Publications by authors named "Sandeep Kaushik"

36 Publications

Growth performance of using billet method in Garhwal Himalaya, India.

Saudi J Biol Sci 2021 May 23;28(5):2709-2717. Epub 2021 Mar 23.

Department of Plant Physiology, Slovak University of Agriculture, A.Hlinku 2, 94976 Nitra, Slovakia.

Medicinal mushrooms have been used in various treatments from a very long time, among which, is one of the most important medicinal mushroom. It is cultivated worldwide to meet its ever-increasing demand in the market. It is generally cultivated by bed log (Sawdust) and wood log (billet) method. This study was an attempt to observe the growth performance of on poplar billets () in the Sherpur Village (Dehradun) and Manjgaun village (Tehri Garhwal) of Garhwal Himalaya, India. The farmers' field with empty house/ rooms having proper growing conditions especially humidity and light were used for the cultivation of . The spawn was inoculated in poplar wood billets and these billets were installed in well prepared soil. The results demonstrated that cropping cycle of was shorter (132-136 days) in Sherpur Village (Dehradun) as compared to Manjgaun village (141-145 days) in Tehri Garhwal. Further the results also revealed that yield was decreased in the subsequent flushes. In Village Sherpur, the fruiting bodies of were harvested between 64-66 days, 100-101  days and 135-136  days during first, second and third flush after the installation of billets, respectively. However; in village Manjgaun, the fruiting bodies of were harvested between 69 and 71 days, 107-108  days and 144-145 days in first, second and third after the installation of billets respectively. Warmer temperature in Village Sherpur resulted in the early emergence and development of the fruiting bodies as compared to village Manjgaun where pinhead and fruiting body development was delayed due to the lower temperature during cropping cycle.
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http://dx.doi.org/10.1016/j.sjbs.2021.03.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117109PMC
May 2021

RRBP1 rewires cisplatin resistance in oral squamous cell carcinoma by regulating Hippo pathway.

Br J Cancer 2021 Jun 24;124(12):2004-2016. Epub 2021 Mar 24.

Institute of Life Sciences, Bhubaneswar, Odisha, India.

Background: Chemoresistance is one of the major factors for treatment failure in OSCC. Identifying key resistance triggering molecules will be useful strategy for developing novel treatment methods.

Methods: To identify the causative factors of chemoresistance, we performed RNA sequencing and global proteomic profiling of human OSCC lines presenting with sensitive, early and late cisplatin-resistance patterns.

Results: From the common set of dysregulated genes from both the analysis, RRBP1 was identified to be upregulated in both early and late cisplatin-resistant cells with respect to the sensitive counterpart. Analysis of OSCC patient sample indicates that RRBP1 expression is upregulated in chemotherapy-non-responder tumours as compared to chemotherapy-responder tumours. Genetic (knockout) or pharmacological (Radezolid, represses expression of RRBP1) inhibition of RRBP1 restores cisplatin-mediated cell death in chemo-resistant OSCC. Mechanistically, RRBP1 regulates Yes-associated protein1 (YAP1), a key protein in the Hippo pathway to induce chemoresistance. The PDC xenograft data suggests that knockout of RRBP1 induces cisplatin-mediated cell death and facilitates a significant reduction of tumour burden.

Conclusion: Overall, our data suggests that (I) RRBP1 is a major driver of cisplatin-resistance in OSCC, (II) RRBP1 regulates YAP1 expression to mediate cisplatin-resistance, (III) Radezolid represses RRBP1 expression and (IV) targeting RRBP1 reverses cisplatin-induced chemoresistance in advanced OSCC.
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http://dx.doi.org/10.1038/s41416-021-01336-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184829PMC
June 2021

Reproductive success in : A role of post-insemination association of male and female.

Saudi J Biol Sci 2021 Mar 22;28(3):1539-1543. Epub 2020 Dec 22.

Department of Botany, Hindu College Moradabad (Mahatma Jyotiba Phule Rohilkhand University Bareilly), India.

Reproductive success is attained by various mechanisms in insects. Prolonged post insemination association is one such mechanism to increase the reproductive success. The present study was conducted to assess the role of post insemination association of mating partners on reproductive performance in Chrysomelidae beetle, Pallister. The matings were disrupted at different time intervals and fecundity and percent egg viability of the females were recorded. In addition, the mounting attempts, mating attempts, time to commencement of mating and latent period were also recorded. It was hypothesized that: (1) the mounting and mating attempts would not exist, (2) copulation duration, would not affect the reproductive performance, and (3) the beetle would not exhibit the mate guarding behaviour. Interestingly, results revealed that 6.00 ± 1.3 and 6.59 ± 0.93 mounting and mating attempts are needed to establish successful mating. The results revealed that males improved their percent egg viability with a mating duration ranging from nearly 30-50 min. While fecundity increased with a mating duration of above 30 min and up to a duration of 60 min. This result concluded that males of this beetle display post copulatory mate guarding behaviour after 60 min in which male rides on female's back with his aedeagus inserted in the female genital tract.
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http://dx.doi.org/10.1016/j.sjbs.2020.12.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938115PMC
March 2021

Intranasal immunization with peptide-based immunogenic complex enhances BCG vaccine efficacy in a murine model of tuberculosis.

JCI Insight 2021 02 22;6(4). Epub 2021 Feb 22.

International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.

Prime-boost immunization strategies are required to control the global tuberculosis (TB) pandemic, which claims approximately 3 lives every minute. Here, we have generated an immunogenic complex against Mycobacterium tuberculosis (M.tb), consisting of promiscuous T cell epitopes (M.tb peptides) and TLR ligands assembled in liposomes. Interestingly, this complex (peptide-TLR agonist-liposomes; PTL) induced significant activation of CD4+ T cells and IFN-γ production in the PBMCs derived from PPD+ healthy individuals as compared with PPD- controls. Furthermore, intranasal delivery of PTL significantly reduced the bacterial burden in the infected mice by inducing M.tb-specific polyfunctional (IFN-γ+IL-17+TNF-α+IL-2+) immune responses and long-lasting central memory responses, thereby reducing the risk of TB recurrence in DOTS-treated infected animals. The transcriptome analysis of peptide-stimulated immune cells unveiled the molecular basis of enhanced protection. Furthermore, PTL immunization significantly boosted the Bacillus Calmette-Guerin-primed (BCG-primed) immune responses against TB. The greatly enhanced efficacy of the BCG-PTL vaccine model in controlling pulmonary TB projects PTL as an adjunct vaccine against TB.
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http://dx.doi.org/10.1172/jci.insight.145228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934935PMC
February 2021

CMTM6 drives cisplatin resistance by regulating Wnt signaling through the ENO-1/AKT/GSK3β axis.

