Publications by authors named "Ajinkya Patil"

8 Publications

  • Page 1 of 1

Importance of genetic data in resolving cryptic species: A century old problem of understanding the distribution of Minervarya syhadrensis Annandale 1919, (Anura: Dicroglossidae).

Zootaxa 2020 Nov 4;4869(4):zootaxa.4869.4.1. Epub 2020 Nov 4.

Department of Zoology, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.

Frogs of the genus Minervarya are cryptic and widely distributed in South Asia. However, many of them lack information about the precise type locality, genetic data, and distribution range. The present study aimed to examine the genetic affinities of a widely distributed species Minervarya syhadrensis around its type locality in the northern Western Ghats (Pune, Maharashtra). We studied the type specimen of M. syhadrensis and collected similar sized Minervarya frogs from Pune district. In the field, we observed two different calls from morphologically similar (M. syhadrensis like) males suggesting the sympatric occurrence of two cryptic species (that we initially named Minervarya species A and Minervarya species B). We analyzed morphology, call pattern, and mitochondrial 16S rRNA gene sequence of both species. Minervarya species A has a long call with a low pulse repetition rate and higher dominant frequency compared to that of the Minervarya species B. These species cannot be differentiated based on morphometric data. However, they can be sorted out using morphological characters such as the presence of longitudinal skin folds on the dorsal side (Minervarya species A) and differences in foot webbing. DNA sequences of Minervarya species A and Minervarya species B are matching with those of M. caperata and M. agricola respectively. After studying the type specimens of M. syhadrensis and M. caperata, we found morphological similarities (longitudinal skin folds) with the samples of Minervarya species A collected during the present study. Based on the results of our study (morphology and genetic) and available literature, we propose to redefine M. syhadrensis as applying to the lineage initially named Minervarya species A, and to treat the species M. caperata as a junior synonym of M. syhadrensis. Our study will be helpful in further taxonomic revision of the genus, and provides natural history information for M. syhadrensis and M. agricola.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11646/zootaxa.4869.4.1DOI Listing
November 2020

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection.

Cell 2021 01 20;184(1):76-91.e13. Epub 2020 Oct 20.

Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address:

Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.10.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574718PMC
January 2021

The genome sequence of Mesua ferrea and comparative demographic histories of forest trees.

Gene 2021 Feb 8;769:145214. Epub 2020 Oct 8.

Computational Evolutionary Genomics Lab, Department of Biological Sciences, IISER Bhopal, Bhauri, Madhya Pradesh, India. Electronic address:

Mesua ferrea (Family: Calophyllaceae) is a tropical forest plant used for timber, biofuel, and traditional medicine. Colloquially, it is known as Nagkesar (Cobra saffron) and is the state flower of Tripura (India). In this study, we perform the whole-genome assembly of Mesua ferrea using ~180X coverage paired-end Illumina data. Our de novo assembly is 614 Mega-base pair (Mbp), has an N50 of 392 Kilo-base pairs (Kbp), and an assembly quality comparable to other published Malpighiales genomes. Further, we collate the genomic datasets of 14 additional forest tree species to compare the temporal dynamics of Effective Population Size (N) and find evidence of a substantial bottleneck in all tropical forest plants during Mid-Pleistocene glaciations. The availability of this high-quality draft genome assembly will prove to be a useful resource for functional and comparative genomic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2020.145214DOI Listing
February 2021

Epidemiological and Clinical Characteristics of COVID-19 in Indian Children in the Initial Phase of the Pandemic.

Indian Pediatr 2020 Oct 28;57(10):914-917. Epub 2020 Jul 28.

Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India.

Objective: To assess the epidemiological and clinical characteristics of pediatric inpatients with COVID-19, early in the pandemic.

Methods: Clinical and laboratory profile and outcomes were studied for children (aged 1 month - 18 years) presenting between 1 April, 2020 and 20 May, 2020 with positive nasopharyngeal swab for SARS-CoV-2 by RT-PCR.

Results: 50 children (56% male) with median (IQR) age of 6 (2-12) years were included. Majority (56%) were from families belonging to Kuppuswamy upper lower socioeconomic class. 45 (90%) had positive household contact, and 33 (66%) had overcrowding at home. 29 (58%) children were asymptomatic while 20 (40%) had mild symptoms. Fever, cough, and sore throat were the most common symptoms. High C-reactive protein levels were seen in 15 (30%) children. There was no mortality.

Conclusion: The disease burden appears high in lower socio-economic group with majority having a positive household contact. Milder disease pattern in the pediatric age group is reiterated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605483PMC
October 2020

Genome-wide CRISPR screens reveal genetic mediators of cereblon modulator toxicity in primary effusion lymphoma.

