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1.  Tracking the migration of the Indian continent using the carbonate clumped isotope technique on Phanerozoic soil carbonates 
Scientific Reports  2016;6:22187.
Approximately 140 million years ago, the Indian plate separated from Gondwana and migrated by almost 90° latitude to its current location, forming the Himalayan-Tibetan system. Large discrepancies exist in the rate of migration of Indian plate during Phanerozoic. Here we describe a new approach to paleo-latitudinal reconstruction based on simultaneous determination of carbonate formation temperature and δ18O of soil carbonates, constrained by the abundances of 13C-18O bonds in palaeosol carbonates. Assuming that the palaeosol carbonates have a strong relationship with the composition of the meteoric water, δ18O carbonate of palaeosol can constrain paleo-latitudinal position. Weighted mean annual rainfall δ18O water values measured at several stations across the southern latitudes are used to derive a polynomial equation: δ18Ow = −0.006 × (LAT)2 − 0.294 × (LAT) − 5.29 which is used for latitudinal reconstruction. We use this approach to show the northward migration of the Indian plate from 46.8 ± 5.8°S during the Permian (269 M.y.) to 30 ± 11°S during the Triassic (248 M.y.), 14.7 ± 8.7°S during the early Cretaceous (135 M.y.), and 28 ± 8.8°S during the late Cretaceous (68 M.y.). Soil carbonate δ18O provides an alternative method for tracing the latitudinal position of Indian plate in the past and the estimates are consistent with the paleo-magnetic records which document the position of Indian plate prior to 135 ± 3 M.y.
doi:10.1038/srep22187
PMCID: PMC4773985  PMID: 26931069
2.  Hepatitis B Virus X Protein Upregulates hELG1/ ATAD5 Expression through E2F1 in Hepatocellular Carcinoma 
The precise mechanism by which HBx protein of hepatitis B virus (HBV) impacts on hepato-carcinogenesis remain largely elusive despite strong evidences for its' involvement in the process. Here, we have investigated the role of HBx on expression of a novel gene hELG1/ATAD5, which is required for genome maintenance and its' importance in hepatocarcinogenesis. This study has for the first time showed that the expression of this gene was significantly higher in human cancer such as HBV-associated hepatocellular carcinoma (HCC) and in different HCC cell lines compared to normal liver. In addition, a significant elevation in ATAD5 expression was also found in HBx transfected HCC cell lines implicating HBx mediated transcriptional regulation on ATAD5. Using different deletion mutant constructs of putative promoter, the active promoter region was first identified here and subsequently the regulatory region of HBx was mapped by promoter-luciferase assay. But ChIP assay with anti-HBx antibody revealed that HBx was not physically present in ATAD5 transcription machinery whereas anti-E2F1 antibody showed the presence of E2F1 in the complex. Luciferase assay with E2F1 binding site mutant had further confirmed it. Moreover, both loss-and gain-of-function studies of ATAD5 showed that ATAD5 could enhance HBV production in transfected cells whereas knock down of ATAD5 increased the sensitivity of HCC cell line to chemotherapeutics 5-fluorouracil. Overall, this data suggests that a positive feedback loop regulation between ATAD5 and HBV contributed to both viral replication and chemo-resistance of HCC cells.
doi:10.7150/ijbs.12310
PMCID: PMC4679396  PMID: 26722215
hepatitis B virus; hepatocellular carcinoma
3.  Correlation of intracranial atherosclerosis with carotid stenosis in ischemic stroke patients 
Introduction:
Carotid stenosis is a major risk factor for ischemic stroke. However, the effect of carotid stenosis on the site of stroke is still under investigation.
Aims:
This study aimed to elucidate how the presence of carotid stenosis influenced the pattern of stroke and also how it interacted with other risk factors for stroke.
Materials and Methods:
Thirty-eight patients with ischemic stroke were included in this study and were investigated with carotid artery Doppler and magnetic resonance angiography for carotid stenosis and intracranial stenosis in the circle of Willis, respectively. Other known risk factors of stroke were also studied in and compared between the subgroups with and without carotid stenosis.
