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1.
Nat Commun ; 15(1): 5458, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937429

ABSTRACT

Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Cryoelectron Microscopy , Epitopes , Animals , Antibodies, Neutralizing/immunology , Humans , Antibodies, Viral/immunology , Epitopes/immunology , Sigmodontinae , Single-Domain Antibodies/immunology , Single-Domain Antibodies/chemistry , Viral Fusion Proteins/immunology , Viral Fusion Proteins/chemistry , Female , Camelus/immunology , Camelus/virology
2.
bioRxiv ; 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38659837

ABSTRACT

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that can cause severe disease in humans with case fatality rates of 10-40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we used structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-GnH-DS-Gc). A cryo-EM structure of this complex provides the molecular basis for GP38's association on the viral surface, reveals the structure of Gn, and demonstrates that GP38-Gn restrains the Gc fusion loops in the prefusion conformation, facilitated by an N-linked glycan attached to Gn. Immunization with GP38-GnH-DS-Gc conferred 40% protection against lethal IbAr10200 challenge in mice. These data define the architecture of a GP38-Gn-Gc protomer and provide a template for structure-guided vaccine antigen development.

3.
J Virol ; 98(2): e0137223, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38214525

ABSTRACT

Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the Henipavirus genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus, Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks.


Subject(s)
Hendra Virus , Henipavirus Infections , Henipavirus , Nipah Virus , Viral Proteins , Humans , Glycoproteins/metabolism , Hendra Virus/physiology , Henipavirus/physiology , Nipah Virus/genetics , Nipah Virus/metabolism , Peptides/metabolism , Viral Fusion Proteins , Viral Proteins/metabolism
4.
Article in English | MEDLINE | ID: mdl-38083467

ABSTRACT

Intracellular oxidative stress generation is a root cause of the dysfunctioning of mitochondria that is accountable for neurodegenerative disorders. In nano-CeO2, the intrinsic redox cycle (Ce3+ ⇔ Ce4+) confers them with a distinct oxygen buffering ability. Thus, increasing the Ce3+/Ce4+ ratio by preferentially engineering oxygen vacancies is expected to boost the antioxidant characteristics in CeO2 nanocrystals (NCs) and hold promise in nanotherapeutics of neurodegenerative disorders. Here, a pristine, economic, and scalable synthesis route with rapid nucleation-growth to yield monodispersed CeO2 NCs of 4 nm has been employed. The NCs demonstrated sustained colloidal stability (zeta potential ~ -30.3±7.2 mV). The survival rate (~96.1% for 0.1 mg/mL) of healthy L929 cells and cell apoptosis induced on the SH-SY5Y cells (~ 30.2% for 0.1 mg/mL) indicate nano-CeO2s' prospects in nanomedicine. The formulated sustainable synthesis strategy for the enrichment of defects in these NCs is anticipated to pave the way for nanocrystal-based-treatments in smart healthcare.Clinical Relevance-This investigation signifies the oxygen vacancy-dependent therapeutic efficacy of CeO2 NCs by ensuring ~96.1% survival rate of L929 cells while demonstrating cell apoptosis on SH-SY5Y cells (~ 30.2%) to establish newer insights on treatment of neurodegenerative disorders.


Subject(s)
Nanoparticles , Neuroblastoma , Neurodegenerative Diseases , Humans , Reactive Oxygen Species , Nanoparticles/chemistry , Oxygen/chemistry
6.
Natl J Maxillofac Surg ; 14(2): 213-220, 2023.
Article in English | MEDLINE | ID: mdl-37661977

