80 research outputs found

    The Human Rights Regime: A Critique of ‘Universality’ in a Patriarchal World

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    The international human rights regime can be traced to the embodiment of human rights provisions in the United Nations Charter and the Universal Declaration of Human Rights sixty years ago. The 60th anniversary of the Universal Declaration of Human Rights is an opportunity to remind ourselves that the task of securing universal human rights is not over; it has merely begun. Human rights cannot be universal without human rights for women. Since human right’s of women are still in jeopardy, we need to continue our efforts to move the human rights discourse for women from rhetoric to reality

    Structural Basis for DNA Recognition by FoxO1 and Its Regulation by Posttranslational Modification

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    SummaryFoxO transcription factors regulate the transcription of genes that control metabolism, cellular proliferation, stress tolerance, and possibly life span. A number of posttranslational modifications within the forkhead DNA-binding domain regulate FoxO-mediated transcription. We describe the crystal structures of FoxO1 bound to three different DNA elements and measure the change in FoxO1-DNA affinity with acetylation and phosphorylation. The structures reveal additional contacts and increased DNA distortion for the highest affinity DNA site. The flexible wing 2 region of the forkhead domain was not observed in the structures but is necessary for DNA binding, and we show that p300 acetylation in wing 2 reduces DNA affinity. We also show that MST1 phosphorylation of FoxO1 prevents high-affinity DNA binding. The observation that FoxO-DNA affinity varies between response elements and with posttranslational modifications suggests that modulation of FoxO-DNA affinity is an important component of FoxO regulation in health and misregulation in disease

    Quantifying polarization changes induced by rotating Dove prisms and K-mirrors

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    Dove prisms and K-mirrors are devices extensively used for rotating the wavefront of an optical field. These devices have several applications, including measurement of orbital angular momentum, microscopy, beam steering and pattern recognition. However, the wavefront rotation achieved through these devices is always accompanied by polarization changes in the incident field, which is an undesirable feature in many of these applications. Although the polarization changes induced by a Dove prism have been explored to quite some extent, no such study is available for a K-mirror. In this letter, we theoretically and experimentally investigate polarization changes induced in the transmitted field by a rotating K-mirror. For quantifying such polarization changes, we define a quantity, mean polarization change D, which ranges from 0 to {\pi}. We find that K-mirrors can reduce D to about 0.03{\pi}, for any incident state of polarization; however, reducing D to the same extent with a Dove prism is practically unviable. Therefore, K-mirrors are better alternatives to Dove prisms in applications in which the polarization changes accompanying wavefront rotation need to be minimum.Comment: Main text: 12 pages, Supplementary Information: 11 page

    Adenomatoid odontogenic tumor with impacted mandibular canine: a case report

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    The Adenomatoid Odontogenic Tumor (AOT) is a rare, slow growing, benign, odontogenic epithelial tumor with characteristic clinical and histological features; which usually arise in the second or third decade. It is a tumor composed of odontogenic epithelium in a variety of histoarchitectural patterns which are embedded in a mature connective tissue stroma. It is mostly encountered in young patients with a greater predilection for females. Maxilla is the predilection site of occurrence, most commonly associated with an unerupted maxillary canine. It presents as a symptom-free lesion and is frequently discovered during routine radiographic examination. This case report describes an unusual case of 20 year old male with only a one month history of tumor in the anterior mandible. The tumor was a well circumscribed intraosseous lesion with an embedded tooth. Histological evidence of calcification was present. The present case lends support to the categorization of AOT as a mixed odontogenic tumo

    Effect of antenatal corticosteroids on neonatal outcome in term elective caesarean section: a randomised controlled trial

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    Background: Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications. Thus, the aim of this randomized controlled trial was to assess the effect of antenatal corticosteroids on neonatal outcome among term pregnant women undergoing elective caesarean section.Methods: It was an open labelled randomized controlled trial conducted among women with term pregnancy of 37-38+6 weeks and planned for caesarean section at term and who were willing to participate in the study. We randomized 50 pregnant women into intervention group which received antenatal corticosteroids in the form of injection dexamethasone 12 mg IM, 4 doses at 12 hourly intervals before term elective caesarean section and 50 pregnant women into control group which did not receive antenatal corticosteroid. Fetal outcomes were compared in both groups after caesarean section. Data were analysed using SPSS vs.20.Results: Nearly half (54%) of pregnant women belonged age group of 21-25 years and majority (58%) of pregnant women belonged to 38-39 weeks of gestation. Out of 50 pregnant women in intervention group, only two percent neonates developed RDS, four percent neonates developed transient tachypnea of neonate (TTN) and six percent neonates required NICU admission which was lower than control group. However, difference between fetal outcomes in intervention and control group was not statistically significant (p>0.05).Conclusions: Administration of prophylactic antenatal corticosteroids before 48 hours of elective term caesarean section does not have impact on fetal outcome in our study

