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  1. Article ; Online: Identification of Pseudo-R genes in Vitis vinifera and characterization of their role as immunomodulators in host-pathogen interactions.

    Garewal, Naina / Pathania, Shivalika / Bhatia, Garima / Singh, Kashmir

    Journal of advanced research

    2022  

    Abstract: ... the key to disarming pathogenic invasions. Thus, deciphering the roles of pseudo-R genes in plant defense ...

    Abstract Introduction: Duplication events are fundamental to co-evolution in host-pathogen interactions. Pseudogenes (Ψs) are dysfunctional paralogs of functional genes and resistance genes (Rs) in plants are the key to disarming pathogenic invasions. Thus, deciphering the roles of pseudo-R genes in plant defense is momentous.
    Objectives: This study aimed to functionally characterize diverse roles of the resistance Ψs as novel gene footprints and as significant gene regulators in the grapevine genome.
    Methods: PlantPseudo pipeline and HMM-profiling identified whole-genome duplication-derived (WGD) Ψs associated with resistance genes (Ψ-Rs). Further, novel antifungal and antimicrobial peptides were characterized for fungal associations using protein-protein docking with Erysiphe necator proteins. miRNA and tasiRNA target sites and transcription factor (TF) binding sites were predicted in Ψ-Rs. Finally, differential co-expression patterns in Ψ-Rs-lncRNAs-coding genes were identified using the UPGMA method.
    Results: 2,746 Ψ-Rs were identified from 31,032 WGD Ψs in the genome of grapevine. 69-antimicrobial and 81-antifungal novel peptides were generated from Ψ-Rs. The putative genic potential was predicted for five novel antifungal peptides which were further characterized by docking against E. necator proteins. 395 out of 527 resistance loci-specific Ψ-Rs were acting as parental gene mimics. Further, to explore the diverse roles of Ψ-Rs in plant-defense, we identified 37,026 TF-binding sites, 208 miRNA, and 99 tasiRNA targeting sites on these Ψ-Rs. 194 Ψ-Rs were exhibiting tissue-specific expression patterns. The co-expression network analysis between Ψs-lncRNA-genes revealed six out of 79 pathogen-responsive Ψ-Rs as significant during pathogen invasion.
    Conclusions: Our study provides pathogen responsive Ψ-Rs integral for pathogen invasion, which will offer a useful resource for future experimental validations. In addition, our findings on novel peptide generations from Ψ-Rs offer valuable insights which can serve as a useful resource for predicting novel genes with the futuristic potential of being investigated for their bioactivities in the plant system.
    Language English
    Publishing date 2022-08-03
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2541849-X
    ISSN 2090-1224 ; 2090-1224
    ISSN (online) 2090-1224
    ISSN 2090-1224
    DOI 10.1016/j.jare.2022.07.014
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  2. Article ; Online: Nek7 conformational flexibility and inhibitor binding probed through protein engineering of the R-spine.

    Byrne, Matthew J / Nasir, Nazia / Basmadjian, Christine / Bhatia, Chitra / Cunnison, Rory F / Carr, Katherine H / Mas-Droux, Corine / Yeoh, Sharon / Cano, Céline / Bayliss, Richard

    The Biochemical journal

    2020  Volume 477, Issue 8, Page(s) 1525–1539

    Abstract: ... Nek7 crystal structures exhibit an improperly formed regulatory-spine (R-spine), characteristic ... residues into the R-spine of Nek7 with the aim to stabilise the active conformation of the kinase through R ... spine stacking. The strong R-spine mutant Nek7SRS retained catalytic activity and was crystallised ...

