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Differential Expression of Iron Deficiency Responsive Rice Genes under Low Phosphorus and Iron Toxicity Conditions and Association of OsIRO3 with Yield in Acidic Soils

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Rice science 2023年第1期30卷 58-69页

作者： Ernieca Lyngdoh NONGBRI Sudip DAS karma landup bhutia Aleimo G.MOMIN Mayank RAI Wricha TYAGI School of Crop Improvement College of Post Graduate Studies in Agricultural SciencesCentral Agricultural University(Imphal)Umiam 793103India

With the hypothesis that iron(Fe) deficiency responsive genes may play a role in Fe toxicity conditions,we studied five such genes OsNAS1,OsNAS3,OsIRO2,OsIRO3 and OsYSL16 across six contrasting rice genotypes for expression under high Fe and low phosphorus(P) conditions,and sequence polymorphism.Genotypes Sahbhagi Dhan,Chakhao Poirieton and Shasharang were high yielders with no bronzing symptom visible under Fe toxic field conditions,and BAM350 and BAM811 were low yielders but did not show bronzing symptoms.Hydroponic screening revealed that the number of crown roots and root length can be traits for consideration for identifying Fe toxicity tolerance in rice genotypes.Fe contents in rice roots and shoots of a high-yielding genotype KMR3 showing leaf bronzing were significantly high.In response to 24 h high Fe stress,the expression levels of OsNAS3 were up-regulated in all genotypes except KMR3.In response to 48 h high Fe stress,the expression levels of OsNAS1 were3-fold higher in tolerant Shasharang,whereas in KMR3,it was significantly down-regulated.Even in response to 7 d excess Fe stress,the transcript abundances of OsIRO2 and OsNAS3 were contrasting in genotypes Shasharang and KMR3.This suggested that the reported Fe deficiency genes had a role in Fe toxicity and that in genotype KMR3 under excess Fe stress,there was disruption of metal homeostasis.Under the 48 h low P conditions,OsIRO2 and OsYSL16 were significantly up-regulated in Fe tolerant genotype Shasharang and in low P tolerant genotype Chakhao Poirieton,respectively.In silico sequence analysis across 3 024 rice genotypes revealed polymorphism for 4 genes.Sequencing across OsIRO3and OsNAS3 revealed nucleotide polymorphism between tolerant and susceptible genotypes for Fe toxicity.Non-synonymous single nucleotide polymorphisms and insertion/deletions(InDels) differing in tolerant and susceptible genotypes were identified.A marker targeting 25-bp InDel in OsIRO3,when run on a diverse panel of 43 rice genotypes and a biparental population,was associated

关键词： acidic soil low phosphorus iron toxicity OsNAS1 OsIRO3 rice yield

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Contrast-enhanced multidetector computed tomography features and histogram analysis can differentiate ameloblastomas from central giant cell granulomas

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World Journal of Radiology 2022年第9期14卷 329-341页

作者： Adarsh Ghosh Meyyappan Lakshmanan Smita Manchanda Ashu Seith Bhalla Prem Kumar Ongkila bhutia Asit Ranjan Mridha Department of Radiology Children's Hospital of PhiladelphiaPhiladelphiaPA 19104United States Department of Radiology All India Institute of Medical SciencesNew Delhi 110029India Department of Radiodiagnosis All India Institute of Medical SciencesNew Delhi 110029India Department of Oral&Maxillofacial Surgery All India Institute of Medical SciencesNew Delhi 110029India Department of Pathology All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India

BACKGROUND No qualitative or quantitative analysis of contrast-enhanced computed tomography(CT)images has been reported for the differentiation between ameloblastomas and central giant cell granulomas(CGCGs).AIM To describe differentiating multidetector CT(MDCT)features in CGCGs and ameloblastomas and to compare differences in enhancement of these lesions qualitatively and using histogram analysis.METHODS MDCT of CGCGs and ameloblastomas was retrospectively reviewed to evaluate qualitative imaging descriptors.Histogram analysis was used to compare the extent of enhancement of the soft tissue.Fisher’s exact tests and Mann–Whitney U test were used for statistical analysis(P49.05 HU in the tumour providing 100%sensitivity and 85%specificity in identifying a CGCG.CONCLUSION A multilocular,lytic sclerotic lesion with significant hyperenhancement in soft tissue,which spares the angle of the mandible and has matrix mineralization,should indicate prospective diagnosis of CGCG.