Results:
In patients without carotid stenosis, anterior cerebral artery was the commonest site of stenosis. In patients with carotid stenosis, middle cerebral artery was the commonest site of stenosis. Overall, middle cerebral artery was the commonest territory of stroke. Patients with hypertension, diabetes and history of smoking had preferential stenosis of the anterior cerebral artery.
doi:10.4103/0972-2327.165473
PMCID: PMC4683879  PMID: 26713012
Carotid stenosis; intracranial atherosclerosis; ischemic stroke
4.  Prevalence of Skin Changes in Diabetes Mellitus and its Correlation with Internal Diseases: A Single Center Observational Study 
Indian Journal of Dermatology  2015;60(5):465-469.
Background and Aim:
This single-center observational cross-sectional study has been done in an attempt to find out the prevalence of various skin manifestations in diabetes patients (DM) and their correlation with diabetes control and complications.
Materials and Methods:
Skin manifestations present over 12 months among those attend diabetes clinic were included in the study. Apart from demographic data and type, patients were also screened for micro vascular complications and control of diabetes over last 3 months.
Results and Discussion:
Sixty (n = 60) diabetes patisents (Type 1 DM, 9 patients and Type 2 DM 51 patients) have been found to have various skin lesions. Thirty-one (51.67%) patients presented with infectious conditions, vascular complications were present in 21 (35%) and dermatomes belonging to the miscellaneous group were present in 50 (83.33%) patients. Pyoderma, diabetic dermopathy, and pruritus without skin lesions were found to be most common manifestations in infective, vascular and miscellaneous group, respectively. Higher level of HB1AC was found in patient with diabetic bulla (10.5 ± 0), scleredema (9.75 ± 0.77), lichen planus (9.3 ± 1.6), and acanthosis nigricans (9.15 ± 0.89). Patients with psoriasis and vitiligo had statistically significant lower level of glycosylated hemoglobin (P =< 0.001 and 0.03, respectively). However, no association of any kind of skin manifestation with DM with other microangiopathic complications was found in this study.
doi:10.4103/0019-5154.164363
PMCID: PMC4601413  PMID: 26538693
Diabetes mellitus; micro vascular complications; observational study; skin manifestations
5.  miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression 
Carcinogenesis  2012;33(10):1897-1908.
Increasing evidence shows the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines, MDA-MB-231 and MCF-7, to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3′-untranslated region (UTR) and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 was significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet that blocks miR-21, thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.
doi:10.1093/carcin/bgs198
PMCID: PMC3463153  PMID: 22678116
6.  Fish oil prevents breast cancer cell metastasis to bone 
The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in ω-3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression, including breast cancer. The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone, here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone, indicating suppression of cancer cell metastasis to bone. These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture. The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored. Aberrant increased expression of CD44 is associated with generation of cancer stem cells, which contribute to metastasis of breast cancer cells. We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism. Furthermore, we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice, which were fed fish oil diet than those in control diet. Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone. Our results identify a novel function of the fish oil active components, DHA and EPA, which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion.
doi:10.1016/j.bbrc.2010.10.063
PMCID: PMC2993881  PMID: 20971068
7.  Palonosetron and palonosetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: A prospective, randomized, double-blind comparative study 
Background:
Laparoscopic cholecystectomy (LC) is associated with a high risk of postoperative nausea and vomiting (PONV). Palonosetron is a newer 5HT3 receptor antagonist, which is routinely used in our institution to prevent PONV in patients scheduled for LC, under general anesthesia (GA). We formulated this study to find out whether the palonosetron and dexamethasone combination will be a better choice than palonosetron alone in the prevention of PONV.
Materials and Methods:
Sixty American Society of Anesthesiologists (ASA) physical status I and II patients, scheduled for LC under GA, were randomized to receive either palonosetron or a combination of palonosetron and dexamethasone. The number of complete responders (no emesis, no requirement of rescue anti-emetic medication) and the four-point nausea score was recorded at 2, 6, 24, 48 h postoperatively and the data was analyzed statistically.
