Gorbachev's Vladivostok initiatives

In July 1986, sixteen months after becoming General Secretary of the Communist Party of the Soviet Union (CPSU), Mikhail sergeyevich Gorbachov made a three-week tour of the Soviet Far East. He visited main cities and town, industrial centers, agricultural communities, as well as military and naval installations. Most importantof all, Gorbachev delivered an important speech at Vladivostok on July 28. Apart from a lengthy consideration of domestic policy issues, Gorbachev defined in his speech Soviet interests, attitudes and aims in Asia and the Pacific in a fresh light, taking Asian convictions and views (as he saw them) into consideration. Gorbachev came to power at a time when the Soviet Union urgently needed economic reinvigoration at home, yet his predecessors, especialy Brezhnev, had given insufficient attention to developing a comprehensive strategy for the Asian-Pacific region. Soviet leaders, as Ross Babbage argued, had failed to appreciate the region's economic dynamism and had tended to be overly pre-occupied with security issues. Their drive to build up their military power in the region had created serious political obstacles in external relations with neighbouring countries as important as China, Japan and the Unites States. As a result, the Soviet Union was rather isolated in the region

Rapidly Evolving R Genes in Diverse Grass Species Confer Resistance to Rice Blast Disease

We show that the genomes of maize, sorghum, and brachypodium contain genes that, when transformed into rice, confer resistance to rice blast disease. The genes are resistance genes (R genes) that encode proteins with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains (NBS–LRR proteins). By using criteria associated with rapid molecular evolution, we identified three rapidly evolving R-gene families in these species as well as in rice, and transformed a randomly chosen subset of these genes into rice strains known to be sensitive to rice blast disease caused by the fungus Magnaporthe oryzae. The transformed strains were then tested for sensitivity or resistance to 12 diverse strains of M. oryzae. A total of 15 functional blast R genes were identified among 60 NBS–LRR genes cloned from maize, sorghum, and brachypodium; and 13 blast R genes were obtained from 20 NBS–LRR paralogs in rice. These results show that abundant blast R genes occur not only within species but also among species, and that the R genes in the same rapidly evolving gene family can exhibit an effector response that confers resistance to rapidly evolving fungal pathogens. Neither conventional evolutionary conservation nor conventional evolutionary convergence supplies a satisfactory explanation of our findings. We suggest a unique mechanism termed “constrained divergence,” in which R genes and pathogen effectors can follow only limited evolutionary pathways to increase fitness. Our results open avenues for R-gene identification that will help to elucidate R-gene vs. effector mechanisms and may yield new sources of durable pathogen resistance.Organismic and Evolutionary Biolog

Upregulation of microRNA-125b contributes to leukemogenesis and increases drug resistance in pediatric acute promyelocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Although current chemotherapy regimens have remarkably improved the cure rate of pediatric acute promyelocytic leukemia (APL) over the past decade, more than 20% of patients still die of the disease, and the 5-year cumulative incidence of relapse is 17%. The precise gene pathways that exert critical control over the determination of cell lineage fate during the development of pediatric APL remain unclear.</p> <p>Methods</p> <p>In this study, we analyzed <it>miR-125b </it>expression in 169 pediatric acute myelogenous leukemia (AML) samples including 76 APL samples before therapy and 38 APL samples after therapy. The effects of enforced expression of <it>miR-125b </it>were evaluated in leukemic cell and drug-resistant cell lines.</p> <p>Results</p> <p><it>miR-125b </it>is highly expressed in pediatric APL compared with other subtypes of AML and is correlated with treatment response, as well as relapse of pediatric APL. Our results further demonstrated that <it>miR-125b </it>could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor BCL2-antagonist/killer 1 (Bak1). Remarkably, <it>miR-125b </it>was also found to be up-regulated in leukemic drug-resistant cells, and transfection of a <it>miR-125b </it>duplex into AML cells can increase their resistance to therapeutic drugs,</p> <p>Conclusions</p> <p>These findings strongly indicate that <it>miR-125b </it>plays an important role in the development of pediatric APL at least partially mediated by repressing BAK1 protein expression and could be a potential therapeutic target for treating pediatric APL failure.</p

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis

FIMO: A Challenge Formal Dataset for Automated Theorem Proving

We present FIMO, an innovative dataset comprising formal mathematical problem statements sourced from the International Mathematical Olympiad (IMO) Shortlisted Problems. Designed to facilitate advanced automated theorem proving at the IMO level, FIMO is currently tailored for the Lean formal language. It comprises 149 formal problem statements, accompanied by both informal problem descriptions and their corresponding LaTeX-based informal proofs. Through initial experiments involving GPT-4, our findings underscore the existing limitations in current methodologies, indicating a substantial journey ahead before achieving satisfactory IMO-level automated theorem proving outcomes

Electrospinning 3D bioactive glasses for wound healing

An electrospinning technique was used to produce three-dimensional (3D) bioactive glass fibrous scaffolds, in the SiO2-CaO system, for wound healing applications. Previously, it was thought that 3D cotton wool-like structures could only be produced when the sol contained calcium nitrate, implying that the Ca2+ and its electronic charge had a significant effect on the structure produced. Here, fibres with a 3D appearance were also electrospun from compositions containing only silica. A polymer binding agent was added to inorganic sol-gel solutions, enabling electrospinning prior to bioactive glass network formation and the polymer was removed by calcination. While the addition of Ca2+ contributes to the 3D morphology, here we show that other factors, such as relative humidity, play an important role in producing the 3D cotton-wool-like macrostructure of the fibres. A human dermal fibroblast cell line (CD-18CO) was exposed to dissolution products of the samples. Cell proliferation and metabolic activity tests were carried out and a VEGF ELISA showed a significant increase in VEGF production in cells exposed to the bioactive glass samples compared to control in DMEM. A novel SiO2-CaO nanofibrous scaffold was created that showed tailorable physical and dissolution properties, the control and composition of these release products are important for directing desirable wound healing interactions