The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum ...disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.
Objective
Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential ...mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA.
Although grounded theory and qualitative content analysis are similar in some respects, they differ as well; yet the differences between the two have rarely been made clear in the literature. The ...purpose of this article was to clarify ambiguities and reduce confusion about grounded theory and qualitative content analysis by identifying similarities and differences in the two based on a literature review and critical reflection on the authors’ own research. Six areas of difference emerged: (a) background and philosophical base, (b) unique characteristics of each method, (c) goals and rationale of each method, (d) data analysis process, (e) outcomes of the research, and (f) evaluation of trustworthiness. This article provides knowledge that can assist researchers and students in the selection of appropriate research methods for their inquiries.
Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross‐sectional studies. We explored the effects of relative skeletal muscle mass and ...changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population‐based 7‐year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check‐up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight–adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7‐year follow‐up period. Using Cox proportional hazard analysis, compared with the lowest sex‐specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio AHR = 0.44, 95% confidence interval CI = 0.38‐0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02‐4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59‐0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90‐6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.
To clarify transmissibility of the severe acute respiratory syndrome coronavirus 2 Omicron variant, we determined serial intervals and secondary attack rates among household contacts in South Korea. ...Mean serial interval for 12 transmission pairs was 2.9 days, and secondary attack rate among 25 households was 50.0%, raising concern about a rapid surge in cases.
MYH9, a widely expressed gene encoding nonmuscle myosin heavy chain, is also expressed in podocytes and is associated with glomerular pathophysiology. However, the mechanisms underlying MYH9-related ...glomerular diseases associated with proteinuria are poorly understood. Therefore, we investigated the role and mechanism of MYH9 in diabetic kidney injury. MYH9 expression was decreased in glomeruli from diabetic patients and animals and in podocytes treated with Ang II in vitro. Ang II treatment and siRNA-mediated MYH9 knockdown in podocytes resulted in actin cytoskeleton reorganization, reduced cell adhesion, actin-associated protein downregulation, and increased albumin permeability. Ang II treatment increased NOX4 expression and ROS generation. The Ang II receptor blocker losartan and the ROS scavenger NAC restored MYH9 expression in Ang II-treated podocytes, attenuated disrupted actin cytoskeleton and decreased albumin permeability. Furthermore, MYH9 overexpression in podocytes restored the effects of Ang II on the actin cytoskeleton and actin-associated proteins. Ang II-mediated TRPC6 activation reduced MYH9 expression. These results suggest that Ang II-mediated MYH9 depletion in diabetic nephropathy may increase filtration barrier permeability by inducing structural and functional podocyte injury through TRPC6-mediated Ca
influx by NOX4-mediated ROS generation. These findings reveal a novel MYH9 function in maintaining urinary filtration barrier integrity. MYH9 may be a potential target for treating diabetic nephropathy.
Abstract
A submerged dielectric barrier discharge plasma reactor (underwater DBD) has been used to inactivate biofilm produced by three different food-borne pathogens, namely
Escherichia coli
O157:H7 ...(ATCC 438),
Cronobacter sakazakii
(ATCC 29004), and
Staphylococcus aureus
(KCCM 40050). The inactivation that were obtained after 90 minutes of plasma operation were found to measure 5.50 log CFU/coupon, 6.88 log CFU/coupon and 4.20 log CFU/coupon for
Escherichia coli
O157:H7 (ATCC 438),
Cronobacter sakazakii
(ATCC 29004), and
Staphylococcus aureus
(KCCM 40050), respectively. Secondary Electron Images (SEI) obtained from Field Emission Scanning Electron Microscopy (FE-SEM) show the biofilm morphology and its removal trend by plasma operation at different time intervals. An attenuated total reflectance Fourier transform infrared (ATR-FTIR) measurement was performed to elucidate the biochemical changes that occur on the bacterial cell and extracellular polymeric substance (EPS) of biofilm during the plasma inactivation process. The ATR-FTIR measurement shows the gradual reduction of carbohydrates, proteins, and lipid and DNA peak regions with increased plasma exposure time. The presence of an EPS layer on the upper surface of the biofilm plays a negative and significant role in its removal from stainless steel (SS) coupons.
To evaluate the influence of myoma characteristics on cesarean myomectomy and to demonstrate its additional advantages.
Retrospective data were collected from 292 women with myomas who had undergone ...cesarean section at Kangnam Sacred Heart Hospital between 2007 and 2019. We performed subgroup analysis according to the type, weight, number, and size of myomas. Preoperative and postoperative hemoglobin levels, operative time, estimated blood loss, length of hospital stay, incidence of transfusion, uterine artery embolization, ligation, hysterectomy, and postoperative complications were compared among subgroups.
There were 119 patients who had cesarean myomectomy and 173 who had cesarean section only. An increase in postoperative hospitalization and operation time was observed in the cesarean myomectomy group compared to that in the caesarean section only group (mean difference, 0.7 days, p = 0.01, 13.5 minutes, p <0.001). Estimated blood loss, hemoglobin differences, and transfusion rates were higher in the cesarean myomectomy than in the cesarean section only group. There were no differences in postoperative complications (fever, bladder injury, and ileus) between the two groups. No hysterectomy cases were reported in the cesarean myomectomy group. In subgroup analysis, the larger and heavier the myoma, the higher the risk of bleeding that led to transfusion. Estimated blood loss, differences in hemoglobin, and transfusion rate increased depending on myoma size and weight. A significant increase in postoperative hospitalization was observed in women with larger and heavier myomas. However, there was no statistical difference among the three types of myomas.
In cesarean myomectomy, larger (≥ 10 cm), and heavier myomas (≥ 500 g), were associated with postoperative outcomes, but not the number or type of myoma. The safety of cesarean myomectomy is not inferior to that of caesarean section only, considering its positive effects such as gynecological symptom relief and avoidance of the next surgery.
Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier ...integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.
PDF
