MEDIATOR SUBUNIT17 is required for transcriptional optimization of root system architecture in Arabidopsis.

Sucrose and auxin are well-known determinants of root system architecture (RSA). However, the factors that connect the signaling pathways evoked by these two critical factors during root development are poorly understood. In this study, we report the role of MEDIATOR SUBUNIT17 (MED17) in RSA and its involvement in the transcriptional integration of sugar and auxin signaling pathways in Arabidopsis (Arabidopsis thaliana). Sucrose regulates root meristem activation through the TARGET OF RAPAMYCIN-E2 PROMOTER BINDING FACTOR A (TOR-E2FA) pathway, and auxin regulates lateral root (LR) development through AUXIN RESPONSE FACTOR-LATERAL ORGAN BOUNDARIES DOMAIN (ARF-LBDs). Both sucrose and auxin play a vital role during primary and LR development. However, there is no clarity on how sucrose is involved in the ARF-dependent regulation of auxin-responsive genes. This study establishes MED17 as a nodal point to connect sucrose and auxin signaling. Transcription of MED17 was induced by sucrose in an E2FA/B-dependent manner. Moreover, E2FA/B interacted with MED17, which can aid in the recruitment of the Mediator complex on the target promoters. Interestingly, E2FA/B and MED17 also occupied the promoter of ARF7, but not ARF19, leading to ARF7 expression, which then activates auxin signaling and thus initiates LR development. MED17 also activated cell division in the root meristem by occupying the promoters of cell-cycle genes, thus regulating their transcription. Thus, MED17 plays an important role in relaying the transcriptional signal from sucrose to auxin-responsive and cell-cycle genes to regulate primary and lateral root development, highlighting the role of the Mediator as the transcriptional processor for optimal root system architecture in Arabidopsis.

Mediator complex: an important regulator of root system architecture.

Mediator, a multiprotein complex, is an important component of the transcription machinery. In plants, the latest reports from our group and some other studies have established that Mediator functions as a signal processor that conveys transcriptional signals from transcription factors to RNA polymerase II. It has been found to be involved in different developmental and stress-adaptation conditions ranging from embryo, root, and shoot development to flowering and senescence and also in response to different biotic and abiotic stresses. In the last one decade, significant progress has been made in understanding the role of Mediator subunits in root development. They have been shown to transcriptionally regulate development of almost all the components of root system architecture - primary root, lateral root and root hair. Their role has also been appreciated in nutrient acquisition through root. In this review, we have discussed all the known functions of Mediator subunits during root development. We have also highlighted the role of Mediator as a nodal point for processing different hormone signaling that regulate root morphogenesis and growth.

MEDIATOR SUBUNIT17 integrates jasmonate and auxin signaling pathways to regulate thermomorphogenesis.

Plant adjustment to environmental changes involves complex crosstalk between extrinsic and intrinsic cues. In the past two decades, extensive research has elucidated the key roles of PHYTOCHROME-INTERACTING FACTOR4 (PIF4) and the phytohormone auxin in thermomorphogenesis. In this study, we identified a previously unexplored role of jasmonate (JA) signaling components, the Mediator complex, and their integration with auxin signaling during thermomorphogenesis in Arabidopsis (Arabidopsis thaliana). Warm temperature induces expression of JA signaling genes including MYC2, but, surprisingly, this transcriptional activation is not JA dependent. Warm temperature also promotes accumulation of the JA signaling receptor CORONATINE INSENSITIVE1 (COI1) and degradation of the JA signaling repressor JASMONATE-ZIM-DOMAIN PROTEIN9, which probably leads to de-repression of MYC2, enabling it to contribute to the expression of MEDIATOR SUBUNIT17 (MED17). In response to warm temperature, MED17 occupies the promoters of thermosensory genes including PIF4, YUCCA8 (YUC8), INDOLE-3-ACETIC ACID INDUCIBLE19 (IAA19), and IAA29. Moreover, MED17 facilitates enrichment of H3K4me3 on the promoters of PIF4, YUC8, IAA19, and IAA29 genes. Interestingly, both occupancy of MED17 and enrichment of H3K4me3 on these thermomorphogenesis-related promoters are dependent on PIF4 (or PIFs). Altered accumulation of COI1 under warm temperature in the med17 mutant suggests the possibility of a feedback mechanism. Overall, this study reveals the role of the Mediator complex as an integrator of JA and auxin signaling pathways during thermomorphogenesis.

