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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  Polymorphisms in CaSR and CLDN14 Genes Associated with Increased Risk of Kidney Stone Disease in Patients from the Eastern Part of India 
PLoS ONE  2015;10(6):e0130790.
Kidney stone disease (KSD) is a major clinical problem imposing a large burden for both healthcare and economy globally. In India, the prevalence of kidney stone disease is rapidly increasing. This study aimed to evaluate the association between genetic defects in vitamin D receptor (VDR), calcium sensing receptor (CaSR) and claudin 14 (CLDN14) genes and kidney stone disease in patients from eastern India. We enrolled 200 consecutive kidney stone patients (age 18–60 years) (cases) and their corresponding sex and age matched 200 normal individuals (controls). To identify genetic variants responsible for KSD, we performed sequence analysis of VDR, CaSR and CLDN14 genes. Four non-synonymous (rs1801725, rs1042636, rs1801726 and rs2228570), one synonymous (rs219780) and three intronic single nucleotide polymorphisms (SNPs) (rs731236, rs219777 and rs219778) were identified. Genotype and allele frequency analysis of these SNPs revealed that, rs1801725 (Ala986Ser), rs1042636 (Arg990Gly) of CaSR gene and rs219778, rs219780 (Thr229Thr) of CLDN14 gene were significantly associated with KSD. Serum calcium levels were significantly higher in subjects carrying 986Ser allele and calcium excretion was higher in subjects bearing 990Gly allele. In conclusion, rs1801725, rs1042636, rs219778 and rs219780 SNPs were associated with kidney stone risk in patients from the eastern part of India.
doi:10.1371/journal.pone.0130790
PMCID: PMC4480968  PMID: 26107257
10.  A comparative evaluation of the performance of commercially available rapid immunochromatographic tests for the diagnosis of visceral leishmaniasis in Bangladesh 
Parasites & Vectors  2015;8:331.
Background
Accurate and early diagnosis of Visceral Leishmaniasis (VL) is a prerequisite for proper treatment and restricting disease propagation in enldemic foci. An rK39 antigen-based immunochromatographic test is now recommended for its diagnostic accuracy and operational feasibility at point of care. In endemic regions of Bangladesh, rK39 or rKE16 antigen-based Rapid Diagnostic Tests (RDTs) are routinely performed on whole blood for diagnosis of VL. However, manufacturer’s instructions require use of serum. Therefore, we wanted to assess whether the diagnostic accuracy of these RDTs is as good on whole blood as on serum.
Methods
We evaluated and compared the sensitivity and specificity of five different commercially available RDTs on whole blood and on serum. We enrolled 30 VL patients, 35 endemic healthy controls and 30 Tuberculosis (TB) patients in our study from Mymensingh, a hyper-endemic region in Bangladesh.
Results
The sensitivity of all RDTs ranged between 96.67 % (95 % CI: 82.72-99.44 %) and 100 % (95 % CI: 96.34-100 %). The specificity ranged between 93.85 % (95 % CI: 84.97-98.26 %) and 98.46 % (95 % CI: 91.69-99.74 %), except for the Onsite leishmania Ab (Rev B) kit which showed markedly lower specificity (31.25-58.46 %). There was no significant difference in sensitivity and specificity between blood and serum. The Cohen kappa index (k >0.97) indicated excellent agreement.
Conclusions
We conclude from the study that the use of blood for RDT in lieu of serum is appropriate for diagnosis of VL in peripheral endemic regions provided the manufacturer recommendations are followed and the RDT is of good quality.
doi:10.1186/s13071-015-0935-x
PMCID: PMC4474327  PMID: 26077956
Immunochromatographic test; Diagnosis; Visceral leishmaniasis; Bangladesh
11.  Measurement of pion, kaon and proton production in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s} = 7$$\end{document}s=7 TeV 
Adam, J. | Adamová, D. | Aggarwal, M. M. | Rinella, G. Aglieri | Agnello, M. | Agrawal, N. | Ahammed, Z. | Ahmed, I. | Ahn, S. U. | Aimo, I. | Aiola, S. | Ajaz, M. | Akindinov, A. | Alam, S. N. | Aleksandrov, D. | Alessandro, B. | Alexandre, D. | Molina, R. Alfaro | Alici, A. | Alkin, A. | Alme, J. | Alt, T. | Altinpinar, S. | Altsybeev, I. | Prado, C. Alves Garcia | Andrei, C. | Andronic, A. | Anguelov, V. | Anielski, J. | Antičić, T. | Antinori, F. | Antonioli, P. | Aphecetche, L. | Appelshäuser, H. | Arcelli, S. | Armesto, N. | Arnaldi, R. | Aronsson, T. | Arsene, I. C. | Arslandok, M. | Augustinus, A. | Averbeck, R. | Azmi, M. D. | Bach, M. | Badalà, A. | Baek, Y. W. | Bagnasco, S. | Bailhache, R. | Bala, R. | Baldisseri, A. | Ball, M. | Pedrosa, F. Baltasar Dos Santos | Baral, R. C. | Barbano, A. M. | Barbera, R. | Barile, F. | Barnaföldi, G. G. | Barnby, L. S. | Barret, V. | Bartalini, P. | Bartke, J. | Bartsch, E. | Basile, M. | Bastid, N. | Basu, S. | Bathen, B. | Batigne, G. | Camejo, A. Batista | Batyunya, B. | Batzing, P. C. | Bearden, I. G. | Beck, H. | Bedda, C. | Behera, N. K. | Belikov, I. | Bellini, F. | Martinez, H. Bello | Bellwied, R. | Belmont, R. | Belmont-Moreno, E. | Belyaev, V. | Bencedi, G. | Beole, S. | Berceanu, I. | Bercuci, A. | Berdnikov, Y. | Berenyi, D. | Bertens, R. A. | Berzano, D. | Betev, L. | Bhasin, A. | Bhat, I. R. | Bhati, A. K. | Bhattacharjee, B. | Bhom, J. | Bianchi, L. | Bianchi, N. | Bianchin, C. | Bielčík, J. | Bielčíková, J. | Bilandzic, A. | Biswas, S. | Bjelogrlic, S. | Blanco, F. | Blau, D. | Blume, C. | Bock, F. | Bogdanov, A. | Bøggild, H. | Boldizsár, L. | Bombara, M. | Book, J. | Borel, H. | Borissov, A. | Borri, M. | Bossú, F. | Botje, M. | Botta, E. | Böttger, S. | Braun-Munzinger, P. | Bregant, M. | Breitner, T. | Broker, T. A. | Browning, T. A. | Broz, M. | Brucken, E. J. | Bruna, E. | Bruno, G. E. | Budnikov, D. | Buesching, H. | Bufalino, S. | Buncic, P. | Busch, O. | Buthelezi, Z. | Buxton, J. T. | Caffarri, D. | Cai, X. | Caines, H. | Diaz, L. Calero | Caliva, A. | Villar, E. Calvo | Camerini, P. | Carena, F. | Carena, W. | Castellanos, J. Castillo | Castro, A. J. | Casula, E. A. R. | Cavicchioli, C. | Sanchez, C. Ceballos | Cepila, J. | Cerello, P. | Chang, B. | Chapeland, S. | Chartier, M. | Charvet, J. L. | Chattopadhyay, S. | Chattopadhyay, S. | Chelnokov, V. | Cherney, M. | Cheshkov, C. | Cheynis, B. | Barroso, V. Chibante | Chinellato, D. D. | Chochula, P. | Choi, K. | Chojnacki, M. | Choudhury, S. | Christakoglou, P. | Christensen, C. H. | Christiansen, P. | Chujo, T. | Chung, S. U. | Cicalo, C. | Cifarelli, L. | Cindolo, F. | Cleymans, J. | Colamaria, F. | Colella, D. | Collu, A. | Colocci, M. | Balbastre, G. Conesa | Valle, Z. Conesa del | Connors, M. E. | Contreras, J. G. | Cormier, T. M. | Morales, Y. Corrales | Maldonado, I. Cortés | Cortese, P. | Cosentino, M. R. | Costa, F. | Crochet, P. | Albino, R. Cruz | Cuautle, E. | Cunqueiro, L. | Dahms, T. | Dainese, A. | Danu, A. | Das, D. | Das, I. | Das, S. | Dash, A. | Dash, S. | De, S. | Caro, A. De | Cataldo, G. de | Cuveland, J. de | Falco, A. De | Gruttola, D. De | Marco, N. De | Pasquale, S. De | Deisting, A. | Deloff, A. | Dénes, E. | D’Erasmo, G. | Bari, D. Di | Mauro, A. Di | Nezza, P. Di | Corchero, M. A. Diaz | Dietel, T. | Dillenseger, P. | Divià, R. | Djuvsland, Ø. | Dobrin, A. | Dobrowolski, T. | Gimenez, D. Domenicis | Dönigus, B. | Dordic, O. | Dubey, A. K. | Dubla, A. | Ducroux, L. | Dupieux, P. | Ehlers, R. J. | Elia, D. | Engel, H. | Erazmus, B. | Erhardt, F. | Eschweiler, D. | Espagnon, B. | Estienne, M. | Esumi, S. | Eum, J. | Evans, D. | Evdokimov, S. | Eyyubova, G. | Fabbietti, L. | Fabris, D. | Faivre, J. | Fantoni, A. | Fasel, M. | Feldkamp, L. | Felea, D. | Feliciello, A. | Feofilov, G. | Ferencei, J. | Téllez, A. Fernández | Ferreiro, E. G. | Ferretti, A. | Festanti, A. | Figiel, J. | Figueredo, M. A. S. | Filchagin, S. | Finogeev, D. | Fionda, F. M. | Fiore, E. M. | Fleck, M. G. | Floris, M. | Foertsch, S. | Foka, P. | Fokin, S. | Fragiacomo, E. | Francescon, A. | Frankenfeld, U. | Fuchs, U. | Furget, C. | Furs, A. | Girard, M. Fusco | Gaardhøje, J. J. | Gagliardi, M. | Gago, A. M. | Gallio, M. | Gangadharan, D. R. | Ganoti, P. | Gao, C. | Garabatos, C. | Garcia-Solis, E. | Gargiulo, C. | Gasik, P. | Germain, M. | Gheata, A. | Gheata, M. | Ghosh, P. | Ghosh, S. K. | Gianotti, P. | Giubellino, P. | Giubilato, P. | Dziadus, E. Gladysz | Glässel, P. | Ramirez, A. Gomez | Zamora, P. González | Gorbunov, S. | Görlich, L. | Gotovac, S. | Grabski, V. | Graczykowski, L. K. | Grelli, A. | Grigoras, A. | Grigoras, C. | Grigoriev, V. | Grigoryan, A. | Grigoryan, S. | Grinyov, B. | Grion, N. | Grosse-Oetringhaus, J. F. | Grossiord, J.-Y. | Grosso, R. | Guber, F. | Guernane, R. | Guerzoni, B. | Gulbrandsen, K. | Gulkanyan, H. | Gunji, T. | Gupta, A. | Gupta, R. | Haake, R. | Haaland, Ø. | Hadjidakis, C. | Haiduc, M. | Hamagaki, H. | Hamar, G. | Hanratty, L. D. | Hansen, A. | Harris, J. W. | Hartmann, H. | Harton, A. | Hatzifotiadou, D. | Hayashi, S. | Heckel, S. T. | Heide, M. | Helstrup, H. | Herghelegiu, A. | Corral, G. Herrera | Hess, B. A. | Hetland, K. F. | Hilden, T. E. | Hillemanns, H. | Hippolyte, B. | Hristov, P. | Huang, M. | Humanic, T. J. | Hussain, N. | Hussain, T. | Hutter, D. | Hwang, D. S. | Ilkaev, R. | Ilkiv, I. | Inaba, M. | Ionita, C. | Ippolitov, M. | Irfan, M. | Ivanov, M. | Ivanov, V. | Izucheev, V. | Jacobs, P. M. | Jahnke, C. | Jang, H. J. | Janik, M. A. | Jayarathna, P. H. S. Y. | Jena, C. | Jena, S. | Bustamante, R. T. Jimenez | Jones, P. G. | Jung, H. | Jusko, A. | Kalinak, P. | Kalweit, A. | Kamin, J. | Kang, J. H. | Kaplin, V. | Kar, S. | Uysal, A. Karasu | Karavichev, O. | Karavicheva, T. | Karpechev, E. | Kebschull, U. | Keidel, R. | Keijdener, D. L. D. | Keil, M. | Khan, K. H. | Khan, M. M. | Khan, P. | Khan, S. A. | Khanzadeev, A. | Kharlov, Y. | Kileng, B. | Kim, B. | Kim, D. W. | Kim, D. J. | Kim, H. | Kim, J. S. | Kim, M. | Kim, M. | Kim, S. | Kim, T. | Kirsch, S. | Kisel, I. | Kiselev, S. | Kisiel, A. | Kiss, G. | Klay, J. L. | Klein, C. | Klein, J. | Klein-Bösing, C. | Kluge, A. | Knichel, M. L. | Knospe, A. G. | Kobayashi, T. | Kobdaj, C. | Kofarago, M. | Köhler, M. K. | Kollegger, T. | Kolojvari, A. | Kondratiev, V. | Kondratyeva, N. | Kondratyuk, E. | Konevskikh, A. | Kouzinopoulos, C. | Kovalenko, O. | Kovalenko, V. | Kowalski, M. | Kox, S. | Meethaleveedu, G. Koyithatta | Kral, J. | Králik, I. | Kravčáková, A. | Krelina, M. | Kretz, M. | Krivda, M. | Krizek, F. | Kryshen, E. | Krzewicki, M. | Kubera, A. M. | Kučera, V. | Kucheriaev, Y. | Kugathasan, T. | Kuhn, C. | Kuijer, P. G. | Kulakov, I. | Kumar, J. | Kumar, L. | Kurashvili, P. | Kurepin, A. | Kurepin, A. B. | Kuryakin, A. | Kushpil, S. | Kweon, M. J. | Kwon, Y. | Pointe, S. L. La | Rocca, P. La | Fernandes, C. Lagana | Lakomov, I. | Langoy, R. | Lara, C. | Lardeux, A. | Lattuca, A. | Laudi, E. | Lea, R. | Leardini, L. | Lee, G. R. | Lee, S. | Legrand, I. | Lehnert, J. | Lemmon, R. C. | Lenti, V. | Leogrande, E. | Monzón, I. León | Leoncino, M. | Lévai, P. | Li, S. | Li, X. | Lien, J. | Lietava, R. | Lindal, S. | Lindenstruth, V. | Lippmann, C. | Lisa, M. A. | Ljunggren, H. M. | Lodato, D. F. | Loenne, P. I. | Loggins, V. R. | Loginov, V. | Loizides, C. | Lopez, X. | Torres, E. López | Lowe, A. | Lu, X.-G. | Luettig, P. | Lunardon, M. | Luparello, G. | Maevskaya, A. | Mager, M. | Mahajan, S. | Mahmood, S. M. | Maire, A. | Majka, R. D. | Malaev, M. | Cervantes, I. Maldonado | Malinina, L. | Mal’Kevich, D. | Malzacher, P. | Mamonov, A. | Manceau, L. | Manko, V. | Manso, F. | Manzari, V. | Marchisone, M. | Mareš, J. | Margagliotti, G. V. | Margotti, A. | Margutti, J. | Marín, A. | Markert, C. | Marquard, M. | Martin, N. A. | Blanco, J. Martin | Martinengo, P. | Martínez, M. I. | Martínez García, G. | Pedreira, M. Martinez | Martynov, Y. | Mas, A. | Masciocchi, S. | Masera, M. | Masoni, A. | Massacrier, L. | Mastroserio, A. | Masui, H. | Matyja, A. | Mayer, C. | Mazer, J. | Mazzoni, M. A. | Mcdonald, D. | Meddi, F. | Menchaca-Rocha, A. | Meninno, E. | Pérez, J. Mercado | Meres, M. | Miake, Y. | Mieskolainen, M. M. | Mikhaylov, K. | Milano, L. | Milosevic, J. | Minervini, L. M. | Mischke, A. | Mishra, A. N. | Miśkowiec, D. | Mitra, J. | Mitu, C. M. | Mohammadi, N. | Mohanty, B. | Molnar, L. | Zetina, L. Montaño | Montes, E. | Morando, M. | Godoy, D. A. Moreira De | Moretto, S. | Morreale, A. | Morsch, A. | Muccifora, V. | Mudnic, E. | Mühlheim, D. | Muhuri, S. | Mukherjee, M. | Müller, H. | Mulligan, J. D. | Munhoz, M. G. | Murray, S. | Musa, L. | Musinsky, J. | Nandi, B. K. | Nania, R. | Nappi, E. | Naru, M. U. | Nattrass, C. | Nayak, K. | Nayak, T. K. | Nazarenko, S. | Nedosekin, A. | Nellen, L. | Ng, F. | Nicassio, M. | Niculescu, M. | Niedziela, J. | Nielsen, B. S. | Nikolaev, S. | Nikulin, S. | Nikulin, V. | Noferini, F. | Nomokonov, P. | Nooren, G. | Norman, J. | Nyanin, A. | Nystrand, J. | Oeschler, H. | Oh, S. | Oh, S. K. | Ohlson, A. | Okatan, A. | Okubo, T. | Olah, L. | Oleniacz, J. | Silva, A. C. Oliveira Da | Oliver, M. H. | Onderwaater, J. | Oppedisano, C. | Velasquez, A. Ortiz | Oskarsson, A. | Otwinowski, J. | Oyama, K. | Ozdemir, M. | Pachmayer, Y. | Pagano, P. | Paić, G. | Pajares, C. | Pal, S. K. | Pan, J. | Pandey, A. K. | Pant, D. | Papikyan, V. | Pappalardo, G. S. | Pareek, P. | Park, W. J. | Parmar, S. | Passfeld, A. | Paticchio, V. | Paul, B. | Pawlak, T. | Peitzmann, T. | Costa, H. Pereira Da | Filho, E. Pereira De Oliveira | Peresunko, D. | Lara, C. E. Pérez | Peskov, V. | Pestov, Y. | Petráček, V. | Petrov, V. | Petrovici, M. | Petta, C. | Piano, S. | Pikna, M. | Pillot, P. | Pinazza, O. | Pinsky, L. | Piyarathna, D. B. | Płoskoń, M. | Planinic, M. | Pluta, J. | Pochybova, S. | Podesta-Lerma, P. L. M. | Poghosyan, M. G. | Polichtchouk, B. | Poljak, N. | Poonsawat, W. | Pop, A. | Porteboeuf-Houssais, S. | Porter, J. | Pospisil, J. | Prasad, S. K. | Preghenella, R. | Prino, F. | Pruneau, C. A. | Pshenichnov, I. | Puccio, M. | Puddu, G. | Pujahari, P. | Punin, V. | Putschke, J. | Qvigstad, H. | Rachevski, A. | Raha, S. | Rajput, S. | Rak, J. | Rakotozafindrabe, A. | Ramello, L. | Raniwala, R. | Raniwala, S. | Räsänen, S. S. | Rascanu, B. T. | Rathee, D. | Razazi, V. | Read, K. F. | Real, J. S. | Redlich, K. | Reed, R. J. | Rehman, A. | Reichelt, P. | Reicher, M. | Reidt, F. | Ren, X. | Renfordt, R. | Reolon, A. R. | Reshetin, A. | Rettig, F. | Revol, J.-P. | Reygers, K. | Riabov, V. | Ricci, R. A. | Richert, T. | Richter, M. | Riedler, P. | Riegler, W. | Riggi, F. | Ristea, C. | Rivetti, A. | Rocco, E. | Cahuantzi, M. Rodríguez | Manso, A. Rodriguez | Røed, K. | Rogochaya, E. | Rohr, D. | Röhrich, D. | Romita, R. | Ronchetti, F. | Ronflette, L. | Rosnet, P. | Rossi, A. | Roukoutakis, F. | Roy, A. | Roy, C. | Roy, P. | Montero, A. J. Rubio | Rui, R. | Russo, R. | Ryabinkin, E. | Ryabov, Y. | Rybicki, A. | Sadovsky, S. | Šafařík, K. | Sahlmuller, B. | Sahoo, P. | Sahoo, R. | Sahoo, S. | Sahu, P. K. | Saini, J. | Sakai, S. | Saleh, M. A. | Salgado, C. A. | Salzwedel, J. | Sambyal, S. | Samsonov, V. | Castro, X. Sanchez | Šándor, L. | Sandoval, A. | Sano, M. | Santagati, G. | Sarkar, D. | Scapparone, E. | Scarlassara, F. | Scharenberg, R. P. | Schiaua, C. | Schicker, R. | Schmidt, C. | Schmidt, H. R. | Schuchmann, S. | Schukraft, J. | Schulc, M. | Schuster, T. | Schutz, Y. | Schwarz, K. | Schweda, K. | Scioli, G. | Scomparin, E. | Scott, R. | Seeder, K. S. | Seger, J. E. | Sekiguchi, Y. | Selyuzhenkov, I. | Senosi, K. | Seo, J. | Serradilla, E. | Sevcenco, A. | Shabanov, A. | Shabetai, A. | Shadura, O. | Shahoyan, R. | Shangaraev, A. | Sharma, A. | Sharma, N. | Shigaki, K. | Shtejer, K. | Sibiriak, Y. | Siddhanta, S. | Sielewicz, K. M. | Siemiarczuk, T. | Silvermyr, D. | Silvestre, C. | Simatovic, G. | Simonetti, G. | Singaraju, R. | Singh, R. | Singha, S. | Singhal, V. | Sinha, B. C. | Sinha, T. | Sitar, B. | Sitta, M. | Skaali, T. B. | Slupecki, M. | Smirnov, N. | Snellings, R. J. M. | Snellman, T. W. | Søgaard, C. | Soltz, R. | Song, J. | Song, M. | Song, Z. | Soramel, F. | Sorensen, S. | Spacek, M. | Spiriti, E. | Sputowska, I. | Stassinaki, M. Spyropoulou | Srivastava, B. K. | Stachel, J. | Stan, I. | Stefanek, G. | Steinpreis, M. | Stenlund, E. | Steyn, G. | Stiller, J. H. | Stocco, D. | Strmen, P. | Suaide, A. A. P. | Sugitate, T. | Suire, C. | Suleymanov, M. | Sultanov, R. | Šumbera, M. | Symons, T. J. M. | Szabo, A. | Toledo, A. Szanto de | Szarka, I. | Szczepankiewicz, A. | Szymanski, M. | Takahashi, J. | Tanaka, N. | Tangaro, M. A. | Takaki, J. D. Tapia | Peloni, A. Tarantola | Tariq, M. | Tarzila, M. G. | Tauro, A. | Muñoz, G. Tejeda | Telesca, A. | Terasaki, K. | Terrevoli, C. | Teyssier, B. | Thäder, J. | Thomas, D. | Tieulent, R. | Timmins, A. R. | Toia, A. | Trogolo, S. | Trubnikov, V. | Trzaska, W. H. | Tsuji, T. | Tumkin, A. | Turrisi, R. | Tveter, T. S. | Ullaland, K. | Uras, A. | Usai, G. L. | Utrobicic, A. | Vajzer, M. | Vala, M. | Palomo, L. Valencia | Vallero, S. | Maarel, J. Van Der | Hoorne, J. W. Van | Leeuwen, M. van | Vanat, T. | Vyvre, P. Vande | Varga, D. | Vargas, A. | Vargyas, M. | Varma, R. | Vasileiou, M. | Vasiliev, A. | Vauthier, A. | Vechernin, V. | Veen, A. M. | Veldhoen, M. | Velure, A. | Venaruzzo, M. | Vercellin, E. | Limón, S. Vergara | Vernet, R. | Verweij, M. | Vickovic, L. | Viesti, G. | Viinikainen, J. | Vilakazi, Z. | Baillie, O. Villalobos | Vinogradov, A. | Vinogradov, L. | Vinogradov, Y. | Virgili, T. | Vislavicius, V. | Viyogi, Y. P. | Vodopyanov, A. | Völkl, M. A. | Voloshin, K. | Voloshin, S. A. | Volpe, G. | Haller, B. von | Vorobyev, I. | Vranic, D. | Vrláková, J. | Vulpescu, B. | Vyushin, A. | Wagner, B. | Wagner, J. | Wang, H. | Wang, M. | Wang, Y. | Watanabe, D. | Weber, M. | Weber, S. G. | Wessels, J. P. | Westerhoff, U. | Wiechula, J. | Wikne, J. | Wilde, M. | Wilk, G. | Wilkinson, J. | Williams, M. C. S. | Windelband, B. | Winn, M. | Yaldo, C. G. | Yamaguchi, Y. | Yang, H. | Yang, P. | Yano, S. | Yasnopolskiy, S. | Yin, Z. | Yokoyama, H. | Yoo, I.-K. | Yurchenko, V. | Yushmanov, I. | Zaborowska, A. | Zaccolo, V. | Zaman, A. | Zampolli, C. | Zanoli, H. J. C. | Zaporozhets, S. | Zarochentsev, A. | Závada, P. | Zaviyalov, N. | Zbroszczyk, H. | Zgura, I. S. | Zhalov, M. | Zhang, H. | Zhang, X. | Zhang, Y. | Zhao, C. | Zhigareva, N. | Zhou, D. | Zhou, Y. | Zhou, Z. | Zhu, H. | Zhu, J. | Zhu, X. | Zichichi, A. | Zimmermann, A. | Zimmermann, M. B. | Zinovjev, G. | Zyzak, M.