ABSTRACT

Purpose: The study aimed to determine the muscle pattern of medial pterygoid, lateral pterygoid, and masseter (length, cross-section, and angulation) in adult non-orthodontic patients and its effect on craniofacial structures. Methods: The study was conducted from January 14, 2019 to January 14, 2020. Ethical clearance of this study was obtained from the ethical committee Ethical Clearance was obtained from Faculty of Dental Sciences, IMS, BHU, Institutional Ethical Committee with Ref no. Dean/2019/EC/1824 dated 23.04.2019 of the university. The sample size was estimated using the G-power statistical program. Power analysis indicated a minimum sample size of 27. Inclusion and exclusion criteria were set. Consent was taken from participants. Seventy-seven subjects who were willing to participate and have given written consent were enrolled for the study. Participants were sent for lateral cephalometry (Dolphin Cephalometric software) Dolphin Imaging and management solution, for 6 angular and 11 linear measurements. Nineteen subjects did not turn up for the scan. Twenty-eight participants underwent MRI (magnetic resonance imaging) to evaluate muscle patterns (masseter, medial, and lateral pterygoid). The intra-class correlation coefficient (ICC), Kolmogorov-Smirnov (KS) test, descriptive statistics, and multiple regression analysis were computed. The P value was set as ≤0.001(highly statistically significant) and ≤0.05 (significant relation). Results: There was a highly statistically significant (p ≤ 0.001) association between masseter length to upper facial height (N-Ans) and ramal length (Cd-Go). Length of medial pterygoid was significantly related (p ≤ 0.05) with SNB and length of body of mandible (Pog-Go). The cross-section of this muscle showed significant relation with upper facial height (N-Ans) and ramal length (Cd-Go). The correlation of the length of lateral pterygoid with upper facial height (N-Ans) and maxillary length (A-Ptm) was highly significant. Conclusion: The muscle pattern has a significant correlation with maxillofacial morphology. The masseter muscle is the longest and thickest (cross-section) and is angulated vertically than the other two muscles (medial pterygoid and lateral pterygoid). Of the three muscles, the medial pterygoid influences more common craniofacial parameters suggestive of its symbiotic activity. Lateral pterygoid affects the maxillary length and facial height.

7.
Small ; 19(37): e2300549, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37203304

ABSTRACT

Next-generation electronics and energy technologies can now be developed as a result of the design, discovery, and development of novel, environmental friendly lead (Pb)-free ferroelectric materials with improved characteristics and performance. However, there have only been a few reports of such complex materials' design with multi-phase interfacial chemistry, which can facilitate enhanced properties and performance. In this context, herein, novel lead-free piezoelectric materials (1-x)Ba0.95 Ca0.05 Ti0.95 Zr0.05 O3 -(x)Ba0.95 Ca0.05 Ti0.95 Sn0.05 O3 , are reported, which are represented as (1-x)BCZT-(x)BCST, with demonstrated excellent properties and energy harvesting performance. The (1-x)BCZT-(x)BCST materials are synthesized by high-temperature solid-state ceramic reaction method by varying x in the full range (x = 0.00-1.00). In-depth exploration research is performed on the structural, dielectric, ferroelectric, and electro-mechanical properties of (1-x)BCZT-(x)BCST ceramics. The formation of perovskite structure for all ceramics without the presence of any impurity phases is confirmed by X-ray diffraction (XRD) analyses, which also reveals that the Ca2+ , Zr4+ , and Sn4+ are well dispersed within the BaTiO3 lattice. For all (1-x)BCZT-(x)BCST ceramics, thorough investigation of phase formation and phase-stability using XRD, Rietveld refinement, Raman spectroscopy, high-resolution transmission electron microscopy (HRTEM), and temperature-dependent dielectric measurements provide conclusive evidence for the coexistence of orthorhombic + tetragonal (Amm2 + P4mm) phases at room temperature. The steady transition of Amm2 crystal symmetry to P4mm crystal symmetry with increasing x content is also demonstrated by Rietveld refinement data and related analyses. The phase transition temperatures, rhombohedral-orthorhombic (TR-O ), orthorhombic- tetragonal (TO-T ), and tetragonal-cubic (TC ), gradually shift toward lower temperature with increasing x content. For (1-x)BCZT-(x)BCST ceramics, significantly improved dielectric and ferroelectric properties are observed, including relatively high dielectric constant εr ≈ 1900-3300 (near room temperature), εr ≈ 8800-12 900 (near Curie temperature), dielectric loss, tan δ ≈ 0.01-0.02, remanent polarization Pr ≈ 9.4-14 µC cm-2 , coercive electric field Ec ≈ 2.5-3.6 kV cm-1 . Further, high electric field-induced strain S ≈ 0.12-0.175%, piezoelectric charge coefficient d33 ≈ 296-360 pC N-1 , converse piezoelectric coefficient ( d 33 ∗ ) ave ${( {d_{33}^*} )}_{{\rm{ave}}}$ ≈ 240-340 pm V-1 , planar electromechanical coupling coefficient kp ≈ 0.34-0.45, and electrostrictive coefficient (Q33 )avg ≈ 0.026-0.038 m4 C-2 are attained. Output performance with respect to mechanical energy demonstrates that the (0.6)BCZT-(0.4)BCST composition (x = 0.4) displays better efficiency for generating electrical energy and, thus, the synthesized lead-free piezoelectric (1-x)BCZT-(x)BCST samples are suitable for energy harvesting applications. The results and analyses point to the outcome that the (1-x)BCZT-(x)BCST ceramics as a potentially strong contender within the family of Pb-free piezoelectric materials for future electronics and energy harvesting device technologies.