JCI Insight 2021 02 22;6(4). Epub 2021 Feb 22.

Institute of Life Sciences, Bhubaneswar, India.

Rewiring tumor cells to undergo drug-induced apoptosis is a promising way to overcome chemoresistance. Therefore, identifying causative factors for chemoresistance is of high importance. Unbiased global proteome profiling of sensitive, early, and late cisplatin-resistant oral squamous cell carcinoma (OSCC) lines identified CMTM6 as a top-ranked upregulated protein. Analyses of OSCC patient tumor samples demonstrated significantly higher CMTM6 expression in chemotherapy (CT) nonresponders as compared with CT responders. In addition, a significant association between higher CMTM6 expression and poorer relapse-free survival in esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, and lung squamous cell carcinoma was observed from Kaplan-Meier plot analysis. Stable knockdown (KD) of CMTM6 restored cisplatin-mediated cell death in chemoresistant OSCC lines. Upon CMTM6 overexpression in CMTM6-KD lines, the cisplatin-resistant phenotype was rescued. The patient-derived cell xenograft model of chemoresistant OSCC displaying CMTM6 depletion restored the cisplatin-induced cell death and tumor burden substantially. The transcriptome analysis of CMTM6-KD and control chemoresistant cells depicted enrichment of the Wnt signaling pathway. We demonstrated that CMTM6 interaction with membrane-bound Enolase-1 stabilized its expression, leading to activation of Wnt signaling mediated by AKT-glycogen synthase kinase-3β. CMTM6 has been identified as a stabilizer of programmed cell death ligand 1. Therefore, as CMTM6 facilitates tumor cells for immune evasion and mediates cisplatin resistance, it could be a promising therapeutic target for treating therapy-resistant OSCC.
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http://dx.doi.org/10.1172/jci.insight.143643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934946PMC
February 2021

Zero Echo Time MRAC on FDG-PET/MR Maintains Diagnostic Accuracy for Alzheimer's Disease; A Simulation Study Combining ADNI-Data.

Front Neurosci 2020 26;14:569706. Epub 2020 Nov 26.

GE Healthcare, Waukesha, WI, United States.

Aim: Attenuation correction using zero-echo time (ZTE) - magnetic resonance imaging (MRI) (ZTE-MRAC) has become one of the standard methods for brain-positron emission tomography (PET) on commercial PET/MR scanners. Although the accuracy of the net tracer-uptake quantification based on ZTE-MRAC has been validated, that of the diagnosis for dementia has not yet been clarified, especially in terms of automated statistical analysis. The aim of this study was to clarify the impact of ZTE-MRAC on the diagnosis of Alzheimer's disease (AD) by performing simulation study.

Methods: We recruited 27 subjects, who underwent both PET/computed tomography (CT) and PET/MR (GE SIGNA) examinations. Additionally, we extracted 107 subjects from the Alzheimer Disease Neuroimaging Initiative (ADNI) dataset. From the PET raw data acquired on PET/MR, three FDG-PET series were generated, using two vendor-provided MRAC methods (ZTE and Atlas) and CT-based AC. Following spatial normalization to Montreal Neurological Institute (MNI) space, we calculated each patient's specific error maps, which correspond to the difference between the PET image corrected using the CTAC method and the PET images corrected using the MRAC methods. To simulate PET maps as if ADNI data had been corrected using MRAC methods, we multiplied each of these 27 error maps with each of the 107 ADNI cases in MNI space. To evaluate the probability of AD in each resulting image, we calculated a cumulative -value using a fully automated method which had been validated not only in the original ADNI dataset but several multi-center studies. In the method, PET score = 1 is the 95% prediction limit of AD. PET score and diagnostic accuracy for the discrimination of AD were evaluated in simulated images using the original ADNI dataset as reference.

Results: Positron emission tomography score was slightly underestimated both in ZTE and Atlas group compared with reference CTAC (-0.0796 ± 0.0938 vs. -0.0784 ± 0.1724). The absolute error of PET score was lower in ZTE than Atlas group (0.098 ± 0.075 vs. 0.145 ± 0.122, < 0.001). A higher correlation to the original PET score was observed in ZTE vs. Atlas group ( : 0.982 vs. 0.961). The accuracy for the discrimination of AD patients from normal control was maintained in ZTE and Atlas compared to CTAC (ZTE vs. Atlas. vs. original; 82.5% vs. 82.1% vs. 83.2% (CI 81.8-84.5%), respectively).

Conclusion: For FDG-PET images on PET/MR, attenuation correction using ZTE-MRI had superior accuracy to an atlas-based method in classification for dementia. ZTE maintains the diagnostic accuracy for AD.
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http://dx.doi.org/10.3389/fnins.2020.569706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725704PMC
November 2020

Editorial: Multi-Omics Approaches to Study Signaling Pathways.

Front Bioeng Biotechnol 2020 4;8:829. Epub 2020 Sep 4.

Amity Medical School, Amity Stem Cell Institute, Amity University Haryana, Gurugram, India.

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http://dx.doi.org/10.3389/fbioe.2020.00829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499333PMC
September 2020

Essential amino acid profiling of the four lac hosts belonging to genus : its implications on lac productivity.

Physiol Mol Biol Plants 2020 Sep 26;26(9):1867-1874. Epub 2020 Aug 26.

Department of Botany, University of Delhi, Delhi, 110007 India.

The Indian lac insect (), a hemipteran, phloem sap sucking sedentary insect is an important bioresource which thrives on tender twigs of more than 400 plant species belonging to various genera and families. The most common commercial host plants for lac cultivation are big trees hence cultivation was concentrated mainly to dense forests across the country till last decade. Recently, a new bushy host plant belonging to the genus Flemingia has been introduced so that lac can be cultivated on farmlands like other cash crops. The insect is sedentary and feeds on the phloem sap of the host plants, the only source of its nutrition. Interestingly, the biological attributes of the insect as well as the qualitative and quantitative production of lac is influenced by the host plant on which the insect feeds upon. The present study was thus aimed at deciphering the effect of phloem sap constituents obtained from four plant host taxa belonging to the same genus viz. , , and (essential amino acids only-EAAs) on lac productivity. Moreover, a newer method for phloem sap collection i.e. Dot-blot in addition to the facilitated exudation using EDTA was also investigated. Dot-blot method for phloem sap collection also came out to be a promising method for field studies; although slightly higher concentration of EAAs were obtained from EDTA method, thus the later was used for further analysis. Phloem sap of four plant host taxa belonging to the same genus were qualitatively and quantitatively analysed for seven EAAs (Arginine, Glycine, Leucine, Methionine, Phenylalanine Tyrosine and Valine). Amino acid concentration regime and further analysis done using statistical tools (ANOVA and PCA) points out the EAA concentration in the phloem sap is in congruency with the lac production data obtained through previous studies as  >  >  > . The present study thus scientifically points out that can be a promising plant for lac cultivation on the basis of higher EAA content as compared to the rest three.
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http://dx.doi.org/10.1007/s12298-020-00860-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468028PMC
September 2020

COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2.