A 10-Year Study of the Outcome of Wilms' Tumor in Central India and Identifying Practice Gaps.

Introduction: Despite remarkable improvement in Wilms' tumor (WT) survival in Western world, sub-optimal outcome in resource-constrained settings is influenced by late presentation, larger size, and poor access to treatment. This prompted us to study the outcome at a tertiary care center and to identify the global and local practice gaps. Materials and Methods: A retrospective, observational study of WT was conducted from October 2009 to September 2019 at a tertiary care setting. Following the National Wilms' Tumor Study Group protocol, an upfront nephrectomy (unilateral resectable tumors) and preoperative chemotherapy (large/unresectable Stage I-III) were followed. The records were reviewed for demographics, stage, preoperative chemotherapy, predictive factors, and outcome. Survival curves were plotted by the Kaplan-Meier method, and analysis was performed using the SPSS software version 16. Results: One hundred and fifty-six children were included, median age was 4.1 years, with a male predominance. The most common stages of the presentation were II (40.4%) and III (34.6%). An upfront surgery was done in 27.6%, while remaining received preoperative chemotherapy. The median follow-up was 22 months, and the events included relapse in 46 (29.48%) and death in 54 (34.61%). The mean survival time was 45.7 (95% confidence interval [CI], 41.08-50.30). The 2-year overall survival was 65.38% (95% CI, 59-73), and the 2-year event-free survival was 36% (95% CI, 32-41). On comparison of the impact of preoperative chemotherapy, the survival estimates in Stages I-III and relapse rate were statistically similar, tumor size reduced significantly, and tumor spill was significantly lower (P < 0.05). Conclusion: WT is associated with late presentation, sub-optimal survival, and higher relapse in our setting associated with practice gaps related to the management including practice violations.

The kinase module of the Mediator complex: an important signalling processor for the development and survival of plants.

Mediator, a multisubunit protein complex, is a signal processor that conveys regulatory information from transcription factors to RNA polymerase II and therefore plays an important role in the regulation of gene expression. This megadalton complex comprises four modules, namely, the head, middle, tail, and kinase modules. The first three modules form the core part of the complex, whereas association of the kinase module is facultative. The kinase module is able to alter the function of Mediator and has been established as a major transcriptional regulator of numerous developmental and biochemical processes. The kinase module consists of MED12, MED13, CycC, and kinase CDK8. Upon association with Mediator, the kinase module can alter its structure and function dramatically. In the past decade, research has established that the kinase module is very important for plant growth and development, and in the fight against biotic and abiotic challenges. However, there has been no comprehensive review discussing these findings in detail and depth. In this review, we survey the regulation of kinase module subunits and highlight their many functions in plants. Coordination between the subunits to process different signals for optimum plant growth and development is also discussed.

Etiology-Based Decision-Making Protocol for Pediatric Cholelithiasis.

OBJECTIVES: We reviewed hospital records of pediatric cholelithiasis to develop an etiology-based decision-making protocol. METHODS: This retrospective study was conducted on consecutive pediatric cholelithiasis patients from July, 2014 to June, 2019 in a tertiary care center. Pediatric cholelithiasis was classified according to etiology, and the outcome of medical/surgical treatment was noted. RESULTS: Data of 354 pediatric patients were analyzed. Commonest (56.2%) etiology was idiopathic; followed by ceftriaxone pseudo-lithiasis (26.8%). Pigment stones were associated with the highest rate of complications. Non-hemolytic stones had a lower complication rate and a high rate of resolution with medical therapy. CONCLUSIONS: Hemolytic and symptomatic stones warrant an early cholecystectomy, whereas asymptomatic idiopathic stones, ceftriaxone stones, and TPN-induced stones are candidates for medical therapy under close observation.

Fabrication of a SnO2-Based Hydroelectric Cell for Green Energy Production.

