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31.
Crystal structure of Staphylococcal β‐ketoacyl‐ACP reductase 1 (SaFabG1) complexed with NADPH is determined at 2.5 Å resolution. The enzyme is essential in FAS‐II pathway and utilizes NADPH to reduce β‐ketoacyl‐ACP to (S)‐β‐hydroxyacyl‐ACP. Unlike the tetrameric FabGs, dimeric SaFabG1 shows positive homotropic cooperativity towards NADPH. Analysis of FabG:NADPH binary crystal structure endorses that NADPH interacts directly with the helices α4 and α5 those are present on a dimerization interface. A steady shift in tryptophan (of α4 helix) emission peak upon steady increment of NADPH concentration reveals that the dimeric interface is formed by α4‐α4′ and α5‐α5′ helices. This dimeric interface imparts positive homotropic cooperativity towards NADPH. PEG, a substrate mimicking molecule is also found near the active site of the enzyme. Proteins 2012; © 2011 Wiley Periodicals, Inc. 相似文献
32.
Rita Ghosh Sudipta Bhowmik Angshuman Bagchi Dipankar Das Somnath Ghosh 《European biophysics journal : EBJ》2010,39(8):1243-1249
Acridines and their derivatives are well-known probes for nucleic acids as well as being relevant in the field of drug development
to establish new chemotherapeutic agents. We have shown from molecular modelling studies that 9-phenyl acridine and some of
its derivatives can act as inhibitors of topoisomerase I and thus have potential to act as anticancer agents. Rational design
of new compounds for therapeutics requires knowledge about their structural stability and interactions with various cellular
macromolecules. In this regard it is important to know how these molecules would interact with DNA. Here we report the interaction
of 9-phenyl acridine (ACPH) with calf thymus DNA (CT-DNA) based on various biophysical and molecular modelling studies. Spectrophotometric
studies indicated that ACPH binds to CT-DNA. DNA melting studies revealed that binding of ACPH to CT-DNA resulted in a small
increase in melting temperature, which is unlikely in case of classical intercalator; rather, it indicates external binding.
Viscosity measurements show that ACPH exhibits groove binding. Competitive binding of ACPH to CT-DNA pre-bound to ethidium
bromide (EB) showed slow quenching. Measurement of the binding constant of ACPH by fluorescent intercalator displacement (FID)
assay corroborated the notion that there was groove binding. Molecular modelling studies also supported this finding. Results
indicate that binding of ACPH is through partial intercalation in the minor groove of DNA. 相似文献
33.
Three coordination complexes of formula [Ni(L1)2(H2O)4].4H2O (1), [Mn(L2)2(H2O)4] (2) and [Mn(L2)2(H2O)2]n (3) [L1H = 6-methylpyridine-3-carboxylic acid, L2H = 3-(3-pyridyl)acrylic acid] have been synthesized and structurally characterized by X-ray single crystal analysis. A 3D network is achieved through H-bonding in 1 and 2, while crystal packing of complex 3 shows a 3D supramolecular coordination polymer. Thermal properties have been investigated by thermogravimetric analysis. Luminescence study features the presence of LMCT and metal purterbed ligand centered emission bands. 相似文献
34.
Talgat M. Inerbaev Sudipta Seal Artëm E. Masunov 《Journal of molecular modeling》2010,16(10):1617-1623
We report plane wave basis density functional theory (DFT) calculations of the oxygen vacancies formation energy in nanocrystalline
CeO
2-x
in comparison with corresponding results for bulk and (111) CeO2 surface. Effects of strong electronic correlation of Ce4f states are taken into account through the use of an effective on-site Coulomb repulsive interaction within DFT+U approach. Different combinations of exchange-correlation functionals and corresponding U values reported in the literature are tested and the obtained results compared with experimental data. We found that both
absolute values and trends in oxygen vacancy formation energy depend on the value of U and associated with degree of localization of Ce4f states. Effect of oxygen vacancy and geometry optimization method on spatial spin distribution in model ceria nanoparticles
is also discussed. 相似文献
35.
