Publications by authors named "Shivani Singh"

63 Publications

Pulmonary cysticercosis in an urban South African child.

Pediatr Pulmonol 2021 Sep 28. Epub 2021 Sep 28.

Dept Paediatrics & Child Health, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

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http://dx.doi.org/10.1002/ppul.25682DOI Listing
September 2021

Bacterial exo-polysaccharides in biofilms: role in antimicrobial resistance and treatments.

J Genet Eng Biotechnol 2021 Sep 23;19(1):140. Epub 2021 Sep 23.

Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.

Background: Bacterial biofilms are aggregation or collection of different bacterial cells which are covered by self-produced extracellular matrix and are attached to a substratum. Generally, under stress or in unfavorable conditions, free planktonic bacteria transform themselves into bacterial biofilms and become sessile.

Main Body: Various mechanisms involving interaction between antimicrobial and biofilm matrix components, reduced growth rates, and genes conferring antibiotic resistance have been described to contribute to enhanced resistance. Quorum sensing and multi-drug resistance efflux pumps are known to regulate the internal environment within the biofilm as well as biofilm formation; they also protect cells from antibiotic attack or immune attacks. This review summarizes data supporting the importance of exopolysaccharides during biofilm formation and its role in antibiotic resistance.

Conclusions: Involvement of quorum sensing and efflux pumps in antibiotic resistance in association with exopolysaccharides. Also, strategies to overcome or attack biofilms are provided.
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http://dx.doi.org/10.1186/s43141-021-00242-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460681PMC
September 2021

Balancing Benefits and Risks: Do ICS Modify the Lung Microbiome?

Am J Respir Crit Care Med 2021 Sep 23. Epub 2021 Sep 23.

New York University, Pulmonary and Critical Care Medicine, New York, New York, United States;

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http://dx.doi.org/10.1164/rccm.202109-2024EDDOI Listing
September 2021

Regeneration of the anterior palatal alveolar cortex after treatment of bimaxillary protrusioncristina.

Authors:
Shivani Singh

J Clin Orthod 2021 Jul;55(7):398-412

Department of Orthodontics and Dentofacial Orthopedics, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Madhav Nagar, Eshwar Nagar, Manipal, India.

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July 2021

Identification and Optimization of a Minor Allele-Specific siRNA to Prevent PNPLA3 I148M-Driven Nonalcoholic Fatty Liver Disease.

Nucleic Acid Ther 2021 Oct 23;31(5):324-340. Epub 2021 Jul 23.

Cardiometabolic Disorders, Amgen Research, South San Francisco, California, USA.

Human genome wide association studies confirm the association of the rs738409 single nucleotide polymorphism (SNP) in the gene encoding protein patatin like phospholipase domain containing 3 () with nonalcoholic fatty liver disease (NAFLD); the presence of the resulting mutant PNPLA3 I148M protein is a driver of nonalcoholic steatohepatitis (NASH). While -deficient mice do not display an adverse phenotype, the safety of knocking down endogenous wild type in humans remains unknown. To expand the scope of a potential targeted NAFLD therapeutic to both homozygous and heterozygous rs738409 populations, we sought to identify a minor allele-specific small interfering RNA (siRNA). Limiting our search to SNP-spanning triggers, a series of chemically modified siRNA were tested for activity and selectivity toward rs738409 mRNA. Conjugation of the siRNA to a triantennary -acetylgalactosamine (GalNAc) ligand enabled screening using adeno-associated virus to overexpress human versus human in mouse livers. Structure-activity relationship optimization yielded potent and minor allele-specific compounds that achieved high levels of mRNA and protein knockdown of human but not . Testing of the minor allele-specific siRNA in -expressing mice fed a NASH-inducing diet prevented -driven disease phenotypes, thus demonstrating the potential of a precision medicine approach to treating NAFLD.
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http://dx.doi.org/10.1089/nat.2021.0026DOI Listing
October 2021

Universal quantum computing using single-particle discrete-time quantum walk.

Sci Rep 2021 Jun 2;11(1):11551. Epub 2021 Jun 2.

The Institute of Mathematical Sciences, C. I. T. Campus, Taramani, Chennai, 600113, India.

Quantum walk has been regarded as a primitive to universal quantum computation. In this paper, we demonstrate the realization of the universal set of quantum gates on two- and three-qubit systems by using the operations required to describe the single particle discrete-time quantum walk on a position space. The idea is to utilize the effective Hilbert space of the single qubit and the position space on which it evolves in order to realize multi-qubit states and universal set of quantum gates on them. Realization of many non-trivial gates and engineering arbitrary states is simpler in the proposed quantum walk model when compared to the circuit based model of computation. We will also discuss the scalability of the model and some propositions for using lesser number of qubits in realizing larger qubit systems.
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http://dx.doi.org/10.1038/s41598-021-91033-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172914PMC
June 2021

Pediatric Index of Mortality 3-An Evaluation of Function Among ICUs In South Africa.

