Activity

Our pathologically verified model of beta-cell destruction in FT1DM will contribute to anti-virus therapy of type 1 diabetes in the near future.Since fulminant type 1 diabetes was reported as a distinct subtype of type 1 diabetes in 2000, the Committee on Type 1 diabetes, Japan Diabetes Society has continuously recruited patients and conducted genomic research to elucidate the genetic basis of fulminant type 1 diabetes. The contribution of the human leukocyte antigen complex (HLA) to genetic susceptibility to fulminant type 1 diabetes was compared with that of other subtypes in 2009. The alleles and haplotypes associated with fulminant type 1 diabetes were found to be different from acute-onset and slowly progressive type 1 diabetes. DRB1*1501-DQB1*0602, a protective haplotype against acute-onset type 1 diabetes, does not provide protection against fulminant type 1 diabetes and DRB1*0802-DQB1*0302, a susceptible haplotype to acute-onset type 1 diabetes, does not confer susceptibility to fulminant type 1 diabetes. Recently, the first genome-wide association study (GWAS) of fulminant type 1 diabetes was performed in Japanese individuals. A strong association was observed with multiple single nucleotide polymorphisms (SNPs) in the HLA region, and the strongest association was observed with rs9268853 in the class II DR region. In addition, 11 SNPs outside the HLA region showed some evidence of association with the disease. In particular, rs11170445 in CSAD/lnc-ITGB7-1 on chromosome 12q13.13 showed an association at a genome-wide significance level. Fine mapping revealed that rs3782151 in CSAD/lnc-ITGB7-1 showed the lowest P value. CSAD/lnc-ITGB7-1 was found to be strongly associated with susceptibility to fulminant, but not classical, autoimmune type 1 diabetes, implicating this locus in the distinct phenotype of fulminant type 1 diabetes.Twenty years have passed since the first article on fulminant type 1 diabetes (FT1D) was published. FT1D is characterized by an extremely rapid onset of ketoacidosis, high plasma glucose and, conversely, a near-normal glycosylated hemoglobin level. Digestive or flu-like symptoms frequently precede the onset of ketoacidosis. Patients are usually negative for islet-related autoantibodies, with near-complete destruction of pancreatic β-cells, even at the onset of disease. Massive infiltration of immunocytes (insulitis) can be seen in the islets of patients with new-onset FT1D, but this subsides within a few weeks. Early discovery and development of research on FT1D were carried out in Japan, with some reports from Korea and China. Recently, the recognition of FT1D as an immune-related adverse effect of immune-checkpoint inhibitor therapy for various malignant tumors in some patients has drawn the attention of Western countries. selleck chemical The discovery and successful establishment of FT1D as a disease entity was the product of three essential factors (1) accumulated research data spanning more than 10 years; (2) fortuitous clinical observation; and (3) organization of a dedicated Japanese research committee. We anticipate that continued investigations of FT1D by a new generation of researchers will further elucidate the pathogenesis and yield new therapies.The Japan Diabetes Society’s Committee to Promote Female Diabetologists conducted a questionnaire survey from May to June 2017 to investigate the work style and living situation of diabetologists. The survey targeted 5298 Board Certified Diabetologists (diabetologists), with answers obtained from 1566 diabetologists (male, n = 1003 females, n = 563). Ninety-four percent of the males and 72% of the females worked full time. Twenty-one percent of the male subjects and 7% of the female subjects were heads of clinical departments, and 23% of the male subjects and 13% of the female subjects were diabetes training instructors, showing that there were fewer women than men in both roles. Regarding the allocation of time per day, men spent 10.7 h working, while women spent 8.5 h working. Both men and women slept 6.3 h. Men spent 1.0 h on housework, while women spent 3.3 h on housework. Men spent 0.7 h on childcare and nursing care, while women, spent 2.8 h. link2 Among diabetologists in the childrearing generation, men spent 1.4 h providing childcare and nursing care, while women spent 4.9 h, showing that women spent significantly more time on these tasks than men. To encourage female diabetologists to work more actively, to reduce overworking on the part of male diabetologists, and to enhance the careers of both men and women as diabetologists, we conclude it necessary to improve the workplace environment and for the Japan Diabetes Society to offer support.

The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease (COVID-19) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein based on the ratio of synonymous to nonsynonymous substitution. Such tests cannot, however, detect changes in the function of RNA molecules.

Here we apply a test for branch-specific oversubstitution of mutations within narrow windows of the genome without reference to the genetic code.