Gohar Mazmanian Michael Kovshilovsky Debbie Yen Aditya Mohanty Sudipta Mohanty Alex Nee Robert M. Nissen 《Genesis (New York, N.Y. : 2000)》2010,48(1):20-30
Nodal‐signaling is required for specification of mesoderm, endoderm, establishing left–right asymmetry, and craniofacial development. Wdr68 is a WD40‐repeat domain‐containing protein recently shown to be required for endothelin‐1 (edn1) expression and subsequent lower jaw development. Previous reports detected the Wdr68 protein in multiprotein complexes containing mammalian members of the dual‐specificity tyrosine‐regulated kinase (dyrk) family. Here we describe the characterization of the zebrafish dyrk1b homolog. We report the detection of a physical interaction between Dyrk1b and Wdr68. We also found perturbations of nodal signaling in dyrk1b antisense morpholino knockdown (dyrk1b‐MO) animals. Specifically, we found reduced expression of lft1 and lft2 (lft1/2) during gastrulation and a near complete loss of the later asymmetric lft1/2 expression domains. Although wdr68‐MO animals did not display lft1/2 expression defects during gastrulation, they displayed a near complete loss of the later asymmetric lft1/2 expression domains. While expression of ndr1 was not substantially effected during gastrulation, ndr2 expression was moderately reduced in dyrk1b‐MO animals. Analysis of additional downstream components of the nodal signaling pathway in dyrk1b‐MO animals revealed modestly expanded expression of the dorsal axial mesoderm marker gsc while the pan‐mesodermal marker bik was largely unaffected. The endodermal markers cas and sox17 were also moderately reduced in dyrk1b‐MO animals. Notably, and similar to defects previously reported for wdr68 mutant animals, we also found reduced expression of the pharyngeal pouch marker edn1 in dyrk1b‐MO animals. Taken together, these data reveal a role for dyrk1b in endoderm formation and craniofacial patterning in the zebrafish. genesis 48:20–30, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
36.
Fluorescence Correlation Spectroscopy (FCS) can measure diffusion on the cell surface with unparalleled sensitivity. In appropriate situations, this can be the most sensitive and accurate method for measuring receptor interaction and oligomerization. Here we attempt to describe FCS in sufficient detail so that the reader is able to judge when there is a compelling reason to choose this technique, understand the basic theory behind it, construct a FCS spectrometer in the laboratory, and analyze the data to obtain a meaningful estimate of the physical parameters. 相似文献
37.
Hilary K. Brown Sudipta Saha Timothy C.Y. Chan Angela M. Cheung Michael Fralick Marzyeh Ghassemi Margaret Herridge Janice Kwan Shail Rawal Laura Rosella Terence Tang Adina Weinerman Yona Lunsky Fahad Razak Amol A. Verma 《CMAJ》2022,194(4):E112
Background:Disability-related considerations have largely been absent from the COVID-19 response, despite evidence that people with disabilities are at elevated risk for acquiring COVID-19. We evaluated clinical outcomes in patients who were admitted to hospital with COVID-19 with a disability compared with patients without a disability.Methods:We conducted a retrospective cohort study that included adults with COVID-19 who were admitted to hospital and discharged between Jan. 1, 2020, and Nov. 30, 2020, at 7 hospitals in Ontario, Canada. We compared in-hospital death, admission to the intensive care unit (ICU), hospital length of stay and unplanned 30-day readmission among patients with and without a physical disability, hearing or vision impairment, traumatic brain injury, or intellectual or developmental disability, overall and stratified by age (≤ 64 and ≥ 65 yr) using multivariable regression, controlling for sex, residence in a long-term care facility and comorbidity.Results:Among 1279 admissions to hospital for COVID-19, 22.3% had a disability. We found that patients with a disability were more likely to die than those without a disability (28.1% v. 17.6%), had longer hospital stays (median 13.9 v. 7.8 d) and more readmissions (17.6% v. 7.9%), but had lower ICU admission rates (22.5% v. 28.3%). After adjustment, there were no statistically significant differences between those with and without disabilities for in-hospital death or admission to ICU. After adjustment, patients with a disability had longer hospital stays (rate ratio 1.36, 95% confidence interval [CI] 1.19–1.56) and greater risk of readmission (relative risk 1.77, 95% CI 1.14–2.75). In age-stratified analyses, we observed longer hospital stays among patients with a disability than in those without, in both younger and older subgroups; readmission risk was driven by younger patients with a disability.Interpretation:Patients with a disability who were admitted to hospital with COVID-19 had longer stays and elevated readmission risk than those without disabilities. Disability-related needs should be addressed to support these patients in hospital and after discharge.A successful public health response to the COVID-19 pandemic requires accurate and timely identification of, and support for, high-risk groups. There is increasing recognition that marginalized groups, including congregate care residents, racial and ethnic minorities, and people experiencing poverty, have elevated incidence of COVID-19.1,2 Older age and comorbidities such as diabetes are also risk factors for severe COVID-19 outcomes.3,4 One potential high-risk group that has received relatively little attention is people with disabilities.The World Health Organization estimates there are 1 billion people with disabilities globally.5 In North America, the prevalence of disability is 20%, with one-third of people older than 65 years having a disability.6 Disabilities include physical disabilities, hearing and vision impairments, traumatic brain injury and intellectual or