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Article ; Online: Temporal bone management in external and middle ear carcinoma.

Gowrishankar, Shravan / Borsetto, Daniele / Marinelli, John / Panizza, Ben

Current opinion in otolaryngology & head and neck surgery

2024 Volume 32, Issue 2, Page(s) 138–142

Abstract: Purpose of review: The purpose of this review is to outline the temporal bone management of external and middle ear carcinoma. The review will outline the current evidence involved in deciding which surgical approach to take, as well as new advances in ... ...

Abstract	Purpose of review: The purpose of this review is to outline the temporal bone management of external and middle ear carcinoma. The review will outline the current evidence involved in deciding which surgical approach to take, as well as new advances in auditory rehabilitation and immunotherapy. Recent findings: Traditional surgical approaches include lateral temporal bone resection, subtotal temporal bone resection and total temporal bone resection. They can also involve parotidectomy and neck dissection depending on extension of disease into these areas. Options for auditory rehabilitation include osseointegrated hearing aids, transcutaneous bone-conduction implants, and active middle ear implants. Recent advances in immunotherapy have included the use of anti-PD-1 monoclonal antibodies. Summary: The mainstay of management of temporal bone disease involves surgical resection. Early-stage tumours classified according to the Pittsburgh staging tool can often be treated with lateral temporal bone resection, whereas late-stage tumours might need subtotal or total temporal bone resection. Parotidectomy and neck dissection might also be indicated if there is a risk of occult regional disease. Recent advances in immunotherapy have been promising, particularly around anti-PD-1 inhibitors. However, larger clinical trials will be required to test the extent of efficacy, particularly around combination use with surgery.
MeSH term(s)	Humans ; Neoplasm Staging ; Temporal Bone/surgery ; Ear Neoplasms/pathology ; Ear Neoplasms/surgery ; Carcinoma/pathology ; Ear, Middle/surgery
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	1232518-1
ISSN	1531-6998 ; 1068-9508
ISSN (online)	1531-6998
ISSN	1068-9508
DOI	10.1097/MOO.0000000000000959
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Article ; Online: Essential Role for an Isoform of Escherichia coli Translation Initiation Factor IF2 in Repair of Two-Ended DNA Double-Strand Breaks.

Mallikarjun, Jillella / Gowrishankar, J

Journal of bacteriology

2022 Volume 204, Issue 4, Page(s) e0057121

Abstract: In Escherichia coli, three isoforms of the essential translation initiation factor IF2 (IF2-1, IF2-2, and IF2-3) are generated from separate in-frame initiation codons ... ...

Abstract	In Escherichia coli, three isoforms of the essential translation initiation factor IF2 (IF2-1, IF2-2, and IF2-3) are generated from separate in-frame initiation codons in
MeSH term(s)	DNA/metabolism ; DNA Breaks, Double-Stranded ; DNA Repair ; DNA Replication ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Peptide Initiation Factors/genetics ; Peptide Initiation Factors/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism
Chemical Substances	Peptide Initiation Factors ; Protein Isoforms ; DNA (9007-49-2)
Language	English
Publishing date	2022-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/jb.00571-21
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Article ; Online: Role for DNA double strand end-resection activity of RecBCD in control of aberrant chromosomal replication initiation in Escherichia coli.

Goswami, Sayantan / Gowrishankar, Jayaraman

Nucleic acids research

2022 Volume 50, Issue 15, Page(s) 8643–8657

Abstract: Replication of the circular bacterial chromosome is initiated from a locus oriC with the aid of an essential protein DnaA. One approach to identify factors acting to prevent aberrant oriC-independent replication initiation in Escherichia coli has been ... ...