The measurement of primary \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pi ^{\pm }$$\end{document}π±, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$K^{\pm }$$\end{document}K±, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p$$\end{document}p and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\overline{{p}}}$$\end{document}p¯ production at mid-rapidity (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$|y| <$$\end{document}|y|< 0.5) in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$=$$\end{document}= 7 TeV performed with a large ion collider experiment at the large hadron collider (LHC) is reported. Particle identification is performed using the specific ionisation energy-loss and time-of-flight information, the ring-imaging Cherenkov technique and the kink-topology identification of weak decays of charged kaons. Transverse momentum spectra are measured from 0.1 up to 3 GeV/\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$c$$\end{document}c for pions, from 0.2 up to 6 GeV/\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$c$$\end{document}c for kaons and from 0.3 up to 6 GeV/\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$c$$\end{document}c for protons. The measured spectra and particle ratios are compared with quantum chromodynamics-inspired models, tuned to reproduce also the earlier measurements performed at the LHC. Furthermore, the integrated particle yields and ratios as well as the average transverse momenta are compared with results at lower collision energies.
doi:10.1140/epjc/s10052-015-3422-9
PMCID: PMC4446008  PMID: 26041975
12.  Burden and Correlates of HIV among Men Who Have Sex with Men in West Bengal, India: Analysis of Sentinel Surveillance Data 
PLoS ONE  2015;10(5):e0127232.
Background
Little is known about the socio-behavioral risk factors for HIV acquisition among hard-to-reach men who have sex with men (MSM) population in India, particularly from the densely populated eastern part. Thus to measure the burden and correlates of HIV among MSM in West Bengal state of eastern India, a cross-sectional analysis of the national HIV Sentinel Surveillance (HSS) data was conducted.
Methods
In 2011, between July and September, involving all sentinel sites of the state, 1237 consenting MSM were anonymously interviewed and tested for HIV following national guidelines. Using a short, structured questionnaire, information was collected on socio-behavioral factors along with sexual practices and was analyzed to determine burden of HIV and the role of its socio-behavioral correlates on HIV acquisition.
Results
Among participants, mean age was 23.4 years, 44.55% were “Kothis” (usually receptive partner) and 25.1% admitted receiving money for sex with man. HIV sero-positivity was 5.09%. Using logistic regression method, for both bivariate and multivariate (with saturated model) analyses, transport-workers [adjusted odds ratio (AOR)=8.95, 95% confidence interval (95%CI): 1.09-73.71), large business-owners/self-employed (AOR=8.46, 95%CI: 1.25-57.49), small business-owners/cultivators (AOR=7.90, 95%CI: 1.67-37.38), those who visited the sentinel site for official purposes (AOR=7.60, 95%CI: 1.21-47.83) and paying money for having sex with men (AOR=3.03, 95%CI: 1.10-8.33) were strongly associated with higher HIV sero-positivity with than their counterparts. Using the parsimonious model for multivariate analysis, Kothis (AOR=4.64, 95%CI: 1.03-20.89), paying (AOR=2.96, 95%CI: 1.15-7.58) or receiving (AOR=2.06, 95%CI: 1.06-3.99) money for having sex with a man were associated with higher risk of HIV.
Conclusions
Focused intervention targeting the high risk MSM subgroups including Kothis, transport-workers, business-owners/self-employed and those who exchanged money for having sex with men, seemed to be the need of the hour for preventing the spread of HIV infection within and from this understudied population.
doi:10.1371/journal.pone.0127232
PMCID: PMC4440763  PMID: 25996926
13.  Sertraline-induced potentiation of the CYP3A4-dependent neurotoxicity of carbamazepine: An in vitro study 
Epilepsia  2015;56(3):439-449.
SUMMARY
Objective
Drug toxicity is a hurdle to drug development and to clinical translation of basic research. Antiepileptic drugs such as carbamazepine (CBZ) and selective serotonin reuptake inhibitors such as sertraline (SRT) are commonly co-prescribed to patients with epilepsy and comorbid depression. Because SRT may interfere with cytochrome P450 (CYP) enzyme activity and CYPs have been implicated in the conversion of CBZ to reactive cytotoxic metabolites, we investigated in vitro models to determine whether SRT affects the neurotoxic potential of CBZ and the mechanisms involved.
Methods
Human fetal brain-derived dopaminergic neurons, human brain microvascular endothelial cells (HBMECs), and embryonic kidney (HEK) cells were used to evaluate cytotoxicity of CBZ and SRT individually and in combination. Nitrite and glutathione (GSH) levels were measured with drug exposure. To validate the role of CYP3A4 in causing neurotoxicity, drug metabolism was compared to cell death in HEK CYP3A4 overex-pressed and cells pretreated with the CYP3A4 inhibitor ketoconazole.
Results
In all cellular systems tested, exposure to CBZ (127 μM) or SRT (5 μM) alone caused negligible cytotoxicity. By contrast CBZ, tested at a much lower concentration (17 μM) in combination with SRT (5 μM), produced prominent cytotoxicity within 15 min exposure. In neurons and HBMECs, cytotoxicity was associated with increased nitrite levels, suggesting involvement of free radicals as a pathogenetic mechanism. Pretreatment of HBMECs with reduced GSH or with the GSH precursor N-acetyl-L-cysteine prevented cytotoxic response. In HEK cells, the cytotoxic response to the CBZ + SRT combination correlated with the rate of CBZ biotransformation and production of 2-hydroxy CBZ, further suggesting a causative role of reactive metabolites. In the same system, cytotoxicity was potentiated by overexpression of CYP3A4, and prevented by CYP3A4 inhibitor.
Significance
These results demonstrate an unexpected neurotoxic interaction between CBZ and SRT, apparently related to increased CYP3A4-mediated production of reactive CBZ metabolites. The potential clinical implications of these findings are discussed.
doi:10.1111/epi.12923
PMCID: PMC4413932  PMID: 25656284
CYP3A4; Cytotoxicity; Drug interaction; Human; Ketoconazole; Neurotoxicity
14.  MK591, a Second Generation Leukotriene Biosynthesis Inhibitor, Prevents Invasion and Induces Apoptosis in the Bone-Invading C4-2B Human Prostate Cancer Cells: Implications for the Treatment of Castration-Resistant, Bone-Metastatic Prostate Cancer 
PLoS ONE  2015;10(4):e0122805.
Castration-resistant prostate cancer (CRPC) is a major clinical challenge for which no cure is currently available primarily because of the lack of proper understanding about appropriate molecular target(s). Previously we observed that inhibition of 5-lipoxygenase (5-Lox) activity induces apoptosis in some types of prostate cancer cells, suggesting an important role of 5-Lox in the viability of prostate cancer cells. However, nothing is known about the role of 5-Lox in the survival of castration-resistant, metastatic prostate cancer cells. Thus, we tested the effects of MK591, a second-generation, specific inhibitor of 5-Lox activity, on the viability and metastatic characteristics of CRPC cells. We observed that MK591 effectively kills the bone-invading C4-2B human prostate cancer cells (which bear characteristics of CRPC), but does not affect normal, non-cancer fibroblasts (which do not express 5-Lox) in the same experimental conditions. We also observed that MK591 dramatically inhibits the in vitro invasion and soft-agar colony formation of C4-2B cells. Interestingly, we found that treatment with MK591 dramatically down-regulates the expression of c-Myc and its targets at sub-lethal doses. In light of frequent over-activation of c-Myc in a spectrum of aggressive cancers (including CRPC), and the challenges associated with inhibition of c-Myc (because of its non-enzymatic nature), our novel findings of selective killing, and blockade of invasive and soft-agar colony-forming abilities of the castration-resistant, bone-metastatic C4-2B prostate cancer cells by MK591, open up a new avenue to attack CRPC cells for better management of advanced prostate cancer while sparing normal, non-cancer body cells.
doi:10.1371/journal.pone.0122805
PMCID: PMC4398363  PMID: 25875826
15.  Simultaneous Inhibition of Key Growth Pathways in Melanoma Cells and Tumor Regression by a Designed Bidentate Constrained Helical Peptide 
Biopolymers  2014;101(4):344-358.