developmental disabilities.5,6 Although activity limitations experienced by people with disabilities are heterogeneous,5,6 people with disabilities share high rates of risk factors for acquiring COVID-19, including poverty, residence in congregate care and being members of racialized communities.7–9 People with disabilities may be more reliant on close contact with others to meet their daily needs, and some people with disabilities, especially intellectual developmental disabilities, may have difficulty following public health rules. Once they acquire SARS-CoV-2 infection, people with disabilities may be at risk for severe outcomes because they have elevated rates of comorbidities.10 Some disabilities (e.g., spinal cord injuries and neurologic disabilities) result in physiologic changes that increase vulnerability to respiratory diseases and may mask symptoms of acute respiratory disease, which may delay diagnosis.11–13 There have also been reports of barriers to high-quality hospital care for patients with disabilities who have COVID-19, including communication issues caused by the use of masks and restricted access to support persons.14–17Some studies have suggested that patients with disabilities and COVID-19 are at elevated risk for severe disease and death, with most evaluating intellectual or developmental disability.13,18–26 Yet, consideration of disability-related needs has largely been absent from the COVID-19 response, with vaccine eligibility driven primarily by age and medical comorbidity, limited accommodations made for patients with disabilities who are in hospital, and disability data often not being captured in surveillance programs.14–17 To inform equitable pandemic supports, there is a need for data on patients with a broad range of disabilities who have COVID-19. We sought to evaluate standard clinical outcomes in patients admitted to hospital with COVID-1927 (i.e., in-hospital death, intensive care unit [ICU] admission, hospital length of stay and unplanned 30-d readmission) for patients with and without a disability, overall and stratified by age. We hypothesized that patients with a disability would have worse outcomes because of a greater prevalence of comorbidities,10 physiologic characteristics that increase morbidity risk11–13 and barriers to high-quality hospital care.14–17 相似文献
38.
Sudipta?Misra Rahul?Kundurahulkundu@yahoo.com" title="rskundu_ad@sancharnet.in rahulkundu@yahoo.com" itemprop="email" data-track="click" data-track-action="Email author" data-track-label="">Email author 《Aquatic Ecology》2005,39(3):315-324
The paper deals with the spatial and the temporal variability of the population dynamics of five key molluscan species at two rocky intertidal shores on the southern Saurashtra coastline of India. The intertidal belts of the two selected stations, Veraval and Diu, are about 100 km apart and differ in their coast characteristics and level of human interference. The slope and the substrate types of the two stations are not uniform and the exposure of intertidal belt of these predominantly rocky shores during low tides is also not significantly long. The study revealed that a general, species specific pattern of spatial and temporal variations existed in the population abundance and density of the species studied. There was considerable spatial variability in some species examined but most species showed no clear seasonal trends for the population abundance. The Veraval coast, in spite of being affected by heavy human interference, is still a favourable place for Chiton, Turbo cornatus and Turbo intercoastalis than Diu, though the latter is relatively less affected by anthropogenic influences. It appears that the subtratum type, short exposure duration and moderate wave action of the Arabian Sea are most active controlling factors for higher distribution of these species at Veraval. 相似文献
39.
Samuel C. Hames Sudipta Sinnya Jean-Marie Tan Conrad Morze Azadeh Sahebian H. Peter Soyer Tarl W. Prow 《PloS one》2015,10(1)
Background
Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions.Objective
The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible.Methods
Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group.Results
The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group.Conclusions
The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face. 相似文献40.
Anand Kant Das Rucha Pandit Sudipta Maiti 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1672)
Certain neurodegenerative diseases are thought to be initiated by the aggregation of amyloidogenic proteins. However, the mechanism underlying toxicity remains obscure. Most of the suggested mechanisms are generic in nature and do not directly explain the neuron-type specific lesions observed in many of these diseases. Some recent reports suggest that the toxic aggregates impair the synaptic vesicular machinery. This may lead to an understanding of the neuron-type specificity observed in these diseases. A disruption of the vesicular machinery can also be deleterious for extra-synaptic, especially somatic, neurotransmission (common in serotonergic and dopaminergic systems which are specifically affected in Alzheimer''s disease (AD) and Parkinson''s disease (PD), respectively), though this relationship has remained unexplored. In this review, we discuss amyloid-induced damage to the neurotransmitter vesicular machinery, with an eye on the possible implications for somatic exocytosis. We argue that the larger size of the system, and the availability of multi-photon microscopy techniques for directly visualizing monoamines, make the somatic exocytosis machinery a more tractable model for understanding the effect of amyloids on all types of vesicular neurotransmission. Indeed, exploring this neglected connection may not just be important, it may be a more fruitful route for understanding AD and PD. 相似文献