Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications

FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells

PREDICT DIABETES INCIDENCE WITH HBA1C AND OTHER ITEMS

In diabetes screening with hemoglobin A1c in lieu of plasma glucose, the optimum cut-off point for predicting the incidence of diabetes mellitus in the four-year period was examined. In addition, considerations were given on items in the screening and questionnaire aside from hemoglobin A1c, which would be useful in predicting diabetes aside from hemoglobin A1c. The optimum cut-off point of hemoglobin A1c to predict diabetes, based on receiver operating characteristic curve, was 5.3 percent (sensitivity, 84.2%; specificity, 92.1%). Based on the logistic regression analysis, useful items (other than hemoglobin A1c) were alanine aminotransferase and γ-glutamyl transpeptidase. A combined application of hemoglobin A1c with alanine aminotransferase and γ-glutamyl transpeptidase for predicting the incidence of diabetes in the four-year period resulted in the sensitivity of 86.8% and the specificity of 96.3%. When the combined application was compared with the sole use of hemoglobin A1c at 5.3%, the combined use was superior to the latter in terms of both sensitivity and specificity, resulting in the reduction of false positives by more than 50%

Loss of symbiont infectivity following thermal stress can be a factor limiting recovery from bleaching in cnidarians

Increases in seawater temperature can cause coral bleaching through loss of symbiotic algae (dinoflagellates of the family Symbiodiniaceae). Corals can recover from bleaching by recruiting algae into host cells from the residual symbiont population or from the external environment. However, the high coral mortality that often follows mass-bleaching events suggests that recovery is often limited in the wild. Here, we examine the effect of pre-exposure to heat stress on the capacity of symbiotic algae to infect cnidarian hosts using the Aiptasia (sea-anemone)-Symbiodiniaceae model system. We found that the symbiont strainBreviolumsp. CS-164 (ITS2 type B1), both free-living and in symbiosis, loses the capacity to infect the host following exposure to heat stress. This loss of infectivity is reversible, however, a longer exposure to heat stress increases the time taken for reversal. Under the same experimental conditions, the loss of infectivity was not observed in another strainBreviolum psygmophilumCCMP2459 (ITS2 type B2). Our results suggest that recovery from bleaching can be limited by the loss of symbiont infectivity following exposure to heat stress

Adapting global shared socio-economic pathways for national scenarios in Japan

A Correction to this article was published. This article has been updated.Shared socio-economic pathways (SSPs) are alternative global development scenarios focused on the mitigation of and adaptation to climate change. However, global SSPs would need revised versions for regional or local assessment, which is the so-called extended version, because global narratives may lack region-specific important drivers, national policy perspectives, and unification of data for each nation. Thus, it is necessary to construct scenarios that can be used for governments in response to the SSPs to reflect national and sub-national unique situations. This study presents national SSP scenarios, specifically focusing on Japan (hereafter, Japan SSPs), as well as a process for developing scenarios that qualitatively links to global SSPs. We document the descriptions of drivers and basic narratives of Japan SSPs coherent with global SSPs, based on workshops conducted by local researchers and governments. Moreover, we provide a common data set of population and GDP using the national scale. Japan SSPs emphasized population trends different from global SSPs and influencing factors, citizen participation, industrial development resulting from economic change, distribution, and inequality of sub-national population, among others. We selected data sets from existing population projections that have been widely used by Japanese researchers; the data show that the population and GDP of Japan SSPs are expected to be about 20-25% less than global SSPs by 2100