• Volume 44, Issue 2

      June 2019

    • Interaction network analysis of YBX1 for identification of therapeutic targets in adenocarcinomas

      SURIYA NARAYANAN MURUGESAN BIRENDRA SINGH YADAV PRAMOD KUMAR MAURYA AMIT CHAUDHARY SWATI SINGH ASHUTOSH MANI

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      Human Y-box binding protein-1 (YBX1) is a member of highly conserved cold-shock domain protein family, which isinvolved in transcriptional as well as translational regulation of many genes. Nuclear localization of YBX1 has beenobserved in various cancer types and it’s overexpression has been linked to adverse clinical outcome and poor therapyresponse, but no diagnostic or therapeutic correlation has been established so far. This study aimed to identify differentiallyexpressed novel genes among the interactors of YBX1 in different cancer types. Analysis of RNA-Seq data for colorectal,lung, prostate and stomach adenocarcinoma identified 39 unique genes, which are differentially expressed in the fouradenocarcinoma types. Gene-enrichment analysis for the differentially expressed genes from individual adenocarcinomawith focus on unique genes resulted in a total of 57 gene sets specific to each adenocarcinoma. Gene ontology forcommonly expressed genes suggested the pathways and possible mechanisms through which they affect each adenocarcinomatype considered in the study. Gene regulatory network constructed for the common genes and network topologywas analyzed for the central nodes. Here 12 genes were found to play important roles in the network formation; amongthem, two genes FOXM1 and TOP2A were found to be in central network formation, which makes them a common targetfor therapeutics. Furthermore, five common differentially expressed genes in all adenocarcinomas were also identified.

    • New clues into the mechanisms of rice domestication

      PADUBIDRI V SHIVAPRASAD

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      Domestication of rice involved incorporation of specific yield-related changes in wild species of rice. This agriculturalprocess has been of significant interest for plant biologists. The recent advance in genomics has provided new tools toinvestigate the genetic basis and consequences of domestication. Several genes involved in domestication and diversificationprocess have been characterized, and as expected, this list is over-represented by transcription factors and their cofactors.Most often the modification orchestrated expression levels of genes such as those coding for transcription factors. Ithas been proposed that transcriptional regulators and their regulation is likely a major theme controlling morphologicaldifferences between crops and their progenitors. However, recent data indicate that single amino acid changes in genescoding for key proteins as well as epigenetic and small RNA-mediated pathways also contributed towards domestication-associatedphenotypes.

    • Regeneration and evaluation of somaclones of sugarcane variety Co86032 for yellow leaf disease resistance and yield traits

      PRAVEEN KONA MHEMANTH KUMAR KHP REDDY TM HEMALATHA DM REDDY N P ESWAR REDDY P LATHA

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      The present investigation was focussed on regeneration, evaluation and screening of somaclones for yellow leaf disease(YLD) resistance using in vitro mutagenesis from a popular susceptible sugarcane variety Co86032 using four chemicalmutagens at three levels of concentration (sodium azide (SA) at 0.5 mg L-1, 1.0 mg L-1, 1.5 mg L-1; sodium nitrite (SN)at 3 mg L-1, 5 mg L-1, 7 mg L-1; ethyl methane sulphonate (EMS) at 0.6 lML-1, 0.8 lML-1, 1.0 lML-1 and 2,4 D at 4mg L-1, 5 mg L-1, 6 mg L-1). A total of 1138 tissue culture seedlings obtained were evaluated for virus resistance both innatural field conditions and in controlled greenhouse condition after aphid vector transmission and presence or absence ofvirus was observed by visual screening and reverse transcription-polymerase chain reaction method. Four out of 207asymptomatic plants (16T22, 16T23, 16T29 and 16T31) were devoid of virus coat protein band and were considered to beYLD resistant. The obtained resistance somaclones showed inferior yield traits so they have to be exploited as parents inhybridization programmes with commercial varieties to impart YLD resistance ultimately yielding agronomically superiorYLD-resistant varieties in sugarcane.

    • Green synthesis of zinc oxide nanoparticles and evaluation of anti-angiogenesis, anti-inflammatory and cytotoxicity properties