8.
Acta Biomater ; 147: 377-390, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35609802

ABSTRACT

The versatility of ZnO quantum dots (QDs) exhibiting size-tunable visible photoluminescence has propelled them to the forefront of leading-edge innovations in healthcare. At the nano-bio interface, enhancing the singly-ionized oxygen vacancy defects (VO•) through holistic, sustainable synthesis protocols driven by the synergistic influence of QDs' nucleation-growth kinetics has implications on their bioactivity, physiochemical, and optical performance. Recently, robust continuous flow platforms have transcended the conventional batch reactors by alleviating the concerns of "hot-spot" formation due to inhomogeneous heat distribution, acute energy consumption, poor quality, and yield. However, complexities exist in translating batch chemistries into flow processes. Here, a unique, rationally designed continuous flow synthesis of luminescent defect-engineered ZnO QDs (E-QDs) via helical-reactor assembly that can adequately synthesize on a large scale is reported. The crux of this lies in the amalgamation of "green chemistry" and flow synthesis, which results in Lamer-mechanism mediated monodispersed E-QDs demonstrating high photoluminescence quantum yield (PLQY) of 89% under an accurately regulated synthesis environment. Process intensification corroborated that the bio-stable E-QDs manifested admirable photostability, broad-spectrum UV-shielding (400-250 nm), colloidal stability, in vitro biocompatibility against L929 and HaCaT cells, and antioxidant activity. These attributes were better compared to the commercial ZnO nanoparticles (ZnOC-NPs) used for skin UV protection. Delving deeper, the main drivers for the high density of intrinsic VO• formation (Iv/Io∼42.5) were revealed to be the reactor's hydrodynamic performance and the improvised heating rate (2.5°C/sec). Hence, these E-QDs have potential as a new, safe, and economical multifunctional active ingredient for skin UV protection and antioxidants for treating ROS-mediated disorders. STATEMENT OF SIGNIFICANCE: UV filters exhibiting questionable UV-attenuation efficacy and phototoxicity are significant impediments to the healthcare industry emphasizing skin cancer prevention. Although least explored, VO•-governed aberrant photoactive, biological, and surface-reactive qualities of engineered ZnO QDs (E-QDs) have created ample room to investigate these hallmarks for skin UV protection. However, the bottlenecks in stereotypical ZnO QDs production confined by inefficient process control are annihilated by continuous flow strategies. Herein, the high-throughput continuous flow helical reactor assembly was designed and fabricated to successfully showcase optimized transport properties, reproducibility, yield, and quality E-QDs. Anticipating a skyrocketing demand for E-QDs as bioactive-sunscreen components, the comprehensive investigation has demonstrated unprecedented biofunctionality and ROS-scavenging behaviour, even upon UVR exposure, contrary to the traditional nanoparticulate ZnO UV filters.


Subject(s)
Quantum Dots , Zinc Oxide , Luminescence , Quantum Dots/chemistry , Reactive Oxygen Species , Reproducibility of Results , Zinc Oxide/chemistry , Zinc Oxide/pharmacology
9.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 3): 5134-5143, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36742538

ABSTRACT

To examine the changes of upper airway cross sectional area in each phase of respiration in different degrees of severity of OSAS with computed tomography and cephalometry to decide on further treatment. A Prospective study was done in the Department of Radiology and Imaging, Kasturba Medical College, Mangalore, spanning over a period from March 2017 to December 2019. 50 patients were included in the study including control group. Patients who had at least 2-3 major symptoms of sleep apnea such as snoring, daytime somnolence, and apnea were included in this study. All patients were examined and then subjected to polysomnography(PSG) and upper airway CT. Patients with apnea-hypopnea index (AHI) of < 5 on Polysomnography were included in the control group and those with AHI of > 5 were categorized in to the study group Cross-sectional area of the airway at the level of the nasopharynx, oropharynx and the hypopharynx were obtained. Standard cephalometric measurements were made on a lateral radiograph of skull/ CT scanogram. Of the 36 patients in the study group, 31 patients were males and 5 were females. In the control group of 12 patients, 8 were males and 4 females. The cross sectional area at the lower border of the nasopharynx which is also the level of the nasopharyngeal sphincter was the most affected level in OSAS (p value of < 0.0001). Mean uvular diameter in the control group was 9.6 mm and in the OSAS group it was 11.2 mm. The mean length of the soft palate was 36.4 mm in the controls, 39.5 mm in the mild/moderate OSAS and 41.2 mm in the severe OSAS group. Obstructive sleep apnea is a complex disorder characterized by apneic episodes during sleep. In this study the most common site of obstruction is nasopharyngeal sphincter and the oropharynx. Although PSG is the diagnostic test of choice, imaging plays an important role in planning surgical and conventional treatment.