Results:
The number of complete responders, as well as the nausea score, did not vary significantly (P=0.718) between the two groups over the 48-h postoperative period.
Conclusions:
The palonosetron and dexamethasone combination was not more effective than palonosetron alone in the prevention of PONV, in patients undergoing LC under GA.
doi:10.4103/0259-1162.94751
PMCID: PMC4173407  PMID: 25885375
Complete responders; four-point nausea score; 5HT3 receptor antagonist
8.  SIMVASTATIN INDUCES DEREPRESSION OF PTEN EXPRESSION VIA NFκB TO INHIBIT BREAST CANCER CELL GROWTH 
Cellular signalling  2010;22(5):749-758.
Sustained activation of Akt kinase acts as a focal regulator to increase cell growth and survival, which cause tumorigenesis including breast cancer. Statins, potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, display anticancer activity. The molecular mechanisms by which statins block cancer cell growth are poorly understood. We demonstrate that in the tumors derived from MDA-MB-231 human breast cancer cell xenografts, simvastatin significantly inhibited phosphorylation of Akt with concomitant attenuation of expression of the anti-apoptotic protein BclXL. In many cancer cells, BclXL is a target of NFκB. Simvastatin inhibited the DNA binding and transcriptional activities of NF κ B resulting in marked reduction in transcription of BclXL. Signals transmitted by anti-neoplastic mechanism implanted in the cancer cells serve to obstruct the initial outgrowth of tumors. One such mechanism represents the action of the tumor suppressor protein PTEN, which negatively regulates Akt kinase activity. We provide the first evidence for significantly increased levels of PTEN in the tumors of simvastatin-administered mice. Importantly, simvastatin markedly prevented binding of NFκB to the two canonical recognition elements, NFRE-1 and NFRE-2 present in the PTEN promoter. Contrary to the transcriptional suppression of BclXL, simvastatin significantly increased the transcription of PTEN. Furthermore, expression of NFκ B p65 subunit inhibited transcription of PTEN, resulting in reduced protein expression, which leads to enhanced phosphorylation of Akt. Taken together, our data present a novel bifaceted mechanism where simvastatin acts on a nodal transcription factor NFκ B, which attenuates the expression of anti-apoptotic BclXL and simultaneously derepresses the expression of anti-proliferative/proapoptotic tumor suppressor PTEN to prevent breast cancer cell growth.
doi:10.1016/j.cellsig.2009.12.010
PMCID: PMC2826504  PMID: 20060890
Statin; Breast tumor; BclXL; Akt kinase
9.  Patent foramen ovale and atrial septal aneurysm in cryptogenic stroke 
Postgraduate Medical Journal  2007;83(977):173-177.
Up to 40% of acute ischaemic strokes in young adults are cryptogenic in nature, that is, no cause is determined. In more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm. The commonest method of investigation is echocardiography (preferably transoesophageal echocardiography). On the basis of available evidence, low risk patients are treated with antiplatelet agents and high risk patients with warfarin. There are inconclusive data on the efficacy of PFO closure to prevent stroke recurrence. However, if there is recurrent stroke or intolerance to medical therapy, percutaneous closure is carried out.
doi:10.1136/pgmj.2006.051094
PMCID: PMC2599987  PMID: 17344571
atrial septal defect; cryptogenic stroke; patent foramen ovale
10.  Oxidative stress-induced cell cycle blockage and a protease-independent programmed cell death in microaerophilic Giardia lamblia 
Giardia lamblia is a microaerophilic human gastrointestinal parasite and considered as an early-diverged eukaryote. In vitro oxidative stress generation plays a significant role in cell cycle progression and cell death of this parasite. In the present study hydrogen peroxide, metronidazole, and a modified growth medium without cysteine and ascorbic acid have been chosen as oxidative stress-inducing agents. Cell cycle progression has been found to be regulated by different types of oxidative stresses. Apoptosis is not an established pathway in Giardia, which is devoid of ideal mitochondria, but in the present investigation, apoptosis-like programmed cell death has been found by the experiments like AnnexinV-FITC assay, DNA fragmentation pattern, etc. On the contrary, Caspase-9 assay, which confirms the caspase-mediated apoptotic pathway, has been found to be negative in all the stress conditions. Protease inhibitor assay confirmed that, even in absence of any proteases, programmed cell death does occur in this primitive eukaryote. All these results signify a novel pathway of programmed suicidal death in Giardia lamblia under oxidative stress. This is the first demonstration of protease-independent programmed cell death regulation in Giardia exclusive for its own specialties.