      GHASEM RAHIMI KALATEH SHAH MOHAMMAD MASOUD HOMAYOUNI TABRIZI TOURAN ARDALAN SOHEYLA YADAMANI ELHAM SAFAVI

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      In this study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using the extract of Hyssops officinalis L. via greenmethod and confirmed by transmission electron microscopy, field emission scanning electron microscopy, X-ray powderdiffraction and Fourier transforms infrared spectroscopy techniques. In the in vivo section, the anti-angiogenesis and antiinflammatoryproperties of the NPs were evaluated by the chorioallantoic membrane (CAM) assay and mouse paw edematest (induced by carrageenan), respectively. In the in vitro section, changes in the expression of angiogenesis genes (VEGFand VEGFR) and inflammatory genes (IL-1B and IL-10) were investigated by real-time quantitative polymerase chainreaction technique. In order to evaluate the cytotoxicity of ZnO-NPs, 3-5, 4-dimethylthiazol-2-yl) -5, 2-tetrazolium bromide(MTT) test was used on MDA-MB231 breast adenocarcinoma cell line. The results of the CAM assay showed that theZnO-NPs significantly reduced the number and length of blood vessels, as well as the size and weight of the embryos.Evaluation of mouse paw edema showed that the NPs are able to decrease inflammation. Changes in the expression patternof VEGF and VEGFR genes in MCF7 cells showed that the NPs have inhibitory effect on the expression of both genes.Expression levels of IL-10 and IL-1B genes also increased and decreased, respectively. The MTT test showed that the NPhave the ability to decrease breast cancer cells. In conclusion, our results confirm that the ZnO-NPs synthesized by greenmethod have promising anti-cancer properties.

    • Investigating the role of Ebp1 in Chandipura virus infection

      DHRITIMAN DEY AYAE HONDA DHRUBAJYOTI CHATTOPADHYAY

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      ErbB-3 binding protein 1 (Ebp1) is a host protein which binds ErbB-3 receptor to induce signalling events for cell growthregulation. In addition, Ebp1 also interacts with ribonucleoprotein complexes. In recent times, Ebp1 was found to play anantagonistic role in viral infections caused by Influenza and Rinderpest viruses. In our present work we have tried tounderstand the role of Ebp1 in Chandipura virus (CHPV) infection. We have observed an induction in Ebp1 expressionupon CHPV infection similar to other viruses. However, unlike other viruses an overexpressed Ebp1 only reduces viralprotein expression, but does not affect its progeny formation. Additionally, this effect is being carried out in an indirectmanner, as there is no interaction between Ebp1 and viral proteins. This is despite Ebp1’s presence in viral inclusion bodies.

    • Cell-free chromatin: A newly described mediator of systemic inflammation

      SHAHID CHAUDHARY INDRANEEL MITTRA

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      Recent research has shown that cell-free chromatin (cfCh) particles that are released from the billions of cells that die in thebody everyday can enter into healthy cells, integrate into their genomes and induce dsDNA breaks and apoptotic responses.Genomic integration of cfCh activates NF$/kappa$B suggesting a novel mechanism of induction of systemic inflammation. SinceDNA damage and inflammation are underlying pathologies in multiple devastating acute and chronic disease conditions,the discovery of agents that can inactivate cfCh may provide therapeutic possibilities.

    • Multifaceted role of keratins in epithelial cell differentiation and transformation

      CRISMITA DMELLO SAUMYA S SRIVASTAVA RICHA TIWARI PRATIK R CHAUDHARI SHARADA SAWANT MILIND M VAIDYA

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      Keratins, the epithelial-predominant members of the intermediate filament superfamily, are expressed in a pairwise, tissuespecificand differentiation-dependent manner. There are 28 type I and 26 type II keratins, which share a common structurecomprising a central coiled coil a-helical rod domain flanked by two nonhelical head and tail domains. These domainsharbor sites for major posttranslational modifications like phosphorylation and glycosylation, which govern keratin functionand dynamics. Apart from providing structural support, keratins regulate various signaling machinery involved in cellgrowth, motility, apoptosis etc. However, tissue-specific functions of keratins in relation to cell proliferation and differentiationare still emerging. Altered keratin expression pattern during and after malignant transformation is reported tomodulate different signaling pathways involved in tumor progression in a context-dependent fashion. The current reviewfocuses on the literature related to the role of keratins in the regulation of cell proliferation, differentiation and transformationin different types of epithelia.

    • Comparison of Treponema pallidum genomes for the prediction of resistance genes

      RONALDO OMIZOLO DE SOUZA KESIA ESTHER DA SILVA RODRIGO MATHEUS PEREIRA SIMONE SIMIONATTO

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      Syphilis is a sexually transmitted infection caused by Treponema pallidum, which is highly prevalent in several countries,including Brazil. The use of bioinformatics’ tools for the identification of resistance genes is an important practice for thestudy of microorganisms, such as T. pallidum. In this study, the complete genomes of 43 strains of T. pallidum, isolatedfrom different countries, were analyzed. A total of 41,514 sequences were obtained, and compared against prokaryoteresistance gene databases using BLASTn, BLASTx and RGI for gene alignment and prediction. From the alignments, itwas possible to identify antibiotic resistance genes for each strain. The genes identified in each comparison were groupedaccording to the antibiotic category in which they show resistance to. The antibiotic-resistant genes related to drugs used totreat syphilis were grouped separately. The in silico tools used have shown to be effective in identifying resistance genes ingenomes of T. pallidum strains. Due to the lack of research and accurate information regarding the antibiotic resistancegenes in T. pallidum, this study serves as a basis for studies in molecular biology whose aim is the identification of thesegenes, besides being a reference to help in the control and treatment of this infection.