PLoS Pathog 2020 08 21;16(8):e1008762. Epub 2020 Aug 21.

Biology Department, University of Massachusetts, Amherst, Massachusetts, United States of America.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly emerging, highly transmissible, and pathogenic coronavirus in humans that has caused global public health emergencies and economic crises. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism(s) through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor-binding domain (RBD) of the spike (S) glycoprotein to recognize angiotensin-converting enzyme 2 (ACE2) receptors on the human cells; this initiates host-cell entry by promoting viral-host cell membrane fusion through large-scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the structure of RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and its significance in drug discovery and explain the receptor recognition mechanisms of coronaviruses. Further, we provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins and their receptor-binding specificity and discuss the differences in their antigenicity based on biophysical and structural characteristics.
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http://dx.doi.org/10.1371/journal.ppat.1008762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444525PMC
August 2020

The impact of atlas-based MR attenuation correction on the diagnosis of FDG-PET/MR for Alzheimer's diseases- A simulation study combining multi-center data and ADNI-data.

PLoS One 2020 3;15(6):e0233886. Epub 2020 Jun 3.

Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.

Background: The purpose of this study was to assess the impact of vendor-provided atlas-based MRAC on FDG PET/MR for the evaluation of Alzheimer's disease (AD) by using simulated images.

Methods: We recruited 47 patients, from two institutions, who underwent PET/CT and PET/MR (GE SIGNA) examination for oncological staging. From the PET raw data acquired on PET/MR, two FDG-PET series were generated, using vendor-provided MRAC (atlas-based) and CTAC. The following simulation steps were performed in MNI space: After spatial normalization and smoothing of the PET datasets, we calculated the error map for each patient, PETMRAC/PETCTAC. We multiplied each of these 47 error maps with each of the 203 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases after the identical normalization and smoothing. This resulted in 203*47 = 9541 datasets. To evaluate the probability of AD in each resulting image, a cumulative t-value was calculated automatically using commercially-available software (PMOD PALZ) which has been used in multiple large cohort studies. The diagnostic accuracy for the discrimination of AD and predicting progression from mild cognitive impairment (MCI) to AD were evaluated in simulated images compared with ADNI original images.

Results: The accuracy and specificity for the discrimination of AD-patients from normal controls were not substantially impaired, but sensitivity was slightly impaired in 5 out of 47 datasets (original vs. error; 83.2% [CI 75.0%-89.0%], 83.3% [CI 74.2%-89.8%] and 83.1% [CI 75.6%-88.3%] vs. 82.7% [range 80.4-85.0%], 78.5% [range 72.9-83.3%,] and 86.1% [range 81.4-89.8%]). The accuracy, sensitivity and specificity for predicting progression from MCI to AD during 2-year follow-up was not impaired (original vs. error; 62.5% [CI 53.3%-69.3%], 78.8% [CI 65.4%-88.6%] and 54.0% [CI 47.0%-69.1%] vs. 64.8% [range 61.5-66.7%], 75.7% [range 66.7-81.8%,] and 59.0% [range 50.8-63.5%]). The worst 3 error maps show a tendency towards underestimation of PET scores.

Conclusion: FDG-PET/MR based on atlas-based MR attenuation correction showed similar diagnostic accuracy to the CT-based method for the diagnosis of AD and the prediction of progression of MCI to AD using commercially-available software, although with a minor reduction in sensitivity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269241PMC
August 2020

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO).

Respir Res 2020 May 24;21(1):126. Epub 2020 May 24.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.

Background: Asthma-COPD overlap (ACO) refers to a group of poorly studied and characterised patients reporting with disease presentations of both asthma and COPD, thereby making both diagnosis and treatment challenging for the clinicians. They exhibit a higher burden in terms of both mortality and morbidity in comparison to patients with only asthma or COPD. The pathophysiology of the disease and its existence as a unique disease entity remains unclear. The present study aims to determine whether ACO has a distinct metabolic and immunological mediator profile in comparison to asthma and COPD.

Methods: Global metabolomic profiling using two different groups of patients [discovery (D) and validation (V)] were conducted. Serum samples obtained from moderate and severe asthma [n = 34(D); n = 32(V)], moderate and severe COPD [n = 30(D); 32(V)], ACO patients [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using gas chromatography mass spectrometry (GC-MS). Multiplexed analysis of 25 immunological markers (IFN-γ (interferon gamma), TNF-α (tumor necrosis factor alpha), IL-12p70 (interleukin 12p70), IL-2, IL-4, IL-5, IL-13, IL-10, IL-1α, IL-1β, TGF-β (transforming growth factor), IL-6, IL-17E, IL-21, IL-23, eotaxin, GM-CSF (granulocyte macrophage-colony stimulating factor), IFN-α (interferon alpha), IL-18, NGAL (neutrophil gelatinase-associated lipocalin), periostin, TSLP (thymic stromal lymphopoietin), MCP-1 (monocyte chemoattractant protein- 1), YKL-40 (chitinase 3 like 1) and IL-8) was also performed in the discovery cohort.

Results: Eleven metabolites [serine, threonine, ethanolamine, glucose, cholesterol, 2-palmitoylglycerol, stearic acid, lactic acid, linoleic acid, D-mannose and succinic acid] were found to be significantly altered in ACO as compared with asthma and COPD. The levels and expression trends were successfully validated in a fresh cohort of subjects. Thirteen immunological mediators including TNFα, IL-1β, IL-17E, GM-CSF, IL-18, NGAL, IL-5, IL-10, MCP-1, YKL-40, IFN-γ, IL-6 and TGF-β showed distinct expression patterns in ACO. These markers and metabolites exhibited significant correlation with each other and also with lung function parameters.

Conclusions: The energy metabolites, cholesterol and fatty acids correlated significantly with the immunological mediators, suggesting existence of a possible link between the inflammatory status of these patients and impaired metabolism. The present findings could be possibly extended to better define the ACO diagnostic criteria, management and tailoring therapies exclusively for the disease.
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http://dx.doi.org/10.1186/s12931-020-01390-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245917PMC
May 2020

Attenuation correction using 3D deep convolutional neural network for brain 18F-FDG PET/MR: Comparison with Atlas, ZTE and CT based attenuation correction.

PLoS One 2019 7;14(10):e0223141. Epub 2019 Oct 7.