    Abstract Nek7 is a serine/threonine-protein kinase required for proper spindle formation and cytokinesis. Elevated Nek7 levels have been observed in several cancers, and inhibition of Nek7 might provide a route to the development of cancer therapeutics. To date, no selective and potent Nek7 inhibitors have been identified. Nek7 crystal structures exhibit an improperly formed regulatory-spine (R-spine), characteristic of an inactive kinase. We reasoned that the preference of Nek7 to crystallise in this inactive conformation might hinder attempts to capture Nek7 in complex with Type I inhibitors. Here, we have introduced aromatic residues into the R-spine of Nek7 with the aim to stabilise the active conformation of the kinase through R-spine stacking. The strong R-spine mutant Nek7SRS retained catalytic activity and was crystallised in complex with compound 51, an ATP-competitive inhibitor of Nek2 and Nek7. Subsequently, we obtained the same crystal form for wild-type Nek7WT in apo form and bound to compound 51. The R-spines of the three well-ordered Nek7WT molecules exhibit variable conformations while the R-spines of the Nek7SRS molecules all have the same, partially stacked configuration. Compound 51 bound to Nek2 and Nek7 in similar modes, but differences in the precise orientation of a substituent highlights features that could be exploited in designing inhibitors that are selective for particular Nek family members. Although the SRS mutations are not required to obtain a Nek7-inhibitor structure, we conclude that it is a useful strategy for restraining the conformation of a kinase in order to promote crystallogenesis.
    MeSH term(s) Catalysis ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/metabolism ; Humans ; Kinetics ; Mutation ; NIMA-Related Kinases/chemistry ; NIMA-Related Kinases/genetics ; NIMA-Related Kinases/metabolism ; Protein Binding ; Protein Conformation ; Protein Engineering
    Chemical Substances Enzyme Inhibitors ; NEK2 protein, human (EC 2.7.11.1) ; NEK7 protein, human (EC 2.7.11.1) ; NIMA-Related Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2020-03-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20200128
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  3. Article: The Role of Replication-Associated Repair Factors on R-Loops.

    Bhatia, Vaibhav / Herrera-Moyano, Emilia / Aguilera, Andrés / Gómez-González, Belén

    Genes

    2017  Volume 8, Issue 7

    Abstract: The nascent RNA can reinvade the DNA double helix to form a structure termed the R-loop ... where a single-stranded DNA (ssDNA) is accompanied by a DNA-RNA hybrid. Unresolved R-loops can impede ... understood. In this sense, a connection between R-loops and certain chromatin markers has been reported ...

    Abstract The nascent RNA can reinvade the DNA double helix to form a structure termed the R-loop, where a single-stranded DNA (ssDNA) is accompanied by a DNA-RNA hybrid. Unresolved R-loops can impede transcription and replication processes and lead to genomic instability by a mechanism still not fully understood. In this sense, a connection between R-loops and certain chromatin markers has been reported that might play a key role in R-loop homeostasis and genome instability. To counteract the potential harmful effect of R-loops, different conserved messenger ribonucleoprotein (mRNP) biogenesis and nuclear export factors prevent R-loop formation, while ubiquitously-expressed specific ribonucleases and DNA-RNA helicases resolve DNA-RNA hybrids. However, the molecular events associated with R-loop sensing and processing are not yet known. Given that R-loops hinder replication progression, it is plausible that some DNA replication-associated factors contribute to dissolve R-loops or prevent R-loop mediated genome instability. In support of this, R-loops accumulate in cells depleted of the BRCA1, BRCA2 or the Fanconi anemia (FA) DNA repair factors, indicating that they play an active role in R-loop dissolution. In light of these results, we review our current view of the role of replication-associated DNA repair pathways in preventing the harmful consequences of R-loops.
    Language English
    Publishing date 2017-06-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes8070171
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  4. Article: Fragrance material review on dihydrocarveol (R,R,R).

    Bhatia, S P / Letizia, C S / Api, A M

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

    2008  Volume 46 Suppl 11, Page(s) S121–2

    Abstract: A toxicologic and dermatologic review of dihydrocarveol (R,R,R) when used as a fragrance ingredient ...

    Abstract A toxicologic and dermatologic review of dihydrocarveol (R,R,R) when used as a fragrance ingredient is presented.
    MeSH term(s) Molecular Structure ; Monoterpenes/administration & dosage ; Monoterpenes/chemistry ; Monoterpenes/toxicity ; Perfume/chemistry
    Chemical Substances Monoterpenes ; Perfume ; 2-methyl-5-(1-methylethenyl)cyclohexanol (ZR76810L52)
    Language English
    Publishing date 2008-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2008.06.041
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  5. Book ; Online: Least $k$th-Order and R\'{e}nyi Generative Adversarial Networks

    Bhatia, Himesh / Paul, William / Alajaji, Fady / Gharesifard, Bahman / Burlina, Philippe

    2020  

    Abstract: ... divergence. Another novel GAN generator loss function is next proposed in terms of R\'{e}nyi cross-entropy ... functionals with order $\alpha >0$, $\alpha\neq 1$. It is demonstrated that this R\'{e}nyi-centric generalized ... the equilibrium point satisfied by the original GAN based on the Jensen-R\'{e}nyi divergence, a natural extension ...