    • Macromolecular properties and partial amino acid sequence of a Kunitz-type protease inhibitor from okra (Abelmoschus esculentus) seeds

      DEBPARNA DATTA GOTTFRIED POHLENTZ SARADAMONI MONDAL M BALA DIVYA LALITHA GURUPRASAD MICHAEL MORMANN MUSTI J SWAMY

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      A Kunitz-type protease inhibitor (OPI, okra protease inhibitor) has been purified from okra (Abelmoschus esculentus) seedsby a combination of ammonium sulfate precipitation, anion-exchange chromatography and reverse-phase high-performanceliquid chromatography. The protein shows an apparent mass of 21 kDa on sodium dodecyl sulfate-polyacrylamide gelelectrophoresis under reducing condition. OPI exhibits inhibitory activity against trypsin. Analysis of the far-UV circulardichroism spectrum showed that the protein contains ~39% b-sheets but only ~5% a-helices. The protein is thermallyquite stable, and exhibits a cooperative thermal unfolding transition at ~70 deg C, as determined by circular dichroismspectroscopy and differential scanning fluorimetry. De novo sequencing of OPI by nanoESI-Q-ToF mass spectrometry (MS) allowed the assignment of about 83% of its primary structure, which indicated that the protein shares 43% sequence identitywith a putative 21 kDa trypsin inhibitor from Theobroma bicolor. An intramolecular disulfide linkage between Cys149 andCys156 was also detected. The protein showed ~24 and ~25% sequence identity with a-amylase/subtilisin inhibitor frombarley and soybean (Kunitz) trypsin inhibitor, respectively. Comparative structure modeling of OPI revealed a structuralfold similar to other Kunitz-type TIs. The presence of Cys149–Cys156 disulfide bond as detected by MS and a seconddisulfide bond connecting Cys44–Cys91, conserved in all Kunitz-type TIs, is also identified in the model.

    • Over-expression of Hsp83 in grossly depleted hsrω lncRNA background causes synthetic lethality and l(2)gl phenocopy in Drosophila

      MUKULIKA RAY SUNDARAM ACHARYA SAKSHI SHAMBHAVI SUBHASH C LAKHOTIA

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      We examined interactions between the 83 kDa heat-shock protein (Hsp83) and hsrω long noncoding RNAs (lncRNAs) in hsrω66 Hsp90GFP homozygotes, which almost completely lack hsrω lncRNAs but over-express Hsp83. All +/+; hsrω66 Hsp90GFP progeny died before the third instar. Rare Sp/CyO; hsrω66 Hsp90GFP reached the third instar stage but phenocopied l(2)gl mutants, becoming progressively bulbous and transparent with enlarged brain and died after prolonged larval life. Additionally, ventral ganglia too were elongated. However, hsrω66 Hsp90GFP/TM6B heterozygotes, carrying +/ + or Sp/CyO second chromosomes, developed normally. Total RNA sequencing (+/+, +/+; hsrω66/hsrω66, Sp/CyO; hsrω66/ hsrω66, +/+; Hsp90GFP/Hsp90GFP and Sp/CyO; hsrω66 Hsp90GFP/hsrω66 Hsp90GFP late third instar larvae) revealed similar effects on many genes in hsrω66 and Hsp90GFP homozygotes. Besides additive effect on many of them, numerous additional genes were affected in Sp/CyO; hsrω66 Hsp90GFP larvae, with l(2)gl and several genes regulating the central nervous system being highly down-regulated in surviving Sp/CyO; hsrω66 Hsp90GFP larvae, but not in hsrω66 or Hsp90GFP single mutants. Hsp83 and several omega speckle-associated hnRNPs were bioinformatically found to potentially bind with these gene promoters and transcripts. Since Hsp83 and hnRNPs are also known to interact, elevated Hsp83 in an altered background of hnRNP distribution and dynamics, due to near absence of hsrω lncRNAs and omega speckles, can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumoursuppressor genes such as l(2)gl.

    • Overexpression of serum exosomal HOTAIR is correlated with poor survival and poor response to chemotherapy in breast cancer patients

      SHICONG TANG KAI ZHENG YIYIN TANG ZHEN LI TIANNING ZOU DEQUAN LIU

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      To investigate the source of serum exosomal HOTAIR, to uncover the diagnostic and prognostic values of serum exosomalHOTAIR, and to discern the expression of serum exosomal HOTAIR between neoadjuvant chemotherapy and response totamoxifen therapy. Samples were collected from the Third Affiliated Hospital of Kunming Medical University, TumorHospital of Yunnan. Exosomes were isolated from serum, cell culture medium and tumor tissues. We used transmissionelectron microscopy and western immunoblotting assay to characterize exosomes, and real-time PCR (qPCR) to assessHOTAIR expression. Neoadjuvant chemotherapy and tamoxifen therapy were carried out according to establishedguidelines. Breast cancer patients expressed higher serum exosomal HOTAIR than did healthy individuals (P<0.001).Serum exosomal HOTAIR levels 3 months after surgery were markedly decreased compared with levels before surgery(P<0.001), and the expression level of exosomal HOTAIR in cell culture medium increased with time in both breastcancer cell lines (72 h>48 h>24 h, 48 h vs 24 h [P<0.05]; 72 h vs 24 h [P<0.01]). Expression of serum exosomalHOTAIR in nude mice was notably greater than in the mock control group (P<0.001). The results of the ROC analysisrevealed an AUC for serum exosomal HOTAIR of 0.9178 with a 95% CI of 0.8407–1.017 (P<0.01). The AUC for theCA15-3 cell line was 0.7378 (95% CI, 0.5585–0.9170; P = 0.03). High expression of exosomal HOTAIR led to a worsedisease-free survival (P = 0.0481) and overall survival (P = 0.0463). In the high-expression chemotherapy group, sixpatients achieved a partial response (PR) and eight demonstrated stable disease (SD) and nine patients achieved PR and twoSD in the low-expression group (P = 0.048). In the low-expression tamoxifen group, one patient had a recurrence of breastcancer and another 10 patients exhibited no recurrence, while six showed recurrence, and seven had none in the highexpressiongroup (P = 0.035). We isolated exosomes successfully, and demonstrated that serum exosomal HOTAIRoriginated from primary breast cancer tissue. We conclude that serum exosomal HOTAIR exhibits the potential to be adiagnostic and prognostic biomarker. High expression of serum exosomal HOTAIR was also correlated with poorneoadjuvant chemotherapy and response to tamoxifen therapy.

    • Restriction enzymes and their use in molecular biology: An overview

      FRANCESCA DI FELICE GIOACCHINO MICHELI GIORGIO CAMILLONI

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      Restriction enzymes have been identified in the early 1950s of the past century and have quickly become key players in themolecular biology of DNA. Forty years ago, the scientists whose pioneering work had explored the activity and sequencespecificity of these enzymes, contributing to the definition of their enormous potential as tools for DNA characterization,mapping and manipulation, were awarded the Nobel Prize. In this short review, we celebrate the history of these enzymes inthe light of their many different uses, as these proteins have accompanied the history of DNA for over 50 years representingactive witnesses of major steps in the field.

    • ABCG2 aptamer selectively delivers doxorubicin to drug-resistant breast cancer cells

      SHIRIN HASHEMITABAR REZVAN YAZDIAN-ROBATI MARYAM HASHEMI MOHAMMAD RAMEZANI KHALIL ABNOUS FATEMEH KALALINIA

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      Chemotherapy is the most widely used treatment for cancer therapy, but its efficacy is limited by the side effects of non-specificcytotoxic drugs. Ligand-based targeting drug-delivery system is a solution to circumvent this issue. In this study, an ABCG2aptamer–doxorubicin complex was prepared, and its efficacy in targeted drug delivery tomitoxantrone-resistance breast cancer cellline (MCF7/MX) was evaluated. The formation of aptamer–doxorubicin physical complex was analyzed by fluorometric analysis.The cytotoxicities of doxorubicin and aptamer–doxorubicin complex on MCF7 and MCF7/MX cell lines were evaluated by theMTT assay, and IC50 values were obtained. Cellular uptake of aptamer–doxorubicin complex was assessed by flow cytometrycellular uptake assay. Results: Fluorometric analysis of aptamer–doxorubicin showed 1–1.5 molar ratio of the drug to the aptamercould efficiently quenchDox fluorescence.MTTassay results showed that MCF7/MXcells were more resistant to doxorubicin thanMCF7 cells (IC50 : 3.172 ± 0.536 and 1.456 ± 0.154 lM, respectively). Flow cytometry andMTTassay results showed that theaptamer–doxorubicin complex could increase the uptake and cytotoxicity of doxorubicin inMCF7/MX cell line in comparison withfree doxorubicin, while the same treatments had no effect on IC50 of Dox on MCF7 cells. The results proposed that the ABCG2aptamer–drug complex can be effectively used for specific drug delivery to ABCG2-overexpressing cells.

    • Shengjiang Powder ameliorates myocardial injury in septic rats by downregulating the phosphorylation of P38-MAPK