10.
Indian J Community Med ; 45(4): 435-439, 2020.
Article in English | MEDLINE | ID: mdl-33623196

ABSTRACT

BACKGROUND: Hypertension prevalence is related to dietary sodium chloride intake. People are consuming much more sodium than is physiologically necessary. The consumption of processed food in urban India has led to a prevalence of 24%-30% of hypertension. The people have a special liking of such type of foods. This study aimed at assessing consumption of sodium among the study subjects to compare habitual additional consumption of sodium among hypertensive and normotensive patients and to find its associate factors impacting hypertension. MATERIALS AND METHODS: The hospital based, cross-sectional study was conducted on patients attending the outpatient department of general medicine. The sample size was 520 patients. Habitual additional intake of each patient was assessed by a food frequency table. RESULTS: As the age advances, the proportion of hypertensive patients increases (P < 0.05). Among hypertensive patients, 38.65% were not doing exercise (P < 0.05). The body mass index >25 was found among 11.92% normotensives and among 25.38% hypertensives (P < 0.05). There were 23% of hypertensive patients who could not receive dietary advice (P < 0.05). Habitual additional sodium consumption is more among 15-25 years age group (P < 0.05). Habitual additional sodium intake mean for those who were taking a pinch of salt is higher (P < 0.05). Habitual additional sodium intake is found to be significantly impacted by younger age, diagnosis, and lack of dietary advice (P < 0.05, P < 0.05, and P < 0.05). CONCLUSION: Most of the age groups are consuming more than 2 g habitual additional sodium which is more than the World Health Organization-recommended maximum levels. The dietary advice was given to hypertensives that had a positive impact on habitual additional sodium intake.

11.
J Pharm Biomed Anal ; 174: 396-405, 2019 Sep 10.
Article in English | MEDLINE | ID: mdl-31212140

ABSTRACT

A specific liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) assay was developed and validated for simultaneous determination of two active metabolites of isosorbide dinitrate (ISDN), namely, isosorbide 2-mononitrate (IS 2-MN) and isosorbide 5-mononitrate (IS 5-MN). A simple protein precipitation extraction technique was employed using 13C6 isosorbide 5-mononitrate as the internal standard. The two isomers were separated on a chiral column and mass detection was carried out by electrospray ionization (ESI) in negative multiple reaction monitoring (MRM) mode (ESI -ve). As neutral organic nitrates do not ionize well in ESI ion source, adduct formation of IS 2-MN and IS 5-MN were evaluated. Acetate adduct ions of IS 2-MN and IS 5-MN were well ionized and fragmentable in the negative mode by liquid chromatography electrospray ionization/tandem mass spectrometry. These acetates adduct ions, of IS 2-MN and IS 5-MN were selected as parent mass for quantitation. The method was developed and validated in rat and human plasma with K2EDTA as an anticoagulant. This simultaneous quantitation method was shown to be linear over a working range of 25.0 ng/mL to 5050 ng/mL and 12.4 ng/mL to 2500 ng/mL for IS 2-MN (r2 > 0.99) and IS 5-MN (r2 > 0.99), respectively, in rat and human plasma. Sensitivity was determined as 25.0 ng/mL for IS 2-MN and 12.4 ng/mL for IS 5-MN in rat and human plasma. Inter- and intra-day accuracy and precision were within ±15% in both method validations. This validated method was subsequently applied to a pharmacokinetic (PK) study of ISDN in rat after oral administration.