Protein-protein interactions are part of a large number of signaling networks and potential targets for drug development. However, discovering molecules that can specifically inhibit such interactions is a major challenge. S100B, a calcium-regulated protein, plays a crucial role in the proliferation of melanoma cells through protein-protein interactions. In this article, we report the design and development of a bidentate conformationally constrained peptide against dimeric S100B based on a natural tight binding peptide, TRTK-12. The helical conformation of the peptide was constrained by substitution of α-amino isobutyric acid----an amino acid having high helical propensity----in positions which do not interact with S100B. A branched bidentate version of the peptide, bound to S100B tightly with a dissociation constant of 8 nM. When conjugated to a cell penetrating peptide, it caused growth inhibition and rapid apoptosis in melanoma cells. The molecule exerts anti-proliferative action through simultaneous inhibition of key growth pathways including reactivation of wild-type p53 and inhibition of Akt and STAT-3 phosphorylation. The apoptosis induced by the bidentate constrained helix is caused by direct migration of p53 to mitochondria. At moderate intravenous dose, the peptide completely inhibits melanoma growth in a mouse model without any significant observable toxicity. The specificity was shown by lack of ability of a double mutant peptide to cause tumor regression at the same dose level. The methodology described here for direct protein-protein interaction inhibition may be effective for rapid development of inhibitors against relatively weak protein-protein interactions for de novo drug development.
doi:10.1002/bip.22505
PMCID: PMC4107132  PMID: 24839139
16.  Hedgehog Signaling Pathway Is Active in GBM with GLI1 mRNA Expression Showing a Single Continuous Distribution Rather than Discrete High/Low Clusters 
PLoS ONE  2015;10(3):e0116390.
Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression—as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution—unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the “high-Hh” cluster of MB but 5.6 fold higher than that of the “low-Hh” cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.
doi:10.1371/journal.pone.0116390
PMCID: PMC4361547  PMID: 25775002
17.  Oxygen-18 isotope of breath CO2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes 
Scientific Reports  2015;5:8137.
Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( 18O)-isotopic fractionations of CO2. To investigate how CA activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of 18O in breath CO2, while a marked depletion of 18O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of 18O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C 18O 16O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D.
doi:10.1038/srep08137
PMCID: PMC4311236  PMID: 25633556
18.  Production of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {\Sigma (1385)^{\pm }}$$\end{document}Σ(1385)± and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {\Xi (1530)^{0}}$$\end{document}Ξ(1530)0 in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {\sqrt{s}=}$$\end{document}s= 7 TeV 
Abelev, B. | Adam, J. | Adamová, D. | Aggarwal, M. M. | Rinella, G. Aglieri | Agnello, M. | Agostinelli, A. | Agrawal, N. | Ahammed, Z. | Ahmad, N. | Ahmed, I. | Ahn, S. U. | Ahn, S. A. | Aimo, I. | Aiola, S. | Ajaz, M. | Akindinov, A. | Alam, S. N. | Aleksandrov, D. | Alessandro, B. | Alexandre, D. | Alici, A. | Alkin, A. | Alme, J. | Alt, T. | Altinpinar, S. | Altsybeev, I. | Alves Garcia Prado, C. | Andrei, C. | Andronic, A. | Anguelov, V. | Anielski, J. | Antičić, T. | Antinori, F. | Antonioli, P. | Aphecetche, L. | Appelshäuser, H. | Arcelli, S. | Armesto, N. | Arnaldi, R. | Aronsson, T. | Arsene, I. C. | Arslandok, M. | Augustinus, A. | Averbeck, R. | Awes, T. C. | Azmi, M. D. | Bach, M. | Badalà, A. | Baek, Y. W. | Bagnasco, S. | Bailhache, R. | Bala, R. | Baldisseri, A. | Baltasar Dos Santos Pedrosa, F. | Baral, R. C. | Barbera, R. | Barile, F. | Barnaföldi, G. G. | Barnby, L. S. | Barret, V. | Bartke, J. | Basile, M. | Bastid, N. | Basu, S. | Bathen, B. | Batigne, G. | Batista Camejo, A. | Batyunya, B. | Batzing, P. C. | Baumann, C. | Bearden, I. G. | Beck, H. | Bedda, C. | Behera, N. K. | Belikov, I. | Bellini, F. | Bellwied, R. | Belmont-Moreno, E. | Belmont , R. | Belyaev, V. | Bencedi, G. | Beole, S. | Berceanu, I. | Bercuci, A. | Berdnikov, Y. | Berenyi, D. | Berger, M. E. | Bertens, R. A. | Berzano, D. | Betev, L. | Bhasin, A. | Bhat, I. R. | Bhati, A. K. | Bhattacharjee, B. | Bhom, J. | Bianchi, L. | Bianchi, N. | Bianchin, C. | Bielčík, J. | Bielčíková, J. | Bilandzic, A. | Bjelogrlic, S. | Blanco, F. | Blau, D. | Blume, C. | Bock, F. | Bogdanov, A. | Bøggild, H. | Bogolyubsky, M. | Böhmer, F. V. | Boldizsár, L. | Bombara, M. | Book, J. | Borel, H. | Borissov, A. | Bossú, F. | Botje, M. | Botta, E. | Böttger, S. | Braun-Munzinger, P. | Bregant, M. | Breitner, T. | Broker, T. A. | Browning, T. A. | Broz, M. | Bruna, E. | Bruno, G. E. | Budnikov, D. | Buesching, H. | Bufalino, S. | Buncic, P. | Busch, O. | Buthelezi, Z. | Caffarri, D. | Cai, X. | Caines, H. | Calero Diaz, L. | Caliva, A. | Calvo Villar, E. | Camerini, P. | Carena, F. | Carena, W. | Castillo Castellanos, J. | Casula, E. A. R. | Catanescu, V. | Cavicchioli, C. | Ceballos Sanchez, C. | Cepila, J. | Cerello, P. | Chang, B. | Chapeland, S. | Charvet, J. L. | Chattopadhyay, S. | Chattopadhyay, S. | Chelnokov, V. | Cherney, M. | Cheshkov, C. | Cheynis, B. | Chibante Barroso, V. | Chinellato, D. D. | Chochula, P. | Chojnacki, M. | Choudhury, S. | Christakoglou, P. | Christensen, C. H. | Christiansen, P. | Chujo, T. | Chung, S. U. | Cicalo, C. | Cifarelli, L. | Cindolo, F. | Cleymans, J. | Colamaria, F. | Colella, D. | Collu, A. | Colocci, M. | Conesa Balbastre, G. | Conesa del Valle, Z. | Connors, M. E. | Contreras, J. G. | Cormier, T. M. | Corrales Morales, Y. | Cortese, P. | Cortés Maldonado, I. | Cosentino, M. R. | Costa, F. | Crochet, P. | Cruz Albino, R. | Cuautle, E. | Cunqueiro, L. | Dainese, A. | Dang, R. | Danu, A. | Das, D. | Das, I. | Das, K. | Das, S. | Dash, A. | Dash, S. | De, S. | Delagrange, H. | Deloff, A. | Dénes, E. | D’Erasmo, G. | De Caro, A. | de Cataldo, G. | de Cuveland, J. | De Falco, A. | De Gruttola, D. | De Marco, N. | De Pasquale, S. | de Rooij, R. | Diaz Corchero, M. A. | Dietel, T. | Dillenseger, P. | Divià, R. | Di Bari, D. | Di Liberto, S. | Di Mauro, A. | Di Nezza, P. | Djuvsland, Ø. | Dobrin, A. | Dobrowolski, T. | Domenicis Gimenez, D. | Dönigus, B. | Dordic, O. | Dørheim, S. | Dubey, A. K. | Dubla, A. | Ducroux, L. | Dupieux, P. | Dutta