Nuclear Medicine Department, Groupe Hospitalier Pitié-Salpêtrière C. Foix, APHP, Paris, France.

One of the main technical challenges of PET/MRI is to achieve an accurate PET attenuation correction (AC) estimation. In current systems, AC is accomplished by generating an MRI-based surrogate computed tomography (CT) from which AC-maps are derived. Nevertheless, all techniques currently implemented in clinical routine suffer from bias. We present here a convolutional neural network (CNN) that generated AC-maps from Zero Echo Time (ZTE) MR images. Seventy patients referred to our institution for 18FDG-PET/MR exam (SIGNA PET/MR, GE Healthcare) as part of the investigation of suspected dementia, were included. 23 patients were added to the training set of the manufacturer and 47 were used for validation. Brain computed tomography (CT) scan, two-point LAVA-flex MRI (for atlas-based AC) and ZTE-MRI were available in all patients. Three AC methods were evaluated and compared to CT-based AC (CTAC): one based on a single head-atlas, one based on ZTE-segmentation and one CNN with a 3D U-net architecture to generate AC maps from ZTE MR images. Impact on brain metabolism was evaluated combining voxel and regions-of-interest based analyses with CTAC set as reference. The U-net AC method yielded the lowest bias, the lowest inter-individual and inter-regional variability compared to PET images reconstructed with ZTE and Atlas methods. The impact on brain metabolism was negligible with average errors of -0.2% in most cortical regions. These results suggest that the U-net AC is more reliable for correcting photon attenuation in brain FDG-PET/MR than atlas-AC and ZTE-AC methods.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223141PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779234PMC
March 2020

The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice.

J Biol Chem 2019 05 11;294(21):8555-8563. Epub 2019 Apr 11.

International Centre for Genetic Engineering and Biotechnology, New Delhi 110 067, India. Electronic address:

The widespread availability and use of modern synthetic therapeutic agents have led to a massive decline in ethnomedical therapies. However, these synthetic agents often possess toxicity leading to various adverse effects. For instance, anti-tubercular treatment (ATT) is toxic, lengthy, and severely impairs host immunity, resulting in posttreatment vulnerability to reinfection and reactivation of tuberculosis (TB). Incomplete ATT enhances the risk for the generation of multidrug- or extensively drug-resistant (MDR or XDR, respectively) variants of ), the TB-causing microbe. Therefore, a new therapeutic approach that minimizes these risks is urgently needed to combat this deadly disease and prevent future TB epidemics. Previously, we have shown that the phytochemical bergenin induces T helper 1 (Th1)- and Th17 cell-based protective immune responses and potently inhibits mycobacterial growth in a murine model of infection, suggesting bergenin as a potential adjunct agent to TB therapy. Here, we combined ATT therapy with bergenin and found that this combination reduces immune impairment and the length of treatment in mice. We observed that co-treatment with the anti-TB drug isoniazid and bergenin produces additive effects and significantly reduces bacterial loads compared with isoniazid treatment alone. The bergenin co-treatment also reduced isoniazid-induced immune impairment; promoted long-lasting, antigen-specific central memory T cell responses; and acted as a self-propelled vaccine. Of note, bergenin treatment significantly reduced the bacterial burden of a multidrug-resistant TB strain. These observations suggest that bergenin is a potent immunomodulatory agent that could be further explored as a potential adjunct to TB therapy.
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http://dx.doi.org/10.1074/jbc.RA119.008005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544861PMC
May 2019

Estimation of nuclear DNA content and its variation among Indian Tea accessions by flow cytometry.

Physiol Mol Biol Plants 2019 Mar 11;25(2):339-346. Epub 2018 Aug 11.

3Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh 201303 India.

Nuclear DNA content and genome size variation among 36 Indian tea accessions were analyzed by flow cytometry. Initial standardization of protocols for isolation of nuclei, DNA staining and selection of an internal standard for tea accessions which have significantly high amount of phenolic secondary metabolites in their cytosol was carried out. Results obtained revealed that 2C DNA content of Indian tea is 7.46 pg which corresponds to 1C genome size of 3673 Mb. Inter accession variation in 2C DNA content was also observed among 35 diploid taxa ranging from 7.23 to 7.73 pg which was significant at 1% probability level. The 2C DNA content of triploid (UPASI 3) was observed to be 11.47 pg which is concurrent with the expected value. Results obtained showed that Assam and Cambod type tea accession have higher 2C DNA content of 7.73 pg whereas Assam Cambod hybrids and Assam China hybrids have reduction in DNA content with 2C amounts, 7.23 and 7.32 pg DNA respectively. The present study suggests that the species involved in origin of Indian tea must have differed in their genome sizes owing to significant inter accession variation in nuclear DNA content.
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http://dx.doi.org/10.1007/s12298-018-0587-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419702PMC
March 2019

Effect of scattering and differential attenuation on beam profile in the presence of high-density intensity modifying compensator.

J Cancer Res Ther 2019 Mar;15(Supplement):S110-S114

Department of Physics, Chaudhary Bansilal University, Bhiwani, Haryana, India.

Aim: The aim of this study is to investigate the effect of scattering and differential attenuation on dose profile of 6 MV photon beam in the presence of cadmium (Cd)-free compensator which has been used in compensator-based intensity-modulated radiotherapy.

Materials And Methods: Totally, 10 slabs of Cd-free compensator having thicknesses ranging from 2.4 to 61.4 mm have been prepared. Dose profiles have been taken using computer-controlled radiation field analyzer for five field sizes from 30 mm × 30 mm to 200 mm × 200 mm and at three depths in water phantom. Off-axis dose variation (ODV) has been measured with off-axis percentage depth dose scan and with ion chamber by measuring point dose at two diagonal points with respect to dose at central axis point in a plane and at three depths.

Results: A decrease in beam flatness has been observed with increase in compensator thickness and depth in phantom. ODV has been found to increase with compensator thickness. Selective beam hardening has been observed due to differential attenuation from compensator. Point dose measurements show approximately 20% and 23% underdose region at 70 and 106 mm off-axis diagonal point, respectively, as compared to dose at central axis point for a field size of 200 mm × 200 mm at a depth of 15 mm, with 30.2-mm slab thickness. Significant increase in scattered penumbra has been observed with field size and thickness of compensator due to increase in scattered photon.

Conclusions: The presence of compensator changes photon beam mean energy along the cross-section resulted in decreased beam flatness and increased scattering. This may lead to overestimation of dose along off-axis within radiation field if change in flatness is not taken into account and more exposure to healthy tissues in penumbral region due to large-angle scattering.
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http://dx.doi.org/10.4103/jcrt.JCRT_661_17DOI Listing
March 2019

Unraveling the mechanism of l-gulonate-3-dehydrogenase inhibition by ascorbic acid: Insights from molecular modeling.