      YIMING QIAN FENGHUA QIAN WEIWEI ZHANG LEI ZHAO MENGWEN SHEN CHUNLEI DING JIAN GUO

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      Sepsis is the systemic inflammatory response caused by infection. Cardiac dysfunction is an acknowledged result of sepsis.Shengjiang Powder, a prescribed traditional Chinese medicine, showed anti-infection and antipyretic functions in ourprevious study. In this study, we established a septic rat model via cecal ligation puncture (CLP) to evaluate the effects ofShengjiang Powder on sepsis and the involvement of P38 mitogen activated protein kinase (P38-MAPK) signaling. The 10main ingredients of Shengjiang Powder were identified by LC–MS. The results of this study indicated that ShengjiangPowder at a concentration of 3.0 g/kg with SB203580 (an inhibitor of P38-MAPK) could improve myocardial injury,ameliorate the histopathological abnormalities, decrease apoptosis and upregulate proliferating cell nuclear antigen (PCNA)levels in myocardial tissues. Further, cytokine mRNA expression levels (tumor necrosis factor - alpha, TNF-a and interleukin6, IL-6) were decreased by Shengjiang Powder and SB203580 in the myocardial tissues. Furthermore, the p-P38protein level in myocardial tissues was upregulated in septic rats but decreased upon treatment with Shengjiang Powder andSB203580; however, the relative protein level of P38 showed no significant changes. Collectively, Shengjiang Powdershowed a myocardial protective effect on rats with CLP-induced sepsis.

    • PM2.5 affects establishment of immune tolerance in newborn mice by reducing PD-L1 expression

      LI YAN CAIHUI GONG LINYAN YING WENLONG FU SHA LIU JIHONG DAI ZHOU FU

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      This study was conducted to determine whether exposure to particulate matter 2.5 (PM2.5) affects the immune tolerance ofneonatal mice via the regulation of PD-L1 expression. One-week-old BALB/c mice were exposed to PM2.5 for 8 days.From day 8 to day 18, the mice were treated with 5 lg house dust mite (HDM) (i. n.) every two days. Adenovirus-carriedPD-L1 overexpression vectors were infected into mice via nasal inhalation 6 days after exposure to PM2.5. Airway hyperresponsiveness(AHR) was examined in mice 19 days after exposure to PM2.5, and the related parameters of airwayinflammation were studied on day 22. Co-exposure to PM2.5 and HDM reduced PD-L1 expression but greatly increasedinfiltration of inflammatory cells, which was reversed by PD-L1 overexpression. Co-exposure to PM2.5 and HDM alsoelevated serum IL-4, IL-5 and IL-13 levels and reduced TGF-b level. Exposure to PM2.5 alone slightly increased thenumbers of dendritic cells (DCs) but reduced the numbers of antigen-presenting cells expressing PD-L1 and Treg cells.Therefore, early exposure to PM2.5 reduced PD-L1 expression in the lungs of neonatal mice, which interfered with immunetolerance establishment and subsequently resulted in allergic airway inflammation.

    • 14-3-3 proteins mediate the localization of Centrin2 to centrosome

      ARUNABHA BOSE SORAB N DALAL

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      14-3-3$/epsilon$ and 14-3-3γ localize to the centrosome and regulate centrosome duplication, by inhibiting cdc25C function. As14-3-3γ and 14-3-3$/epsilon$ form a complex with centrosomal proteins, we asked if this ability was required to regulate centrosomeduplication. The results in this report demonstrate that 14-3-3$/epsilon$ and 14-3-3γ form a complex with Centrin2 and that thebinding site is located in the N-terminal EF hand in Centrin2, EF1. A Centrin2 mutant that does not form a complex with14-3-3 proteins displays a punctate cytoplasmic localization and does not localize to the centrosome. These results suggestthat in addition to negatively regulating centrosome duplication as previously reported, 14-3-3 proteins might also berequired for centriole biogenesis by regulating the localization of Centrin2 at the centrosome.

    • Diet-dependent habitat shifts at different life stages of two sympatric primate species

      JOSEPH J ERINJERY MEWA SINGH RAFI KENT

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      A shift or expansion of the realized niche at different life stages is often ignored while implementing conservation actions.We tested whether habitat extent and associations at different life stages of two sympatric primate species belonging to thesame taxonomic family vary with respect to their dietary requirements. We expected the groups and solitary males of afrugivorous species to have a smaller extent of suitable habitat than those of a folivorous species. We used MaxEntmodelling to create habitat suitability maps using occurrence records and high-resolution remotely sensed environmentallayers for groups and solitary males of highly frugivorous lion-tailed macaques and highly folivorous Nilgiri langurs in theWestern Ghats, India. We found that the Nilgiri langur groups and lion-tailed macaque groups occupied a similar extent inour study area. However, due to weaker restrictions, the Nilgiri langur groups were observed to inhabit a broader variety ofhabitats than the lion-tailed macaque groups. Solitary males of both the lion-tailed macaque and Nilgiri langur migratethroughout the landscape, with only a 50% habitat overlap with their respective groups. We propose that a species’ dietaryrequirements have differential effects on habitat use, especially during dispersal, at the solitary stage in males.