The generation of electricity by dissociating water into H3O+ and OH- ions through a hydroelectric cell (HEC) without liberating any toxic waste has achieved a groundbreaking feat. Nanoporous magnesium-doped SnO2 and cobalt-doped SnO2 materials have been prepared via a novel sol-gel method. The X-ray diffraction patterns of Mg-doped SnO2 and Co-doped SnO2 completely match with those of pure SnO2, which confirms the interstitial substitution of Mg and Co in the pristine SnO2. The results shown by Brunauer-Emmett-Teller theory curves illustrate the surface area of Mg-doped SnO2 and Co-doped SnO2 to be 46.22 and 46.81 m2/g, respectively, with their pore radii being ∼3 nm. The synthesized nanoparticles were pressed into square pellets of area 4.08 cm2. A zinc electrode was pasted on one side of each pellet and silver was painted on the other side to develop the HECs. The fabricated HECs of Mg-doped SnO2 and Co-doped SnO2 with 4.08 cm2 area deliver short-circuit current, open-circuit voltage, and off-load output power of 41.69 mA, 0.787 V, and 32.81 mW and 77.52 mA, 0.454 V, and 35.19 mW, respectively. Cyclic voltammetry of both materials exhibited cathodic and anodic peaks in relation to the redox reactions taking place at Zn and silver electrodes. Nyquist curves of both HECs in the wet state confirm the ionic diffusion of split H3O+ and OH- ions as compared to the dry state. An off-load output power of 35.19 mW delivered by the HEC of Co-doped SnO2 with 4.08 cm2 area is quite promising and has great potential to replace other green energy sources.

The role of tonsillectomy in pediatric IgA nephropathy.

OBJECTIVES: To review pediatric cases of IgA nephropathy (IgAN) in 6 patients who underwent tonsillectomy and had marked improvement of their renal symptoms and to review the appropriate indications for tonsillectomy for this disease. DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: Six children (age range, 8-15 years) with renal biopsy-proved IgAN who were referred by a pediatric nephrologist for recurrent tonsillitis. INTERVENTION: Tonsillectomy. MAIN OUTCOME MEASURES: Resolution of clinical features of IgAN, including proteinuria, gross and microscopic hematuria, and stabilization of renal function. RESULTS: The 6 patients in this series had marked clinical and laboratory improvement of their nephropathy. CONCLUSIONS: In a select group of pediatric cases of IgAN with mild to moderate disease and recurrent tonsillitis, tonsillectomy can be a useful adjuvant treatment to improve urinary symptoms and renal function. IgA nephropathy is a common indication for tonsillectomy in Japan but is seen less often in the United States. Otolaryngologists should be aware of this indication for tonsillectomy.

Utility of computed tomographic renal angiogram in the management of childhood hypertension.

The purpose of this study was to evaluate the utility of computed tomography (CT) renal angiogram (CTRA) in the management of childhood hypertension. This is a retrospective study of 24 children with clinical suspicion of renovascular disease who underwent CTRA examinations. CTRA demonstrated surgically correctable etiology of hypertension in 38% of the patients [5 with renal artery stenosis (RAS) and 4 with renal pathology]. In 5 patients, CTRA findings of RAS were confirmed by catheter angiogram. CTRA missed RAS in 1 patient in whom catheter angiogram showed beaded narrowing of the renal artery. All 6 patients with RAS had resolution of hypertension immediately after angioplasty or surgery. One patient with diffuse renal artery stenosis had an ipsilateral multicystic dysplastic kidney. In this patient hypertension resolved spontaneously as the dysplastic kidney shrunk in size. Seven patients had a renal etiology for hypertension. In 3 of these patients hypertension resolved after nephrectomy. Malignant hypertension in the 4th patient with reflux nephropathy was controlled medically after she underwent bilateral ureteral reimplantation. The remaining 3 patients with renal etiology were managed medically. We found that the etiology was central for hypertension in 4 patients with brain abnormalities, obesity in 1 overweight patient, essential hypertension in 4 patients, and thoracic aorta coarctation in 1 patient. Our study showed that in all except 1 instance CTRA could diagnose a surgically correctable cause for hypertension. CTRA provided useful information for the management of pediatric hypertension in all our patients.