Assembly of different length of polyubiquitins on the catalytic cysteine of E2 enzymes without E3 ligase; a novel application of non-reduced/reduced 2-dimensional electrophoresis

AbstractIn this study using non-reduced/reduced 2-dimensional electrophoresis (NR/R-2DE), we clearly demonstrated that E3-independent ubiquitination by Ube2K produced not only unanchored but also Ube2K-linked polyubiquitins through thioester and isopeptide bonds. E3-independent assembly of polyubiquitins on the catalytic cysteine of Ube2K strongly supports the possibility of ‘en bloc transfer’ for polyubiquitination. From the same analyses of E3-independent ubiquitination products by other E2s, we also found that different lengths of polyubiquitins were linked to different E2s through thioester bond; longer chains by Cdc34 like Ube2K, short chains by Ube2g2, and mono-ubiquitin by UbcH10. Our results suggest that E2s possess the different intrinsic catalytic activities for polyubiquitination

Safety and tissue yield for percutaneous native kidney biopsy according to practitioner and ultrasound technique

BACKGROUND: Although percutaneous renal biopsy remains an essential tool in the diagnosis and treatment of renal diseases, in recent times the traditional procedure of nephrologists has been performed by non-nephrologists rather than nephrologists at many institutions. The present study assessed the safety and adequacy of tissue yield during percutaneous renal biopsy according to practitioners and techniques based on ultrasound. METHODS: This study included 658 native renal biopsies performed from 2005 to 2010 at a single centre. The biopsies were performed by nephrologists or expert ultrasound radiologists using the ultrasound-marked blind or real-time ultrasound-guided techniques. RESULTS: A total of 271 ultrasound-marked blind biopsies were performed by nephrologists, 170 real-time ultrasound-guided biopsies were performed by nephrologists, and 217 real-time ultrasound-guided biopsies were performed by radiologists during the study period. No differences in post-biopsy complications such as haematoma, need for transfusion and intervention, gross haematuria, pain, or infection were observed among groups. Glomerular numbers of renal specimens from biopsies performed by nephrologists without reference to any technique were higher than those obtained from real-time ultrasound-guided biopsies performed by expert ultrasound radiologists. CONCLUSIONS: Percutaneous renal biopsy performed by nephrologists was not inferior to that performed by expert ultrasound radiologists as related to specimen yield and post-biopsy complications

Age of first experience of gender incongruence among transgender and non-binary individuals

Objective Gender incongruence (GI) is a condition in which an individual’s gender identity, role, and expression differ from their assigned sex. This study aimed to evaluate when GI first arises in transgender and non-binary individuals seeking hormone therapy and their years living untreated in South Korea. Methods This retrospective study analyzed GI patients seeking gender-affirming hormone therapy (GAHT) or surgery between 2015 and 2021. The recorded data included gender identity, legal transition status, age of onset of GI, age at the initiation of therapy, and total therapy duration. Results In total, 337 patients were enrolled, including 149 (44.2%) transgender men, 153 (45.4%) transgender women, and 35 (10.4%) non-binary individuals. The mean age of onset of GI was 10.6 years (standard deviation, 5.1). Of the total patients, 29% had an onset of GI before age 6 years (preschool), 61% before age 12 (elementary-school), and 87% before age 15 (middle-school). Patients lived with GI for almost 14 years before GAHT initiation at a median age of 23.0 years. 90% of transgender men, 82.3% of transgender women, and 85% of non-binary patients disclosed their gender identities to their families. Regarding social transition, 31.5% of transgender men, 16.3% of transgender women, and none of the non-binary patients (P<0.005) changed their legal gender markers. Conclusion Many transgender and non-binary individuals experience GI early in life. These findings emphasized the need for early evaluation, timely gender-affirming care, and more accessible legal processes for gender marker changes in South Korea, aiming to enhance the safety and well-being of these individuals

Improved survival in patients with recurrent Wilms tumor: the experience of the Seoul National University Children's Hospital

The survival in cases with relapsed Wilms tumor is dismal. Recently, however the introduction of new therapeutic agents and experimental strategies has improved the survival. We analysed the survival of patients with relapsed Wilms tumor according to the treatment period. During the early period 1983-1993, patients who had received two drugs were treated with doxorubicin and the others were treated with cisplatin and etoposide, whereas during the late period 1994-2004, patients were treated with combinations of cyclophosphamide/etoposide and carboplatin/etoposide. During the early period, 8 of 57 experienced relapse, and 8 of 41 relapsed during the late period. Only 2 patients treated during the early period survived in complete response (CR), whereas during the late period, 5 patients remained alive in CR, and 3 of those received high-dose chemotherapy (HDC) with autologous peripheral stem cell rescue (SCR). The estimated 5 yr event-free survival rate was 37.5% in the entire study group, 50% for patients in the late period, and 25% for patients in the early period (p=0.38). The survival in patients with relapsed Wilms tumor dramatically improved during the late period and HDC with SCR was one of the effective salvage strategies

PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Antifungal and antiaflatoxigenic methylenedioxy-containing compounds and piperine-like synthetic compounds

Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure-activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 mu g/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 mu g/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes.ope

Inappropriate antidiuretic hormone syndrome presenting as ectopic antidiuretic hormone-secreting gastric adenocarcinoma: a case report

INTRODUCTION: Although the syndrome of inappropriate antidiuretic hormone has connection with various malignant tumors, there are few reports associated with advanced gastric cancer. CASE PRESENTATION: We describe the case of a 63-year-old Korean male with inappropriate antidiuretic hormone syndrome due to an ectopic antidiuretic hormone-producing advanced gastric adenocarcinoma manifested with overt serum hypo-osmolar hyponatremia and high urinary sodium concentrations. His adrenal, thyroidal, and renal functioning were normal, and the hyponatremia improved following removal of the tumor. The cancer cells were immunostained and found to be positive for the antidiuretic hormone. To our knowledge, this is the first report of an antidiuretic hormone-secreting advanced gastric adenocarcinoma associated with the syndrome of inappropriate antidiuretic hormone, showing cancer cells immunostained for the antidiuretic hormone. CONCLUSIONS: Although a strong relationship between gastric cancer and the syndrome of inappropriate antidiuretic hormone remains to be established, we suggest that gastric cancer could be included as a differential diagnosis of cancer that is associated with the syndrome of antidiuretic hormone

Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life

A preterm female infant born at 27 weeks of gestation with a birth weight of 990 g developed acute hypotonia, apnea, hypotension and bradycardia mimicking septic shock syndrome at 14h after birth. Laboratory tests indicated a severe hypermagnesemia of 45 mg/dL. The renal function, complete blood count and maternal blood concentrations of magnesium were normal, and the blood cultures were negative. The patient recovered with treatment including exchange transfusion. However, the etiology of the severe hypermagnesemia remains unknown