Majumdar, A. K. | Hilden, T. E. | Ehlers, R. J. | Elia, D. | Engel, H. | Erazmus, B. | Erdal, H. A. | Eschweiler, D. | Espagnon, B. | Esposito, M. | Estienne, M. | Esumi, S. | Evans, D. | Evdokimov, S. | Fabris, D. | Faivre, J. | Falchieri, D. | Fantoni, A. | Fasel, M. | Fehlker, D. | Feldkamp, L. | Felea, D. | Feliciello, A. | Feofilov, G. | Ferencei, J. | Fernández Téllez, A. | Ferreiro, E. G. | Ferretti, A. | Festanti, A. | Figiel, J. | Figueredo, M. A. S. | Filchagin, S. | Finogeev, D. | Fionda, F. M. | Fiore, E. M. | Floratos, E. | Floris, M. | Foertsch, S. | Foka, P. | Fokin, S. | Fragiacomo, E. | Francescon, A. | Frankenfeld, U. | Fuchs, U. | Furget, C. | Furs, A. | Fusco Girard, M. | Gaardhøje, J. J. | Gagliardi, M. | Gago, A. M. | Gallio, M. | Gangadharan, D. R. | Ganoti, P. | Gao, C. | Garabatos, C. | Garcia-Solis, E. | Gargiulo, C. | Garishvili, I. | Gerhard, J. | Germain, M. | Gheata, A. | Gheata, M. | Ghidini, B. | Ghosh, P. | Ghosh, S. K. | Gianotti, P. | Giubellino, P. | Gladysz-Dziadus, E. | Glässel, P. | Gomez Ramirez, A. | González-Zamora, P. | Gorbunov, S. | Görlich, L. | Gotovac, S. | Graczykowski, L. K. | Grelli, A. | Grigoras, A. | Grigoras, C. | Grigoriev, V. | Grigoryan, A. | Grigoryan, S. | Grinyov, B. | Grion, N. | Grosse-Oetringhaus, J. F. | Grossiord, J.-Y. | Grosso, R. | Guber, F. | Guernane, R. | Guerzoni, B. | Guilbaud, M. | Gulbrandsen, K. | Gulkanyan, H. | Gumbo, M. | Gunji, T. | Gupta, A. | Gupta, R. | Khan, K. H. | Haake, R. | Haaland, Ø. | Hadjidakis, C. | Haiduc, M. | Hamagaki, H. | Hamar, G. | Hanratty, L. D. | Hansen, A. | Harris, J. W. | Hartmann, H. | Harton, A. | Hatzifotiadou, D. | Hayashi, S. | Heckel, S. T. | Heide, M. | Helstrup, H. | Herghelegiu, A. | Herrera Corral, G. | Hess, B. A. | Hetland, K. F. | Hippolyte, B. | Hladky, J. | Hristov, P. | Huang, M. | Humanic, T. J. | Hussain, N. | Hussain, T. | Hutter, D. | Hwang, D. S. | Ilkaev, R. | Ilkiv, I. | Inaba, M. | Innocenti, G. M. | Ionita, C. | Ippolitov, M. | Irfan, M. | Ivanov, M. | Ivanov, V. | Jachołkowski, A. | Jacobs, P. M. | Jahnke, C. | Jang, H. J. | Janik, M. A. | Jayarathna, P. H. S. Y. | Jena, C. | Jena, S. | Jimenez Bustamante, R. T. | Jones, P. G. | Jung, H. | Jusko, A. | Kadyshevskiy, V. | Kalinak, P. | Kalweit, A. | Kamin, J. | Kang, J. H. | Kaplin, V. | Kar, S. | Karasu Uysal, A. | Karavichev, O. | Karavicheva, T. | Karpechev, E. | Kebschull, U. | Keidel, R. | Keijdener, D. L. D. | SVN, M. Keil | Khan, M. M. | Khan, P. | Khan, S. A. | Khanzadeev, A. | Kharlov, Y. | Kileng, B. | Kim, B. | Kim, D. W. | Kim, D. J. | Kim, J. S. | Kim, M. | Kim, M. | Kim, S. | Kim, T. | Kirsch, S. | Kisel, I. | Kiselev, S. | Kisiel, A. | Kiss, G. | Klay, J. L. | Klein, J. | Klein-Bösing, C. | Kluge, A. | Knichel, M. L. | Knospe, A. G. | Kobdaj, C. | Kofarago, M. | Köhler, M. K. | Kollegger, T. | Kolojvari, A. | Kondratiev, V. | Kondratyeva, N. | Konevskikh, A. | Kovalenko, V. | Kowalski, M. | Kox, S. | Koyithatta Meethaleveedu, G. | Kral, J. | Králik, I. | Kravčáková, A. | Krelina, M. | Kretz, M. | Krivda, M. | Krizek, F. | Kryshen, E. | Krzewicki, M. | Kučera, V. | Kucheriaev, Y. | Kugathasan, T. | Kuhn, C. | Kuijer, P. G. | Kulakov, I. | Kumar, J. | Kurashvili, P. | Kurepin, A. | Kurepin, A. B. | Kuryakin, A. | Kushpil, S. | Kweon, M. J. | Kwon, Y. | Ladron de Guevara, P. | Lagana Fernandes, C. | Lakomov, I. | Langoy, R. | Lara, C. | Lardeux, A. | Lattuca, A. | La Pointe, S. L. | La Rocca, P. | Lea, R. | Leardini, L. | Lee, G. R. | Legrand, I. | Lehnert, J. | Lemmon, R. C. | Lenti, V. | Leogrande, E. | Leoncino, M. | León Monzón, I. | Lévai, P. | Li, S. | Lien, J. | Lietava, R. | Lindal, S. | Lindenstruth, V. | Lippmann, C. | Lisa, M. A. | Ljunggren, H. M. | Lodato, D. F. | Loenne, P. I. | Loggins, V. R. | Loginov, V. | Lohner, D. | Loizides, C. | Lopez, X. | López Torres, E. | Lu, X.-G. | Luettig, P. | Lunardon, M. | Luparello, G. | Ma, R. | Maevskaya, A. | Mager, M. | Mahapatra, D. P. | Mahmood, S. M. | Maire, A. | Majka, R. D. | Malaev, M. | Maldonado Cervantes, I. | Malinina, L. | Mal’Kevich, D. | Malzacher, P. | Mamonov, A. | Manceau, L. | Manko, V. | Manso, F. | Manzari, V. | Marchisone, M. | Mareš, J. | Margagliotti, G. V. | Margotti, A. | Marín, A. | Markert, C. | Marquard, M. | Martashvili, I. | Martin, N. A. | Martinengo, P. | Martínez, M. I. | Martínez García, G. | Martin Blanco, J. | Martynov, Y. | Mas, A. | Masciocchi, S. | Masera, M. | Masoni, A. | Massacrier, L. | Mastroserio, A. | Matyja, A. | Mayer, C. | Mazer, J. | Mazzoni, M. A. | Meddi, F. | Menchaca-Rocha, A. | Meninno, E. | Mercado Pérez, J. | Meres, M. | Miake, Y. | Mikhaylov, K. | Milano, L. | Milosevic, J. | Mischke, A. | Mishra, A. N. | Miśkowiec, D. | Mitra, J. | Mitu, C. M. | Mlynarz, J. | Mohammadi, N. | Mohanty, B. | Molnar, L. | Montaño Zetina, L. | Montes, E. | Morando, M. | Moreira De Godoy, D. A. | Moretto, S. | Morreale, A. | Morsch, A. | Muccifora, V. | Mudnic, E. | Mühlheim, D. | Muhuri, S. | Mukherjee, M. | Müller, H. | Munhoz, M. G. | Murray, S. | Musa, L. | Musinsky, J. | Nandi, B. K. | Nania, R. | Nappi, E. | Nattrass, C. | Nayak, K. | Nayak, T. K. | Nazarenko, S. | Nedosekin, A. | Nicassio, M. | Niculescu, M. | Niedziela, J. | Nielsen, B. S. | Nikolaev, S. | Nikulin, S. | Nikulin, V. | Nilsen, B. S. | Noferini, F. | Nomokonov, P. | Nooren, G. | Norman, J. | Nyanin, A. | Nystrand, J. | Oeschler, H. | Oh, S. | Oh, S. K. | Okatan, A. | Okubo, T. | Olah, L. | Oleniacz, J. | Oliveira Da Silva, A. C. | Onderwaater, J. | Oppedisano, C. | Ortiz Velasquez, A. | Oskarsson, A. | Otwinowski, J. | Oyama, K. | Ozdemir, M. | Sahoo, P. | Pachmayer, Y. | Pachr, M. | Pagano, P. | Paić, G. | Pajares, C. | Pal, S. K. | Palmeri, A. | Pant, D. | Papikyan, V. | Pappalardo, G. S. | Pareek, P. | Park, W. J. | Parmar, S. | Passfeld, A. | Patalakha, D. I. | Paticchio, V. | Paul, B. | Pawlak, T. | Peitzmann, T. | Pereira Da Costa, H. | Pereira De Oliveira Filho, E. | Peresunko, D. | Pérez Lara, C. E. | Pesci, A. | Peskov, V. | Pestov, Y. | Petráček, V. | Petran, M. | Petris, M. | Petrovici, M. | Petta, C. | Piano, S. | Pikna, M. | Pillot, P. | Pinazza, O. | Pinsky, L. | Piyarathna, D. B. | Płoskoń, M. | Planinic, M. | Pluta, J. | Pochybova, S. | Podesta-Lerma, P. L. M. | Poghosyan, M. G. | Pohjoisaho, E. H. O. | Polichtchouk, B. | Poljak, N. | Pop, A. | Porteboeuf-Houssais, S. | Porter, J. | Potukuchi, B. | Prasad, S. K. | Preghenella, R. | Prino, F. | Pruneau, C. A. | Pshenichnov, I. | Puccio, M. | Puddu, G. | Pujahari, P. | Punin, V. | Putschke, J. | Qvigstad, H. | Rachevski, A. | Raha, S. | Rajput, S. | Rak, J. | Rakotozafindrabe, A. | Ramello, L. | Raniwala, R. | Raniwala, S. | Räsänen, S. S. | Rascanu, B. T. | Rathee, D. | Rauf, A. W. | Razazi, V. | Read, K. F. | Real, J. S. | Redlich, K. | Reed, R. J. | Rehman, A. | Reichelt, P. | Reicher, M. | Reidt, F. | Renfordt, R. | Reolon, A. R. | Reshetin, A. | Rettig, F. | Revol, J.