Minjiwarra : archaeological evidence of human occupation of Australia’s northern Kimberley by 50,000 BP

Recent archaeological research in Australia’s north-eastern Kimberley has luminescence dated a large red sedimentary feature, known as Minjiwarra, with artefacts in stratified contexts from the late Holocene to ∼50,000 years ago. This site is located on the Drysdale River, with preliminary excavations undertaken as part of an ARC Linkage Project. Deeply stratified sites in association with rockshelters are uncommon across the NE Kimberley and basal dates at open cultural deposits vary greatly. Most of them are mid-Holocene in age. However, Minjiwarra appears to cover the entire span of potential human occupation in this region, with associated lithic technology, reported on here

Survival of massive allografts in segmental oncological bone defect reconstructions

Reconstructions of large segmental bone defects after resection of bone tumours with massive structural allografts have a high number of reported complications including fracture, infection and non-union. Our goal is to report the survival and complications of massive allografts in our patients. A total of 32 patients were evaluated for fracture, infection, non-union rate and survival of their massive allograft reconstructions. The average follow-up for this group was five years and three months. The total fracture rate was 13% with a total infection rate of 16%. We found a low union rate of 25%. The total survival of the allografts was 80.8% (± 18.7%) after five years. We found a five-year allograft survival of 80.8% which is comparable with other studies

Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions

Background: CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach. Methods: To determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d+ tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography. Results: Anti-CD1d VHH1D17 strongly enhances annexin V binding to CD1d+ tumor cells but this does not reflect induction of apoptosis. Instead, we show that VHH1D17 enhances presentation of phosphatidylserine (PS) in CD1d and that this is saposin dependent. The crystal structure of the VHH1D17-CD1d(endogenous lipid) complex demonstrates that VHH1D17 binds the A′-pocket of CD1d, leaving the lipid headgroup solvent exposed, and has an electro-negatively charged patch which could be involved in the enhanced PS presentation by CD1d. Presentation of PS in CD1d does not trigger phagocytosis but leads to greatly enhanced binding of T-cell immunoglobulin and mucin domain containing molecules (TIM)-1 to TIM-3, TIM-4 and induces TIM-3 signaling. Conclusion: Our findings reveal the existence of an immune modulatory CD1d(PS)-TIM axis with potentially unexpected implications for immune regulation in both physiological and pathological conditions

Declining Orangutan Encounter Rates from Wallace to the Present Suggest the Species Was Once More Abundant

BACKGROUND: Bornean orangutans (Pongo pygmaeus) currently occur at low densities and seeing a wild one is a rare event. Compared to present low encounter rates of orangutans, it is striking how many orangutan each day historic collectors like Alfred Russel Wallace were able to shoot continuously over weeks or even months. Does that indicate that some 150 years ago encounter rates with orangutans, or their densities, were higher than now? METHODOLOGY/PRINCIPAL FINDINGS: We test this hypothesis by quantifying encounter rates obtained from hunting accounts, museum collections, and recent field studies, and analysing whether there is a declining trend over time. Logistic regression analyses of our data support such a decline on Borneo between the mid-19th century and the present. Even when controlled for variation in the size of survey and hunting teams and the durations of expeditions, mean daily encounter rates appear to have declined about 6-fold in areas with little or no forest disturbance. CONCLUSIONS/SIGNIFICANCE: This finding has potential consequences for our understanding of orangutans, because it suggests that Bornean orangutans once occurred at higher densities. We explore potential explanations-habitat loss and degradation, hunting, and disease-and conclude that hunting fits the observed patterns best. This suggests that hunting has been underestimated as a key causal factor of orangutan density and distribution, and that species population declines have been more severe than previously estimated based on habitat loss only. Our findings may require us to rethink the biology of orangutans, with much of our ecological understanding possibly being based on field studies of animals living at lower densities than they did historically. Our approach of quantifying species encounter rates from historic data demonstrates that this method can yield valuable information about the ecology and population density of species in the past, providing new insight into species' conservation needs

Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500 years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview