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71.
Zhuo Ma Sukalyani Banik Harshita Rane Vanessa T. Mora Seham M. Rabadi Christopher R. Doyle David G. Thanassi Meenakshi Malik 《Molecular microbiology》2014,91(5):976-995
Francisella tularensis is a category A biodefence agent that causes a fatal human disease known as tularaemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host‐generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defences to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant‐sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild‐type F. tularensis LVS levels by either transcomplementation, inhibition of ROS generation or infection in NADPH oxidase deficient (gp91Phox?/?) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox?/? mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defence mechanisms of F. tularensis. 相似文献
72.
Muthukumaresan Kuppuswamy Thirumalai Arpita Roy Suma Sanikommu Jesu Arockiaraj Mukesh Pasupuleti 《Journal of peptide science》2014,20(5):341-348
The indiscriminate usage of antibiotics has created a major problem in the form of antibiotic resistance. Even though new antimicrobial drug discovery programs have been in place from the last two decades, still we are unsuccessful in identifying novel molecules that have a potential to become new therapeutic agents for the treatment of microbial infections. A major problem in most screening studies is the requirement of high‐throughput techniques. Given this, we present here an enzyme‐based robust method for screening antimicrobial agent's active against Escherichia coli. This method is based upon the ability of the intracellular innate enzyme to cleave o‐nitrophenyl β‐d ‐galactopyranoside (non‐chromogenic) to o‐nitrophenolate (ONP) (chromogenic) upon the membrane damage or disruption. In comparison with the other currently available methods, we believe that our method provides an opportunity for real‐time monitoring of the antimicrobial agents action by measuring the ONP generation in a user‐friendly manner. Even though this method can be applied to other strain, our experience shows that one has to be careful especially when the pigments or metabolites present in the bacteria have the same wavelength absorbance. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
73.
Reema Roshan Shruti Shridhar Mayuresh A. Sarangdhar Arpita Banik Mrinal Chawla Manali Garg Vijay PAL Singh Beena Pillai 《RNA (New York, N.Y.)》2014,20(8):1287-1297
Several microRNAs have been implicated in neurogenesis, neuronal differentiation, neurodevelopment, and memory. Development of miRNA-based therapeutics, however, needs tools for effective miRNA modulation, tissue-specific delivery, and in vivo evidence of functional effects following the knockdown of miRNA. Expression of miR-29a is reduced in patients and animal models of several neurodegenerative disorders, including Alzheimer''s disease, Huntington''s disease, and spinocerebellar ataxias. The temporal expression pattern of miR-29b during development also correlates with its protective role in neuronal survival. Here, we report the cellular and behavioral effect of in vivo, brain-specific knockdown of miR-29. We delivered specific anti-miRNAs to the mouse brain using a neurotropic peptide, thus overcoming the blood-brain-barrier and restricting the effect of knockdown to the neuronal cells. Large regions of the hippocampus and cerebellum showed massive cell death, reiterating the role of miR-29 in neuronal survival. The mice showed characteristic features of ataxia, including reduced step length. However, the apoptotic targets of miR-29, such as Puma, Bim, Bak, or Bace1, failed to show expected levels of up-regulation in mice, following knockdown of miR-29. In contrast, another miR-29 target, voltage-dependent anion channel1 (VDAC1), was found to be induced several fold in the hippocampus, cerebellum, and cortex of mice following miRNA knockdown. Partial restoration of apoptosis was achieved by down-regulation of VDAC1 in miR-29 knockdown cells. Our study suggests that regulation of VDAC1 expression by miR-29 is an important determinant of neuronal cell survival in the brain. Loss of miR-29 results in dysregulation of VDAC1, neuronal cell death, and an ataxic phenotype. 相似文献
74.
Ross N. Cuthbert Amanda Callaghan Arnaud Sentis Arpita Dalal Jaimie T. A. Dick 《Ecological Entomology》2020,45(2):243-250
1. Multiple predator interactions may profoundly alter ecological community dynamics and can complicate predictions of simpler pairwise predator–prey interaction strengths. In particular, multiple predator effects may lessen or enhance prey risk, with implications for community-level stability. Such emergent effects may modulate natural enemy efficacy towards target organisms. 2. In the present study, a functional response approach was used to quantify emergent multiple predator effects among natural enemies towards the disease vector mosquito complex, Culex pipiens. Conspecific multiple predator–predator interactions of the cyclopoid copepod Macrocyclops albidus (intermediate predator) were quantified by comparing multiple predator consumption simulations, based on individual consumption rates, with multiple predator consumption rates that were experimentally observed. Further, the study examined the influence of the presence of a predator at a higher trophic level, Chaoborus flavicans, on copepod group predation. 3. Both predators displayed type II functional responses, with C. flavicans consuming significantly more prey than M. albidus individually. Overall consumption levels of mosquitoes increased with greater predator density and richness. Antagonistic or synergistic emergent multiple predator effects between conspecifics of M. albidus were not detected, and the higher-level predator did not reduce effects of the intermediate predator. Accordingly, evidence for additive multiple predator interactions was found. 4. The lack of predator–predator interference between cyclopoid copepods and larval chaoborid midges provides strong support for their combined application in mosquito biocontrol. It is proposed that there should be increased examination of multiple predator effects in assessments of natural enemy efficacies to better understand overall predatory effects within communities and utilities in vector control. 相似文献
75.