Comput Biol Chem 2018 Dec 27;77:146-153. Epub 2018 Sep 27.

3B's Research Group, Head Quarters of European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017, Guimarães, Portugal. Electronic address:

l-Gulonate dehydrogenase (GuDH) is a crucial enzyme in the non-phosphorylated sugar metabolism or glucuronate-xylulose (GX) pathway. Some naturally occurring compounds inhibit GuDH. Ascorbic acid is one of such inhibitors for GuDH. However, the exact mechanism by which ascorbic acid inhibits GuDH is still unknown. In this study, we try to investigate GuDH inhibition using computational approaches by generating a model for buffalo GuDH. We used this model to perform blind dockings of ascorbic acid to GuDH. Some docked conformations of ascorbic acid bind near Asp39 and have steric clashes with crystal structure conformation of NADH. To assess the dynamic stability of the GuDH-ascorbic acid complex, we performed six molecular dynamics simulations for GuDH, three each in its free form and in complex with ascorbic acid for 50 ns, to obtain 300 ns of trajectories in total. During the simulations, ascorbic acid interacted with several residues nearby Asp39. As Asp39 is an important residue for NADH binding and specificity, the interaction of ascorbic acid near Asp39 hinders further NADH binding and ultimately affects the enzymatic functioning of GuDH. In this study, we analyze these interactions between ascorbic acid and GuDH. Our analysis reveals novel details on the mechanism of GuDH inhibition by ascorbic acid.
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http://dx.doi.org/10.1016/j.compbiolchem.2018.09.015DOI Listing
December 2018

Improving PET/MR brain quantitation with template-enhanced ZTE.

Neuroimage 2018 11 19;181:403-413. Epub 2018 Jul 19.

Department of Radiology, Nippon Medical School, Tokyo, Japan.

Purpose: The impact of MR-based attenuation correction on PET quantitation accuracy is an ongoing cause of concern for advanced brain research with PET/MR. The purpose of this study was to evaluate a new, template-enhanced zero-echo-time attenuation correction method for PET/MR scanners.

Methods: 30 subjects underwent a clinically-indicated F-FDG-PET/CT, followed by PET/MR on a GE SIGNA PET/MR. For each patient, a 42-s zero echo time (ZTE) sequence was used to generate two attenuation maps: one with the standard ZTE segmentation-based method; and another with a modification of the method, wherein pre-registered anatomical templates and CT data were used to enhance the segmentation. CT data, was used as gold standard. Reconstructed PET images were qualified visually and quantified in 68 volumes-of-interest using a standardized brain atlas.

Results: Attenuation maps were successfully generated in all cases, without manual intervention or parameter tuning. One patient was excluded from the quantitative analysis due to the presence of multiple brain metastases. The PET bias with template-enhanced ZTE attenuation correction was measured to be -0.9% ± 0.9%, compared with -1.4% ± 1.1% with regular ZTE attenuation correction. In terms of absolute bias, the new method yielded 1.1% ± 0.7%, compared with 1.6% ± 0.9% with regular ZTE. Statistically significant bias reduction was obtained in the frontal region (from -2.0% to -1.0%), temporal (from -1.2% to -0.2%), parietal (from -1.9% to -1.1%), occipital (from -2.0% to -1.1%) and insula (from -1.4% to -1.1%).

Conclusion: These results indicate that the co-registration of pre-recorded anatomical templates to ZTE data is feasible in clinical practice and can be effectively used to improve the performance of segmentation-based attenuation correction.
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http://dx.doi.org/10.1016/j.neuroimage.2018.07.029DOI Listing
November 2018

Zero TE-based pseudo-CT image conversion in the head and its application in PET/MR attenuation correction and MR-guided radiation therapy planning.

Magn Reson Med 2018 10 18;80(4):1440-1451. Epub 2018 Feb 18.

GE Healthcare, Munich, Germany.

Purpose: To describe a method for converting Zero TE (ZTE) MR images into X-ray attenuation information in the form of pseudo-CT images and demonstrate its performance for (1) attenuation correction (AC) in PET/MR and (2) dose planning in MR-guided radiation therapy planning (RTP).

Methods: Proton density-weighted ZTE images were acquired as input for MR-based pseudo-CT conversion, providing (1) efficient capture of short-lived bone signals, (2) flat soft-tissue contrast, and (3) fast and robust 3D MR imaging. After bias correction and normalization, the images were segmented into bone, soft-tissue, and air by means of thresholding and morphological refinements. Fixed Hounsfield replacement values were assigned for air (-1000 HU) and soft-tissue (+42 HU), whereas continuous linear mapping was used for bone.

Results: The obtained ZTE-derived pseudo-CT images accurately resembled the true CT images (i.e., Dice coefficient for bone overlap of 0.73 ± 0.08 and mean absolute error of 123 ± 25 HU evaluated over the whole head, including errors from residual registration mismatches in the neck and mouth regions). The linear bone mapping accounted for bone density variations. Averaged across five patients, ZTE-based AC demonstrated a PET error of -0.04 ± 1.68% relative to CT-based AC. Similarly, for RTP assessed in eight patients, the absolute dose difference over the target volume was found to be 0.23 ± 0.42%.

Conclusion: The described method enables MR to pseudo-CT image conversion for the head in an accurate, robust, and fast manner without relying on anatomical prior knowledge. Potential applications include PET/MR-AC, and MR-guided RTP.
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http://dx.doi.org/10.1002/mrm.27134DOI Listing
October 2018

Joint estimation of activity and attenuation for PET using pragmatic MR-based prior: application to clinical TOF PET/MR whole-body data for FDG and non-FDG tracers.

Phys Med Biol 2018 02 12;63(4):045006. Epub 2018 Feb 12.

GE Global Research, Niskayuna, NY, United States of America. Author to whom any correspondence should be addressed.

Accurate and robust attenuation correction remains challenging in hybrid PET/MR particularly for torsos because it is difficult to segment bones, lungs and internal air in MR images. Additionally, MR suffers from susceptibility artifacts when a metallic implant is present. Recently, joint estimation (JE) of activity and attenuation based on PET data, also known as maximum likelihood reconstruction of activity and attenuation, has gained considerable interest because of (1) its promise to address the challenges in MR-based attenuation correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology, which is known to be the key to the success of JE. In this paper, we implement a JE algorithm using an MR-based prior and evaluate the algorithm using whole-body PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA PET/MR scanners with TOF capability. The weight of the MR-based prior is spatially modulated, based on MR signal strength, to control the balance between MRAC and JE. Large prior weights are used in strong MR signal regions such as soft tissue and fat (i.e. MR tissue classification with a high degree of certainty) and small weights are used in low MR signal regions (i.e. MR tissue classification with a low degree of certainty). The MR-based prior is pragmatic in the sense that it is convex and does not require training or population statistics while exploiting synergies between MRAC and JE. We demonstrate the JE algorithm has the potential to improve the robustness and accuracy of MRAC by recovering the attenuation of metallic implants, internal air and some bones and by better delineating lung boundaries, not only for FDG but also for more specific non-FDG tracers such as Ga-DOTATOC and F-Fluoride.
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http://dx.doi.org/10.1088/1361-6560/aaa8a6DOI Listing
February 2018

Zero-Echo-Time and Dixon Deep Pseudo-CT (ZeDD CT): Direct Generation of Pseudo-CT Images for Pelvic PET/MRI Attenuation Correction Using Deep Convolutional Neural Networks with Multiparametric MRI.