Pediatr Crit Care Med 2021 09;22(9):813-821

Department of Paediatrics and Child Health and Red Cross War Memorial Children's Hospital Intensive Care Unit, University of Cape Town, Cape Town, South Africa.

Objectives: To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model.

Design: This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay.

Setting: Nine units that care for children within tertiary or quaternary academic hospitals in South Africa.

Patients: All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old.

Interventions: None.

Measurements And Main Results: There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6-59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79-0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients.

Conclusions: The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.
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http://dx.doi.org/10.1097/PCC.0000000000002693DOI Listing
September 2021

COVID-19 and neurology perspective.

Horm Mol Biol Clin Investig 2021 Feb 23;42(1):69-75. Epub 2021 Feb 23.

Department of Radio-diagnosis, Index Medical College, Hospital and Research Centre, Indore, Madhya Pradesh, India.

COVID-19 caused by SARS CoV2 (The novel corona virus) has already taken lives of many people across the globe even more than anyone could have imagined. This outbreak occurred in China and since then it is expanding its devastating effects by leaps and bounds. Initially it appeared to be an outbreak of pneumonia but soon it was found to be much more than that and the infectivity was found to be very high. This is the reason that it has taken whole globe in its trap and become a pandemic in such a short span of time. Death is occurring because it is a new virus and human body has no specific antibodies for it. Presently there is no approved vaccine so everyone is susceptible but people with co-morbidities appear to be in more risk and the best way for protection is social distancing and increasing one's natural immunity by taking healthy diet and exercise. When a person is infected the clinical presentation ranges from asymptomatic to severe ARDS, sudden onset of anosmia, headache, cough may be the initial symptoms. This review is focused on immunopathology and effect of COVID-19 on neurological disorders and also the neurological manifestations and the treatment.
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http://dx.doi.org/10.1515/hmbci-2020-0069DOI Listing
February 2021

Naturally Inspired Pyrimidines Analogues for Alzheimer's Disease.

Curr Neuropharmacol 2021 ;19(2):136-151

Department of Pharmaceutical Sciences, M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana, (Ambala), Haryana, India.

Alzheimer's disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.
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http://dx.doi.org/10.2174/1570159X18666201111110136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033975PMC
January 2021

Yeast Nucleolin Nsr1 Impedes Replication and Elevates Genome Instability at an Actively Transcribed Guanine-Rich G4 DNA-Forming Sequence.

Genetics 2020 12 26;216(4):1023-1037. Epub 2020 Oct 26.

Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, Houston, Texas 77030

A significant increase in genome instability is associated with the conformational shift of a guanine-run-containing DNA strand into the four-stranded G-quadruplex (G4) DNA. The mechanism underlying the recombination and genome rearrangements following the formation of G4 DNA has been difficult to elucidate but has become better clarified by the identification and functional characterization of several key G4 DNA-binding proteins. Mammalian nucleolin (NCL) is a highly specific G4 DNA-binding protein with a well-defined role in the transcriptional regulation of genes with associated G4 DNA-forming sequence motifs at their promoters. The consequence of the interaction between G4 DNA and nucleolin in respect to the genome instability has not been previously investigated. We show here that the yeast nucleolin Nsr1 is enriched at a G4 DNA-forming sequence and is a major factor in inducing the genome instability associated with the cotranscriptionally formed G4 DNA in the yeast genome. We also show that Nsr1 results in impeding replication past such a G4 DNA-forming sequence. The G4-associated genome instability and the G4 DNA-binding require the arginine-glycine-glycine (RGG) repeats located at the C-terminus of the Nsr1 protein. Nsr1 with the deletion of RGG domain supports normal cell growth and is sufficient for its pre-rRNA processing function. However, the truncation of the RGG domain of Nsr1 significantly weakens its interaction with G4 DNA and restores unhindered replication, overall resulting in a sharp reduction in the genome instability associated with a guanine-rich G4 DNA-forming sequence. Our data suggest that the interaction between Nsr1 with the intact RGG repeats and G4 DNA impairs genome stability by precluding the access of G4-resolving proteins and impeding replication.
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http://dx.doi.org/10.1534/genetics.120.303736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768239PMC
December 2020

Quantum walks and Dirac cellular automata on a programmable trapped-ion quantum computer.

Nat Commun 2020 Jul 24;11(1):3720. Epub 2020 Jul 24.

Joint Quantum Institute, Department of Physics, University of Maryland, College Park, MD, 20742, USA.