    Abstract We investigate the use of parametrized families of information-theoretic measures to generalize the loss functions of generative adversarial networks (GANs) with the objective of improving performance. A new generator loss function, called least $k$th-order GAN (L$k$GAN), is first introduced, generalizing the least squares GANs (LSGANs) by using a $k$th order absolute error distortion measure with $k \geq 1$ (which recovers the LSGAN loss function when $k=2$). It is shown that minimizing this generalized loss function under an (unconstrained) optimal discriminator is equivalent to minimizing the $k$th-order Pearson-Vajda divergence. Another novel GAN generator loss function is next proposed in terms of R\'{e}nyi cross-entropy functionals with order $\alpha >0$, $\alpha\neq 1$. It is demonstrated that this R\'{e}nyi-centric generalized loss function, which provably reduces to the original GAN loss function as $\alpha\to1$, preserves the equilibrium point satisfied by the original GAN based on the Jensen-R\'{e}nyi divergence, a natural extension of the Jensen-Shannon divergence. Experimental results indicate that the proposed loss functions, applied to the MNIST and CelebA datasets, under both DCGAN and StyleGAN architectures, confer performance benefits by virtue of the extra degrees of freedom provided by the parameters $k$ and $\alpha$, respectively. More specifically, experiments show improvements with regard to the quality of the generated images as measured by the Fr\'echet Inception Distance (FID) score and training stability. While it was applied to GANs in this study, the proposed approach is generic and can be used in other applications of information theory to deep learning, e.g., the issues of fairness or privacy in artificial intelligence.
    Keywords Computer Science - Machine Learning ; Computer Science - Information Theory ; Statistics - Machine Learning
    Subject code 006
    Publishing date 2020-06-03
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Eighty years of gene-for-gene relationship and its applications in identification and utilization of R genes

    Kaur, Bhavjot / Bhatia, Dharminder / Mavi, G. S.

    Journal of genetics. 2021 Oct., v. 100, no. 2

    2021  

    Abstract: ... cloning of several resistance (R) genes in plants. These R genes have been deployed and altered ... biotechnological tools. Identification of R genes and their corresponding Avr genes in many cases played ... a significant role in understanding of R-Avr gene interactions. Rapid cloning of R genes and editing ...

    Abstract The gene-for-gene relationship of host–pathogen interaction explained by H. H. Flor in mid of the 20th century set a milestone in understanding the biochemical and genetic basis of plant diseases and several components involved in plant–pathogen interactions. It highlighted the importance of accomplishing differential sets and understanding the pathogen population structure, it further led to the identification and cloning of several resistance (R) genes in plants. These R genes have been deployed and altered for fighting against diseases in a large number of crops using various conventional approaches and biotechnological tools. Identification of R genes and their corresponding Avr genes in many cases played a significant role in understanding of R-Avr gene interactions. Rapid cloning of R genes and editing of susceptible R genes are the other avenues that have broadened the horizon of utilizing R genes in crop improvement programmes. Further, combining R genes with quantitative disease resistance genes has paved the way to develop durable resistance in cultivars. The recent advances in genetics, genomics, bioinformatics and other OMICS tools are now providing greater prospects for deeper understanding of host–pathogen interaction.
    Keywords bioinformatics ; cultivars ; disease resistance ; gene-for-gene relationship ; genomics ; host-pathogen relationships ; pathogens ; population structure
    Language English
    Dates of publication 2021-10
    Size p. 50.
    Publishing place Springer India
    Document type Article
    Note Review
    ZDB-ID 3039-9
    ISSN 0973-7731 ; 0958-8361 ; 0022-1333
    ISSN (online) 0973-7731
    ISSN 0958-8361 ; 0022-1333
    DOI 10.1007/s12041-021-01300-7
    Database NAL-Catalogue (AGRICOLA)

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  7. Book ; Online: National framework for One Health

    Bhatia, Rajesh

    2021  

    Institution FAO
    Author's details by Dr. Rajesh Bhatia ; Food and Agriculture Organization of the United Nations
    Language English
    Size 1 Online-Ressource (ix, 41 Seiten)
    Publisher Food and Agriculture Organization of the United Nations
    Publishing place New Delhi
    Publishing country India
    Document type Book ; Online
    Note Open Access
    HBZ-ID HT020990602
    ISBN 978-92-5-134192-6 ; 92-5-134192-3
    DOI 10.4060/cb4072en
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  8. Article ; Online: Effect of r-TMS over standard therapy in decreasing muscle tone of spastic cerebral palsy patients.

    Gupta, Meena / Lal Rajak, Bablu / Bhatia, Dinesh / Mukherjee, Arun

    Journal of medical engineering & technology

    2016  Volume 40, Issue 4, Page(s) 210–216

    Abstract: ... employed to date. Besides these, recently repetitive Transcranial magnetic stimulation (r-TMS) is a new ... The aim of this study was to observe the effects of r-TMS on muscle spasticity in CP patients ... years, 107.9 (SD = 26.33) cm, 21.40 (SD = 12.63) kg, respectively). r-TMS frequencies of 5 Hz and 10 Hz ...