PMCID: PMC2769235  PMID: 19920926
Giardia lamblia; oxidative stress; reactive oxygen species; programmed cell death; apoptosis; early branching eukaryotes
11.  Interaction of small ribosomal and transfer RNAs with a protein from Leishmania donovani. 
Nucleic Acids Research  1994;22(9):1663-1669.
Using synthetic antisense RNA from the 5'-untranslated region of the beta-tubulin gene as probe in gel retardation assays, a heat stable RNA-binding factor was identified in promastigotes of the kinetoplastid protozoan Leishmania donovani. The same or similar factors interact with several small ribosomal RNA (srRNA) species and, more weakly, with tRNA, as shown by binding and competition experiments. Deletion analysis indicated involvement of repeated purine-rich motifs on the antisense RNA, in the reaction. Related, conserved motifs occur on at least two of the srRNAs. By a modified Western blot assay, the RNA-binding species was identified as a single, small polypeptide. The activity is apparently specific for the promastigote stage of the parasite, being undetectable in amastigotes. The properties of this RNA-binding factor suggest that it is a novel, previously uncharacterized protein.
Images
PMCID: PMC308046  PMID: 8202369
12.  Anti-oxidative effect of turmeric on frying characteristics of soybean oil 
Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen. This study aimed to find out the thermal and oxidative stability of soybean oil when potatoes marinated with turmeric were deep fried in the oil. Two sets of experiment were carried out. In one set, 1 L of oil was heated for 24 h (8 h daily for 3 consecutive days) and 200 g of potato chips without any marination were fried each time twice daily. Foods were fried in batches to replicate the commercial practice of the food industries. The temperature maintained during the whole experiment was at 180–190 °C i.e. at the frying temperature. About 50 ml of the oil sample was collected after every 4 h. In the second set, another 1 L of soybean oil was heated for 24 h in the similar manner and potato chips marinated with turmeric was fried twice daily. Oil samples were collected as before and comparative studies were done. The chemical parameters like acid value, peroxide value, content of 4-hydroxy-2-trans-nonenal (HNE) and fatty acid composition for all the oil samples of each set were determined. The comparative studies on peroxide value and content of HNE revealed that the antioxidant property of curcumin in turmeric helped in reducing the oxidation of the oil initially, but with increase in duration of time, the antioxidant potency got gradually reduced. The loss of unsaturated fatty acids were calculated from the fatty acid composition and it was found that loss of unsaturation in soybean oil where turmeric marinated potatoes were fried was 6.37 % while the controlled one showed 7.76 % loss after 24 h of heating. These results indicated higher thermal and oxidative stability of the soybean oil in presence of turmeric. However, the antioxidant effect gradually decreased with increase in duration of heating.
doi:10.1007/s13197-013-1156-y
PMCID: PMC4348280  PMID: 25745253
Turmeric; Curcumin; Soybean oil; Deep frying; Antioxidant
13.  Vascular Transformation of Bilateral Cervical Lymph Node Sinuses: A Rare Entity Masquerading as Tumor Recurrence 
Journal of Maxillofacial & Oral Surgery  2014;14(Suppl 1):397-400.
Vascular transformation of sinuses (VTS) is a rare and reactive vasoproliferative disorder infrequently affecting the cervical lymph nodes. It is characterized by effacement of nodal architecture by variable expansion of the subcapsular, intermediate, and medullary sinuses. We report a very rare and unique case of VTS in bilateral cervical lymph nodes along with angiolipomatous hamartoma in a postoperative patient of squamous cell carcinoma of buccal mucosa clinically masquerading as tumor recurrence. To the best of our knowledge, only 15 cases of VTS have been reported in cervical lymph nodes till date and associated angiolipomatous or angiomyomatous hamartoma-like area was noted only in two cases of cervical lymph node VTS.
doi:10.1007/s12663-014-0637-5
PMCID: PMC4379302  PMID: 25848149
Vascular transformation of sinuses; Cervical; Post-operative; Post-radiotherapy; Hamartoma
14.  Quantitative estimates of dietary intake with special emphasis on snacking pattern and nutritional status of free living adults in urban slums of Delhi: impact of nutrition transition 
BMC nutrition  2015;1:22.