The quantum walk formalism is a widely used and highly successful framework for modeling quantum systems, such as simulations of the Dirac equation, different dynamics in both the low and high energy regime, and for developing a wide range of quantum algorithms. Here we present the circuit-based implementation of a discrete-time quantum walk in position space on a five-qubit trapped-ion quantum processor. We encode the space of walker positions in particular multi-qubit states and program the system to operate with different quantum walk parameters, experimentally realizing a Dirac cellular automaton with tunable mass parameter. The quantum walk circuits and position state mapping scale favorably to a larger model and physical systems, allowing the implementation of any algorithm based on discrete-time quantum walks algorithm and the dynamics associated with the discretized version of the Dirac equation.
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http://dx.doi.org/10.1038/s41467-020-17519-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381638PMC
July 2020

A non-canonical promoter element drives spurious transcription of horizontally acquired bacterial genes.

Nucleic Acids Res 2020 05;48(9):4891-4901

Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

RNA polymerases initiate transcription at DNA sequences called promoters. In bacteria, the best conserved promoter feature is the AT-rich -10 element; a sequence essential for DNA unwinding. Further elements, and gene regulatory proteins, are needed to recruit RNA polymerase to the -10 sequence. Hence, -10 elements cannot function in isolation. Many horizontally acquired genes also have a high AT-content. Consequently, sequences that resemble the -10 element occur frequently. As a result, foreign genes are predisposed to spurious transcription. However, it is not clear how RNA polymerase initially recognizes such sequences. Here, we identify a non-canonical promoter element that plays a key role. The sequence, itself a short AT-tract, resides 5 base pairs upstream of otherwise cryptic -10 elements. The AT-tract alters DNA conformation and enhances contacts between the DNA backbone and RNA polymerase.
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http://dx.doi.org/10.1093/nar/gkaa244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229825PMC
May 2020

Small-molecule G-quadruplex stabilizers reveal a novel pathway of autophagy regulation in neurons.

Elife 2020 02 11;9. Epub 2020 Feb 11.

Department of Neurobiology and Anatomy, The University of Texas McGovern Medical School at Houston, Houston, United States.

Guanine-rich DNA sequences can fold into four-stranded G-quadruplex (G4-DNA) structures. G4-DNA regulates replication and transcription, at least in cancer cells. Here, we demonstrate that, in neurons, pharmacologically stabilizing G4-DNA with G4 ligands strongly downregulates the gene. is a critical gene for the initiation of autophagy that exhibits decreased transcription with aging. Using an in vitro assay, we show that a putative G-quadruplex-forming sequence (PQFS) in the first intron of the gene folds into a G4. An antibody specific to G4-DNA and the G4-DNA-binding protein PC4 bind to the PQFS. Mice treated with a G4 stabilizer develop memory deficits. Brain samples from aged mice contain G4-DNA structures that are absent in brain samples from young mice. Overexpressing the G4-DNA helicase Pif1 in neurons exposed to the G4 stabilizer improves phenotypes associated with G4-DNA stabilization. Our findings indicate that G4-DNA is a novel pathway for regulating autophagy in neurons.
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http://dx.doi.org/10.7554/eLife.52283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012600PMC
February 2020

Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes.

PLoS Negl Trop Dis 2019 06 3;13(6):e0007470. Epub 2019 Jun 3.

Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.

Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions. In the past decades, drug resistant P. vivax parasites have emerged, mainly in Southeast Asia, but while some molecular markers of resistance have been identified, none have so far been confirmed experimentally, which limits interpretation of the markers, and hence our ability to monitor and control the spread of resistance. Some of these potential markers have been identified through P. vivax genome-wide population genetic analyses, which highlighted genes under recent evolutionary selection in Southeast Asia, where chloroquine resistance is most prevalent. These genes could be involved in drug resistance, but no experimental proof currently exists to support this hypothesis. In this study, we used Plasmodium knowlesi, the most closely related species to P. vivax that can be cultured in human erythrocytes, as a model system to express P. vivax genes and test for their role in drug resistance. We adopted a strategy of episomal expression, and were able to express fourteen P. vivax genes, including two allelic variants of several hypothetical resistance genes. Their expression level and localisation were assessed, confirming cellular locations conjectured from orthologous species, and suggesting locations for several previously unlocalised proteins, including an apical location for PVX_101445. These findings establish P. knowlesi as a suitable model for P. vivax protein expression. We performed chloroquine and mefloquine drug assays, finding no significant differences in drug sensitivity: these results could be due to technical issues, or could indicate that these genes are not actually involved in drug resistance, despite being under positive selection pressure in Southeast Asia. These data confirm that in vitro P. knowlesi is a useful tool for studying P. vivax biology. Its close evolutionary relationship to P. vivax, high transfection efficiency, and the availability of markers for colocalisation, all make it a powerful model system. Our study is the first of its kind using P. knowlesi to study unknown P. vivax proteins and investigate drug resistance mechanisms.
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http://dx.doi.org/10.1371/journal.pntd.0007470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564043PMC
June 2019

Histopathological evaluation of a rare fulminant case of contemporaneous mucormycosis, aspergillosis and actinomycosis.