关键词： Ameloblastoma Granuloma Giant cell Multidetector CT

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Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 173-180页

作者： Bojana Ristic Mohd Omar Faruk Sikder Yangzom D.bhutia Vadivel Ganapathy Department of Cell Biology and Biochemistry Texas Tech University Health Sciences CenterLubbockTX 79430United States

Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.

关键词： Uric acid excretion Intestine ABCG2 Loss-of-function mutations Gouty arthritis Pharmacologic inducers

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The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy

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Asian Journal of Pharmaceutical Sciences 2014年第6期9卷 293-303页

作者： Yangzom D.bhutia Ellappan Babu Puttur D.Prasad Vadivel Ganapathy Department of Biochemistry and Molecular Biology Medical College of GeorgiaGeorgia Regents UniversityAugustaGA 30912USA

Tumor cells have an increased demand for glucose and amino acids to support their rapid growth,and also exhibit alterations in biochemical pathways that metabolize these nutrients.Transport across the plasma membrane is essential to feed glucose and amino acids into these tumor cell-selective metabolic pathways.Transfer of amino acids across biological membranes occurs via a multitude of transporters;tumor cells must upregulate one or more of these transporters to satisfy their increased demand for amino acids.Among the amino acid transporters,SLC6A14 stands out with specific functional features uniquely suited for the biological needs of the tumor cells.This transporter is indeed upregulated in tumors of epithelial origin,including colon cancer,cervical cancer,breast cancer,and pancreatic cancer.Since normal cells express this transporter only at low levels,blockade of this transporter should lead to amino acid starvation selectively in tumor cells,thus having little effect on normal cells.This offers a novel,yet logical,strategy for the treatment of cancers that are associated with upregulation of SLC6A14.In addition,a variety of amino acid-based prodrugs are recognized as substrates by SLC6A14,thus raising the possibility that anticancer drugs can be delivered into tumor cells selectively via this transporter in the form of amino acid prodrugs.This strategy allows exposure of SLC6A14-positive tumor cells to chemotherapy with minimal off-target effects.In conclusion,the amino acid transporter SLC6A14 holds great potential not only as a direct drug target for cancer therapy but also for tumor cell-selective delivery of anticancer drugs.

关键词： Essential amino acids Glutamine addiction Amino acid transporters SLC6A14 Prodrugs Cancer therapy

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Multidetector computed tomography of temporomandibular joint: A road less travelled

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World Journal of Clinical Cases 2015年第5期3卷 442-449页

作者： Shivani Pahwa Ashu Seith Bhalla Ajoy Roychaudhary Ongkila bhutia Department of Radiodiagnosis All India Institute of Medical Sciences New Delhi 110029 India Department of Oral and Maxillofacial Surgery Centre for Dental Education and ResearchAll India Institute of Medical Sciences New Delhi 110029 India

This article reviews the imaging anatomy of temporomandibular joint(TMJ), describes the technique of multi-detector computed tomography(MDCT) of the TMJ, and describes in detail various osseous pathologic afflictions affecting the joint. Traumatic injuries affecting the mandibular condyle are most common, followed by joint ankylosis as a sequel to arthritis. The congenital anomalies are less frequent, hemifacial microsomia being the most commonly encountered anomaly involving the TMJ. Neoplastic afflictions of TMJ are distinctly uncommon, osteochondroma being one of the most common lesions. MDCT enables comprehensive evaluation of osseous afflictions of TMJ, and is a valuable tool for surgical planning. Sagittal, coronal and 3D reformatted images well depict osseous TMJ lesions, and their relationship to adjacent structures.