Abstract	Replication of the circular bacterial chromosome is initiated from a locus oriC with the aid of an essential protein DnaA. One approach to identify factors acting to prevent aberrant oriC-independent replication initiation in Escherichia coli has been that to obtain mutants which survive loss of DnaA. Here, we show that a ΔrecD mutation, associated with attenuation of RecBCD's DNA double strand end-resection activity, provokes abnormal replication and rescues ΔdnaA lethality in two situations: (i) in absence of 5'-3' single-strand DNA exonuclease RecJ, or (ii) when multiple two-ended DNA double strand breaks (DSBs) are generated either by I-SceI endonucleolytic cleavages or by radiomimetic agents phleomycin or bleomycin. One-ended DSBs in the ΔrecD mutant did not rescue ΔdnaA lethality. With two-ended DSBs in the ΔrecD strain, ΔdnaA viability was retained even after linearization of the chromosome. Data from genome-wide DNA copy number determinations in ΔdnaA-rescued cells lead us to propose a model that nuclease-mediated DNA resection activity of RecBCD is critical for prevention of a σ-mode of rolling-circle over-replication when convergent replication forks merge and fuse, as may be expected to occur during normal replication at the chromosomal terminus region or during repair of two-ended DSBs following 'ends-in' replication.
MeSH term(s)	Chromosome Aberrations ; Chromosomes, Bacterial/genetics ; Chromosomes, Bacterial/metabolism ; DNA/metabolism ; DNA Breaks, Double-Stranded ; DNA Replication ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Exonucleases/genetics
Chemical Substances	DNA, Bacterial ; Escherichia coli Proteins ; DNA (9007-49-2) ; Exonucleases (EC 3.1.-)
Language	English
Publishing date	2022-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac670
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Zs.A 1067: Show issues

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Article ; Online: End of the beginning: elongation and termination features of alternative modes of chromosomal replication initiation in bacteria.

Gowrishankar, Jayaraman

PLoS genetics

2015 Volume 11, Issue 1, Page(s) e1004909

Abstract: In bacterial cells, bidirectional replication of the circular chromosome is initiated from a single origin (oriC) and terminates in an antipodal terminus region such that movement of the pair of replication forks is largely codirectional with ... ...

Abstract	In bacterial cells, bidirectional replication of the circular chromosome is initiated from a single origin (oriC) and terminates in an antipodal terminus region such that movement of the pair of replication forks is largely codirectional with transcription. The terminus region is flanked by discrete Ter sequences that act as polar, or direction-dependent, arrest sites for fork progression. Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR) from transcription-associated RNA-DNA hybrids or R-loops. Here, I discuss the distinctive attributes of fork progression and termination associated with different modes of bacterial replication initiation. Two hypothetical models are proposed: that head-on collisions between pairs of replication forks, which are a feature of replication termination in all kingdoms of life, provoke bilateral fork reversal reactions; and that cSDR is characterized by existence of distinct subpopulations in bacterial cultures and a widespread distribution of origins in the genome, each with a small firing potential. Since R-loops are known to exist in eukaryotic cells and to inflict genome damage in G1 phase, it is possible that cSDR-like events promote aberrant replication initiation even in eukaryotes.
MeSH term(s)	Bacillus subtilis/genetics ; Chromosomes, Bacterial/genetics ; DNA Helicases ; DNA Replication/genetics ; DNA, Bacterial/genetics ; Genome, Bacterial ; Replication Origin/genetics ; Ribonucleases ; Transcription, Genetic
Chemical Substances	DNA, Bacterial ; Ribonucleases (EC 3.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1004909
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Article ; Online: Topoisomerase I Essentiality, DnaA-Independent Chromosomal Replication, and Transcription-Replication Conflict in Escherichia coli.

Leela, J Krishna / Raghunathan, Nalini / Gowrishankar, J

Journal of bacteriology

2021 Volume 203, Issue 17, Page(s) e0019521

Abstract: Topoisomerase I (Topo I) of Escherichia coli, encoded ... ...