Subject(s)
Chromatography, Liquid/methods , Isosorbide Dinitrate/analogs & derivatives , Isosorbide Dinitrate/blood , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Administration, Oral , Animals , Blood Chemical Analysis/methods , Humans , Male , Quality Control , Rats , Rats, Sprague-Dawley , Reproducibility of Results
12.
J Pharm Biomed Anal ; 172: 113-119, 2019 Aug 05.
Article in English | MEDLINE | ID: mdl-31029800

ABSTRACT

Bepridil is potent inhibitor of Na+, K+ and Ca+ channel in cardiomyocytes. It has demonstrated strong antianginal effect with type I antiarrhythmic and with minimum antihypertensive therapeutic effect. Till date, a specific LC-MS/MS method to quantify Bepridil concentrations in biological matrix have not been reported yet. In current study, a highly sensitive, specific and simple LC-MS/MS method for quantification of antianginal drug Bepridil in rat plasma is presented. The LC-MS/MS method was validated in terms of selectivity, specificity, sensitivity, accuracy and precision, matrix effect, extraction recovery and stability as per USFDA's bioanalytical method validation guideline. The validated assay was applied for quantification of Bepridil from pharmacokinetic study in rats following oral and intravenous administration. The lower limit of quantification (LLOQ) of Bepridil was 1 ng/mL. The calibration curve ranges from 1 ng/mL to 1000 ng/mL with desirable linearity and r2 > 0.99. The method exhibited 10-fold dilution integrity. The intra-day and inter-day accuracy were within 101.32-96.80% and 102.87-95.35% with coefficient of variation 10.11-2.89% and 10.45-3.97% respectively. No significant interference observed by endogenous peak at the retention time of Bepridil and IS. The assay was free from any matrix effect, precise recovery across the calibration curve range and samples were stable under all experimental conditions. The validated assay was successfully applied to analyze plasma samples of pharmacokinetic study in rat to determine concentrations of Bepridil. In summary, a novel method for analyzing Bepridil in rat plasma has been successfully validated and is now being utilized for quantification of Bepridil from pre-clinical studies.


Subject(s)
Bepridil/blood , Calcium Channel Blockers/blood , Drug Monitoring/methods , Animals , Bepridil/pharmacokinetics , Calcium Channel Blockers/pharmacokinetics , Chromatography, High Pressure Liquid , Limit of Detection , Male , Models, Animal , Rats , Reproducibility of Results , Sensitivity and Specificity , Tandem Mass Spectrometry
13.
Glob Chall ; 2(11): 1800025, 2018 Nov.
Article in English | MEDLINE | ID: mdl-31565311

ABSTRACT

Ideal multifunctional ultraviolet radiation (UVR) absorbents with excellent photostability, high molar absorptivity, broadband UVR screening, and desired skin sensorial properties remain a significant challenge for the sunscreen industry. The potential of the nanocomplex (NCx) formed by microwave synthesis of ZnO quantum dots (QDs) in the presence of Avobenzone (Av) for achieving these goals is reported. The NCx exhibits unique synergy between ZnO QD and Av components, which enhances the photostability and molar absorptivity, extends UVA filtering range, and provides a visible emission that matches the typical human in vivo skin emission color. Density functional theory (DFT) and time-dependent DFT calculations of ZnO-Av hybrid structures and comparison of their spectroscopic features with experiments suggest that ZnO QDs catalyze the formation of highly photostable surface enolate species via aldol condensation reaction. The combination of experiments and computations used in this study can advance the science and technology of photoprotection.

14.
Virulence ; 8(7): 1316-1334, 2017 10 03.
Article in English | MEDLINE | ID: mdl-28436748

ABSTRACT

Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analyzed to understand its mechanisms of virulence, resistance and evolution. Comparative genome analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome. Many intermittent horizontal gene transfer events, insertion sequence (IS) element insertions identified were augmenting resistance machinery and elevating the SNP densities in A. baumannii eventually aiding in their swift evolution. ISAba1, the most widely distributed insertion sequence in A. baumannii was found in multiple sites in PKAB07. Out of many ISAba1 insertions, we identified novel insertions in 9 different genes wherein insertional inactivation of adeN (tetR type regulator) was significant. To assess the significance of this disruption in A. baumannii, adeN mutant and complement strains were constructed in A. baumannii ATCC 17978 strain and studied. Biofilm levels were abrogated in the adeN knockout when compared with the wild type and complemented strain of adeN knockout. Virulence of the adeN knockout mutant strain was observed to be high, which was validated by in vitro experiments and Galleria mellonella infection model. The overexpression of adeJ, a major component of AdeIJK efflux pump observed in adeN knockout strain could be the possible reason for the elevated virulence in adeN mutant and PKB07 strain. Knocking out of adeN in ATCC strain led to increased resistance and virulence at par with the PKAB07. Disruption of tetR type regulator adeN by ISAba1 consequently has led to elevated virulence in this pathogen.


Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/genetics , Acinetobacter baumannii/pathogenicity , Bacterial Proteins/metabolism , Mutagenesis, Insertional , Trans-Activators/metabolism , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/metabolism , Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Humans , Interspersed Repetitive Sequences , Trans-Activators/genetics , Virulence
16.
Clin Case Rep ; 3(5): 331-2, 2015 May.
Article in English | MEDLINE | ID: mdl-25984316

ABSTRACT

The incidence of primary hydatid cyst of peritoneum is 2%. It can present as a palpable abdominal lump. The differential diagnosis is cystic ovarian tumor clinically and radiologically. Peritoneal hydatid disease should be included in differential diagnosis of sonographically diagnosed pelvic cystic lesion.

17.
J Phys Condens Matter ; 27(7): 072201, 2015 Feb 25.
Article in English | MEDLINE | ID: mdl-25629264

ABSTRACT

A 'powder-poling' technique was developed to study electric field induced structural transformations in ferroelectrics exhibiting a morphotropic phase boundary (MPB). The technique was employed on soft PZT exhibiting a large longitudinal piezoelectric response (d(33) ∼ 650 pC N(-1)). It was found that electric poling brings about a considerable degree of irreversible tetragonal to monoclinic transformation. The same transformation was achieved after subjecting the specimen to mechanical stress, which suggests an equivalence of stress and electric field with regard to the structural mechanism in MPB compositions. The electric field induced structural transformation was also found to be accompanied by a decrease in the spatial coherence of polarization.

18.
J Mater Chem B ; 3(22): 4597-4606, 2015 Jun 14.
Article in English | MEDLINE | ID: mdl-32262403

ABSTRACT

Preventing chronic hyperglycaemia and associated oxidative stress is utmost important for the treatment and management of Type 2 Diabetes Mellitus (T2DM). Here we report the role of different size surface defect rich ZnO quantum dots (D-QDs) for inhibiting metabolic enzymes and scavenging free radicals, which plays a key role in reducing hyperglycaemia and oxidative stress. Quantitative analysis of radical scavenging and metabolic enzyme inhibition activity of D-QDs demonstrates a size dependent behaviour, where D-QDs with a smaller diameter shows superior activity compared to larger size D-QDs. Considering the size dependence in surface defect formation, the increased surface defect density in smaller size D-QDs can be considered as the reason behind this enhancement. Detailed studies establishing the underlying mechanism behind potent free radical scavenging and enzyme inhibition provides an intense scientific rationale for considering D-QDs to design safe and effective nanomedicine for T2DM.

19.
Environ Res ; 135: 95-104, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25262081

ABSTRACT

The present work is focused on the preparation of Fe nanorods by the chemical reduction of FeCl3 (aq) using NaBH4 in the presence of glycerol as template followed by annealing of the product at 500°C in the presence of H2 gas flow. Subsequently, its surface has been modified by silica followed by silver nanoparticles to form silica coated Fe (Fe@SiO2) and Ag encapsulated Fe@SiO2 nanostructure employing the Stöber method and silver mirror reaction respectively. XRD pattern of the products confirmed the formation of bcc phase of iron and fcc phase of silver, though silica remained amorphous. FESEM images established the growth of iron nanorods from the annealed product and also formation of silica and silver coating on its surface. The appearance of the characteristics bands in FTIR confirmed the presence of SiO2 on the Fe surface. Magnetic measurements at room temperature indicated the ferromagnetic behavior of as prepared iron nanorods, Fe@SiO2 and silver encapsulated Fe@SiO2 nanostructures. All the samples exhibited strong microwave absorption property in the high frequency range (10GHz), though it is superior for Ag encapsulated Fe@SiO2 (-14.7dB) compared with Fe@SiO2 (-9.7dB) nanostructures of the same thickness. The synthesized Ag encapsulated Fe@SiO2 nanostructure also exhibited the SERS phenomena, which is useful in the detection of the carcinogenic dye crystal violet (CV) upto the concentration of 10(-10)M. All these findings clearly demonstrate that the Ag encapsulated Fe@SiO2 nanostructure could efficiently be used in the environmental remediation.


Subject(s)
Environmental Restoration and Remediation/methods , Gentian Violet/isolation & purification , Iron/chemistry , Nanotubes/chemistry , Silicon Dioxide/chemistry , Silver/chemistry , Spectrum Analysis, Raman , Absorption, Physicochemical , Borohydrides , Environmental Restoration and Remediation/instrumentation , Glycerol , Hot Temperature , Hydrogen , Microscopy, Electron, Scanning , Microwaves , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
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