    Abstract Spastic cerebral palsy (CP) is the one of most common neurological disorders occurring due to damage to the immature brain or any other brain lesion at the time of birth. To aid in making the life of the CP patient meaningful, several interventions such as medical, surgical and rehabilitation have been employed to date. Besides these, recently repetitive Transcranial magnetic stimulation (r-TMS) is a new found approach which is being employed for treating various neurological and psychological conditions. The aim of this study was to observe the effects of r-TMS on muscle spasticity in CP patients by stimulating the motor cortex area of the brain, which is responsible for muscle movements. In this study, 20 subjects diagnosed with CP were recruited and 10 each were placed in two groups, namely the research group (RG) (mean age, height and weight were 7.99 (SD = 4.66) years, 116.7 (SD = 23.57) cm and 21.40 (SD = 10.95) kg, respectively) and the control group (CG) (mean age, height and weight were 8.41 (SD = 4.32) years, 107.9 (SD = 26.33) cm, 21.40 (SD = 12.63) kg, respectively). r-TMS frequencies of 5 Hz and 10 Hz were administered for 15 min daily to patients in RG followed by standard therapy (ST) of 1 h duration daily for 20 days. Moreover, the patients in the control group (CG) were given only standard therapy (ST) of 1 h duration for 20 days. Modified Ashworth Scale (MAS) was used as an outcome measure to determine the level of muscle spasticity. A pre- assessment of MAS score was performed on both RG and CG to determine the level of spasticity prior to starting therapy; and similarly post-assessment after 20 days was done to observe the changes post-therapy. Statistical analysis of pre vs post MAS scores showed that few muscles showed reduction in muscle tightness after administering only ST in the CG. On the contrary, the RG that underwent r-TMS therapy combined with ST showed a significant decrease (p < 0.05) in muscle tightness for all the muscles selected for the therapy.
    MeSH term(s) Adult ; Cerebral Palsy/therapy ; Female ; Humans ; Male ; Middle Aged ; Muscle Spasticity/physiopathology ; Transcranial Magnetic Stimulation
    Language English
    Publishing date 2016
    Publishing country England
    Document type Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 243092-7
    ISSN 1464-522X ; 0309-1902
    ISSN (online) 1464-522X
    ISSN 0309-1902
    DOI 10.3109/03091902.2016.1161854
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  9. Article: A.B.R. in Nager type acrofacial dysostosis syndrome.

    Mishra, A / Shukla, G K / Bhatia, N

    Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India

    2012  Volume 51, Issue 3, Page(s) 45–49

    Abstract: The acrofacial dysostosis of nager is a very rare hereditary syndrome in which findings of mandibulofacial dysostosis are associated with defects of the limbs. The developmental defects of the mesoderm if accompany the neurectodermal malformations, ... ...

    Abstract The acrofacial dysostosis of nager is a very rare hereditary syndrome in which findings of mandibulofacial dysostosis are associated with defects of the limbs. The developmental defects of the mesoderm if accompany the neurectodermal malformations, result in mental retardation and sensorineural hearing impairment. The conductive type of hearing loss is mostly encountered in Nager's syndrome but here we present a case with sensorineural involvement, along with its analysis of auditory brainstem evoked response audiometry (ABR).
    Language English
    Publishing date 2012-10-05
    Publishing country India
    Document type Journal Article
    ZDB-ID 1471137-0
    ISSN 0973-7707 ; 2231-3796 ; 0019-5421
    ISSN (online) 0973-7707
    ISSN 2231-3796 ; 0019-5421
    DOI 10.1007/BF02996529
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  10. Article ; Online: Reply to R. Erro and M. Tinazzi's "Functional (psychogenic) paroxysms: the diagnosis is in the eye of the beholder".

    Ganos, Christos / Edwards, Mark / Bhatia, Kailash P

    Parkinsonism & related disorders

    2014  Volume 20, Issue 3, Page(s) 345

    MeSH term(s) Chorea/diagnosis ; Female ; Humans ; Male ; Somatoform Disorders/diagnosis
    Language English
    Publishing date 2014-03
    Publishing country England
    Document type Comment ; Letter
    ZDB-ID 1311489-x
    ISSN 1873-5126 ; 1353-8020
    ISSN (online) 1873-5126
    ISSN 1353-8020
    DOI 10.1016/j.parkreldis.2013.11.015
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