Background
The nutritional landscape of India is experiencing the fallout of urbanization and globalization. The changes are manifest in dietary patterns as well as health outcomes. The study aimed at assessing household dietary intake pattern with special emphasis on snacking pattern, anthropometric and lipid profiles in low socio-economic status households in an urban slum of Delhi.
Methods
Community based cross-sectional study in 260 households of a purposively selected urban slum in North-East district of Delhi, India. Family dietary surveys including consumption pattern of commercial food products rich in Partially Hydrogenated Vegetable Oils (PHVOs), 24 h dietary recall and assessment of dietary diversity using Household Diet Diversity Scores (HDDS) were done. Assessment of nutritional status using anthropometric and lipid profile on a subsample (n =130) were also conducted.
Results
Median energy and fat intake were adequate. Micronutrient intake was found to be inadequate for vitamin A, riboflavin, calcium and folate. PHVO usage was low (<20 % households). Milk (39 %), green leafy vegetables (25 %) and fruits (25 %) intake were below recommendations. Mean HDDS was 7.87. Prevalence of overweight/obesity was high (66.7 %). Lipid profile showed mean HDL-C levels lower than recommendations for females.
Conclusion
Community based awareness programs for prevention of non-communicable diseases should incorporate healthy diet and lifestyle practices with emphasis on quantity and quality of nutrient intake. This must be considered as an integral part of chronic disease prevention strategy for underprivileged communities in urban India.
doi:10.1186/s40795-015-0018-6
PMCID: PMC4763040  PMID: 26918196
Overweight; Fat consumption; Snacks; Household dietary diversity; Lipid profile
15.  Production of bioethanol as useful biofuel through the bioconversion of water hyacinth (Eichhornia crassipes) 
3 Biotech  2016;6(1):70.
Water hyacinth (Eichhornia crassipes) represents a promising candidate for fuel ethanol production in tropical countries because of their high availability and high biomass yield. Bioconversion of such biomass to bioethanol could be wisely managed through proper technological approach. In this work, pretreatment of water hyacinth (10 %, w/v) with dilute sulfuric acid (2 %, v/v) at high temperature and pressure was integrated in the simulation and economic assessment of the process for further enzymatic saccharification was studied. The maximum sugar yield (425.6 mg/g) through enzymatic saccharification was greatly influenced by the solid content (5 %), cellulase load (30 FPU), incubation time (24 h), temperature (50 °C), and pH (5.5) of the saccharifying medium. Central composite design optimized an ethanol production of 13.6 mg/ml though a mixed fermentation by Saccharomyces cerevisiae (MTCC 173) and Zymomonas mobilis (MTCC 2428). Thus the experiment imparts an economic value to water hyacinths that are cleared from choking waterways.
doi:10.1007/s13205-016-0385-y
PMCID: PMC4754295
Eichhornia crassipes; Pretreatment; Mixed fermentation; Central composite design; Bioethanol
17.  A 5-year Journey with Cutis Laxa in an Indian Child: The De Barsy Syndrome Revisited 
Indian Journal of Dermatology  2016;61(1):81-84.
De Barsy syndrome (DBS), synonymously known as autosomal recessive cutis laxa type III, is an extremely rare condition clinically characterized by cutis laxa, a progeroid appearance, and ophthalmologic abnormalities. We present here an account of 5-year follow-up since the birth of an Indian boy with DBS, who had a few rare and unusual manifestations. In addition, our case probably represents the first reported case of DBS from India.
doi:10.4103/0019-5154.174031
PMCID: PMC4763701  PMID: 26955101
Cutis laxa; De Barsy syndrome; progeria
18.  High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived Lipopolysaccharide 
PLoS ONE  2015;10(11):e0141109.