J Nucl Med 2018 05 30;59(5):852-858. Epub 2017 Oct 30.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California.

Accurate quantification of uptake on PET images depends on accurate attenuation correction in reconstruction. Current MR-based attenuation correction methods for body PET use a fat and water map derived from a 2-echo Dixon MRI sequence in which bone is neglected. Ultrashort-echo-time or zero-echo-time (ZTE) pulse sequences can capture bone information. We propose the use of patient-specific multiparametric MRI consisting of Dixon MRI and proton-density-weighted ZTE MRI to directly synthesize pseudo-CT images with a deep learning model: we call this method ZTE and Dixon deep pseudo-CT (ZeDD CT). Twenty-six patients were scanned using an integrated 3-T time-of-flight PET/MRI system. Helical CT images of the patients were acquired separately. A deep convolutional neural network was trained to transform ZTE and Dixon MR images into pseudo-CT images. Ten patients were used for model training, and 16 patients were used for evaluation. Bone and soft-tissue lesions were identified, and the SUV was measured. The root-mean-squared error (RMSE) was used to compare the MR-based attenuation correction with the ground-truth CT attenuation correction. In total, 30 bone lesions and 60 soft-tissue lesions were evaluated. The RMSE in PET quantification was reduced by a factor of 4 for bone lesions (10.24% for Dixon PET and 2.68% for ZeDD PET) and by a factor of 1.5 for soft-tissue lesions (6.24% for Dixon PET and 4.07% for ZeDD PET). ZeDD CT produces natural-looking and quantitatively accurate pseudo-CT images and reduces error in pelvic PET/MRI attenuation correction compared with standard methods.
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http://dx.doi.org/10.2967/jnumed.117.198051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932530PMC
May 2018

Evaluation of Sinus/Edge-Corrected Zero-Echo-Time-Based Attenuation Correction in Brain PET/MRI.

J Nucl Med 2017 11 4;58(11):1873-1879. Epub 2017 May 4.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.

In brain PET/MRI, the major challenge of zero-echo-time (ZTE)-based attenuation correction (ZTAC) is the misclassification of air/tissue/bone mixtures or their boundaries. Our study aimed to evaluate a sinus/edge-corrected (SEC) ZTAC (ZTAC), relative to an uncorrected (UC) ZTAC (ZTAC) and a CT atlas-based attenuation correction (ATAC). Whole-body F-FDG PET/MRI scans were obtained for 12 patients after PET/CT scans. Only data acquired at a bed station that included the head were used for this study. Using PET data from PET/MRI, we applied ZTAC, ZTAC, ATAC, and reference CT-based attenuation correction (CTAC) to PET attenuation correction. For ZTAC, the bias-corrected and normalized ZTE was converted to pseudo-CT with air (-1,000 HU for ZTE < 0.2), soft-tissue (42 HU for ZTE > 0.75), and bone (-2,000 × [ZTE - 1] + 42 HU for 0.2 ≤ ZTE ≤ 0.75). Afterward, in the pseudo-CT, sinus/edges were automatically estimated as a binary mask through morphologic processing and edge detection. In the binary mask, the overestimated values were rescaled below 42 HU for ZTAC For ATAC, the atlas deformed to MR in-phase was segmented to air, inner air, soft tissue, and continuous bone. For the quantitative evaluation, PET mean uptake values were measured in twenty 1-mL volumes of interest distributed throughout brain tissues. The PET uptake was compared using a paired test. An error histogram was used to show the distribution of voxel-based PET uptake differences. Compared with CTAC, ZTAC achieved the overall PET quantification accuracy (0.2% ± 2.4%, = 0.23) similar to CTAC, in comparison with ZTAC (5.6% ± 3.5%, < 0.01) and ATAC (-0.9% ± 5.0%, = 0.03). Specifically, a substantial improvement with ZTAC (0.6% ± 2.7%, < 0.01) was found in the cerebellum, in comparison with ZTAC (8.1% ± 3.5%, < 0.01) and ATAC (-4.1% ± 4.3%, < 0.01). The histogram of voxel-based uptake differences demonstrated that ZTAC reduced the magnitude and variation of errors substantially, compared with ZTAC and ATAC. ZTAC can provide an accurate PET quantification in brain PET/MRI, comparable to the accuracy achieved by CTAC, particularly in the cerebellum.
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http://dx.doi.org/10.2967/jnumed.116.188268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944168PMC
November 2017

Hybrid ZTE/Dixon MR-based attenuation correction for quantitative uptake estimation of pelvic lesions in PET/MRI.

Med Phys 2017 Mar;44(3):902-913

Department of Radiology and Biomedical Imaging, University of California San Francisco, 1700 4th St, San Francisco, CA 94158, USA.

Purpose: This study introduces a new hybrid ZTE/Dixon MR-based attenuation correction (MRAC) method including bone density estimation for PET/MRI and quantifies the effects of bone attenuation on metastatic lesion uptake in the pelvis.

Methods: Six patients with pelvic lesions were scanned using fluorodeoxyglucose (18F-FDG) in an integrated time-of-flight (TOF) PET/MRI system. For PET attenuation correction, MR imaging consisted of two-point Dixon and zero echo-time (ZTE) pulse sequences. A continuous-value fat and water pseudoCT was generated from a two-point Dixon MRI. Bone was segmented from the ZTE images and converted to Hounsfield units (HU) using a continuous two-segment piecewise linear model based on ZTE MRI intensity. The HU values were converted to linear attenuation coefficients (LAC) using a bilinear model. The bone voxels of the Dixon-based pseudoCT were replaced by the ZTE-derived bone to produce the hybrid ZTE/Dixon pseudoCT. The three different AC maps (Dixon, hybrid ZTE/Dixon, CTAC) were used to reconstruct PET images using a TOF-ordered subset expectation maximization algorithm with a point-spread function model. Metastatic lesions were separated into two classes, bone lesions and soft tissue lesions, and analyzed. The MRAC methods were compared using a root-mean-squared error (RMSE), where the registered CTAC was taken as ground truth.