We recapitulate the finding that the gene encoding Spike protein has been a target of both purifying and positive selection. In addited modeling indicates no change in either Nsp4 or Nsp16 protein structure relative to the most recent common ancestor. These SARS-CoV-2-specific mutations may affect molecular processes mediated by the positive or negative RNA molecules, including transcription, translation, RNA stability, and evasion of the host innate immune system. Our results highlight the importance of considering mutations in viral genomes not only from the perspective of their impact on protein structure, but also how they may impact other molecular processes critical to the viral life cycle.

To investigate the burden of mortality due to ischemic heart disease (IHD) attributable to low levels of physical activity in the Brazilian population (aged ≥ 25 years) before, during and after economic and political crises (2007-2017).

This study was focused on IHD as a cause of death. The International Statistical Classification of Diseases (10th revision) codes related to IHD have been mapped. The data used for the physical activity estimates of the present study refer to surveys with random sampling carried out in the Brazilian territory that considers all domains of physical activity. The contribution of physical activity for mortality due to IHD was estimated using a comparative risk assessment approach. In addition, we verified the association between mortality due to IHD attributable to low levels of physical activity according to the Socio-demographic Index of the Brazilian states.

For males it was estimated that in 2007 and 2017 there were, respectively, 9,585 and 11,821 deaths due to IHD as amic and political crisis highlighted the social inequalities between Brazilian geographic regions for the burden of mortality due to IHD attributable to low levels of physical activity.

Dispersal is an important process affecting population dynamics and connectivity. For marine direct developers, both adults and juveniles may disperse. Although the distribution of juveniles can be initially constrained by their mothers’ choice, they may be able to leave the parental habitat and colonize other habitats. We investigated the effect of habitat quality, patch size and presence of conspecific adults on the colonization of novel habitats by juveniles of the tube-dwelling amphipod

associated with the macroalgal host

.

We tested the factors listed above on the colonization of juveniles by manipulating natural and artificial plants in both the field and laboratory.

In the laboratory, juveniles selected high-quality habitats (i.e., natural alga), where both food and shelter are provided, when low-quality resources (i.e., artificial alga) were also available. In contrast, habitat quality and algal patch size did not affect the colonization by juveniles in the field. Finally, the presence of cgest that C. filosa juveniles can select and colonize novel habitats, and that such process can be partially affected by habitat quality, but not by patch size. Also, the presence of conspecifics may affect the colonization by juveniles. Successful colonization by this specific developmental stage under different scenarios indicates that juveniles may act as a dispersal agent in this species.Maternal thyroid hormones (THs) are known to be crucial in embryonic development in humans, but their influence on other, especially wild, animals remains poorly understood. link3 So far, the studies that experimentally investigated the consequences of maternal THs focused on short-term effects, while early organisational effects with long-term consequences, as shown for other prenatal hormones, could also be expected. In this study, we aimed at investigating both the short- and long-term effects of prenatal THs in a bird species, the Japanese quail Coturnix japonica. We experimentally elevated yolk TH content (the prohormone T4, and its active metabolite T3, as well as a combination of both hormones). We analysed hatching success, embryonic development, offspring growth and oxidative stress as well as their potential organisational effects on reproduction, moult and oxidative stress in adulthood. We found that eggs injected with T4 had a higher hatching success compared with control eggs, suggesting conversion of T4 into T3 by the embryo. We detected no evidence for other short-term or long-term effects of yolk THs. These results suggest that yolk THs are important in the embryonic stage of precocial birds, but other short- and long-term consequences remain unclear. Research on maternal THs will greatly benefit from studies investigating how embryos use and respond to this maternal signalling. Long-term studies on prenatal THs in other taxa in the wild are needed for a better understanding of this hormone-mediated maternal pathway.Hepatocellular carcinoma is the most common type of primary liver cancer in humans. This study aimed to demonstrate anticancer properties of an aqueous extract from Chrysophyllum cainito stem bark (CE) and its underlying mechanisms. Our MTT assay results showed that CE significantly reduced human hepatocellular carcinoma (HepG2) cell viability with the IC50of 100 µg/mL, while human dermal primary fibroblast (HDFa) cells showed less susceptibility in every concentration tested. Determined by Annexin V staining, the proportion of apoptotic HepG2 cells increased in a dose-dependent fashion after 24 hour-exposure of CE. The results from Western blot analysis confirmed that CE reduced procaspase-3, suggesting apoptosis by activating caspase-3 cleavage. Using the DCFH-DA and DiOC6 fluorescent probes, it was found that CE significantly stimulated the generation of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (Δψm), respectively. According to cell cycle analysis, CE (100 µg/mL) profoundly increased the percentage of cells in the sub-G1 phase, indicating cell apoptosis.