-P. | Reygers, K. | Riabov, V. | Ricci, R. A. | Richert, T. | Richter, M. | Riedler, P. | Riegler, W. | Riggi, F. | Rivetti, A. | Rocco, E. | Rodríguez Cahuantzi, M. | Rodriguez Manso, A. | Røed, K. | Rogochaya, E. | Rohni, S. | Rohr, D. | Röhrich, D. | Romita, R. | Ronchetti, F. | Ronflette, L. | Rosnet, P. | Rossi, A. | Roukoutakis, F. | Roy, A. | Roy, C. | Roy, P. | Rubio Montero, A. J. | Rui, R. | Russo, R. | Ryabinkin, E. | Ryabov, Y. | Rybicki, A. | Sadovsky, S. | Šafařík, K. | Sahlmuller, B. | Sahoo, R. | Sahu, P. K. | Saini, J. | Sakai, S. | Salgado, C. A. | Salzwedel, J. | Sambyal, S. | Samsonov, V. | Sanchez Castro, X. | Sánchez Rodríguez, F. J. | Šándor, L. | Sandoval, A. | Sano, M. | Santagati, G. | Sarkar, D. | Scapparone, E. | Scarlassara, F. | Scharenberg, R. P. | Schiaua, C. | Schicker, R. | Schmidt, C. | Schmidt, H. R. | Schuchmann, S. | Schukraft, J. | Schulc, M. | Schuster, T. | Schutz, Y. | Schwarz, K. | Schweda, K. | Scioli, G. | Scomparin, E. | Scott, R. | Segato, G. | Seger, J. E. | Sekiguchi, Y. | Selyuzhenkov, I. | Senosi, K. | Seo, J. | Serradilla, E. | Sevcenco, A. | Shabetai, A. | Shabratova, G. | Shahoyan, R. | Shangaraev, A. | Sharma, A. | Sharma, N. | Sharma, S. | Shigaki, K. | Shtejer, K. | Sibiriak, Y. | Siddhanta, S. | Siemiarczuk, T. | Silvermyr, D. | Silvestre, C. | Simatovic, G. | Singaraju, R. | Singh, R. | Singha, S. | Singhal, V. | Sinha, B. C. | Sinha, T. | Sitar, B. | Sitta, M. | Skaali, T. B. | Skjerdal, K. | Slupecki, M. | Smirnov, N. | Snellings, R. J. M. | Søgaard, C. | Soltz, R. | Song, J. | Song, M. | Soramel, F. | Sorensen, S. | Spacek, M. | Spiriti, E. | Sputowska, I. | Spyropoulou-Stassinaki, M. | Srivastava, B. K. | Stachel, J. | Stan, I. | Stefanek, G. | Steinpreis, M. | Stenlund, E. | Steyn, G. | Stiller, J. H. | Stocco, D. | Stolpovskiy, M. | Strmen, P. | Suaide, A. A. P. | Sugitate, T. | Suire, C. | Suleymanov, M. | Sultanov, R. | Šumbera, M. | Symons, T. J. M. | Szabo, A. | Szanto de Toledo, A. | Szarka, I. | Szczepankiewicz, A. | Szymanski, M. | Takahashi, J. | Tangaro, M. A. | Tapia Takaki, J. D. | Tarantola Peloni, A. | Tarazona Martinez, A. | Tariq, M. | Tarzila, M. G. | Tauro, A. | Tejeda Muñoz, G. | Telesca, A. | Terasaki, K. | Terrevoli, C. | Thäder, J. | Thomas, D. | Tieulent, R. | Timmins, A. R. | Toia, A. | Trubnikov, V. | Trzaska, W. H. | Tsuji, T. | Tumkin, A. | Turrisi, R. | Tveter, T. S. | Ullaland, K. | Uras, A. | Usai, G. L. | Vajzer, M. | Vala, M. | Valencia Palomo, L. | Vallero, S. | Vande Vyvre, P. | Van Der Maarel, J. | Van Hoorne, J. W. | van Leeuwen, M. | Vargas, A. | Vargyas, M. | Varma, R. | Vasileiou, M. | Vasiliev, A. | Vechernin, V. | Veldhoen, M. | Velure, A. | Venaruzzo, M. | Vercellin, E. | Vergara Limón, S. | Vernet, R. | Verweij, M. | Vickovic, L. | Viesti, G. | Viinikainen, J. | Vilakazi, Z. | Villalobos Baillie, O. | Vinogradov, A. | Vinogradov, L. | Vinogradov, Y. | Virgili, T. | Vislavicius, V. | Viyogi, Y. P. | Vodopyanov, A. | Völkl, M. A. | Voloshin, K. | Voloshin, S. A. | Volpe, G. | von Haller, B. | Vorobyev, I. | Vranic, D. | Vrláková, J. | Vulpescu, B. | Vyushin, A. | Wagner, B. | Wagner, J. | Wagner, V. | Wang, M. | Wang, Y. | Watanabe, D. | Weber, M. | Weber, S. G. | Wessels, J. P. | Westerhoff, U. | Wiechula, J. | Wikne, J. | Wilde, M. | Wilk, G. | Wilkinson, J. | Williams, M. C. S. | Windelband, B. | Winn, M. | Yaldo, C. G. | Yamaguchi, Y. | Yang, H. | Yang, P. | Yang, S. | Yano, S. | Yasnopolskiy, S. | Yi, J. | Yin, Z. | Yoo, I.-K. | Yushmanov, I. | Zaccolo, V. | Zach, C. | Zaman, A. | Zampolli, C. | Zaporozhets, S. | Zarochentsev, A. | Závada, P. | Zaviyalov, N. | Zbroszczyk, H. | Zgura, I. S. | Zhalov, M. | Zhang, H. | Zhang, X. | Zhang, Y. | Zhao, C. | Zhigareva, N. | Zhou, D. | Zhou, F. | Zhou, Y. | Zhuo, Zhou | Zhu, H. | Zhu, J. | Zhu, X. | Zichichi, A. | Zimmermann, A. | Zimmermann, M. B. | Zinovjev, G. | Zoccarato, Y. | Zyzak, M.
The production of the strange and double-strange baryon resonances (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Sigma (1385)^{\pm }$$\end{document}Σ(1385)±, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Xi (1530)^{0}$$\end{document}Ξ(1530)0) has been measured at mid-rapidity (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left| y \right| $$\end{document}y\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$<0.5$$\end{document}<0.5) in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$=$$\end{document}= 7 TeV with the ALICE detector at the LHC. Transverse momentum spectra for inelastic collisions are compared to QCD-inspired models, which in general underpredict the data. A search for the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi (1860)$$\end{document}ϕ(1860) pentaquark, decaying in the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Xi \pi $$\end{document}Ξπ channel, has been carried out but no evidence is seen.
doi:10.1140/epjc/s10052-014-3191-x
PMCID: PMC4424041  PMID: 25983644
19.  Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth 
Purpose
Classical pharmacology allows the use and development of conventional phytomedicine faster and more economically than conventional drugs. This approach should be tested for their efficacy in terms of complementarity and disease control. The purpose of this study was to determine the molecular mechanisms by which nimbolide, a triterpenoid found in the well-known medicinal plant Azadirachta indica controls glioblastoma (GBM) growth.
Experimental Design
Using in vitro signaling, anchorage-independent growth, kinase assays, and xenograft models, we investigated the mechanisms of its growth inhibition in glioblastoma.
Results
We show that nimbolide or an ethanol soluble fraction of A. indica leaves (Azt) that contains nimbolide as the principal cytotoxic agent is highly cytotoxic against GBM in vitro and in vivo. Azt caused cell cycle arrest, most prominently at the G1-S stage in GBM cells expressing EGFRvIII, an oncogene present in about 20-25% of GBMs. Azt/nimbolide directly inhibited CDK4/CDK6 kinase activity leading to hypophosphorylation of the retinoblastoma (RB) protein, cell cycle arrest at G1-S and cell death. Independent of RB hypophosphorylation, Azt also significantly reduced proliferative and survival advantage of GBM cells in vitro and in tumor xenografts by downregulating Bcl2 and blocking growth factor induced phosphorylation of Akt, Erk1/2 and STAT3. These effects were specific since Azt did not affect mTOR or other cell cycle regulators. In vivo, Azt completely prevented initiation and inhibited progression of GBM growth.