Results: The RMSE of the maximum standardized uptake values (SUV ) is 11.02% and 7.79% for bone (N = 6) and soft tissue lesions (N = 8), respectively, using Dixon MRAC. The RMSE of SUVmax for these lesions is significantly reduced to 3.28% and 3.94% when using the new hybrid ZTE/Dixon MRAC. Additionally, the RMSE for PET SUVs across the entire pelvis and all patients are 8.76% and 4.18%, for the Dixon and hybrid ZTE/Dixon MRAC methods, respectively.

Conclusion: A hybrid ZTE/Dixon MRAC method was developed and applied to pelvic regions in an integrated TOF PET/MRI, demonstrating improved MRAC. This new method included bone density estimation, through which PET quantification is improved.
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http://dx.doi.org/10.1002/mp.12122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877454PMC
March 2017

Dosimetric analysis of Co-60 source based high dose rate (HDR) brachytherapy: A case series of ten patients with carcinoma of the uterine cervix.

Rep Pract Oncol Radiother 2016 May-Jun;21(3):201-6. Epub 2016 Mar 2.

Roentgen-SAIMS Radiation Oncology Centre, Sri Aurobindo Institute of Medical Sciences, Indore, India.

Aim: To analyse the dosimetric parameters of Co-60 based high dose rate (HDR) brachytherapy plans for patients of carcinoma uterine cervix.

Background: Co-60 high dose rate (HDR) brachytherapy unit has been introduced in past few years and is gaining importance owing to its long half life, economical benefits and comparable clinical outcome compared to Ir-192 HDR brachytherapy.

Materials And Methods: A study was conducted on ten patients with locally advanced carcinoma of the uterine cervix (Ca Cx). Computed tomography (CT) images were taken after three channel applicator insertions. The planning for 7 Gray per fraction (7 Gy/#) was done for Co-60 HDR brachytherapy unit following the American Brachytherapy Society (ABS) guidelines. All the patients were treated with 3# with one week interval between fractions.

Results: The mean dose to high risk clinical target volumes (HRCTV) for D90 (dose to 90% volume) was found to be 102.05% (Standard Deviation (SD): 3.07). The mean D2cc (dose to 2 cubic centimeter volume) of the bladder, rectum and sigmoid were found to be 15.9 Gy (SD: 0.58), 11.5 Gy (SD: 0.91) and 4.1 Gy (SD: 1.52), respectively.

Conclusion: The target coverage and doses to organs at risk (OARs) were achieved as per the ABS guidelines. Hence, it can be concluded that the Co-60 HDR brachytherapy unit is a good choice especially for the centers with a small number of brachytherapy procedures as no frequent source replacement is required like in an Ir-192 HDR unit.
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http://dx.doi.org/10.1016/j.rpor.2016.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002016PMC
September 2016

Brainstem Evoked Response Audiometry (BERA) in Neonates with Hyperbillirubinemia.

Indian J Otolaryngol Head Neck Surg 2016 Sep 3;68(3):334-8. Epub 2014 Dec 3.

Department of ENT, GSVM Medical College, Kanpur, India.

(1) To study the BERA changes in neonates with unconjugated hyperbilirubinemia. (2) To compare the BERA changes in the neonates with unconjugated hyperbilirubinemia before and after therapy. Thirty consecutive term appropriate for gestational age (AGA) neonates presenting to NICU with total serum bilirubin requiring intervention (using the American Academy of Pediatrics guidelines) were included in the study as cases and thirty normal term AGA neonates with uneventful peri-natal period and a maximum measured serum bilirubin <12 mg/dl in case of term baby were included as controls after obtaining informed consent. Initial BERA was done within 3-24 h of hospitalization after obtaining informed consent from parents, at the time of discharge and at 3 month followup. Machine used for recording BERA was intelligent hearing system version 3.3. In our study out of the 30 cases 10 (33.3 %) cases were found to have BERA changes in the form of absent wave forms, raised threshold, prolonged latencies or prolonged inter peak latencies. In our study, it was observed that there was statistically significant correlation (p value < 0.005) between increasing bilirubin level and BERA changes. Correlation of the findings of this study with previous few studies indicates that BERA can be used as a useful non invasive tool to determine auditory functions in the neonate especially changes of early bilirubin toxicity.
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http://dx.doi.org/10.1007/s12070-014-0811-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961629PMC
September 2016

Polyketide Quinones Are Alternate Intermediate Electron Carriers during Mycobacterial Respiration in Oxygen-Deficient Niches.

Mol Cell 2015 Nov 12;60(4):637-50. Epub 2015 Nov 12.

CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research, Rafi Marg, New Delhi 110001, India; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India. Electronic address:

Mycobacterium tuberculosis (Mtb) adaptation to hypoxia is considered crucial to its prolonged latent persistence in humans. Mtb lesions are known to contain physiologically heterogeneous microenvironments that bring about differential responses from bacteria. Here we exploit metabolic variability within biofilm cells to identify alternate respiratory polyketide quinones (PkQs) from both Mycobacterium smegmatis (Msmeg) and Mtb. PkQs are specifically expressed in biofilms and other oxygen-deficient niches to maintain cellular bioenergetics. Under such conditions, these metabolites function as mobile electron carriers in the respiratory electron transport chain. In the absence of PkQs, mycobacteria escape from the hypoxic core of biofilms and prefer oxygen-rich conditions. Unlike the ubiquitous isoprenoid pathway for the biosynthesis of respiratory quinones, PkQs are produced by type III polyketide synthases using fatty acyl-CoA precursors. The biosynthetic pathway is conserved in several other bacterial genomes, and our study reveals a redox-balancing chemicocellular process in microbial physiology.
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http://dx.doi.org/10.1016/j.molcel.2015.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051517PMC
November 2015

Clinical evaluation of zero-echo-time MR imaging for the segmentation of the skull.

J Nucl Med 2015 Mar 12;56(3):417-22. Epub 2015 Feb 12.

Department of Medical Imaging, University Hospital, Zurich, Switzerland.

Unlabelled: MR-based attenuation correction is instrumental for integrated PET/MR imaging. It is generally achieved by segmenting MR images into a set of tissue classes with known attenuation properties (e.g., air, lung, bone, fat, soft tissue). Bone identification with MR imaging is, however, quite challenging, because of the low proton density and fast decay time of bone tissue. The clinical evaluation of a novel, recently published method for zero-echo-time (ZTE)-based MR bone depiction and segmentation in the head is presented here.

