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Despite the identification of driver mutations leading to the initiation of myeloproliferative neoplasms (MPNs), the molecular pathogenesis of MPNs remains incompletely understood. Here, we demonstrate that growth arrest and DNA damage inducible gamma (GADD45g) is expressed at significantly lower levels in patients with MPNs, and JAK2V617F mutation and histone deacetylation contribute to its reduced expression. Downregulation of GADD45g plays a tumor-promoting role in human MPN cells. Gadd45g insufficiency in the murine hematopoietic system alone leads to significantly enhanced growth and self-renewal capacity of myeloid-biased hematopoietic stem cells, and the development of phenotypes resembling MPNs. Mechanistically, the pathogenic role of GADD45g insufficiency is mediated through a cascade of activations of RAC2, PAK1 and PI3K-AKT signaling pathways. These data characterize GADD45g deficiency as a novel pathogenic factor in MPNs. Different gene mutations have been reported as drivers for myeloproliferative neoplasms (MPN). Here, the authors show that Gadd45g insufficiency induces MPN in mouse models and associates with MPN in patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the changes of hematologic and immunological parameters in COVID-19 patients. We collected and analyzed the data of 117 patients who were laboratory confirmed as SARS-CoV-2 infection. The cases were divided into regular group, severe group and critically ill group according to the sixth edition scheme for COVID-19 diagnosis and treatment of China. The laboratory tests included blood routine, cellular and humoral immunity indices, biochemical detections and inflammatory biomarker. Compared with regular patients, severe and critically ill patients had significantly lower lymphocyte count (p < 0.01), decreased red blood cell and hemoglobin (p < 0.01), low levels of immunoglobulin G (p < 0.05) and significantly higher in D-dimer (p < 0.0001), fibrinogen (p < 0.01), white blood cell count (p < 0.01), neutrophil count (p < 0.0001), interleukin-6 (p < 0.05), C-reactive protein (p < 0.01), procalcitonin (p < 0.01), erythrocyte sedimentation rate (p < 0.05), ferritin (p < 0.01) and lactate dehydrogenase (p < 0.0001). The specific immunoglobulin G antibodies to the SARS-CoV-2 in severe and critically ill patients were significantly lower than that in regular patients (p < 0.05). Our findings suggest that the lymphocyte counts, red blood cell counts and the immunoglobulin G antibodies of COVID-19 patients were impaired to varying degrees and the blood was in a state of hypercoagulation, which were more obvious in critically ill patients. [ABSTRACT FROM AUTHOR]

Theoretical models suggest monetary policy is transmitted to commodity prices. We quantify this channel using several empirical methods under daily data. In early 2009, the US real interest rate became negative, with sample mean varying from 1.75 % (in the mid-1997 to January 28, 2009, subsample) to $$-1.50\,\%$$ (in January 29, 2009, to mid-September 2013 subsample). Gold displays higher risk-adjusted returns earlier, while copper and oil have higher risk-adjusted returns more recently. Shocks to the exchange rate and the real interest rate in VARs explain almost 30 % for oil and 32 % for copper more recently when impulse responses are more significant. The time-varying correlation of oil with the real interest rate in the more recent period is $$-0.462$$ , and its correlation with the exchange rate is $$-0.460$$ , compared to $$-0.089$$ and $$-0.120$$ , respectively, in the earlier period. Vine copula methods identify a dependence pattern of C-vine copula with t-copula in almost every pair among commodity prices, the real value of the US dollar and the US real interest rate. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly. Mitochondrial dysfunction plays an important role in the pathogenesis of PD. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a powerful transcription factor, interacting with multiple transcription factors and widely involving in the regulation of mitochondrial biogenesis, oxidative stress, and other processes. The present study investigated the neuroprotective effects and signal transduction mechanisms of the overexpression of PGC-1α on N-methyl-4-phenylpyridinium ion (MPP)-induced mitochondrial damage in SH-SY5Y cell, establishing the cell model of overexpression of PGC-1α and the cell model of PD by using adenoviral vectors and MPP. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was used to investigate the effects of MPP and adenovirus on the cell viability of SH-SY5Y cells and the cell viability of experimental groups. Western blot and real-time PCR analysis were used to detect the expression of PGC-1α. Flow cytometry and ELISA were used to detect mitochondrial membrane potential and the level of cytochrome C, respectively. The level of intracellular ATP and HO was measured by multifunctional fluorescence microplate. Western blot analysis and real-time PCR were used to observe the expression of estrogen-related receptor α (ERRα), peroxisome proliferator-activated receptor γ (PPARγ), nuclear respiratory factor (NRF)-1, and NRF-2. Confocal fluorescence analysis was used to observe subcellular localization of PGC-1α in SH-SY5Y cells under the intervention of MPP. The expression of PGC-1α messenger RNA and protein significantly increased in Adv-PGC-1α + GFP groups, compared with the control and Adv-GFP groups ( P < 0.01). The overexpression of PGC-1α could increase mitochondrial membrane potential, reduce the release of mitochondrial cytochrome C, inhibit HO production, and improve the level of ATP in SH-SY5Y cells. The trend of expression of ERRα, PPARγ, and NRF-1 was more consistent with PGC-1α, the most remarkable change is ERRα, but the expression of NRF-2 has no significant changes. Under the gradually increasing concentration of MPP, microscale PGC-1α gradually appeared in the cytoplasm of SH-SY5Y cells. The overexpression of PGC-1α can inhibit MPP-induced mitochondrial damage in SH-SY5Y cells, and PGC-1α may realize the neuroprotective effects via the ERRα, PPARγ, and NRF-1 pathway. [ABSTRACT FROM AUTHOR]

This thesis reviews the development of family therapy in Taiwan since its commence in 1969 to today, with two focuses on the status quo in practice and in training. The practice of family therapy in local hospitals, social welfare agencies and community counseling institutes are reviewed respectively, with a discussion of the challenges local family therapists encounter. The status quo of local family therapy trainings is also examined in terms of trainers, programs, professional organizations and licensure. The limitations and possible hindrances to the current professional training system are explored, and finally suggestions for the advance of local family therapy professional development in Taiwan are proposed. [ABSTRACT FROM AUTHOR]