Conclusions
Our preclinical findings demonstrate Nimbolide as a potent anti-glioma agent that blocks cell cycle and inhibits glioma growth in vitro and in vivo.
doi:10.1158/1078-0432.CCR-13-0762
PMCID: PMC3947304  PMID: 24170547
20.  Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity 
Molecular Vision  2015;21:12-25.
Purpose
Keratoconus (KC) is characterized by progressive vision loss due to corneal thinning and structural abnormalities. It is hypothesized that KC is caused by deregulated collagen levels and collagen fibril-maturating enzyme lysyl oxidase (LOX). Further, it is currently not understood whether the gene expression deregulated by the corneal epithelium influences KC pathogenesis. We studied (i) the expressions of the LOX, collagen I (COL IA1), collagen IV (COL IVA1), MMP9, and IL6 genes in KC corneal epithelia, (ii) validated their expression levels in patient tissues, and (iii) correlated expression levels with KC disease severity. The primary goal of this study was to evaluate the importance of these genes in the progression of KC.
Methods
We analyzed the gene expression levels of the key proteins LOX, collagens (COL IA1 and COL IVA1), MMP9, and IL6 in debrided corneal epithelia from a large cohort of KC patients (90 eyes) and compared them to control patients (52 eyes) without KC. We measured the total LOX activity in the tears of KC patients compared to controls. We also correlated the protein expression levels of LOX and collagens by immunohistochemistry (IHC) in primary tissues from KC patients (27 eyes) undergoing keratoplasty compared to healthy donor corneas (15 eyes).
Results
We observed a significant reduction in LOX transcript levels in KC corneal epithelia, and LOX activity in KC tears correlated with disease severity. Collagen transcripts were also reduced in KC while MMP9 transcript levels were upregulated and correlated with disease severity. IL6 was moderately increased in KC patients. IHC demonstrated a reduction in the protein expression levels of LOX in the epithelium and collagen IV in the basement membrane of KC patients compared to healthy donor corneas.
Conclusions
The data demonstrates that the structural deformity of the KC cornea may be dependent on reduced expressions of collagens and LOX, as well as on MMP9 elevated by the corneal epithelium.
PMCID: PMC4301596  PMID: 25593510
21.  NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation 
Cellular signalling  2013;25(12):2575-2586.
MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cells proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels.
doi:10.1016/j.cellsig.2013.08.005
PMCID: PMC3896302  PMID: 23981302
microRNA; Renal cancer; PTEN; NFκB
22.  Neem Leaf Glycoprotein Prophylaxis Transduces Immune Dependent Stop Signal for Tumor Angiogenic Switch within Tumor Microenvironment 
PLoS ONE  2014;9(11):e110040.
We have reported that prophylactic as well as therapeutic administration of neem leaf glycoprotein (NLGP) induces significant restriction of solid tumor growth in mice. Here, we investigate whether the effect of such pretreatment (25µg/mice; weekly, 4 times) benefits regulation of tumor angiogenesis, an obligate factor for tumor progression. We show that NLGP pretreatment results in vascular normalization in melanoma and carcinoma bearing mice along with downregulation of CD31, VEGF and VEGFR2. NLGP pretreatment facilitates profound infiltration of CD8+ T cells within tumor parenchyma, which subsequently regulates VEGF-VEGFR2 signaling in CD31+ vascular endothelial cells to prevent aberrant neovascularization. Pericyte stabilization, VEGF dependent inhibition of VEC proliferation and subsequent vascular normalization are also experienced. Studies in immune compromised mice confirmed that these vascular and intratumoral changes in angiogenic profile are dependent upon active adoptive immunity particularly those mediated by CD8+ T cells. Accumulated evidences suggest that NLGP regulated immunomodulation is active in tumor growth restriction and normalization of tumor angiogenesis as well, thereby, signifying its clinical translation.
doi:10.1371/journal.pone.0110040
PMCID: PMC4229107  PMID: 25391149
23.  A study of the prevalence of osteoporosis and hypovitaminosis D in patients with primary knee osteoarthritis 
Introduction
Osteoarthritis and Osteoporosis are highly prevalent disease, so is hypovitaminosis D. We tried to find out prevalence of osteoporosis and hypovitaminosis D in patients suffering from primary knee Osteoarthritis. We also compared the prevalence of oseotoporosis between general population and patients of primary osteoarthritis.
Methods
Patients suffering from primary knee OA were taken from Rheumatology OPD of Medical College Hospital and SSKM Hospital Kolkata, India. For each patient age and sex matched friend or relative of same locality was taken in the study as controls. Hospital staffs that come from different part of state was taken in the study as controls. The control population was the representative of general population.
Results
Total number of participants in this study was 206. Out of which there were 98 cases and 108 controls. BMD status correlates significantly with Primary OA. Serum Vitamin D3 status correlates significantly with Osteoarthritis. Age of the patients correlated significantly with both BMD Status and Knee OA but not with the vVitamin D level. There were significant correlation between the Serum Vitamin D3 status and BMD of the subjects.
Conclusion
Osteoporosis is prevalent both in general population and patients suffering from Knee Osteoarthritis and may increase the disability. The matter is complicated by the fact hypovitaminosis D is also prevalent in the population and positively correlated with both Osteoporosis and osteoarthrosis, though we cannot comment on further pathogenesis because of cross sectional design of the study.
doi:10.1016/j.jcot.2014.09.002
PMCID: PMC4263992  PMID: 25983498
Knee osteoarthitis; Osteoporosis; Hypovitaminosis D
24.  Cerebellar ataxia in a young patient: A rare path to lupus 
Cerebellar ataxia is a rare manifestation of neuropsychiatric systemic lupus erythematosus (SLE). Development of vasculitic infarcts in the cerebellum is the most plausible reason of this manifestation. We report the case of a patient who presented with characteristic skin rashes of lupus along with cerebellar signs. Imaging of brain in this patient revealed prominent cerebellar atrophy. She was treated with mycophenolate mofetil and oral corticosteroid, and there was no further progression of her neurological signs after the initiation of therapy. In the clinical context of varied presentations of neurolupus, this is one of the rare sightings and our treatment protocol holds promise as first-line therapy in future.
doi:10.4103/0976-3147.145212
PMCID: PMC4271393  PMID: 25540550
Ataxia; immunosuppression; systemic lupus erythematosus
25.  TGFβ-Induced Deptor Suppression Recruits mTORC1 and Not mTORC2 to Enhance Collagen I (α2) Gene Expression 
PLoS ONE  2014;9(10):e109608.
Enhanced TGFβ activity contributes to the accumulation of matrix proteins including collagen I (α2) by proximal tubular epithelial cells in progressive kidney disease. Although TGFβ rapidly activates its canonical Smad signaling pathway, it also recruits noncanonical pathway involving mTOR kinase to regulate renal matrix expansion. The mechanism by which chronic TGFβ treatment maintains increased mTOR activity to induce the matrix protein collagen I (α2) expression is not known. Deptor is an mTOR interacting protein that suppresses mTOR activity in both mTORC1 and mTORC2. In proximal tubular epithelial cells, TGFβ reduced deptor levels in a time-dependent manner with concomitant increase in both mTORC1 and mTORC2 activities. Expression of deptor abrogated activity of mTORC1 and mTORC2, resulting in inhibition of collagen I (α2) mRNA and protein expression via transcriptional mechanism. In contrast, neutralization of endogenous deptor by shRNAs increased activity of both mTOR complexes and expression of collagen I (α2) similar to TGFβ treatment. Importantly, downregulation of deptor by TGFβ increased the expression of Hif1α by increasing translation of its mRNA. TGFβ-induced deptor downregulation promotes Hif1α binding to its cognate hypoxia responsive element in the collagen I (α2) gene to control its protein expression via direct transcriptional mechanism. Interestingly, knockdown of raptor to specifically block mTORC1 activity significantly inhibited expression of collagen I (α2) and Hif1α while inhibition of rictor to prevent selectively mTORC2 activation did not have any effect. Critically, our data provide evidence for the requirement of TGFβ-activated mTORC1 only by deptor downregulation, which dominates upon the bystander mTORC2 activity for enhanced expression of collagen I (α2). Our results also suggest the presence of a safeguard mechanism involving deptor-mediated suppression of mTORC1 activity against developing TGFβ-induced renal fibrosis.
doi:10.1371/journal.pone.0109608
PMCID: PMC4198127  PMID: 25333702

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