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Jonsson Thomas posted an update 6 months, 2 weeks ago
How genetic changes are linked to morphological novelties and developmental constraints remains elusive. Here, we investigate genetic apparatuses that distinguish fish fins from tetrapod limbs by analyzing transcriptomes and open-chromatin regions (OCRs). Specifically, we compared mouse forelimb buds with the pectoral fin buds of an elasmobranch, the brown-banded bamboo shark (Chiloscyllium punctatum). A transcriptomic comparison with an accurate orthology map revealed both a mass heterochrony and hourglass-shaped conservation of gene expression between fins and limbs. Furthermore, open-chromatin analysis suggested that access to conserved regulatory sequences is transiently increased during mid-stage limb development. During this stage, stage-specific and tissue-specific OCRs were also enriched. Together, early and late stages of fin/limb development are more permissive to mutations than middle stages, which may have contributed to major morphological changes during the fin-to-limb evolution. We hypothesize that the middle stages are constrained by regulatory complexity that results from dynamic and tissue-specific transcriptional controls.The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.Common side effects of mycophenolate mofetil (MMF) are diarrhea, leukopenia, and infectious complication. The polymorphisms of enzymes affecting MMF clearance could be related to MMF toxicity, and in vitro study revealed that high MMF levels might cause endothelial dysfunction. A 7-year-old Korean male with end-stage renal disease on peritoneal dialysis due to mesangial proliferative glomerulonephritis received a kidney transplantation (KT) from a deceased donor, and immunosuppressive medications including MMF, tacrolimus, and methylprednisolone were started after KT. The patient developed oliguria immediately after surgery, and therapeutic plasmapheresis was initiated with continuous renal replacement therapy for the possibility of graft dysfunction and nephrotic syndrome relapse. Renal function recovered 4 days later, but the patient developed ascites. Diagnostic paracentesis revealed findings that were interpreted as uncomplicated ascites in cirrhosis, not of renal origin. Abdominal ultrasonography showed increased parenchymal echogenicity without cirrhotic change in the liver. Based on a case report and differential diagnosis, we replaced MMF with azathioprine, and 4 weeks later a sudden increment in urine output was detected. Eleven months after KT, the patient is free from ascites. The UGT2B7 802 polymorphism was tested, and wild-type UGT2B7 802 was detected, which is related to low MMF clearance. The low clearance of MMF by UGT2B7 802 wild-type polymorphism might have led to MMF toxicity affecting endothelial dysfunction. This case suggests that refractory ascites could be induced by MMF, and endothelial damage is a possible mechanism.The first documented case of SARS-CoV-2 infection was confirmed in South Africa (SA) in March 2020. The Western Cape (WC) province was the initial epicenter. The pandemic peaked in July 2020 when 76,851 cases were documented and 2,323 deaths reported. COVID-19 can have multisystem involvement. Acute kidney injury (AKI) is well-documented and associated with increased mortality. We report our experience as the pandemic evolved in the WC province, focusing on those patients with a SARS-CoV-2 positive test presenting with AKI. We also reviewed our chronic dialysis cohort and renal transplant recipients who tested positive to assess incidence and outcomes. All patients presenting to nephrology services at the four main public hospitals were included. Information regarding demographics, co-morbidities, medical care, laboratory data, and outcomes were recorded. There were 86 patients referred with AKI, 48 required dialysis, and 47 died. There were 52 patients admitted to the intensive care unit with AKI (37 received dialysis, 1 of whom survived). check details In those presenting with AKI, diabetes, obesity, hypertension, and HIV were the most common comorbidities. Of the 295 patients receiving chronic dialysis within our services, 31 tested positive for SARS-CoV-2, and 6 died. Of the 45 kidney transplant recipients who tested positive, 9 died. Only 3 required dialysis. In conclusion, we report a high rate of AKI and poor prognosis in those requiring kidney replacement therapy, a better prognosis than anticipated was found in our chronic dialysis cohort, and high numbers of admissions were required for renal transplant recipients.Polyuria in post-kidney transplant (KT) patients is a common condition generally attributed to delayed tubular function, fluid administration, and solute diuresis. Since excessive water intake post-KT physiologically suppresses arginine vasopressin (AVP) secretion, central diabetes insipidus (CDI) caused by deficient primary AVP release can be overlooked. Although DDAVP (desmopressin) – a selective AVP V2 receptor agonist – has been used to treat massive polyuria, CDI rarely progresses to kidney injury due to the preservation of fluid balance by thirst-dependent osmoregulation. Administration of DDAVP in post-KT recipients with mild polyuria and subclinical CDI is difficult to assess, and whether long-term use of DDAVP is beneficial for the transplanted kidney has not been established. We present the case of a 36-year-old Japanese female who was diagnosed with subclinical/partial CDI post KT. CDI was caused by a sequela of suprasellar germinoma. Graft function gradually declined without evidence of hypovolemia or hypernatremia, and a kidney biopsy revealed advanced ischemic kidney injury.
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