Abstract	Topoisomerase I (Topo I) of Escherichia coli, encoded by
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Chromosomes, Bacterial/genetics ; Chromosomes, Bacterial/metabolism ; DNA Replication ; DNA Topoisomerases, Type I/genetics ; DNA Topoisomerases, Type I/metabolism ; DNA, Bacterial/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Genome, Bacterial ; Transcription, Genetic
Chemical Substances	Bacterial Proteins ; DNA, Bacterial ; DNA-Binding Proteins ; DnaA protein, Bacteria ; DNA Topoisomerases, Type I (EC 5.99.1.2)
Language	English
Publishing date	2021-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00195-21
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Article ; Online: Direct inhibition of transcription in vitro by the isolated N-terminal domain of the Escherichia coli nucleoid-associated protein H-NS and by its paralogue Hha.

Kapshikar, Rajvardhan M / Gowrishankar, J

Microbiology (Reading, England)

2019 Volume 165, Issue 4, Page(s) 463–474

Abstract: H-NS is an abundant nucleoid-associated protein in the enterobacteria that mediates both chromatin compaction and transcriptional silencing of numerous genes, especially those that have been acquired by horizontal transfer or that are involved in ... ...

Abstract	H-NS is an abundant nucleoid-associated protein in the enterobacteria that mediates both chromatin compaction and transcriptional silencing of numerous genes, especially those that have been acquired by horizontal transfer or that are involved in virulence functions. With two dimerization domains (N-terminal and central) and a C-terminal DNA-binding domain, the 15 kDa H-NS polypeptide can assemble as long polymeric filaments on DNA, and mutations in any of the three domains confer a dominant-negative phenotype in vivo by a subunit-poisoning mechanism. Here we confirm that several of these mutants [L26P, I119T and a truncation beyond residue 92(Δ93)] are also dominant-negative in vitro, in that they reverse the inhibition imposed by native H-NS in two different transcription assay formats (initiation+elongation, or elongation alone). On the other hand, another dominant-negative truncation mutant Δ64 (which possesses only the protein's N-terminal domain) per se completely and unexpectedly inhibited transcription in both assay formats. The Hha protein, which is a paralogue of H-NS and resembles its isolated N-terminal domain, also behaved like Δ64 as an inhibitor of transcription in vitro. We propose that under certain growth conditions, Escherichia coli RNA polymerase may be the direct inhibitory target of Hha, and that this effect is experimentally mimicked by the isolated N-terminal domain of H-NS.
MeSH term(s)	Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; DNA-Directed RNA Polymerases/genetics ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Gene Silencing ; Mutation ; Protein Domains ; Protein Multimerization ; Transcription, Genetic/genetics
Chemical Substances	Bacterial Proteins ; DNA-Binding Proteins ; Escherichia coli Proteins ; H-NS protein, bacteria ; hha protein, E coli ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
Language	English
Publishing date	2019-02-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180712-x
ISSN	1465-2080 ; 1350-0872
ISSN (online)	1465-2080
ISSN	1350-0872
DOI	10.1099/mic.0.000780
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Article: Axonal organelle buildup from loss of AP-4 complex function causes exacerbation of amyloid plaque pathology and gliosis in Alzheimer's disease mouse model.

Orlowski, Alex / Karippaparambil, Joseph / Paumier, Jean-Michel / Ghanta, Shraddha / Pallares, Eduardo / Tandukar, Jamuna / Gao, Ruixuan / Gowrishankar, Swetha

bioRxiv : the preprint server for biology

2024

Abstract: Lysosomes and related precursor organelles robustly build up in swollen axons that surround amyloid plaques and disrupted axonal lysosome transport has been implicated in worsening Alzheimer's pathology. Our prior studies have revealed that loss of ... ...