76.
Arpita Saha Amit Kumar Gaurav Unnati M Pandya Marjia Afrin Ranjodh Sandhu Vishal Nanavaty Brittny Schnur Bibo Li 《Nucleic acids research》2021,49(10):5637
Telomere repeat-containing RNA (TERRA) has been identified in multiple organisms including Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. T. brucei regularly switches its major surface antigen, VSG, to evade the host immune response. VSG is expressed exclusively from subtelomeric expression sites, and we have shown that telomere proteins play important roles in the regulation of VSG silencing and switching. In this study, we identify several unique features of TERRA and telomere biology in T. brucei. First, the number of TERRA foci is cell cycle-regulated and influenced by TbTRF, the duplex telomere DNA binding factor in T. brucei. Second, TERRA is transcribed by RNA polymerase I mainly from a single telomere downstream of the active VSG. Third, TbTRF binds TERRA through its C-terminal Myb domain, which also has the duplex DNA binding activity, in a sequence-specific manner and suppresses the TERRA level without affecting its half-life. Finally, levels of the telomeric R-loop and telomere DNA damage were increased upon TbTRF depletion. Overexpression of an ectopic allele of RNase H1 that resolves the R-loop structure in TbTRF RNAi cells can partially suppress these phenotypes, revealing an underlying mechanism of how TbTRF helps maintain telomere integrity. 相似文献
77.
R Saha U Banik S Bandopadhyay N C Mandal B Bhattacharyya S Roy 《The Journal of biological chemistry》1992,267(9):5862-5867
4,4'-bis(1-anilino-8-naphthalenesulfonic acid (Bis-ANS), an environment-sensitive fluorescent probe for hydrophobic region of proteins, binds specifically to the C-terminal domain of lambda repressor. The binding is characterized by positive cooperativity, the magnitude of which is dependent on protein concentration in the concentration range where dimeric repressor aggregates to a tetramer. In this range, positive cooperativity becomes more pronounced at higher protein concentrations. This suggests a preferential binding of Bis-ANS to the dimeric form of the repressor. Binding of single operator OR1 to the N-terminal domain of the repressor causes enhancement of fluorescence of the C-terminal domain bound Bis-ANS. The binding of single operator OR1 also leads to quenching of fluorescence of tryptophan residues, all of which are located in the hinge or the C-terminal domain. Thus two different fluorescent probes indicate an operator-induced conformational change which affects the C-terminal domain. The significance of this conformational change with respect to the function of lambda repressor has been discussed. 相似文献
78.
Souvik Kar Kiran Kumar Bali Arpita Baisantry Robert Geffers Christian Hartmann Amir Samii Helmut Bertalanffy 《Cellular and molecular neurobiology》2018,38(7):1369-1382
Cerebral cavernous malformations (CCM) are vascular malformations associated with abnormally dilated blood vessels and leaky capillaries that often result in hemorrhages. Despite recent advances, precise understanding of the cellular and molecular mechanism leading to the pathogenesis of CCM remains elusive. Emerging evidence indicates that small nucleolar RNAs (snoRNAs), belonging to the class of non-coding RNAs, may play a significant role as diagnostic markers in human diseases. However, there is no report till date that studied the role of snoRNAs in CCM biology. The objective of the current study was to identify snoRNAs associated with CCM pathogenesis. Using genome-wide small RNA sequencing, we identified a total of 271 snoRNAs reliably expressed in CCM. By applying additional statistical stringency, three snoRNAs (SNORD115-32, SNORD114-22, and SNORD113-3) were found to be significantly downregulated in CCM patient tissue samples (n?=?3) as compared to healthy brains (n?=?3). Deregulation of the selected snoRNAs was further validated by qRT-PCR. Further, cellular localization via in situ hybridization also confirmed robust reduction in the expression of SNORD115-32 and SNORD114-22 in CCM tissues as compared to the healthy controls. By applying high-throughput sequencing and cellular localization analyses, we report here for the first time the genome-wide expression profile of snoRNAs in CCM tissues and a robust downregulation of candidate snoRNAs in CCM conditions. Future studies should warrant the screening in large CCM patient cohorts and will be helpful in the development of potential biomarkers and improved clinical diagnosis. 相似文献
79.
Jayesh Sheth Mehul Mistri Riddhi Bhavsar Dhairya Pancholi Mahesh Kamate Neerja Gupta Madhulika Kabra Sanjiv Mehta Sheela Nampoothiri Arpita Thakker Vivek Jain Raju Shah Frenny Sheth 《BMC neurology》2018,18(1):203