关键词： Temporomandibular joint Temporomandibular joint trauma Congenital anomalies of temporomandibular joint Temporomandibular joint arthritis Multi-detector computed tomography

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Chronic exposure to excess iron promotes EMT and cancer via p53 loss in pancreatic cancer

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 237-251页

作者： Yangzom D.bhutia Jiro Ogura Paul J.Grippo Carolina Torres Toshihiro Sato Mitchell Wachtel Sabarish Ramachandran Ellappan Babu Sathish Sivaprakasam Devaraja Rajasekaran Bradley Schniers Nhu On Logan Smoot Muthusamy Thangaraju Jaya P.Gnana-Prakasam Vadivel Ganapathy Department of Cell Biology and Biochemistry Texas Tech University Health Sciences CenterLubbockTX 79430USA Department of Pharmaceutical Sciences Tohoku University Hospital1-1 Seiryo-machiAoba-kuSendaiMiyagi 980-8574Japan Department of Medicine University of Illinois at ChicagoChicagoIL 60607USA Department of Surgical Pathology Texas Tech University Health Sciences CenterLubbockTX 79430USA Department of Biological Sciences Texas Tech UniversityLubbockTX 79410USA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTX 79410USA Department of Biochemistry and Molecular Biology Augusta UniversityAugustaGA 30912USA Department of Ophthalmology St.Louis UniversitySt.LouisMO 63104USA

Based on the evidence that hemochromatosis, an iron-overload disease, drives hepatocellular carcinoma, we hypothesized that chronic exposure to excess iron, either due to genetic or environmental causes, predisposes an individual to cancer. Using pancreatic cancer as our primary focus, we employed cell culture studies to interrogate the connection between excess iron and cancer, and combined in vitro and in vivo studies to explore the connection further. Ferric ammonium citrate was used as an exogenous iron source. Chronic exposure to excess iron induced epithelial-mesenchymal transition(EMT) in normal and cancer cell lines, loss of p53, and suppression of p53 transcriptional activity evidenced from decreased expression of p53 target genes(p21, cyclin D1, Bax, SLC7A11). To further extrapolate our cell culture data, we generated EL-KrasG12D( EL-Kras) mouse(pancreatic neoplastic mouse model) expressing Hfe+/+ and Hfe-/- genetic background. p53 target gene expression decreased in EL-Kras/Hfe-/- mouse pancreas compared to EL-Kras/Hfe+/+ mouse pancreas. Interestingly, the incidence of acinar-to-ductal metaplasia and cystic pancreatic neoplasms(CPN) decreased in EL-Kras/Hfe-/- mice, but the CPNs that did develop were larger in these mice than in EL-Kras/Hfe+/+ mice. In conclusion, these in vitro and in vivo studies support a potential role for chronic exposure to excess iron as a promoter of more aggressive disease via p53 loss and SLC7A11 upregulation within pancreatic epithelial cells.

关键词： SLC7A11 p53 Iron Heme Epithelial-mesenchymal transition

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craniofacial 软骨肉瘤的二个稀罕案例

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World Journal of Radiology 2012年第6期4卷 283-285页

作者： Pankaj Gupta Ashu Seith Bhalla Venkat Karthikeyan Ongkila bhutia Department of Radiodiagnosis All India Institute of Medical Sciences110029 New DelhiIndia Department of Otorhinolaryngology All India Institute of Medical Sciences110029 New DelhiIndia Department of Orthodontics All India Institute of Medical Sciences110029 New DelhiIndia

The craniofacial region is a rare site for chondrosarcomas.These tumors may have osseous or extraosseous origin.Extraosseous chondrosarcomas have the same histological features as osseous chondrosarcomas.Chondrosarcomas usually present in the fifth to seventh decades of life,although several cases with younger age at presentation have been reported.They usually present as a painless mass that gradually progresses to various complaints,such visual impairment,nasal obstruction,and dental abnormalities.In this article,we present two cases of chondrosarcoma occurring at rather unusual locations.It is important to keep this rare malignancy in the list of differential diagnoses for a mass in the head and neck region,as these tumors may not always show the features typical of this malignancy.

关键词： Craniofacial chondrosarcoma Extraosseous chondrosarcomas Head and neck chondrosarcomas Head and neck masses Sinonasal chondrosarcoma

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