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Snow cover (SC) is an important contributor to atmospheric predictability on subseasonal to seasonal time scales. This paper evaluates the submonthly scale cause-and-effect relationship between SC and surface air temperature (SAT) in Eurasia, which has been typically overlooked in previous statistical analyses of subseasonal to seasonal atmospheric predictability. We focus on the November east–west dipolar SC pattern, a dominant large-scale SC phenomenon. We use an information flow analysis, based on information theory, to infer causal relations not revealed by conventional correlation analysis. This analysis indicates a one-way causality from SAT to SC around the west pole (Europe) in boreal autumn (November), implying that SC has little influence on the time evolution of SAT. In contrast, causality from SC to SAT is significant around the east pole (the Mongolian Plateau). An atmospheric model experiment suggests that the SAT response to SC can persist for a month via snow–albedo feedback, although the response of the upper atmosphere in the model is small. Furthermore, the subseasonal hindcasts show that the contribution of SC may affect the predictability of SAT for up to four weeks around the east pole. We suggest that the geographical and climatological atmospheric conditions are favorable for generating a positive albedo feedback as a “hotspot” of SC–SAT coupling around the east pole in autumn. The agreement of our causality analysis with other analytical and modeling approaches underscores the cause-and-effect relationship between SC and SAT and its contribution to the subseasonal predictability over autumnal Eurasia. [ABSTRACT FROM AUTHOR]

Inosine monophosphate dehydrogenase (IMPDH) is a rate‐limiting enzyme in de novo guanine nucleotide synthesis pathway. Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL‐fusions are susceptible to IMPDH inhibitors in vitro. We also showed that alternate‐day administration of IMPDH inhibitors suppressed the development of MLL‐AF9‐driven AML in vivo without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll‐like receptor (TLR)‐TRAF6‐NF‐κB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1/2 agonist effectively inhibited the development of MLL‐fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL‐fusion AMLs and potentially other aggressive tumors with active TLR signaling. Synopsis: This study describes the potent antileukemia effect of IMPDH inhibitors on MLL‐fusion leukemias, which is partly mediated by the overactivation of TLR‐NF‐kB‐Vcam1 pathway. MLL‐fusion leukemias are particularly susceptible to IMPDH inhibition.An alternate‐day administration of IMPDH inhibitors effectively suppresses MLL‐AF9‐driven leukemogenesis in vivo through myeloid differentiation without any devastating effect on immune function.IMPDH inhibition results in activation of TLR pathway and Vcam1 upregulation in MLL‐fusion leukemia cells.Combined treatment with IMPDH inhibitors and the TLR1/2 agonist shows potent antileukemia effects in vivo. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the association of the type of social support and proactive coping with depressive symptoms (DS) in Japanese people living with human immunodeficiency virus (PLHIV), in order to select effective psychosocial care or intervention. Questionnaires were anonymously collected from randomly recruited participants. The questionnaire included items on demographic characteristics, HIV treatment-related factors, DS, social support, and coping. Hierarchical binary logistic regression was used to identify factors associated with DS. A total of 564 patients completed the questionnaire and 207 (37%) patients reported DS. Demographic factors, such as drug-use-related disorders [adjusted odds ratio (AOR) 7.21, 95% confidence interval (95%CI) 1.95–26.70], unemployment (AOR 3.06, 95%CI 1.50–6.27) and younger age (AOR 0.96, 95%CI 0.94–0.99) were significantly associated with DS. With regard to coping, higher levels of instrumental support seeking (AOR 1.09, 95%CI 1.01–1.18), lower levels of proactive coping (AOR 0.91, 95%CI 0.87–0.96) and lower levels of emotional support seeking (AOR 0.82, 95%CI 0.72–0.92) were significantly associated with DS. Our results highlight the need for psychosocial care to enhance or compensate proactive coping and emotional support seeking abilities in DS. Healthcare workers should pay attention to the mental health of young unemployed PLHIV with drug-use-related disorders. [ABSTRACT FROM AUTHOR]

The iminocoumarin fluorophore is characterized as a new scaffold for sensors for ratiometric imaging. Results show that iminocoumarin is a useful fluorophore for fluorescence microscopic imaging and that ZnIC is useful for studies on the biological functions of [Zn.sup.2}.

A series of fluorescen t Zn(super 2+) sensor molecules with distinct affinities for Zn(super 2+) is developed because biological Zn(super 2+) concentrations vary over a wide range from sub-nanomolar to millimolar. The synaptic release of Zn(super 2+) is measured in hippocampal series in response to high-potassium-induced depolarization.