    • LINC00511 knockdown prevents cervical cancer cell proliferation and reduces resistance to paclitaxel

      BEN-DI MAO PING XU YAN ZHONG WEI-WEI DING QING-ZHI MENG

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      Cervical cancer (CC) is one of the most common female malignancies in the world. Although paclitaxel (PTX) is a criticalchemotherapy agent for the treatment of CC, its treatment outcome is limited by the development of drug resistance. Thepresent study aims to define the role of long non-coding RNA (lncRNA) LINC00511 in the progression of CC with theinvolvement of cell proliferation, apoptosis and resistance to PTX in Hela/PTX cells. CC and adjacent normal tissuesamples were collected from 84 patients with CC, and used to determine LINC0051 expression. PTX-resistant Hela/PTXcell line was constructed, in which LINC0051 was overexpressed or silenced to further investigate the effect of LINC00511on PTX-resistant Hela/PTX cell viability, proliferation, migration, invasion, cell cycle, apoptosis and resistance of CC cellsto PTX. The expression of Bcl-2, Bax, cleaved-caspase-3, matrix metalloproteinase (MMP)-2, MMP-9, multidrug resistanceprotein 1 (MRP1) and P-glycoprotein (P-GP) was also assessed. High-expression of LINC00511 was found in CCwith its close association with the tumor stage, tumor size and lymph node metastasis. After silencing LINC00511expression, the expression of MRP1, P-GP, Bcl-2, MMP-2 and MMP-9 was decreased, while Bax and cleaved-caspase-3increased with more CC cells arrested at G1 phase. Furthermore, silencing of LINC00511 could suppress cell resistance toPTX, cell viability, cell proliferation, migration and invasion yet promoted cell apoptosis in PTX-resistant Hela/PTX cells.Collectively, our findings demonstrate that silencing of LINC00511 could inhibit CC cell resistance to PTX, cell proliferation,migration and invasion, and promote cell apoptosis in CC. Silencing of LINC00511 provides a novel therapeutictarget for CC.

    • A brief note on genes that trigger components of apomixis

      VLADIMIR BRUKHIN RAMAMURTHY BASKAR

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      Apomixis or asexual reproduction through seeds occurs in about 400 species of flowering plants producing geneticallyuniform progeny. During apomixis, meiosis is bypassed and embryos develop by parthenogenesis. However, the endospermcould form either autonomously without fertilization or sexually, depending on the plant species. Most probably, aheterochronic expression of sexually expressed genes is one of the reason that causes apomixis. A better understanding ofthe genetic components regulating apomixis is important for developmental and evolutionary studies and also for engineeringapomixis traits into crop plants that may realize a possibility to propagate hybrid vigor in a range of subsequentgenerations.

    • Inhibition of amyloid fibrillation of apo-carbonic anhydrase by flavonoid compounds

      ALI ES-HAGHI AZADEH EBRAHIM-HABIBI

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      Flavonoids are polyphenol compounds abundantly found in plants and reported to have an inhibitory effect on amyloidfibrillation. The number and position of hydroxyl groups, as well as the arrangement of flavonoids rings, may influencetheir inhibitory effects. In this study, we investigate the effect of structural characteristics of flavonoids on amyloid fibrilformation. For this purpose, five compounds (i.e., biochanin A, daidzein, quercetin, chrysin and fisetin) were selected thatrepresent a variety in the number and position of their hydroxyl groups. The inhibitory effect of these flavonoids on theamyloid fibril formation of apo-carbonic anhydrase (apo-BCA), as a model protein, was evaluated using thioflavin T andtransmission electron microscopy. The results showed that fisetin possessed the most significant inhibitory effect. Interestingly,upon apo-BCA acetylation, none of the tested flavonoids could inhibit the fibrillation process, which indicates thatthe interactions of these compounds with the amine groups of lysine residues could be somewhat important.

    • Biosynthesis of some organic acids and lipids in industrially important microorganisms is promoted by pyruvate carboxylases

      SHOU-FENG ZHAO ZHE CHI GUANG-LEI LIU ZHONG HU LONG-FEI WU ZHEN-MING CHI

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      Pyruvate carboxylase (Pyc) catalyzes formation of oxaloacetic acid from pyruvic acid by fixing one mole of CO2. Manyevidences have confirmed that biosynthesis of some different kinds of organic acids and intracellular and extracellular lipidsis driven by Pyc and over-expression of the PYC gene in the industrial microorganisms can promote production of thedifferent kinds of organic acids and intracellular and extracellular lipids. Therefore, the Pyc from different sources isregarded as a key enzyme in microbial biotechnology and is an important target for metabolic engineering of the industrialmicrobial strains. However, very little is known about the native Pycs and their functions and regulation in the industrialmicroorganisms.

