Warlord: The Political and Military Ambitions of Nazi Germany

There are so many important stories to consider when thinking about World War II. It is easy to think about the popular aspects of the war: the causes, the major figures, the battles, and, of course, the lasting consequences. Yet there are other, lesser known storylines to consider, ones that have taken a backseat to the more popular narratives of the time. It is commonly understood that Nazi Germany was evil and that they had nothing but ill intentions for the rest of Europe and the world. However, it is vital to understand that Germany’s pre-war intentions are notably different from the infamous events that we have come to know. To truly understand German ambitions in the mid-Twentieth Century, it is important to look back at the lasting consequences that Europe faced after the Great War. By studying the political and economic ambitions of Nazi Germany, we can begin to gain a better understanding of their wars of conquest and subsequent victories and defeats in World War II

Mitochondrial DNA signals of late glacial recolonization of Europe from near Eastern refugia

Human populations, along with those of many other species, are thought to have contracted into a number of refuge areas at the height of the last Ice Age. European populations are believed to be, to a large extent, the descendants of the inhabitants of these refugia, and some extant mtDNA lineages can be traced to refugia in Franco-Cantabria (haplogroups H1, H3, V, and U5b1), the Italian Peninsula (U5b3), and the East European Plain (U4 and U5a). Parts of the Near East, such as the Levant, were also continuously inhabited throughout the Last Glacial Maximum, but unlike western and eastern Europe, no archaeological or genetic evidence for Late Glacial expansions into Europe from the Near East has hitherto been discovered. Here we report, on the basis of an enlarged whole-genome mitochondrial database, that a substantial, perhaps predominant, signal from mitochondrial haplogroups J and T, previously thought to have spread primarily from the Near East into Europe with the Neolithic population, may in fact reflect dispersals during the Late Glacial period, ?19–12 thousand years (ka) ago.<br/

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports

Brg1 Is Required for Cdx2-Mediated Repression of Oct4 Expression in Mouse Blastocysts

During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates that suppression of Oct4 expression in the trophectoderm is mediated by Cdx2. Nonetheless, the underlying epigenetic modifiers required for Cdx2-dependent repression of Oct4 are largely unknown. Here we show that the chromatin remodeling protein Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts. By employing a combination of RNA interference (RNAi) and gene expression analysis we found that both Brg1 Knockdown (KD) and Cdx2 KD blastocysts exhibit widespread expression of Oct4 in the trophectoderm. Interestingly, in Brg1 KD blastocysts and Cdx2 KD blastocysts, the expression of Cdx2 and Brg1 is unchanged, respectively. To address whether Brg1 cooperates with Cdx2 to repress Oct4 transcription in the developing trophectoderm, we utilized preimplantation embryos, trophoblast stem (TS) cells and Cdx2-inducible embryonic stem (ES) cells as model systems. We found that: (1) combined knockdown (KD) of Brg1 and Cdx2 levels in blastocysts resulted in increased levels of Oct4 transcripts compared to KD of Brg1 or Cdx2 alone, (2) endogenous Brg1 co-immunoprecipitated with Cdx2 in TS cell extracts, (3) in blastocysts Brg1 and Cdx2 co-localize in trophectoderm nuclei and (4) in Cdx2-induced ES cells Brg1 and Cdx2 are recruited to the Oct4 promoter. Lastly, to determine how Brg1 may induce epigenetic silencing of the Oct4 gene, we evaluated CpG methylation at the Oct4 promoter in the trophectoderm of Brg1 KD blastocysts. This analysis revealed that Brg1-dependent repression of Oct4 expression is independent of DNA methylation at the blastocyst stage. In toto, these results demonstrate that Brg1 cooperates with Cdx2 to repress Oct4 expression in the developing trophectoderm to ensure normal development

Affordability and Access to Essential Medications for Asthma and Chronic Obstructive Pulmonary Disease in Three Low- and Middle-Income Country Settings

INTRODUCTION: Despite the rising burden of chronic respiratory disease globally, and although many respiratory medications are included in the World Health Organization Essential Medications List (WHO-EML), there is limited information concerning the availability and affordability of treatment drugs for respiratory conditions in low- and middle-income countries (LMICs). METHODS: All public and private pharmacies in catchment areas of the Global Excellence in COPD outcomes (GECo) study sites in Bhaktapur, Nepal, Lima, Peru, and Nakaseke, Uganda, were approached in 2017-2019 to assess pricing and availability of medications for the management of asthma and COPD. RESULTS: We surveyed all 63 pharmacies in respective study areas in Nepal (95.2% private), 104 pharmacies in Peru (94.2% private) and 53 pharmacies in Uganda (98.1% private). The availability of any medication for respiratory disease was higher in private (93.3%) compared to public (73.3%) pharmacies. Salbutamol (WHO-EML) monotherapy in any formulation was the most commonly available respiratory medication among the three sites (93.7% Nepal, 86.5% Peru and 79.2% Uganda) while beclomethasone (WHO-EML) was only available in Peru (33.7%) and Nepal (22%). LABA-LAMA combination therapy was only available in Nepal (14.3% of pharmacies surveyed). The monthly treatment cost of respiratory medications was lowest in Nepal according to several cost metrics: the overall monthly cost, the median price ratio comparing medication costs to international reference prices at time of survey in dollars, and in terms of days' wages of the lowest-paid government worker. For the treatment of intermittent asthma, defined as 100 mcg Salbutamol/Albuterol inhaler, days' wages ranged from 0.47 days in Nepal and Peru to 3.33 days in Uganda. CONCLUSION: The availability and pricing of respiratory medications varied across LMIC settings, with medications for acute care of respiratory diseases being more widely available than those for long-term management

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

Single-cell analysis of mesenchymal cells in permeable neural vasculature reveals novel diverse subpopulations of fibroblasts

Abstract Background In the choroid plexus and pituitary gland, vasculature is known to have a permeable, fenestrated phenotype which allows for the free passage of molecules in contrast to the blood brain barrier observed in the rest of the CNS. The endothelium of these compartments, along with secretory, neural-lineage cells (choroid epithelium and pituitary endocrine cells) have been studied in detail, but less attention has been given to the perivascular mesenchymal cells of these compartments. Methods The Hic1 CreERT2 Rosa26 LSL−TdTomato mouse model was used in conjunction with a Pdgfra H2B−EGFP mouse model to examine mesenchymal cells, which can be subdivided into Pdgfra+ fibroblasts and Pdgfra− pericytes within the choroid plexus (CP) and pituitary gland (PG), by histological, immunofluorescence staining and single-cell RNA-sequencing analyses. Results We found that both CP and PG possess substantial populations of distinct Hic1+ mesenchymal cells, including an abundance of Pdgfra+ fibroblasts. Within the pituitary, we identified distinct subpopulations of Hic1+ fibroblasts in the glandular anterior pituitary and the neurosecretory posterior pituitary. We also identified multiple distinct markers of CP, PG, and the meningeal mesenchymal compartment, including alkaline phosphatase, indole-n-methyltransferase and CD34. Conclusions Novel, distinct subpopulations of mesenchymal cells can be found in permeable vascular interfaces, including the CP, PG, and meninges, and make distinct contributions to both organs through the production of structural proteins, enzymes, transporters, and trophic molecules