J Oral Maxillofac Pathol 2019 Jan-Apr;23(1):144-146

Department of Oral Pathology and Microbiology, Maulana Azad Institute of Dental Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/jomfp.JOMFP_64_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503770PMC
May 2019

Stent as an accessory tool in periodontal measurements: An insight.

J Indian Soc Periodontol 2019 Jan-Feb;23(1):81-84

Department of Periodontics, College of Dental Sciences, Davangere, Karnataka, India.

A better reflection of periodontal destruction can be obtained by the measurement of the clinical attachment level (CAL), i.e., the distance from the probe tip to the level of the cementoenamel junction (CEJ). However, there were several problems in CEJ identification. Due to the time consumption and inherent problems in CEJ identification, CAL measurements without using a stent in surveys or other clinical trials are highly questionable. The use of stent is recommended during clinical trials which will minimize the errors in terms of over and underestimation of CALs. Hence, the stent used for vertical probing (vertical/occlusal stent), horizontal probing (furcation stent), and interdental papilla (IDP) stent for IDP-deficiency measurement is discussed to comprehend its clinical applications.
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http://dx.doi.org/10.4103/jisp.jisp_331_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334538PMC
January 2019

Use of different concentrations of hyaluronic acid in interdental papillary deficiency treatment: A clinical study.

J Indian Soc Periodontol 2019 Jan-Feb;23(1):35-41

Department of Periodontics, College of Dental Sciences, Davangere, Karnataka, India.

Background: In the present era, demand of beauty and esthetics has increased rapidly. Interdental papilla construction, especially in the esthetic zone, is one of the most challenging tasks. Interdental papilla loss might occur due to several reasons as a consequence of periodontal surgery, trauma, and others.

Aim And Objective: The present study was aimed to prepare economically feasible injectable form of hyaluronic acid (HA) gel in three different concentrations - 1%, 2%, and 5% HA to evaluate its efficacy in the enhancement of deficient interdental papilla (IDP).

Materials And Methods: A total of 42 sites (mean age range was 29.6-30.6 years) was categorized into three groups; 1% HA group (16 sites), 2% HA group (14 sites), and 5% HA group (12 sites). Total 35 sites were followed up out of 42 in which 2% HA group included only 7 sites. Both maxillary (17 sites) and mandibular (18 sites) sites were included in this study. HA was injected at 2 mm apical to papillary tip at weekly interval for 3 weeks. The IDP augmentation was measured using UNC-15 probe and modified stent at 1, 3, and 6 months. The photographic analysis was done using Image J software.

Results: On clinical measurement, 5% of HA showed highly significant enhancement ( = 0.001) of 19.2%, 20.6% 18.2% at 1, 3, and 6 months, respectively. On photographic analysis, 5% of HA showed 41%, 42.9%, and 39.8% at 1, 3, and 6 months, respectively. However, intergroup comparison showed nonsignificant improvement.

Conclusion: This study results suggest that the use of 5% of HA is effective for interdental deficiency treatment with minimal rebound at the end of 6 months. The modified stent for IDP measurement used in this study for the first time in the literature is highly recommended. The photographic analysis using image J Analyzer serves a useful and dependable tool. Further, long-term clinical studies would throw more insight in this regard.
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http://dx.doi.org/10.4103/jisp.jisp_332_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334549PMC
January 2019

Utility of Glycosylated TIMP3 molecules: Inhibition of MMPs and TACE to improve cardiac function in rat myocardial infarct model.

Pharmacol Res Perspect 2018 12 14;6(6):e00442. Epub 2018 Nov 14.

Cardiometabolic Disorders & Therapeutic Discovery Amgen Discovery Research South San Francisco California.