    • COSCEB: Comprehensive search for column-coherent evolution biclusters and its application to hub gene identification

      ANKUSH MAIND SHITAL RAUT

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      Biclustering is an increasingly used data mining technique for searching groups of co-expressed genes across the subset ofexperimental conditions from the gene-expression data. The group of co-expressed genes is present in the form of variouspatterns called a bicluster. A bicluster provides significant insights related to the functionality of genes and plays animportant role in various clinical applications such as drug discovery, biomarker discovery, gene network analysis, geneidentification, disease diagnosis, pathway analysis etc. This paper presents a novel unsupervised approach ‘COmprehensiveSearch for Column-Coherent Evolution Biclusters (COSCEB)’ for a comprehensive search of biologically significantcolumn-coherent evolution biclusters. The concept of column subspace extraction from each gene pair and LongestCommon Contiguous Subsequence (LCCS) is employed to identify significant biclusters. The experiments have beenperformed on both synthetic as well as real datasets. The performance of COSCEB is evaluated with the help of key issues.The issues are comprehensive search, Deep OPSM bicluster, bicluster types, bicluster accuracy, bicluster size, noise,overlapping, output nature, computational complexity and biologically significant biclusters. The performance of COSCEBis compared with six all-time famous biclustering algorithms SAMBA, OPSM, xMotif, Bimax, Deep OPSM- and UniBic.The result shows that the proposed approach performs effectively on most of the issues and extracts all possible biologicallysignificant column-coherent evolution biclusters which are far more than other biclustering algorithms. Along with theproposed approach, we have also presented the case study which shows the application of significant biclusters for hub geneidentification.

    • Factors influencing the gut microbiome in children: from infancy to childhood

      SHREYAS V KUMBHARE DHRATI V PATANGIA RAVINDRA H PATIL YOGESH S SHOUCHE NITINKUMAR P PATIL

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      The human microbiota plays a crucial role in educating the immune system and influencing host health right since birth.Various maternal factors along with the vertical microbial transfer from the mother, as well as the horizontal environmentaltransmission and internal factors relating to the infant, play a crucial role in modulating the gut microbiota. The early lifemicroflora is highly unstable and undergoes dynamic changes during the first few years, converging towards a morestabilized adult microbiota by co-evolving with the host by the age of 3–4 years. Microbiota studies have underlined therole of dysbiosis in developing several metabolic disorders like obesity, diabetes and immune-related disorders like asthma,to name a few. Thus, understanding early life microbial composition and various factors affecting the microbial communitywill provide a platform for developing strategies/techniques to maintain host health by restoring gut microbial flora. Thisreview focuses on the factors that affect the microbial composition of the foetus in utero, during birth, infancy throughchildhood.

    • Import of human miRNA-RISC complex into Plasmodium falciparum and regulation of the parasite gene expression

      VISHAL DANDEWAD ARYA VINDU JOMON JOSEPH VASUDEVAN SESHADRI

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      During its life cycle, the malarial parasite Plasmodium goes through different asexual stages in human blood, and asexualand sexual stage in mosquito. Expression of stage-specific proteins is important for successful completion of its life cycleand requires tight gene regulation. In case of Plasmodium, due to relative paucity of the transcription factors, it is postulatedthat post-transcriptional regulation plays an important role in stage-specific gene expression. Although miRNA-mediatedgene regulation has been well-established to function in post-transcriptional regulation in many eukaryotes, existence ofsuch a phenomenon or the presence of miRNA-associated factors in Plasmodium remains unclear. A number of miRNAsare shown to be imported into Plasmodium falciparum from erythrocytes and role of these miRNAs is not understood. Herewe show that human Argonaute 2 (hAgo2) a component of the miRISC complex is imported by P. falciparum. In theparasite hAgo2 exists as in a complex with specific human miRNAs like let-7a and miR15a which can potentially target thePlasmodium genes Rad54 and Lipid/sterol:H+ symporter respectively. We show that hAgo2 associates with Rad54, Lipid/sterol:H+ symporter and other P. falciparum transcripts. These results highlight the existence of a mechanism by whichmalarial parasite imports hAgo2-miRNA complex from the host cells to regulate its gene expression.

    • A cross-eyed geneticist’s view III. Mouse chromosomes take a drive

      DURGADAS P KASBEKAR

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    • Elucidating the effect of anti-biofilm activity of bioactive compounds extracted from plants

      DIBYAJIT LAHIRI SUDIPTA DASH RACHAYEETA DUTTA MOUPRIYA NAG

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      Biofilms are dense population of sessile bacterial cells that adhere to the surface, forming a matrix composed ofexopolysaccharide, proteins and DNA. This matrix is termed as extracellular polymeric substance and provides stability tothe cells adhering to it to form biofilms. It also provides nutrients and thus helps in the pathogenesis of biofilm-associatedinfections and resistance. Biofilms promote bacterial persistence by resisting host immune responses and antibiotic treatment.Antibiotics are rendered ineffective when biofilms form due to their relative impermeability, the variable physiologicalstatus of microorganisms, and subpopulations of persistent strains. Another factor that results in the development ofantibiotic resistance within the biofilm is the adaptations that take place within the genes present in the cells dwelling withinthe biofilm. These adaptations decrease the sensitivity of the bacterial cells toward the antibiotics and develop resistance.Hence, an alternative antimicrobial strategy of making use of plant-based products has been observed to be useful to curevarious ailments, as compared to conventional therapy. In this review, we have listed the various biofilm-forming bacteriaand the bioactive compounds being produced from the aerial parts of plants having antibiofilm activity and evaluated themagainst different biofilm-producing bacterial strains.