A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham operated animals on normal diet (control) and WD (WD). To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin (PM), a known LPS antagonist, and curcumin (CU), a compound known to ameliorate chronic kidney disease (CKD), was given to Nx animals on western diet (Nx+WD+PM and Nx+WD+CU, respectively). Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.
doi:10.1371/journal.pone.0141109
PMCID: PMC4651339  PMID: 26580567
20.  Deciphering the mode of action of a mutant Allium sativum Leaf Agglutinin (mASAL), a potent antifungal protein on Rhizoctonia solani 
BMC Microbiology  2015;15:237.
Background
Mutant Allium sativum leaf agglutinin (mASAL) is a potent, biosafe, antifungal protein that exhibits fungicidal activity against different phytopathogenic fungi, including Rhizoctonia solani.
Methods
The effect of mASAL on the morphology of R.solani was monitored primarily by scanning electron and light microscopic techniques. Besides different fluorescent probes were used for monitoring various intracellular changes associated with mASAL treatment like change in mitochondrial membrane potential (MMP), intracellular accumulation of reactive oxygen species (ROS) and induction of programmed cell death (PCD). In addition ligand blot followed by LC-MS/MS analyses were performed to detect the putative interactors of mASAL.
Results
Knowledge on the mode of function for any new protein is a prerequisite for its biotechnological application. Detailed morphological analysis of mASAL treated R. solani hyphae using different microscopic techniques revealed a detrimental effect of mASAL on both the cell wall and the plasma membrane. Moreover, exposure to mASAL caused the loss of mitochondrial membrane potential (MMP) and the subsequent intracellular accumulation of reactive oxygen species (ROS) in the target organism. In conjunction with this observation, evidence of the induction of programmed cell death (PCD) was also noted in the mASAL treated R. solani hyphae.
Furthermore, we investigated its interacting partners from R. solani. Using ligand blots followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses, we identified different binding partners including Actin, HSP70, ATPase and 14-3-3 protein.
Conclusions
Taken together, the present study provides insight into the probable mode of action of the antifungal protein, mASAL on R. solani which could be exploited in future biotechnological applications.
Electronic supplementary material
The online version of this article (doi:10.1186/s12866-015-0549-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s12866-015-0549-7
PMCID: PMC4623900  PMID: 26502719
Mutant Allium sativum leaf agglutinin; Rhizoctonia solani; Antifungal proteins; Molecular targets; PCD; Plasma membrane permeabilization; LC-MS/MS
21.  microRNA-21-induced Dissociation of PDCD4 from Rictor Contributes to Akt-IKKβ-mTORC1 axis to Regulate Select Renal Cancer Cell Invasion 
Experimental cell research  2014;328(1):99-117.
Renal cancer metastasis may result from oncogenic forces that contribute to the primary tumor. We have recently identified microRNA-21 as an oncogenic driver of renal cancer cells. The mechanism by which miR-21 controls renal cancer cell invasion is poorly understood. We show that miR-21 directly downregulates the proapoptotic protein PDCD4 to increase migration and invasion of ACHN and 786-O renal cancer cells as a result of phosphorylation/activation of Akt and IKKβ, which activate NFκB-dependent transcription. Constitutively active (CA) Akt or CA IKKβ blocks PDCD4-mediated inhibition and restores renal cancer cell migration and invasion. PDCD4 inhibits mTORC1 activity, which was reversed by CA IKKβ. Moreover, CA mTORC1 restores cell migration and invasion inhibited by PDCD4- and dominant negative IKKβ. Moreover, PDCD4 negatively regulates mTORC2-dependent Akt phosphorylation upstream of this cascade. We show that PDCD4 forms a complex with rictor, an exclusive component of mTORC2, and that this complex formation is reduced in renal cancer cells due to increased miR-21 expression resulting in enhanced phosphorylation of Akt. Thus our results identify a previously unrecognized signaling node where high miR-21 levels reduce rictor-PDCD4 interaction to increase phosphorylation of Akt and contribute to metastatic fitness of renal cancer cells.