Tissue Inhibitor of Metalloproteinase 3 (TIMP3) is a secreted protein that has a great utility to inhibit elevated metalloproteinase (MMP) activity in injured tissues including infarcted cardiac tissue, inflamed vessels, and joint cartilages. An imbalance between TIMP3 and active MMP levels in the local tissue area may cause worsening of disease progression. To counter balance elevated MMP levels, exogenous administration of TIMP3 appeared to be beneficial in preclinical studies. However, the current form of WT-TIMP3 molecule has a limitation to be a therapeutic candidate due to low production yield, short plasma half-life, injection site retention, and difficulty in delivery, etc. We have engineered TIMP3 molecules by adding extra glycosylation sites or fusing with albumin, Fc, and antibody to improve pharmacokinetic properties. In general, the C-terminal fusion of TIMP3 improved expression and production in mammalian cells and extended half-lives dramatically 5-20 folds. Of note, a site-specific glycosylation at K22S/F34N resulted in a higher level of expression and better cardiac function compared to other fusion proteins in the context of left ventricle ejection fraction (LVEF) changes in a rat myocardial infarction model. It appeared that cardiac efficacy depends on a high ECM binding affinity, in which K22S/F34N and N-TIMP3 showed a higher binding to the ECM compared to other engineered molecules. In conclusion, we found that the ECM binding and sustained residence of injected TIMP3 molecules are important for cardiac tissue localization and inhibition of adverse remodeling activity.
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http://dx.doi.org/10.1002/prp2.442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234480PMC
December 2018

Sarcomatoid Carcinoma: A Clinicopathological Profile of Two Cases with Diagnostic Emphasis.

Contemp Clin Dent 2018 Jun;9(Suppl 1):S164-S167

Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India.

Sarcomatoid carcinoma (SC) is an unusual and aggressive variant of squamous cell carcinoma, which frequently recurs and metastasizes, and is associated with poor survival rate. For this reason, its accurate diagnosis is very important. It is considered to be a biphasic tumor made up of epithelial as well as spindle cell component, but of epithelial origin. The diagnosis often represents a clinicopathologic challenge, and immunohistochemistry plays a key role in the histopathological diagnosis. The reported cases in oral cavity are limited. Here, we present two cases of SC where the use of immunohistochemistry allowed us to achieve a conclusive diagnosis.
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http://dx.doi.org/10.4103/ccd.ccd_43_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006888PMC
June 2018

Applications of Nanomaterials in Dental Science: A Review.

J Nanosci Nanotechnol 2017 Apr;17(4):2235-255

Nanotechnology has revolutionized health care industry in a large scale and its applications are a boon to modern medicine and dental science. It is expected to pervade and further revolutionize the art and science of dentistry and may well have important applications spanning all the aspects of oral diseases, diagnosis, prevention and treatment. Materials science in dentistry has embraced the technology to produce nanomaterials that are being used in caries inhibitors, antimicrobial resins, hard tissue remineralizing agents, targeted drug delivery, scaffolds, bio-membranes, nanocrystalline hydroxyl apatite, restorative cements, adhesion promoters and boosters, bioactive glass, tissue conditioners, reinforced methacrylate resins, root canal disinfectants, friction free orthodontic arch wires and nano composites life. These upcoming technologies have potential to bring about significant benefits in the form of improvement in dental science and to society. The present review presents the latest recent developments in this interdisciplinary field bridging nanotechnology and dental science.
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http://dx.doi.org/10.1166/jnn.2017.13885DOI Listing
April 2017

Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis.

Am J Respir Crit Care Med 2018 07;198(2):245-255

1 Infectious Diseases and Immunity, Wellcome Trust Centre for Global Health Research, and.

Rationale: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection.

Objectives: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB.

Methods: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet-monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects.

Measurements And Main Results: Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations.

Conclusions: Platelets drive a proinflammatory, tissue-degrading phenotype in TB.
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http://dx.doi.org/10.1164/rccm.201710-2102OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058979PMC
July 2018

Interleukin-17 regulates matrix metalloproteinase activity in human pulmonary tuberculosis.

J Pathol 2018 03 18;244(3):311-322. Epub 2018 Jan 18.

Infectious Diseases and Immunity, Imperial College, London, UK.

Tuberculosis (TB) is characterized by extensive pulmonary matrix breakdown. Interleukin-17 (IL-17) is key in host defence in TB but its role in TB-driven tissue damage is unknown. We investigated the hypothesis that respiratory stromal cell matrix metalloproteinase (MMP) production in TB is regulated by T-helper 17 (T -17) cytokines. Biopsies of patients with pulmonary TB were analysed by immunohistochemistry (IHC), and patient bronchoalveolar lavage fluid (BALF) MMP and cytokine concentrations were measured by Luminex assays. Primary human airway epithelial cells were stimulated with conditioned medium from human monocytes infected with Mycobacterium tuberculosis (Mtb) and T -17 cytokines. MMP secretion, activity, and gene expression were determined by ELISA, Luminex assay, zymography, RT-qPCR, and dual luciferase reporter assays. Signalling pathways were examined using phospho-western analysis and siRNA. IL-17 is expressed in TB patient granulomas and MMP-3 is expressed in adjacent pulmonary epithelial cells. IL-17 had a divergent, concentration-dependent effect on MMP secretion, increasing epithelial secretion of MMP-3 (p < 0.001) over 72 h, whilst decreasing that of MMP-9 (p < 0.0001); mRNA levels were similarly affected. Both IL-17 and IL-22 increased fibroblast Mtb-dependent MMP-3 secretion but IL-22 did not modulate epithelial MMP-3 expression. Both IL-17 and IL-22, but not IL-23, were significantly up-regulated in BALF from TB patients. IL-17-driven MMP-3 was dependent on p38 MAP kinase and the PI3K p110α subunit. In summary, IL-17 drives airway stromal cell-derived MMP-3, a mediator of tissue destruction in TB, alone and with monocyte-dependent networks in TB. This is regulated by p38 MAP kinase and PI3K pathways. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838784PMC
March 2018