Blood Adv 2019 07;3(14):2105-2117

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Genome-wide CRISPR/Cas9 screens represent a powerful approach to studying mechanisms of drug action and resistance. Cereblon modulating agents (CMs) have recently emerged as candidates for therapeutic intervention in primary effusion lymphoma (PEL), a highly aggressive cancer caused by Kaposi's sarcoma-associated herpesvirus. CMs bind to cereblon (CRBN), the substrate receptor of the cullin-RING type E3 ubiquitin ligase CRL4, and thereby trigger the acquisition and proteasomal degradation of neosubstrates. Downstream mechanisms of CM toxicity are incompletely understood, however. To identify novel CM effectors and mechanisms of CM resistance, we performed positive selection CRISPR screens using 3 CMs with increasing toxicity in PEL: lenalidomide (LEN), pomalidomide (POM), and CC-122. Results identified several novel modulators of the activity of CRL4 The number of genes whose inactivation confers resistance decreases with increasing CM efficacy. Only inactivation of CRBN conferred complete resistance to CC-122. Inactivation of the E2 ubiquitin conjugating enzyme UBE2G1 also conferred robust resistance against LEN and POM. Inactivation of additional genes, including the Nedd8-specific protease SENP8, conferred resistance to only LEN. SENP8 inactivation indirectly increased levels of unneddylated CUL4A/B, which limits CRL4 activity in a dominant negative manner. Accordingly, sensitivity of SENP8-inactivated cells to LEN is restored by overexpression of CRBN. In sum, our screens identify several novel players in CRL4 function and define pathways to CM resistance in PEL. These results provide rationale for increasing CM efficacy on patient relapse from a less-efficient CM. Identified genes could finally be developed as biomarkers to predict CM efficacy in PEL and other cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2019031732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650732PMC
July 2019

Gene essentiality landscape and druggable oncogenic dependencies in herpesviral primary effusion lymphoma.

Nat Commun 2018 08 15;9(1):3263. Epub 2018 Aug 15.

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.

Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus. Our understanding of PEL is poor and therefore treatment strategies are lacking. To address this need, we conducted genome-wide CRISPR/Cas9 knockout screens in eight PEL cell lines. Integration with data from unrelated cancers identifies 210 genes as PEL-specific oncogenic dependencies. Genetic requirements of PEL cell lines are largely independent of Epstein-Barr virus co-infection. Genes of the NF-κB pathway are individually non-essential. Instead, we demonstrate requirements for IRF4 and MDM2. PEL cell lines depend on cellular cyclin D2 and c-FLIP despite expression of viral homologs. Moreover, PEL cell lines are addicted to high levels of MCL1 expression, which are also evident in PEL tumors. Strong dependencies on cyclin D2 and MCL1 render PEL cell lines highly sensitive to palbociclib and S63845. In summary, this work comprehensively identifies genetic dependencies in PEL cell lines and identifies novel strategies for therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-05506-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093911PMC
August 2018

CK1α and IRF4 are essential and independent effectors of immunomodulatory drugs in primary effusion lymphoma.

Blood 2018 08 28;132(6):577-586. Epub 2018 Jun 28.

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Primary effusion lymphoma (PEL) is an aggressive cancer with few treatment options. The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide have recently been shown to kill PEL cell lines, and lenalidomide is in clinical trials against PEL. IMiDs bind to the CRL4 E3 ubiquitin ligase complex, leading to the acquisition of the Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3), casein kinase 1 α (CK1α), and zinc finger protein 91 (ZFP91) as neosubstrates. IMiDs are effective against multiple myeloma because of degradation of IKZF1 and IKZF3 and the consequent loss of interferon regulatory factor 4 (IRF4) and MYC expression. Lenalidomide is also effective in chromosome 5q deletion-associated myelodysplastic syndrome as a result of degradation of CK1α. An essential IKZF1-IRF4-MYC axis has recently been proposed to underlie the toxicity of IMiDs in PEL. Here, we further investigate IMiD effectors in PEL cell lines, based on genome-wide CRISPR/Cas9 screens for essential human genes. These screens and extensive validation experiments show that, of the 4 neosubstrates, only CK1α is essential for the survival of PEL cell lines. In contrast, IKZF1 and IKZF3 are dispensable, individually or in combination. IRF4 was critical in all 8 PEL cell lines tested, and surprisingly, IMiDs triggered downregulation of IRF4 expression independently of both IKZF1 and IKZF3. Reexpression of CK1α and/or IRF4 partially rescued PEL cell lines from IMiD-mediated toxicity. In conclusion, IMiD toxicity in PEL cell lines is independent of IKZF1 and IKZF3 but proceeds through degradation of the neosubstrate CK1α and downregulation of IRF4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2018-01-828418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085990PMC
August 2018

Reliability of the frontal sinus index as a maturity indicator.

Indian J Dent Res 2013 Jul-Aug;24(4):523

Department of Orthodontics and Dentofacial Orthopedics, SDM College of Dental Sciences and Hospital, Sattur, Dharwad, Karnataka, India.

Aim: The aim of this study was to compare the reliability of frontal sinus as a skeletal maturity indicator in males and females.

Setting And Sample Population: Lateral cephalograms of 75 males and 75 females, both in pre- and post-pubertal stages of development as determined by Middle phalanx of the third finger (MP3) radiographs.

Materials And Methods: Lateral cephalograms were analyzed for frontal sinus maturity. Maximum height, maximum width and height to width ratio of the sinus were calculated. The mean height to width ratio of the sinus at respective MP3 stages were tabulated and subjected to statistical analysis to determine the correlation. Correlation at different MP3 stages between males and females was also determined.

Results: Statistically significant differences were observed between the mean values of F and FG along with F and I stage in males, significant difference between the values of FG stage among males and females were also observed.

Conclusion: Based on statistical and direct comparison of raw data, study concludes that frontal sinus is not reliable as a sole criterion for prediction of skeletal maturity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0970-9290.118372DOI Listing
September 2015