doi:10.1016/j.yexcr.2014.06.022
PMCID: PMC4177976  PMID: 25016284
Renal carcinoma; miR-21; Akt kinase; mTOR
22.  Effect of Different Human Papillomavirus Serological and DNA Criteria on Vaccine Efficacy Estimates 
Lang Kuhs, Krystle A. | Porras, Carolina | Schiller, John T. | Rodriguez, Ana Cecilia | Schiffman, Mark | Gonzalez, Paula | Wacholder, Sholom | Ghosh, Arpita | Li, Yan | Lowy, Douglas R. | Kreimer, Aimée R. | Poncelet, Sylviane | Schussler, John | Quint, Wim | van Doorn, Leen-Jan | Sherman, Mark E. | Sidawy, Mary | Herrero, Rolando | Hildesheim, Allan | Safaeian, Mahboobeh | Lang Kuhs, Krystle A. | Schiller, John T. | Schiffman, Mark | Wacholder, Sholom | Lowy, Douglas R. | Kreimer, Aimée R. | Sherman, Mark E. | Hildesheim, Allan | Safaeian, Mahboobeh | Porras, Carolina | Rodriguez, Ana Cecilia | Gonzalez, Paula | Herrero, Rolando | Gonzalez, Paula | Herrero, Rolando | Ghosh, Arpita | Li, Yan | Poncelet, Sylviane | Schussler, John | Quint, Wim | van Doorn, Leen-Jan | Sidawy, Mary | Self, Steve | Benavides, Adriana | Calzada, Luis Diego | Karron, Ruth | Nayar, Ritu | Roach, Nancy | Cain, Joanna | Davey, Diane | DeMets, David | Fuster, Francisco | Gershon, Ann | Holly, Elizabeth | Raventós, Henriette | Rida, Wasima | Rosero-Bixby, Luis | Suthers, Kristen | Lara, Silvia | Thomas, Sarah | Alfaro, Mario | Barrantes, Manuel | Concepción Bratti, M. | Cárdenas, Fernando | Cortés, Bernal | Espinoza, Albert | Estrada, Yenory | González, Paula | Guillén, Diego | Herrero, Roland | Jiménez, Silvia E. | Morales, Jorge | Villegas, Luis | Morera, Lidia Ana | Pérez, Elmer | Porras, Carolina | Rodríguez, Ana Cecilia | Rivas, Libia | Freer, Enrique | Bonilla, José | García-Piñeres, Alfanso | Silva, Sandra | Atmella, Ivannia | Ramírez, Margarita | Hildesheim, Allan | Kreimer, Aimée R. | Lowy, Douglas R. | Macklin, Nora | Schiffman, Mark | Schiller, John T. | Sherman, Mark | Solomon, Diane | Wacholder, Sholom | Pinto, Ligia | Kemp, Troy | Eklund, Claire | Hutchinson, Martha | Sidawy, Mary | Quint, Wim | van Doorn, Leen-Jan
American Journal of Epidemiology  2014;180(6):599-607.
Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naïve subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naïve subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naïve subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences.
doi:10.1093/aje/kwu168
PMCID: PMC4157699  PMID: 25139208
human papillomavirus; methodological differences; naïve population; vaccine efficacy
23.  Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation 
The Biochemical journal  2011;433(2):393-402.