To Evaluate the Correlation Between Skeletal and Dental Parameters to the Amount of Crowding in Class II Div. 1 Malocclusions.

J Clin Diagn Res 2017 Sep 1;11(9):ZC22-ZC27. Epub 2017 Sep 1.

Head, Department of Orthodontics and Dentofacial Orthopedics, College of Dental Sciences, Davangere, Karnataka, India.

Introduction: Crowding of teeth is one of the most common problem that motivates the patient to seek orthodontic treatment. Determination of etiology of crowding could have a significant effect on treatment planning and prognosis of Class II malocclusion.

Aim: Aim of this study was to evaluate the relationship of skeletal and dental parameters to amount of dental crowding in patients with Class II Divison 1 (div.1) malocclusion.

Materials And Methods: Pretreatment lateral cephalograms and dental casts of 60 patients with skeletal Class II malocclusion were collected for the study. The sample was divided into two groups according to severity of pretreatment mandibular crowding. Group I consisted of cases with crowding ≥3 mm and Group II with crowding <3 mm. Lateral cephalograms for each patient was manually traced and skeletal parameters (effective maxillary and mandibular length, mandibular plane angle, Y Axis, lower anterior face height) and dental parameters (axial inclination of lower incisor, inclination of lower incisor to mandibular plane, interincisal angle) were measured. Unpaired t-test was used for intergroup comparison and relationship between different measurements was investigated using Pearson correlation coefficient.

Results: Among the skeletal parameters measured, only effective mandibular length exhibited statistically significant difference between the two groups. No statistically significant difference was found between the two groups for any of the dental parameters. Significant inverse correlation was found between mandibular crowding and effective mandibular length.

Conclusion: Subjects with Class II div.1 malocclusion and moderate to severe mandibular crowding have significantly smaller effective mandibular base length than subjects with the same malocclusion and slight mandibular crowding.
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http://dx.doi.org/10.7860/JCDR/2017/27675.10566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713849PMC
September 2017

Impact of Cl Doping on Electrochemical Performance in Orthosilicate (LiFeSiO): A Density Functional Theory Supported Experimental Approach.

ACS Appl Mater Interfaces 2017 Aug 1;9(32):26885-26896. Epub 2017 Aug 1.

Electrochemical Energy Laboratory, Department of Energy Science and Engineering, Indian Institute of Technology Bombay , Powai, Mumbai 400076, India.

Safe and high-capacity cathode materials are a long quest for commercial lithium-ion battery development. Among various searched cathode materials, LiFeSiO has taken the attention due to optimal working voltage, high elemental abundance, and low toxicity. However, as per our understanding and observation, the electrochemical performance of this material is significantly limited by the intrinsic low electronic conductivity and slow lithium-ion diffusion, which limits the practical capacity (a theoretical value of ∼330 mAh g). In this report, using first-principles density functional theory based approach, we demonstrate that chlorine doping on oxygen site can enhance the electronic conductivity of the electrode and concurrently improve the electrochemical performance. Experimentally, X-ray diffraction, X-ray photoelectron spectroscopy, and field-emission gun scanning electron microscopy elemental mapping confirms Cl doping in LiFeSiOCl/C (x ≤ 0.1), while electrochemical cycling performance demonstrated improved performance. The theoretical and experimental studies collectively predict that, via Cl doping, the lithium deinsertion voltage associated with the Fe/Fe and Fe/Fe redox couples can be reduced and electronic conductivity can be enhanced, which opens up the possibility of utilization of silicate-based cathode with carbonate-based commercial electrolyte. In view of potential and electronic conductivity benefits, our results indicate that Cl doping can be a promising low-cost method to improve the electrochemical performance of silicate-based cathode materials.
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http://dx.doi.org/10.1021/acsami.7b07502DOI Listing
August 2017

Def1 and Dst1 play distinct roles in repair of AP lesions in highly transcribed genomic regions.

DNA Repair (Amst) 2017 07 10;55:31-39. Epub 2017 May 10.

Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, TX, 77030, USA. Electronic address:

Abasic or AP sites generated by spontaneous DNA damage accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) pathway. We have demonstrated that transcription-coupled nucleotide excision repair (NER) pathway can functionally replace BER to repair those AP sites located on the transcribed strand much like the strand specific repair of UV-induced pyrimidine dimers. Previous reports indicate that Rad26, a yeast homolog of transcription-repair coupling factor CSB, partly mediates strand-specific repair of UV-dimers as well as AP lesions. Here, we report that Def1, known to promote ubiquitination and degradation of stalled RNA polymerase complex, also directs NER to AP lesions on the transcribed strand of an actively transcribed gene but that its function is dependent on metabolic state of the yeast cells. We additionally show that Dst1, a homolog of mammalian transcription elongation factor TFIIS, interferes with NER-dependent repair of AP lesions while suppressing homologous recombination pathway. Overall, Def1 and Dst1 mediate very different outcomes in response to AP-induced transcription arrest.
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http://dx.doi.org/10.1016/j.dnarep.2017.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815317PMC
July 2017

A New Method, "Reverse Yeast Two-Hybrid Array" (RYTHA), Identifies Mutants that Dissociate the Physical Interaction Between Elg1 and Slx5.

Genetics 2017 07 5;206(3):1683-1697. Epub 2017 May 5.

Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel

The vast majority of processes within the cell are carried out by proteins working in conjunction. The Yeast Two-Hybrid (Y2H) methodology allows the detection of physical interactions between any two interacting proteins. Here, we describe a novel systematic genetic methodology, "Reverse Yeast Two-Hybrid Array" (RYTHA), that allows the identification of proteins required for modulating the physical interaction between two given proteins. Our assay starts with a yeast strain in which the physical interaction of interest can be detected by growth on media lacking histidine, in the context of the Y2H methodology. By combining the synthetic genetic array technology, we can systematically screen mutant libraries of the yeast to identify -acting mutations that disrupt the physical interaction of interest. We apply this novel method in a screen for mutants that disrupt the interaction between the N-terminus of Elg1 and the Slx5 protein. Elg1 is part of an alternative replication factor C-like complex that unloads PCNA during DNA replication and repair. Slx5 forms, together with Slx8, a SUMO-targeted ubiquitin ligase (STUbL) believed to send proteins to degradation. Our results show that the interaction requires both the STUbL activity and the PCNA unloading by Elg1, and identify topoisomerase I DNA-protein cross-links as a major factor in separating the two activities. Thus, we demonstrate that RYTHA can be applied to gain insights about particular pathways in yeast, by uncovering the connection between the proteasomal ubiquitin-dependent degradation pathway, DNA replication, and repair machinery, which can be separated by the topoisomerase-mediated cross-links to DNA.
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http://dx.doi.org/10.1534/genetics.117.200451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500160PMC
July 2017

Probiotics: A New Era of Biotherapy.

Adv Biomed Res 2017 7;6:31. Epub 2017 Mar 7.

Department of Oral Medicine and Radiology, Institute of Dental Sciences, Bareilly, Uttar Pradesh, India.

Probiotics or health-beneficial bacteria have only recently been introduced in dentistry after years of successful use in mainly gastrointestinal disorders. The concept of bacteriotherapy was first introduced in the beginning of 20 century. They are administered in different quantities that allow for colon colonization. These products help in stimulating health promoting flora and also suppressing the pathologic colonization and disease spread. The use of probiotic plays an important aspect in dentistry too, ever since the oral infections occupied the prime spot among the other infections affecting the humans. Probiotics strengthen the immune system to combat allergies, stress, exposure to toxic substances, and other diseases. This review is an attempt to discuss briefly the role of probiotics in oral health.
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http://dx.doi.org/10.4103/2277-9175.192625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360003PMC
March 2017

A Comparative Evaluation of Sorption, Solubility, and Compressive Strength of Three Different Glass Ionomer Cements in Artificial Saliva: An Study.

Int J Clin Pediatr Dent 2017 Jan-Mar;10(1):49-54. Epub 2017 Feb 27.

Reader, Department of Pedodontics and Preventive Dentistry, Manav Rachna Dental College, Faridabad, Haryana, India.

Aim: To evaluate and compare the sorption, solubility, and compressive strength of three different glass ionomer cements in artificial saliva - type IX glass ionomer cement, silver-reinforced glass ionomer cement, and zirconia-reinforced glass ionomer cement, so as to determine the material of choice for stress-bearing areas.

Materials And Methods: A total of 90 cylindrical specimens (4 mm diameter and 6 mm height) were prepared for each material following the manufacturer's instructions. After subjecting the specimens to thermocycling, 45 specimens were immersed in artificial saliva for 24 hours for compressive strength testing under a universal testing machine, and the other 45 were evaluated for sorption and solubility, by first weighing them by a precision weighing scale (W1), then immersing them in artificial saliva for 28 days and weighing them (W2), and finally dehydrating in an oven for 24 hours and weighing them (W3).