    The Coenzyme A Level Modulator Hopantenate (HoPan) Inhibits Phosphopantotenoylcysteine Synthetase Activity

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    The pantothenate analogue hopantenate (HoPan) is widely used as a modulator of coenzyme A (CoA) levels in cell biology and disease models-especially for pantothenate kinase associated neurodegeneration (PKAN), a genetic disease rooted in impaired CoA metabolism. This use of HoPan was based on reports that it inhibits pantothenate kinase (PanK), the first enzyme of CoA biosynthesis. Using a combination of in vitro enzyme kinetic studies, crystal structure analysis, and experiments in a typical PKAN cell biology model, we demonstrate that instead of inhibiting PanK, HoPan relies on it for metabolic activation. Once phosphorylated, HoPan inhibits the next enzyme in the CoA pathway-phosphopantothenoylcysteine synthetase (PPCS)-through formation of a nonproductive substrate complex. Moreover, the obtained structure of the human PPCS in complex with the inhibitor and activating nucleotide analogue provides new insights into the catalytic mechanism of PPCS enzymes-including the elusive binding mode for cysteine-and reveals the functional implications of mutations in the human PPCS that have been linked to severe dilated cardiomyopathy. Taken together, this study demonstrates that the molecular mechanism of action of HoPan is more complex than previously thought, suggesting that the results of studies in which it is used as a tool compound must be interpreted with care. Moreover, our findings provide a clear framework for evaluating the various factors that contribute to the potency of CoA-directed inhibitors, one that will prove useful in the future rational development of potential therapies of both human genetic and infectious diseases

    Identification of allosteric hotspots regulating the ribosomal RNA binding by antibiotic resistance-conferring Erm methyltransferases

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    Antibiotic resistance via epigenetic methylation of ribosomal RNA is one of the most prevalent strategies adopted by multidrug resistant pathogens. The erythromycin-resistance methyltransferase (Erm) methylates rRNA at the conserved A2058 position and imparts resistance to macrolides such as erythromycin. However, the precise mechanism adopted by Erm methyltransferases for locating the target base within a complicated rRNA scaffold remains unclear. Here, we show that a conserved RNA architecture, including specific bulge sites, present more than 15 Å from the reaction center, is key to methylation at the pathogenic site. Using a set of RNA sequences site-specifically labeled by fluorescent nucleotide surrogates, we show that base flipping is a prerequisite for effective methylation and that distal bases assist in the recognition and flipping at the reaction center. The Erm–RNA complex model revealed that intrinsically flipped-out bases in the RNA serve as a putative anchor point for the Erm. Molecular dynamic simulation studies demonstrated the RNA undergoes a substantial change in conformation to facilitate an effective protein–rRNA handshake. This study highlights the importance of unique architectural features exploited by RNA to impart fidelity to RNA methyltransferases via enabling allosteric crosstalk. Moreover, the distal trigger sites identified here serve as attractive hotspots for the development of combination drug therapy aimed at reversing resistance

    Profiling of Plant Derived Natural Constituents by Using Magnetic Resonance Techniques

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    Plants are reservoirs of naturally occurring chemical constituents with a wide range of structural diversity. These biological compounds can be derived from different parts of plants such as leaves, barks, seeds, seed coats, flowers, and roots. A broad array of secondary metabolic compounds is present in the plants such as antibiotics, alkaloids, antimicrobials, food-grade pigments, and phenolics which have been reported to possess numerous health-related benefits, including antioxidant, anti-inflammatory, anticancer, and antiobesity activities. Therefore, the identification and detection of these compounds are of utmost importance in order to utilise their benefits into various fields. Wherein, magnetic resonance techniques, such as NMR (nuclear magnetic resonance), MRI (magnetic resonance imaging), and EPR (electron paramagnetic resonance), being far more reproducible, nondestructive, than other analytical techniques such as liquid chromatography, mass spectroscopy, and high-performance liquid chromatography cover a much wider dynamic range of metabolites with easy sample preparation techniques with high speed and fidelity. Hence, these magnetic resonance techniques have been proven to be extremely useful in plant metabolite profiling and disease metabolomics, along with structural elucidation of bioactive compounds from plant sources. Therefore, the present review focuses on the effectiveness of magnetic resonance for the detection of plant-derived metabolites that may lead to new areas of research in various fields such as drug discovery and development, metabolomics, combinatorial chemistry, and assessing overall food safety and quality

    Assessment of Environmental Factors in Occurrence of Uterine Fibroids Among North Indian Women Aged between 35- 49yrs.

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    Uterine fibroids have always been the prime medical issue for females, especially the ones travelling in their reproductive age ( 20-35), with some studies reporting 20-80% of women developing fibroids by th
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