Methods: A new paradigm for MR imaging bone segmentation, based on proton density-weighted ZTE imaging, was disclosed earlier in 2014. In this study, we reviewed the bone maps obtained with this method on 15 clinical datasets acquired with a PET/CT/MR trimodality setup. The CT scans acquired for PET attenuation-correction purposes were used as reference for the evaluation. Quantitative measurements based on the Jaccard distance between ZTE and CT bone masks and qualitative scoring of anatomic accuracy by an experienced radiologist and nuclear medicine physician were performed.

Results: The average Jaccard distance between ZTE and CT bone masks evaluated over the entire head was 52% ± 6% (range, 38%-63%). When only the cranium was considered, the distance was 39% ± 4% (range, 32%-49%). These results surpass previously reported attempts with dual-echo ultrashort echo time, for which the Jaccard distance was in the 47%-79% range (parietal and nasal regions, respectively). Anatomically, the calvaria is consistently well segmented, with frequent but isolated voxel misclassifications. Air cavity walls and bone/fluid interfaces with high anatomic detail, such as the inner ear, remain a challenge.

Conclusion: This is the first, to our knowledge, clinical evaluation of skull bone identification based on a ZTE sequence. The results suggest that proton density-weighted ZTE imaging is an efficient means of obtaining high-resolution maps of bone tissue with sufficient anatomic accuracy for, for example, PET attenuation correction.
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http://dx.doi.org/10.2967/jnumed.114.149997DOI Listing
March 2015

Zero TE MR bone imaging in the head.

Magn Reson Med 2016 Jan 16;75(1):107-14. Epub 2015 Jan 16.

GE Global Research, Bangalore, India.

Purpose: To investigate proton density (PD)-weighted zero TE (ZT) imaging for morphological depiction and segmentation of cranial bone structures.

Methods: A rotating ultra-fast imaging sequence (RUFIS) type ZT pulse sequence was developed and optimized for 1) efficient capture of short T2 bone signals and 2) flat PD response for soft-tissues. An inverse logarithmic image scaling (i.e., -log(image)) was used to highlight bone and differentiate it from surrounding soft-tissue and air. Furthermore, a histogram-based bias-correction method was developed for subsequent threshold-based air, soft-tissue, and bone segmentation.

Results: PD-weighted ZT imaging in combination with an inverse logarithmic scaling was found to provide excellent depiction of cranial bone structures. In combination with bias correction, also excellent segmentation results were achieved. A two-dimensional histogram analysis demonstrates a strong, approximately linear correlation between inverse log-scaled ZT and low-dose CT for Hounsfield units (HU) between -300 HU and 1,500 HU (corresponding to soft-tissue and bone).

Conclusions: PD-weighted ZT imaging provides robust and efficient depiction of bone structures in the head, with an excellent contrast between air, soft-tissue, and bone. Besides structural bone imaging, the presented method is expected to be of relevance for attenuation correction in positron emission tomography (PET)/MR and MR-based radiation therapy planning.
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http://dx.doi.org/10.1002/mrm.25545DOI Listing
January 2016

"Phloem sap analysis of Schleichera oleosa (Lour) Oken, Butea monosperma (Lam) Taub. and Ziziphus mauritiana (Lam) and hemolymph of Kerria lacca (Kerr) using HPLC and tandem mass spectrometry".

Physiol Mol Biol Plants 2013 Oct;19(4):537-45

Department of Botany, University of Delhi, Delhi, 110007 India.

Females of lac insects especially of Kerria lacca (Kerr) secret a resin known as lac for their own protection, which has tremendous applications. Lac insect completes its lifecycle on several host taxa where it exclusively feeds on phloem sap but Schleichera oleosa (Lour.) Oken, Butea monosperma (Lam.) and Ziziphus mauritiana (Lam.) are its major hosts. Analysis of phloem sap constituents as well as hemolymph of lac insect is important because it ultimately gets converted into lac by insect intervention. Main phloem sap constituent's viz. sugars and free amino acids and hemolymph of lac insect were analyzed using HPLC and tandem mass spectrometry, respectively. The results were transformed to relative percentage of the total sugars and free amino acids analyzed in each sample for comparison among lac insect hemolymph and the phloem sap of the three different host taxa. Sucrose (58.9 ± 3.6-85.6 ± 0.9) and trehalose (62.3 ± 0.4) were the predominant sugars in phloem sap of three taxa and hemolymph of lac insect, respectively. Glutamic acid (33.1 ± 1.4-39.8 ± 1.4) was found to be main amino acid among the phloem sap of three taxa while tyrosine (61 ± 2.6) was the major amino acid in hemolymph of lac insect. The relative percentage of non-essential amino acids (60.8 %-69.9 %) was found to be more in all the three host taxa while essential amino acids (30.1 %-35.4 %) were present at a lower relative percentage. In contrast to this, the relative percentage of essential amino acids (81.9 %) was observed to be higher as compared to non-essential amino acids (17.7 %) in lac insect hemolymph. These results led to the detection of lac insect's endosymbionts. Moreover, this study revealed a clue regarding the importance of development of a synthetic diet for this insect so that a precise pathway of lac biosynthesis could be investigated for thorough understanding.
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http://dx.doi.org/10.1007/s12298-013-0194-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781273PMC
October 2013

An ex vivo comparative analysis on shaping ability of four NiTi rotary endodontic instruments using spiral computed tomography.

J Conserv Dent 2013 May;16(3):219-23

Department of Conservative Dentistry and Endodontics, Buddha Institute of Dental Sciences and Hospital, Kankarbagh, Patna, India.

Objective: Analysis of shaping ability of four different rotary endodontic instruments using spiral computed tomography (CT).

Materials And Methods: Eighty freshly extracted human mandibular first molars were used in the present study. Samples were randomly divided into four experimental groups with twenty samples in each group. Images of mesiobuccal canal of each sample were obtained pre- and post-operatively using spiral CT. All samples were prepared using their respective endodontic file systems (group I - ProTaper, group II - K3, group III - RaCe, and group IV - Mtwo). Image analyses were done using image analysis software for evaluation of canal transportation and centering ability. Data was then statistically analyzed using analysis of variance.

Results: There was no statistically significance in transportation in their intergroup difference at any of the three locations (coronal, middle, and apical third). In centering ability there was no statistically significance in the coronal and middle third of the intergroup. However, there was a statistically significance of (P = 0.044) at the apical third between all the groups.

Conclusion: Canals prepared with ProTaper had more canal transportation at all the three levels of root canal (coronal, middle, and apical third). Canals prepared with Mtwo were well centered at coronal and middle third whereas with RaCe canals were centered only at the apical third. All instruments showed some degree of canal aberrations in terms of shaping ability.
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http://dx.doi.org/10.4103/0972-0707.111318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698584PMC
May 2013
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