Results: Group III (zirconomer) shows the highest compressive strength followed by group II (Miracle Mix) and least compressive strength is seen in group I (glass ionomer cement type IX-Extra) with statistically significant differences between the groups. The sorption and solubility values in artificial saliva were highest for glass ionomer cement type IX - Extra-GC (group I) followed by zirconomer-Shofu (group III), and the least value was seen for Miracle Mix-GC (group II).

Conclusion: Zirconia-reinforced glass ionomer cement is a promising dental material and can be used as a restoration in stress-bearing areas due to its high strength and low solubility and sorption rate. It may be a substitute for silver-reinforced glass ionomer cement due to the added advantage of esthetics.

Clinical Significance: This study provides vital information to pediatric dental surgeons on relatively new restorative materials as physical and mechanical properties of the new material are compared with conventional materials to determine the best suited material in terms of durability, strength and dimensional stability. This study will boost confidence among dental surgeons in terms of handling characteristics, cost effectiveness and success rate. This study will help clinically and scientifically; pediatric dental surgeons to use this material in stress-bearing areas in pediatric patients.

How To Cite This Article: Bhatia HP, Singh S, Sood S, Sharma N. A Comparative Evaluation of Sorption, Solubility, and Com-pressive Strength of Three Different Glass Ionomer Cements in Artificial Saliva: An Study. Int J Clin Pediatr Dent 2017;10(1):49-54.
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http://dx.doi.org/10.5005/jp-journals-10005-1407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360804PMC
February 2017

Development of hybrid scaffolds with natural extracellular matrix deposited within synthetic polymeric fibers.

J Biomed Mater Res A 2017 Aug 19;105(8):2162-2170. Epub 2017 Apr 19.

Department of Molecular Biology, Princeton University, Princeton, New Jersey, 08544-1014.

A major challenge of tissue engineering is to generate materials that combine bioactivity with stability in a form that captures the robust nature of native tissues. Here we describe a procedure to fabricate a novel hybrid extracellular matrix (ECM)-synthetic scaffold biomaterial by cell-mediated deposition of ECM within an electrospun fiber mat. Synthetic polymer fiber mats were fabricated using poly(desamino tyrosyl-tyrosine carbonate) (PDTEC) co-spun with poly(ethylene glycol) (PEG) used as a sacrificial polymer. PEG removal increased the overall mat porosity and produced a mat with a layered structure that could be peeled into separate sheets of about 50 μm in thickness. Individual layers had pore sizes and wettability that facilitated cell infiltration over the depth of the scaffold. Confocal microscopy showed the formation of a highly interpenetrated network of cells, fibronectin fibrils, and synthetic fibers mimicking a complex ECM as observed within tissues. Decellularization did not perturb the structure of the matrix or the fiber mat. The resulting hybrid ECM-scaffold promoted cell adhesion and spreading and stimulated new ECM assembly by stem cells and tumor cells. These results identify a new technique for fabricating highly porous synthetic fibrous scaffolds and an approach to supplement them with natural biomimetic cues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2162-2170, 2017.
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http://dx.doi.org/10.1002/jbm.a.36078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493328PMC
August 2017

Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.

Nucleic Acids Res 2017 Jun;45(10):5850-5862

Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

G-quadruplex or G4 DNA is a non-B secondary DNA structure consisting of a stacked array of guanine-quartets that can disrupt critical cellular functions such as replication and transcription. When sequences that can adopt Non-B structures including G4 DNA are located within actively transcribed genes, the reshaping of DNA topology necessary for transcription process stimulates secondary structure-formation thereby amplifying the potential for genome instability. Using a reporter assay designed to study G4-induced recombination in the context of an actively transcribed locus in Saccharomyces cerevisiae, we tested whether co-transcriptional activator Sub1, recently identified as a G4-binding factor, contributes to genome maintenance at G4-forming sequences. Our data indicate that, upon Sub1-disruption, genome instability linked to co-transcriptionally formed G4 DNA in Top1-deficient cells is significantly augmented and that its highly conserved DNA binding domain or the human homolog PC4 is sufficient to suppress G4-associated genome instability. We also show that Sub1 interacts specifically with co-transcriptionally formed G4 DNA in vivo and that yeast cells become highly sensitivity to G4-stabilizing chemical ligands by the loss of Sub1. Finally, we demonstrate the physical and genetic interaction of Sub1 with the G4-resolving helicase Pif1, suggesting a possible mechanism by which Sub1 suppresses instability at G4 DNA.
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http://dx.doi.org/10.1093/nar/gkx201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449603PMC
June 2017
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