled hydroclimate proxies can be obtained from speleothems formed in tropical settings where low seasonality and problematic U-Th dating would discourage the use of high-resolution climate proxies datasets.

Magnesium in subaqueous speleothems as a potential palaeotemperature proxy.

Few palaeoclimate archives beyond the polar regions preserve continuous and datable palaeotemperature proxy time series over multiple glacial-interglacial cycles. This hampers efforts to develop a more coherent picture of global patterns of past temperatures. Here we show that Mg concentrations in a subaqueous speleothem from an Italian cave track regional sea-surface temperatures over the last 350,000 years. The Mg shows higher values during warm climate intervals and converse patterns during cold climate stages. In contrast to previous studies, this implicates temperature, not rainfall, as the principal driver of Mg variability. The depositional setting of the speleothem gives rise to Mg partition coefficients that are more temperature dependent than other calcites, enabling the effect of temperature change on Mg partitioning to greatly exceed the effects of changes in source-water Mg/Ca. Subaqueous speleothems from similar deep-cave environments should be capable of providing palaeotemperature information over multiple glacial-interglacial cycles.

Systematic Evaluation of Chemically Distinct Tissue Optical Clearing Techniques in Murine Lymph Nodes.

Activation of adaptive immunity is a complex process coordinated at multiple levels in both time and the three-dimensional context of reactive lymph nodes (LNs). Although microscopy-based visualization of its spatiotemporal dynamics unravels complexities of developing immune response, such approach is highly limited by light-obstructing nature of tissue components. Recently, tissue optical clearing (TOC) techniques were established to bypass this obstacle and now allow to image and quantify the entire murine organs with cellular resolution. However, the spectrum of TOC is represented by wide variety of chemically distinct methods, each having certain advantages and disadvantages that were unsatisfactorily compared for suitability to LNs clearing. In this study, we have systematically tested 13 typical TOC techniques and assessed their impact on a number of critical factors such as LN transparency, imaging depth, change in size, compatibility with proteinaceous fluorophores, immunostaining, H&E staining, and light-sheet fluorescence microscopy. Based on the detailed data specific to TOC process of murine LNs, we provide a reliable reference for most suitable methods in an application-dependent manner.

Strong population structure deduced from genetics, otolith chemistry and parasite abundances explains vulnerability to localized fishery collapse in a large Sciaenid fish, Protonibea diacanthus.

As pressure on coastal marine resources is increasing globally, the need to quantitatively assess vulnerable fish stocks is crucial in order to avoid the ecological consequences of stock depletions. Species of Sciaenidae (croakers, drums) are important components of tropical and temperate fisheries and are especially vulnerable to exploitation. The black-spotted croaker, Protonibea diacanthus, is the only large sciaenid in coastal waters of northern Australia where it is targeted by commercial, recreational and indigenous fishers due to its food value and predictable aggregating behaviour. Localized declines in the abundance of this species have been observed, highlighting the urgent requirement by managers for information on fine- and broad-scale population connectivity. This study examined the population structure of P. diacanthus across north-western Australia using three complementary methods: genetic variation in microsatellite markers, otolith elemental composition and parasite assemblage composition. The genetic analyses demonstrated that there were at least five genetically distinct populations across the study region, with gene flow most likely restricted by inshore biogeographic barriers such as the Dampier Peninsula. The otolith chemistry and parasite analyses also revealed strong spatial variation among locations within broad-scale regions, suggesting fine-scale location fidelity within the lifetimes of individual fish. The complementarity of the three techniques elucidated patterns of connectivity over a range of spatial and temporal scales. We conclude that fisheries stock assessments and management are required at fine scales (100 s of km) to account for the restricted exchange among populations (stocks) and to prevent localized extirpations of this species. Realistic management arrangements may involve the successive closure and opening of fishing areas to reduce fishing pressure.

Validating the use of embryonic fish otoliths as recorders of sublethal exposure to copper in estuarine sediments.

In this study we explore the use of fish otoliths ('earbones') as a tool for detecting exposure to heavy metals in sediments. Because otoliths are metabolically inert and incorporate chemical impurities during growth, they can potentially provide a more permanent record of pollutant exposure history in aquatic environments than soft tissues. To validate this technique we cultured embryos of a native Australian fish, the common Galaxias (Galaxias maculatus), in the laboratory on sediments spiked with copper in a concentration gradient. Our aims were to test whether exposure to copper contaminated sediments is recorded in the otoliths of embryos and determine over what range in concentrations we can detect differences in exposure. We found elevated copper levels in otoliths of embryos exposed to high copper concentrations in sediments, suggesting that otoliths can be used as a tool to track a history of exposure to elevated copper levels in the environment.

Arsenic in a speleothem from Central China: stadial-interstadial variations and implications.

In a pilot study, arsenic in a stalagmite (SJ3) collected from Central China was measured, and its association with past climate and environment was explored. Most of the SJ3 arsenic concentrations ranged from 120 to 320 ppb with the highest concentrations associated with relatively warm and humid climatic phases and lowest concentrations with cold and dry phases. The SJ3 arsenic record was very similar to the manganese record of SJ3. Variations of arsenic in SJ3 might be controlled by metal oxides of iron, manganese, and aluminum in karst groundwater at the study site, which in turn were closely related with changes in past climate and environment. A considerable proportion of arsenic was in excess over manganese in SJ3, which might be related with incorporation of arsenic into the calcite lattice during the formation of SJ3. It was speculated that more arsenic was released due to stronger weathering of the surface soils and sequestrated by metal oxides in karst groundwater under warm-humid climatic phases than under cold-dry phases. This suggested that climate shift might alter arsenic balance in sedimentary areas and aquifer systems and potentially exert significant influence on global arsenic contamination.

Gender and AIDS: time to act.

Gender has long been recognized as being key to understanding and addressing HIV and AIDS. Gender roles and relations that structure and legitimate women's subordination and simultaneously foster models of masculinity that justify and reproduce men's dominance over women exacerbate the spread and impact of the epidemic. Notions of masculinity prevalent in many parts of the world that equate being a man with dominance over women, sexual conquest and risk-taking are associated with less condom use, more sexually transmitted infections, more partners, including more casual partners, more frequent sex, more abuse of alcohol and more transactional sex. They also contribute to men accessing treatment later than women and at greater cost to public health systems. The imperative of addressing the gender dimensions of AIDS has been clearly and repeatedly articulated. Many interventions have been shown to be effective in addressing gender-related risks and vulnerabilities including programmes designed to reach and engage men, improve women's legal and economic position, integrate gender-based violence prevention into HIV services, and increase girls' access to secondary and tertiary education. Despite this, the political will to act has been sorely lacking and not nearly enough has been done to hold governments and multilateral institutions to account. This paper argues that we can no longer simply pay lip service to the urgent need to act on what we know about gender and AIDS. Simply put, it is time to act.