One of the major symptoms of myelodysplastic syndromes (MDS) is severe cytopenia. Despite cytokine therapies, such as erythropoiesis-stimulating agents, many patients still require blood transfusions, and the development of new therapeutic approaches is needed. In this work, we studied the effects of the inosine-5’-monophosphate (IMP) dehydrogenase (IMPDH) inhibitor FF-10501 on erythropoiesis of human hematopoietic cells. Differentiation of K562 chronic myeloid leukemia cells to an erythroid lineage was promoted by FF-10501 in a dose-dependent manner. Interestingly, we found that metabolic conversion of IMP to hypoxanthine leads to elevation of reactive oxygen species (ROS). The differentiative effects of FF-10501 were abolished by the ROS scavenger dimethylthiourea or the p38 MAPK inhibitor SB203580. Furthermore, FF-10501 promoted erythropoiesis from CD34+hematopoietic stem/progenitor cells, accompanied with ROS accumulation, while high-dose FF-10501 mainly showed cytotoxic effects. These findings denote the potential of IMPDH inhibition therapy with FF-10501 in amelioration of anemia in MDS patients. [ABSTRACT FROM AUTHOR]

We have developed a series of fluorescent Zn2+ sensor molecules with distinct affinities for Zn2+, because biological Zn2+ concentrations vary over a wide range from sub-nanomolar to millimolar. The new sensors have Kd values in the range of 10-8-10-4 M, compared with 2.7 nM for ZnAF-2. They do not fluoresce in the presence of other biologically important metal ions such as calcium or magnesium, and they can detect Zn2+ within 100 ms. In cultured cells, the fluorescence intensity of ZnAF-2 was saturated at low Zn2+ concentration, while that of ZnAF-3 (Kd = 0.79 μM) was not saturated even at relatively high Zn2+ concentrations. In hippocampal slices, we measured synaptic release of Zn2+ in response to high- potassium-induced depolarization. ZnAF-2 showed similar levels of fluorescence increase in dentate gyrus (DG), CA3 and CA1, which were indistinguishable. However, ZnAF-3 showed a fluorescence increase only in DG. Thus, by using a combination of sensor molecules, it was demonstrated for the first time that a higher Zn2+ concentration is released in DO than in CA3 or CA1 and that we can easily visualize Zn2+ concentration over a wide range. We believe that the use of various combinations of ZnAF family members will offer unprecedented versatility for fluorescence-microscopic imaging of Zn2+ in biological applications. [ABSTRACT FROM AUTHOR]

People living with human immunodeficiency virus (HIV) are at high risk of mental health problems. However, little is known about this risk in HIV-infected patients with hemophilia (HPH) who contracted the virus through blood products. This cross-sectional, observational study assessed patients' mood states and the factors associated with them among Japanese HPH to evaluate the need for psychosocial support. HPH completed self-administered questionnaires (Profile of Mood States [POMS] and General Health Questionnaire-28), neuropsychological tests, and brain magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computerized tomography scans. HIV-infected patients with no hemophilia (HPnH) completed POMS and neuropsychological tests. Socio-demographic characteristics and HIV- and hemophilia-related data were obtained from participants' medical records and interviews. A Mann-Whitney U test and chi-squared analyses were conducted. Fifty-six HPH and 388 HPnH completed the questionnaires and neuropsychological tests. HPH had a significantly lower prevalence of tension-anxiety (HPH, 7%; HPnH, 18%; p = 0.049) and a significantly higher prevalence of low vigor (HPH, 63%; HPnH, 32%; p < 0.001). Low vigor in HPH was significantly associated with impaired executive function (low vigor, 66%; high vigor, 33%; p = 0.019) and a social dysfunction score ≥ 3 (moderate; low vigor, 26%; high vigor, 5%; p = 0.047). Our results highlight the high prevalence of low vigor among HPH, leading to impairments in executive and social functions. Therefore, healthcare workers need to pay attention to the vigor, executive function, and social function of HPH., Competing Interests: Ei Kinai received research grants from Chugai Pharmaceutical and CSL Behring and honoraria from Gilead Sciences, ViiV Healthcare, MSD, Chugai Pharmaceutical, Sanofi, Bayer, Takeda Pharmaceutical, Novo Nordisk, Fujimoto Pharmaceutical Corporation, and CSL Behring. Shinichi Oka received research grants from ViiV Healthcare and Gilead Sciences and honoraria from Gilead Sciences and ViiV Healthcare. The remaining authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)