Glen Thirsty: The History and Archaeology of a Desert Well

The archaeology of Glen Thirsty, a desert well in the Amadeus Basin, Central Australia, illustrates the changing relationship between the ranges and desert lowlands during the last 1500 years. Historical records and Aboriginal accounts of the site document the regional importance of Glen Thirsty as one of the few wells in this part of the desert. Archaeological excavations and rock art research show that despite its proximity to Puritjarra with its long, late Pleistocene record of occupation, Glen Thirsty only became an important focus of occupation after 1500 BP. Several lines of evidence independently suggest the establishment and consolidation of a new cultural and economic landscape in the Glen Thirsty area around this time. Growing population pressure and shifts in patterns of land-use and economy in the Central Australian ranges may have provided the impetus for more intensive use of the Glen Thirsty area, although the timing of this was constrained by climatic factors. As a rain-fed well in the lower part of the Amadeus Basin, Glen Thirsty is sensitive to shifts in palaeoclimate and its history reflects changes in regional rainfall patterns during the late Holocene

BSAVA Formulary: Your questions answered

A new edition of the BSAVA Small Animal Formulary has been published. Ian Ramsey explains what is in and what is out of this new version

Monetary Policy and Polish Labour Market in the years 1999 - 2008

This article sets out to analyse how the monetary policy pursued by the National Bank of Poland (NBP) determined the labour market situation in the country in the decade 1999-2008. The article consists of introduction as well as five sections. Section one discusses NBP's strategy of monetary policy in the defined period against monetary strategies implemented in other countries. Section two uses the growth rates of money supply and of real GDP to verify whether the primary purpose of monetary policy, i.e. the inflationary target, was achieved. Section three generally characterises the country's labour market using the levels and dynamics of employment and of unemployment. Section four discusses major instruments of NBP's monetary policy, mainly analysing changes in the central bank's interest rates and their effect on the economic situation and on the labour market. The article concludes with a summation providing synthetic conclusions.Celem artykułu jest analiza wpływu polityki monetarnej Narodowego Banku Polskiego (NBP) na sytuację na rynku pracy w Polsce w ciągu dekady obejmującej lata 1999-2008. Opracowanie składa się z wprowadzenia oraz pięciu części. W pierwszej z nich omówiona została strategia polityki monetarnej NBP w badanym okresie wraz z porównaniem ze strategią przyjmowaną w innych krajach. W części drugiej sprawdzono, czy realizowany był podstawowy cel polityki monetarnej, czyli cel inflacyjny, w kontekście kształtowania się stóp wzrostu podaży pieniądza oraz realnego PKB. W punkcie kolejnym ukazana została ogólna charakterystyka rynku pracy na podstawie kształtowania się poziomu i dynamiki zatrudnienia oraz bezrobocia. W części czwartej omówiono podstawowe instrumenty polityki pieniężnej NBP. Uwaga skoncentrowana została głównie na analizie zmian stóp procentowych banku centralnego oraz ich wpływu na sytuację gospodarczą i rynek pracy. Całość zamknięta została podsumowaniem, w którym zawarto syntetyczne wnioski końcowe

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

Immune microenvironment dysfunctions enable malignification at the onset of myelodysplastic syndromes

View full abstracthttps://openworks.mdanderson.org/leading-edge/1002/thumbnail.jp

Very Late Antigen-1 Marks Functional Tumor-Resident CD8 T Cells and Correlates with Survival of Melanoma Patients.

A major limiting factor in the success of immunotherapy is tumor infiltration by CD8(+) T cells, a process that remains poorly understood. In the present study, we characterized homing receptors expressed by human melanoma-specific CD8(+) T cells. Our data reveal that P-selectin binding and expression of the retention integrin, very late antigen (VLA)-1, by vaccine-induced T cells correlate with longer patient survival. Furthermore, we demonstrate that CD8(+)VLA-1(+) tumor-infiltrating lymphocytes (TILs) are highly enriched in melanoma metastases in diverse tissues. VLA-1-expressing TIL frequently co-express CD69 and CD103, indicating tissue-resident memory T cells (TRM) differentiation. We employed a mouse model of melanoma to further characterize VLA-1-expressing TIL. Our data show that VLA-1(+) TRM develop in murine tumors within 2 weeks, where they exhibit increased activation status, as well as superior effector functions. In addition, in vivo blockade of either VLA-1 or CD103 significantly impaired control of subcutaneous tumors. Together, our data indicate that VLA-1(+) TRM develop in tumors and play an important role in tumor immunity, presenting novel targets for the optimization of cancer immunotherapy

Targeting MCL1-Driven Anti-apoptotic Pathways Overcomes Blast Progression After Hypomethylating Agent Failure in Chronic Myelomonocytic Leukemia

RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Here, using single-cell, multi-omics technologies, we seek to dissect the biological mechanisms underlying the initiation and progression of RAS pathway-mutated CMML. We identify that RAS pathway mutations induce transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs) and downstream monocytic populations in response to cell-intrinsic and -extrinsic inflammatory signaling that also impair the functions of immune cells. HSPCs expand at disease progression after therapy with HMA or the BCL2 inhibitor venetoclax and rely on the NF-κB pathway effector MCL1 to maintain survival. Our study has implications for the development of therapies to improve the survival of patients with RAS pathway-mutated CMML