BMP-2 (bone morphogenetic protein-2) promotes differentiation of osteoblast precursor cells to mature osteoblasts that form healthy bone. In the present study, we demonstrate a novel mechanism of BMP-2-induced osteoblast differentiation. The antioxidant NAC (N-acetyl-L-cysteine) and the flavoprotein enzyme NAD(P)H oxidase inhibitor DPI (diphenyleneiodonium) preventedBMP-2-stimulated alkaline phosphatase expression and mineralized bone nodule formation inmouse 2T3 pre-osteoblasts. BMP-2 elicited a rapid generation of ROS (reactive oxygen species) concomitant with increased activation of NAD(P)H oxidase. NAC and DPI inhibited BMP-2-induced ROS production and NAD(P)H oxidase activity respectively. NAD(P)H oxidases display structurally similar catalytic subunits (Nox1–5) with differential expression in various cells. We demonstrate that 2T3 pre-osteoblasts predominantly express the Nox4 isotype of NAD(P)H oxidase. To extend this finding, we tested the functional effects of Nox4. Adenovirus-mediated expression of dominant-negative Nox4 inhibited BMP-2-induced alkaline phosphatase expression. BMP-2 promotes expression of BMP-2 for maintenance of the osteoblast phenotype. NAC and DPI significantly blocked BMP-2-stimulated expression of BMP2 mRNA and protein due to a decrease in BMP2 gene transcription. Dominant-negative Nox4 also mimicked this effect of NAC and DPI. Our results provide the first evidence for a new signalling pathway linking BMP-2-stimulated Nox4-derived physiological ROS to BMP-2 expression and osteoblast differentiation.
doi:10.1042/BJ20100357
PMCID: PMC4539275  PMID: 21029048
bone morphogenetic protein-2 (BMP-2); bone morphogenetic protein-2 gene autoregulation; bone morphogenetic protein-2 signalling; osteoblast differentiation; reactive oxygen species
24.  Insulin sensitivity index (ISI0, 120) potentially linked to carbon isotopes of breath CO2 for pre-diabetes and type 2 diabetes 
Scientific Reports  2015;5:11959.
New strategies for an accurate and early detection of insulin resistance are important to delay or prevent the acute onset of type 2 diabetes (T2D). Currently, insulin sensitivity index (ISI0,120) is considered to be a viable invasive method of whole-body insulin resistance for use in clinical settings in comparison with other invasive sensitivity indexes like homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). To investigate how these sensitivity indexes link the 13C/12C-carbon isotopes of exhaled breath CO2 to pre-diabetes (PD) and type 2 diabetes in response to glucose ingestion, we studied excretion dynamics of 13C/12C-isotopic fractionations of breath CO2. Here, we show that 13C/12C-isotope ratios of breath CO2 were well correlated with blood glucose, insulin, glycosylated-hemoglobin as well as with HOMA-IR and 1/QUICKI. Conversely, the strongest correlation was observed between 1/ISI0,120 and breath CO2 isotopes. Consequently, we determined several optimal diagnostic cut-off points of 1/ISI0,120 and 13CO2/12CO2-isotope ratios to distinctively track the evolution of PD prior to the onset of T2D. Our findings suggest that isotopic breath CO2 is a novel method for accurate estimation of ISI0,120 and thus may open new perspectives into the isotope-specific non-invasive evaluation of insulin resistance for large-scale real-time diabetes screening purposes.
doi:10.1038/srep11959
PMCID: PMC4493706  PMID: 26148706
25.  Fine needle aspiration cytology of non-hematological neoplasms in pediatric age group: Our experience 
Background:
The role of aspiration cytology has largely been ignored in pediatric population. The present study was undertaken to evaluate the role of fine needle aspiration cytology (FNAC) in non-hematological neoplasms in children in our institution, which is a rural tertiary care center.
Materials and Methods:
A total of 88 cases of non-hematological pediatric mass lesions were studied in which cytopathological diagnosis could be corroborated with histopathology.
Results:
Out of all the cases, 70 (80%) cases were benign tumors and 18 (20%) were malignant tumors. Fibroadenoma (37.9%) comprised the majority of cases in the benign category while small round cell tumors (SRCTs) (44.4%) comprised the majority of cases in the malignant category. Definite diagnosis could be offered based on the cytomorphology in 79.5% cases, while in 20.5% of cases only a broad cytological classification could be offered. Among the malignant lesions, FNAC showed 100% sensitivity while a specific diagnosis was made in 90% of cases.
Conclusion:
FNAC proved to be a rapid and fairly accurate tool in diagnosing non-hematological tumors in the pediatric age group.
doi:10.4103/0970-9371.168841
PMCID: PMC4687206  PMID: 26729976
Fine needle aspiration cytology (FNAC); non-hematological neoplasms; pediatric

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