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51.
Mechanical activity of cells and the stress imposed on them by extracellular environment is a constant source of injury to the plasma membrane (PM). In invasive tumor cells, increased motility together with the harsh environment of the tumor stroma further increases the risk of PM injury. The impact of these stresses on tumor cell plasma membrane and mechanism by which tumor cells repair the PM damage are poorly understood. Ca2+ entry through the injured PM initiates repair of the PM. Depending on the cell type, different organelles and proteins respond to this Ca2+ entry and facilitate repair of the damaged plasma membrane. We recently identified that proteins expressed in various metastatic cancers including Ca2+-binding EF hand protein S100A11 and its binding partner annexin A2 are used by tumor cells for plasma membrane repair (PMR). Here we will discuss the involvement of S100, annexin proteins and their regulation of actin cytoskeleton, leading to PMR. Additionally, we will show that another S100 member – S100A4 accumulates at the injured PM. These findings reveal a new role for the S100 and annexin protein up regulation in metastatic cancers and identify these proteins and PMR as targets for treating metastatic cancers. 相似文献
52.
Manish Jaiswal Nele A. Haelterman Hector Sandoval Bo Xiong Taraka Donti Auinash Kalsotra Shinya Yamamoto Thomas A. Cooper Brett H. Graham Hugo J. Bellen 《PLoS biology》2015,13(7)
Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise. 相似文献
53.
Xuejun Tian Upasana Gala Yongping Zhang Weina Shang Sonal Nagarkar Jaiswal Alberto di Ronza Manish Jaiswal Shinya Yamamoto Hector Sandoval Lita Duraine Marco Sardiello Roy V. Sillitoe Kartik Venkatachalam Hengyu Fan Hugo J. Bellen Chao Tong 《PLoS biology》2015,13(3)
Autophagy helps deliver sequestered intracellular cargo to lysosomes for proteolytic degradation and thereby maintains cellular homeostasis by preventing accumulation of toxic substances in cells. In a forward mosaic screen in Drosophila designed to identify genes required for neuronal function and maintenance, we identified multiple cacophony (cac) mutant alleles. They exhibit an age-dependent accumulation of autophagic vacuoles (AVs) in photoreceptor terminals and eventually a degeneration of the terminals and surrounding glia. cac encodes an α1 subunit of a Drosophila voltage-gated calcium channel (VGCC) that is required for synaptic vesicle fusion with the plasma membrane and neurotransmitter release. Here, we show that cac mutant photoreceptor terminals accumulate AV-lysosomal fusion intermediates, suggesting that Cac is necessary for the fusion of AVs with lysosomes, a poorly defined process. Loss of another subunit of the VGCC, α2δ or straightjacket (stj), causes phenotypes very similar to those caused by the loss of cac, indicating that the VGCC is required for AV-lysosomal fusion. The role of VGCC in AV-lysosomal fusion is evolutionarily conserved, as the loss of the mouse homologues, Cacna1a and Cacna2d2, also leads to autophagic defects in mice. Moreover, we find that CACNA1A is localized to the lysosomes and that loss of lysosomal Cacna1a in cerebellar cultured neurons leads to a failure of lysosomes to fuse with endosomes and autophagosomes. Finally, we show that the lysosomal CACNA1A but not the plasma-membrane resident CACNA1A is required for lysosomal fusion. In summary, we present a model in which the VGCC plays a role in autophagy by regulating the fusion of AVs with lysosomes through its calcium channel activity and hence functions in maintaining neuronal homeostasis. 相似文献
54.
Katerina A. Christopoulos Susan Olender Andrea M. Lopez Helen-Maria Lekas Jessica Jaiswal Will Mellman Elvin Geng Kimberly A. Koester 《PLoS medicine》2015,12(8)
Background
Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART.Methods and Findings
We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting.Conclusions
Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care. 相似文献55.
Guava (Psidium guajava L.), an important fruit crop of several tropical and sub-tropical countries, is facing several agronomic and horticultural
problems such as susceptibility to many pathogens, particularly guava wilting caused by Fusarium oxysporium psidii, low fruit growth, short shelf life of fruits, high seed content, and stress sensitivity. Conventional breeding techniques
have limited scope in improvement of guava owing to long juvenile period, self incompatibility, and heterozygous nature. Conventional
propagation methods, i.e., cutting, grafting or stool layering, for improvement of guava already exist, but the long juvenile
period has made them time consuming and cumbersome. Several biotechnological approaches such as genetic transformation may
be effective practical solutions for such problems and improvement of guava. The improvement of fruit trees through genetic
transformation requires an efficient regeneration system. During the past 2–3 decades, different approaches have been made
for in vitro propagation of guava. An overview on the in vitro regeneration of guava via organogenesis, somatic embryogenesis,
and synthetic seeds is presented. Organogenesis in several different genotypes through various explant selection from mature
tree and seedling plants has been achieved. Factors affecting somatic embryogenesis in guava have been reviewed. Production
of synthetic seeds using embryogenic propagules, i.e., somatic embryos and non-embryogenic vegetative propagules, i.e., shoot
tips and nodal segments have also been achieved. Development of synthetic seed in guava may be applicable for propagation,
short-term storage, and germplasm exchange, and distribution. An initial attempt for genetic transformation has also been
reported. The purpose of this review is to focus upon the current information on in vitro propagation and biotechnological
advances made in guava. 相似文献
56.
