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121.
Peter Boyd Delphine Desjardins Sandeep Kumar Susan M. Fetherston Roger Le-Grand Nathalie Dereuddre-Bosquet Berglind Helgadóttir ásgeir Bjarnason Manjula Narasimhan R. Karl Malcolm 《PloS one》2015,10(5)
BackgroundProduct adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.MethodsA silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal.ResultsIn vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques.ConclusionsVaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials. 相似文献
122.
Korhan Buyukturkoglu Hans Roettgers Jens Sommer Mohit Rana Leonie Dietzsch Ezgi Belkis Arikan Ralf Veit Rahim Malekshahi Tilo Kircher Niels Birbaumer Ranganatha Sitaram Sergio Ruiz 《PloS one》2015,10(8)
Introduction
Obsessive-compulsive disorder (OCD) is a common and chronic condition that can have disabling effects throughout the patient''s lifespan. Frequent symptoms among OCD patients include fear of contamination and washing compulsions. Several studies have shown a link between contamination fears, disgust over-reactivity, and insula activation in OCD. In concordance with the role of insula in disgust processing, new neural models based on neuroimaging studies suggest that abnormally high activations of insula could be implicated in OCD psychopathology, at least in the subgroup of patients with contamination fears and washing compulsions.Methods
In the current study, we used a Brain Computer Interface (BCI) based on real-time functional magnetic resonance imaging (rtfMRI) to aid OCD patients to achieve down-regulation of the Blood Oxygenation Level Dependent (BOLD) signal in anterior insula. Our first aim was to investigate whether patients with contamination obsessions and washing compulsions can learn to volitionally decrease (down-regulate) activity in the insula in the presence of disgust/anxiety provoking stimuli. Our second aim was to evaluate the effect of down-regulation on clinical, behavioural and physiological changes pertaining to OCD symptoms. Hence, several pre- and post-training measures were performed, i.e., confronting the patient with a disgust/anxiety inducing real-world object (Ecological Disgust Test), and subjective rating and physiological responses (heart rate, skin conductance level) of disgust towards provoking pictures.Results
Results of this pilot study, performed in 3 patients (2 females), show that OCD patients can gain self-control of the BOLD activity of insula, albeit to different degrees. In two patients positive changes in behaviour in the EDT were observed following the rtfMRI trainings. Behavioural changes were also confirmed by reductions in the negative valence and in the subjective perception of disgust towards symptom provoking images.Conclusion
Although preliminary, results of this study confirmed that insula down-regulation is possible in patients suffering from OCD, and that volitional decreases of insula activation could be used for symptom alleviation in this disorder. 相似文献123.
Host‐induced gene silencing inhibits the biotrophic pathogen causing downy mildew of lettuce
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Manjula Govindarajulu Lynn Epstein Tadeusz Wroblewski Richard W. Michelmore 《Plant biotechnology journal》2015,13(7):875-883
Host‐induced gene silencing (HIGS) is an RNA interference‐based approach in which small interfering RNAs (siRNAs) are produced in the host plant and subsequently move into the pathogen to silence pathogen genes. As a proof‐of‐concept, we generated stable transgenic lettuce plants expressing siRNAs targeting potentially vital genes of Bremia lactucae, a biotrophic oomycete that causes downy mildew, the most important disease of lettuce worldwide. Transgenic plants, expressing inverted repeats of fragments of either the Highly Abundant Message #34 (HAM34) or Cellulose Synthase (CES1) genes of B. lactucae, specifically suppressed expression of these genes, resulting in greatly reduced growth and inhibition of sporulation of B. lactucae. This demonstrates that HIGS can provide effective control of B. lactucae in lettuce; such control does not rely on ephemeral resistance conferred by major resistance genes and therefore offers new opportunities for durable control of diverse diseases in numerous crops. 相似文献
124.
Nageswara Rao Tipirisetti Suresh Govatati Priyanka Pullari Sravanthi Malempati Murali Krishna Thupurani Shyam Perugu Praveen Guruvaiah Lakshmi Rao K Raghunadha Rao Digumarti Varadacharyulu Nallanchakravarthula Manjula Bhanoori Vishnupriya Satti 《PloS one》2014,9(1)
Background
Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species (ROS). Association of D-loop alterations with breast cancer has been reported in few ethnic groups; however none of the reports were documented from Indian subcontinent.Methodology
We screened the entire mitochondrial D-loop region (1124 bp) of breast cancer patients (n = 213) and controls (n = 207) of south Indian origin by PCR-sequencing analysis. Haplotype frequencies for significant loci, the standardized disequilibrium coefficient (D′) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software.Principal Findings
We identified 7 novel mutations and 170 reported polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (60%) than in II (30%) of D-loop region. The frequencies of 310‘C’ insertion (P = 0.018), T16189C (P = 0.0019) variants and 310‘C’ins/16189C (P = 0.00019) haplotype were significantly higher in cases than in controls. Furthermore, strong LD was observed between nucleotide position 310 and 16189 in controls (D′ = 0.49) as compared to patients (D′ = 0.14).Conclusions
Mitochondrial D-loop alterations may constitute inherent risk factors for breast cancer development. The analysis of genetic alterations in the D-loop region might help to identify patients at high risk for bad progression, thereby helping to refine therapeutic decisions in breast cancer. 相似文献125.
Choudhury Mitali Koduru Tejaswi Naidu Kumar Naveen Salimi Sasan Desai Kavya Prabhu Nagu Prakash Sritharan Manjula 《Biometals》2021,34(3):511-528
BioMetals - Iron-starved Mycobacterium tuberculosis utilises the carboxymycobactin-mycobactin siderophore machinery to acquire iron. These two siderophores have high affinity for ferric iron and... 相似文献
126.
Microparticle powders for nasal delivery were formulated to contain the model drug, zolmitriptan, and varying proportions
of different polymers. The objective of the study was to investigate the effects of these formulative parameters on the surface
chemistry of the spray-dried microparticles and their potential for adhesion to the tested substrates, porcine mucin, and
nasal tissue. The polymers used were chitosans of varying ionization states and molecular weights and hydroxypropyl methyl
cellulose. The surface energies of the surfaces of the microparticles were determined using contact angle measurements and
the van Oss model. The theory of surface thermodynamics was applied to determine the theoretical potential for the different
materials to adhere to the substrates. It was found that the drug or polymers alone, as well as the various formulations,
were more likely to adhere to mucin than to nasal tissue. Further, there was a trend for higher molecular weight chitosans
to adhere better to the substrates than lower molecular weight chitosans. Similarly, adhesion was improved for formulations
with a higher content of polymers. These theoretical predictions may be compared with further experimental results and be
of use in making informed decisions on the choice of formulations for future expensive bio-studies. 相似文献
127.
Manjula R. Shyam 《Ocean Development & International Law》2013,44(2):147-170
Abstract The U.N. Law of the Sea Convention, ambiguous on military uses of the ocean space, weakens the legal basis for the maritime powers to pursue freely their military objectives in the oceans. Repudiation of the Convention by the United States will accelerate the creeping jurisdiction of the littoral states. The Convention enhances the security of the littoral states of the Indian Ocean, all of whom have only limited blue‐water capabilities and have sought to contain the military intrusions of the superpowers into the Indian Ocean. 相似文献
128.
Praveen K. Sobhan Mahendra Seervi Lokesh Deb Saneesh Varghese Anjana Soman Jeena Joseph Krupa Ann Mathew Godi Raghu George Thomas Sreekumar E Manjula S Santosh Kumar T. R 《PloS one》2013,8(4)
Fluorescent protein based signaling probes are emerging as valuable tools to study cell signaling because of their ability to provide spatio- temporal information in non invasive live cell mode. Previously, multiple fluorescent protein probes were employed to characterize key events of apoptosis in diverse experimental systems. We have employed a live cell image based approach to visualize the key events of apoptosis signaling induced by zerumbone, the active principle from ginger Zingiber zerumbet, in cancer cells that enabled us to analyze prominent apoptotic changes in a hierarchical manner with temporal resolution. Our studies substantiate that mitochondrial permeabilisation and cytochrome c dependent caspase activation dominate in zerumbone induced cell death. Bax activation, the essential and early event of cell death, is independently activated by reactive oxygen species as well as calpains. Zerumbone failed to induce apoptosis or mitochondrial permeabilisation in Bax knockout cells and over-expression of Bax enhanced cell death induced by zerumbone confirming the essential role of Bax for mitochondrial permeabilsation. Simultaneous inhibition of reactive oxygen species and calpain is required for preventing Bax activation and cell death. However, apoptosis induced by zerumbone was prevented in Bcl 2 and Bcl-XL over-expressing cells, whereas more protection was afforded by Bcl 2 specifically targeted to endoplasmic reticulum. Even though zerumbone treatment down-regulated survival proteins such as XIAP, Survivin and Akt, it failed to affect the pro-apoptotic proteins such as PUMA and BIM. Multiple normal diploid cell lines were employed to address cytotoxic activity of zerumbone and, in general, mammary epithelial cells, endothelial progenitor cells and smooth muscle cells were relatively resistant to zerumbone induced cell death with lesser ROS accumulation than cancer cells. 相似文献
129.
Sonika Patial Yogesh Saini Sitaram Parvataneni Daniel M. Appledorn Gerald W. Dorn II John J. LaPres Andrea Amalfitano Patricia Senagore Narayanan Parameswaran 《Journal of cellular physiology》2011,226(3):627-637
G‐protein‐coupled receptor kinase 2 (GRK2) is a member of a kinase family originally discovered for its role in the phosphorylation and desensitization of G‐protein‐coupled receptors. It is expressed in high levels in myeloid cells and its levels are altered in many inflammatory disorders including sepsis. To address the physiological role of myeloid cell‐specific GRK2 in inflammation, we generated mice bearing GRK2 deletion in myeloid cells (GRK2?mye). GRK2?mye mice exhibited exaggerated inflammatory cytokine/chemokine production, and organ injury in response to lipopolysaccharide (LPS, a TLR4 ligand) when compared to wild‐type littermates (GRK2fl/fl). Consistent with this, peritoneal macrophages from GRK2?mye mice showed enhanced inflammatory cytokine levels when stimulated with LPS. Our results further identify TLR4‐induced NF‐κB1p105‐ERK pathway to be selectively regulated by GRK2. LPS‐induced activation of NF‐κB1p105‐MEK‐ERK pathway is significantly enhanced in the GRK2?mye macrophages compared to GRK2fl/fl cells and importantly, inhibition of the p105 and ERK pathways in the GRK2?mye macrophages, limits the enhanced production of LPS‐induced cytokines/chemokines. Taken together, our studies reveal previously undescribed negative regulatory role for GRK2 in TLR4‐induced p105‐ERK pathway as well as in the consequent inflammatory cytokine/chemokine production and endotoxemia in mice. J. Cell. Physiol. 226: 627–637, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
130.
Rao DN Manjula G Sailaja K Surekha D Raghunadharao D Rajappa S Vishnupriya S 《Indian journal of human genetics》2011,17(3):175-178