    • Resina draconis inhibits the endoplasmic-reticulum-induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signaling pathway in a tree shrew myocardial ischemia– reperfusion model

      TIAN-RUI YANG TONG ZHANG NING-HUI MU LI-BO RUAN JIN-LAN DUAN RONG-PING ZHANG YUN-BO MIAO

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      Ischemia-reperfusion (IR) is one of the significant medical problems in China. Triphenyltetrazolium chloride (TTC) stainingis used to detect the status of the infarct size, and real-time PCR and western blotting are used to detect expressions ofgenes. TUNEL assay has been used to detect apoptosis. Using a tree shrew myocardial IR model, we found that in thereperfusion period, resina draconis (RD) treatment reduced the infarct size by TTC staining, and significantly enhanced thesuperoxide dismutase expression and down-regulated the malondialdehyde concentration in a dose-dependent manner. Inhearts showing IR, Bax was increased and Bcl-2 was reduced, and RD treatment inhibited the IR-induced Bax expressionand up-regulated the IR suppressed level of Bcl-2. TUNEL assay showed that IR induced the apoptosis of myocardial cells,and RD treatment suppressed the IR-induced apoptosis. CHOP and GRP78 were also upregulated in IR hearts, and RDtreatment could significantly attenuate the CHOP and GRP78 levels compared with IR group. We further found that IRdecreased the miR-423-3p expression and upregulated its target gene ERK both in mRNA and protein levels, and RDtreatment upregulated miR-423-3p expression and downregulated ERK expression compared with the IR group. Importantly,miR-423-3p mimics inhibited IR increased ERK, CHOP and GRP78 expressions, and enhanced IR decreased Bcl-2expression, and inhibited the IR-induced apoptosis of myocardial cells. The findings of this study suggest that RD treatmentinhibited the endoplasmic reticulum induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signalingpathway in a tree shrew myocardial IR model.

    • Protein fingerprinting with digital sequences of linear protein subsequence volumes: a computational study

      G SAMPATH

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      Proteins in a proteome can be identified from a sequence of K integers equal to the digitized volumes of subsequences withL residues from the primary sequence of a stretched protein. Exhaustive computations on the proteins of Helicobacterpylori (UniProt id UP000000210) with L and K in the range 4–8 show that*90% of the proteins can be identified uniquelyin this manner. This computational result can be translated into practice with a nanopore, an emerging technology that doesnot require analyte immobilization, proteolysis or labeling. Unlike other methods, most of which focus on a specific targetprotein, nanopore-based methods enable the identification of multiple proteins from a sample in a single run. Recent workby Kennedy, Kolmogorov and associates shows that the blockade current due to a protein molecule translocating through ananopore is roughly proportional to one or more contiguous residues. The present study points to a modified version inwhich the volumes of subsequences (rather than of single residues) may be obtained by integrating the blockade current dueto L contiguous residues. The advantages arising from this include lower detector bandwidth, elimination of thehomopolymer problem and reduced noise. Because an identifier is based on near as well as distant (up to 2KL-L) residues,this approach uses more global information than an approach based on single residues and short-range correlations. Theresults of the study, which are available in a data supplement, are discussed in detail. Potential implementation issues areaddressed.

    • Phosphorylation mapping of Laminin b1-chain: Kinases in association with active sites

      KLEIO-MARIA VERROU PANAGIOTA ANGELIKI GALLIOU MARIA PAPAIOANNOU GEORGIOS KOLIAKOS

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      Laminins are a major constituent of the extracellular matrix (ECM). Laminin-111, the most extensively studied lamininisoform, consists of the a1, the b1 and the c1 chain, and is involved in many cellular processes, like adhesion, migrationand differentiation. Given the regulatory role of phosphorylation in protein function, it is important to identify thephosphorylation sites of human laminin b1-chain sequence (LAMB1). Therefore, we computationally predicted all possiblephosphorylation sites in LAMB1. For the first time, we identified the possibly responsible kinases foralready in vitro experimentally observed phosphorylated residues in LAMB1. All known functional (active) sites ofLAMB1, were recorded after an extensive literature search and combined with the experimentally observed and ourpredicted phosphorylated residues. This generated a detailed phosphorylation map of LAMB1. Five kinases (PKA, PKC,CKII, CKI and GPCR1) were indicated important, while the role of PKA, PKC and CKII, kinases known for ectophosphorylationactivity, was highlighted. The activity of PKA and PKC was associated with the active site RIQNLLKITNLRIKFVKLHTLGDNLLDS.Also, predicted phosphorylations inside two amyloidogenic (DSITKYFQMSLE,VILQHSAADIAR) and two anti-cancerous (YIGSR and PDSGR) sites suggested a possible role in the development of thecorresponding diseases.

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