R. Prasanna A. Sood P. Jaiswal S. Nayak V. Gupta V. Chaudhary M. Joshi C. Natarajan 《Applied Biochemistry and Microbiology》2010,46(2):119-134
Cyanobacteria are a simple, but primitive and diverse group of microorganisms, with characteristics in common to both bacteria and algae. Their success as a group in a wide range of habitats has been attributed to their unique physiological characters and high adaptive ability under a wide range of environmental conditions. The potential of cyanobacteria as a source of a variety of compounds such as polysaccharides, lipids, proteins, vitamins, sterols, enzymes, pharmaceuticals and other fine chemicals is well recognized, and their demand is now on an increasing trend. This compilation reviews the salient advances in the discovery of bioactive compounds from cyanobacteria and their significance in agriculture and industry. 相似文献
57.
Alkalophilic bacterial consortium developed by continuous enrichment in the chemostat in presence of 4-chlorosalicylic acid
as sole source of carbon and energy contained six bacterial strains, Micrococcus luteus (csa101), Deinococcus radiothilus (csa102), csa103 (Burkholderia gladioli), Alloiococcus otilis (csa104), Micrococcus diversus (csa105), Micrococcus luteus (csa106), identified by the Biolog test method. The strains were tested for utilization of organic compounds in which one
of the strains (csa101) had higher potency to utilize dibenzofuran (DF) as sole carbon and energy source identified as Serratia marcescens on the basis of 16S rDNA. The degradation of DF by bacterial strain proceeded through an oxidative route as indicated by
2,2′3-trihydroxybiphenyl, 2-hydroxy-6-(2-hydroxyphenyl)-6-oxo-2,4-hexadienoic acid, salicylic acid, and catechol, which was
identified by gas chromatography–mass spectrometry. 相似文献
58.
The problem of predicting the enzymes and non-enzymes from the protein sequence information is still an open problem in bioinformatics. It is further becoming more important as the number of sequenced information grows exponentially over time. We describe a novel approach for predicting the enzymes and non-enzymes from its amino-acid sequence using artificial neural network (ANN). Using 61 sequence derived features alone we have been able to achieve 79 percent correct prediction of enzymes/non-enzymes (in the set of 660 proteins). For the complete set of 61 parameters using 5-fold cross-validated classification, ANN model reveal a superior model (accuracy = 78.79 plus or minus 6.86 percent, Q(pred) = 74.734 plus or minus 17.08 percent, sensitivity = 84.48 plus or minus 6.73 percent, specificity = 77.13 plus or minus 13.39 percent). The second module of ANN is based on PSSM matrix. Using the same 5-fold cross-validation set, this ANN model predicts enzymes/non-enzymes with more accuracy (accuracy = 80.37 plus or minus 6.59 percent, Q(pred) = 67.466 plus or minus 12.41 percent, sensitivity = 0.9070 plus or minus 3.37 percent, specificity = 74.66 plus or minus 7.17 percent). 相似文献
59.
An increase in cell number is one of the most prominent characteristics of cancer cells. This may be caused by an increase in cell proliferation or decrease in cell death. Queuine is one of the modified base which is found at first anticodon position of specific tRNAs. It is ubiquitously present throughout the living system except mycoplasma and yeast. The tRNAs of Q-family are completely modified to Q-tRNAs in terminally differentiated somatic cells, however hypomodification of Q-tRNA is closely associated with cell proliferation and malignancy. Queuine participates at various cellular functions such as regulation of cell proliferation, cell signaling and alteration in the expression of growth associated proto-oncogenes. Like other proto-oncogenes bcl2 is known to involve in cell survival by inhibiting apoptosis. Queuine or Q-tRNA is suggested to inhibit cell proliferation but the mechanism of regulation of cell proliferation by queuine or Q-tRNA is not well understood. Therefore, in the present study regulation in cell proliferation by queuine in vivo and in vitro as well as the expression of cell death regulatory protein Bcl2 are investigated. For this DLAT cancerous mouse, U87 cell line and HepG2 cell line are treated with different concentrations of queuine and the effect of queuine on cell proliferation and apoptosis are studied. The results indicate that queuine down regulates cell proliferation and expression of Bcl2 protein, suggesting that queuine promotes cell death and participates in the regulation of cell proliferation. 相似文献
60.
Singh N Pandey SK Anand N Dwivedi R Singh S Sinha SK Chaturvedi V Jaiswal N Srivastava AK Shah P Siddiqui MI Tripathi RP 《Bioorganic & medicinal chemistry letters》2011,21(15):4404-4408
An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 μg/mL against M. tuberculosis and very good inhibition of α-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 μg/mL. The present study opens a new gate to synthesize antitubercular agents for diabetic TB patients. In silico docking studies indicate that mycobacterial dihydrofolate reductase is the possible target of these compounds. 相似文献