Abstract	Lysosomes and related precursor organelles robustly build up in swollen axons that surround amyloid plaques and disrupted axonal lysosome transport has been implicated in worsening Alzheimer's pathology. Our prior studies have revealed that loss of Adaptor protein-4 (AP-4) complex function, linked primarily to Spastic Paraplegia (HSP), leads to a similar build of lysosomes in structures we term "AP-4 dystrophies". Surprisingly, these AP-4 dystrophies were also characterized by enrichment of components of APP processing machinery, β-site cleaving enzyme 1 (BACE1) and Presenilin 2. Our studies examining whether the abnormal axonal lysosome build up resulting from AP-4 loss could lead to amyloidogenesis revealed that the loss of AP-4 complex function in an Alzheimer's disease model resulted in a strong increase in size and abundance of amyloid plaques in the hippocampus and corpus callosum as well as increased microglial association with the plaques. Interestingly, we found a further increase in enrichment of the secretase, BACE1, in the axonal swellings of the plaques of Alzheimer model mice lacking AP-4 complex compared to those having normal AP-4 complex function, suggestive of increased amyloidogenic processing under this condition. Additionally, the exacerbation of plaque pathology was region-specific as it did not increase in the cortex. The burden of the AP-4 linked axonal dystrophies/AP-4 dystrophies was higher in the corpus callosum and hippocampus compared to the cortex, establishing the critical role of AP-4 -dependent axonal lysosome transport and maturation in regulating amyloidogenic amyloid precursor protein processing.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.31.587499
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Article ; Online: Cross-subunit catalysis and a new phenomenon of recessive resurrection in Escherichia coli RNase E.

Ali, Nida / Gowrishankar, Jayaraman

Nucleic acids research

2019 Volume 48, Issue 2, Page(s) 847–861

Abstract: RNase E is a 472-kDa homo-tetrameric essential endoribonuclease involved in RNA processing and turnover in Escherichia coli. In its N-terminal half (NTH) is the catalytic active site, as also a substrate 5'-sensor pocket that renders enzyme activity ... ...

Abstract	RNase E is a 472-kDa homo-tetrameric essential endoribonuclease involved in RNA processing and turnover in Escherichia coli. In its N-terminal half (NTH) is the catalytic active site, as also a substrate 5'-sensor pocket that renders enzyme activity maximal on 5'-monophosphorylated RNAs. The protein's non-catalytic C-terminal half (CTH) harbours RNA-binding motifs and serves as scaffold for a multiprotein degradosome complex, but is dispensable for viability. Here, we provide evidence that a full-length hetero-tetramer, composed of a mixture of wild-type and (recessive lethal) active-site mutant subunits, exhibits identical activity in vivo as the wild-type homo-tetramer itself ('recessive resurrection'). When all of the cognate polypeptides lacked the CTH, the active-site mutant subunits were dominant negative. A pair of C-terminally truncated polypeptides, which were individually inactive because of additional mutations in their active site and 5'-sensor pocket respectively, exhibited catalytic function in combination, both in vivo and in vitro (i.e. intragenic or allelic complementation). Our results indicate that adjacent subunits within an oligomer are separately responsible for 5'-sensing and cleavage, and that RNA binding facilitates oligomerization. We propose also that the CTH mediates a rate-determining initial step for enzyme function, which is likely the binding and channelling of substrate for NTH's endonucleolytic action.
MeSH term(s)	Binding Sites/genetics ; Catalysis ; Catalytic Domain/genetics ; Endoribonucleases/chemistry ; Endoribonucleases/genetics ; Escherichia coli/chemistry ; Escherichia coli/genetics ; Multienzyme Complexes/chemistry ; Multienzyme Complexes/genetics ; Mutation/genetics ; Peptides/genetics ; Polyribonucleotide Nucleotidyltransferase/chemistry ; Polyribonucleotide Nucleotidyltransferase/genetics ; Protein Conformation ; Protein Multimerization/genetics ; RNA/chemistry ; RNA/genetics ; RNA Helicases/chemistry ; RNA Helicases/genetics ; RNA-Binding Motifs/genetics
Chemical Substances	Multienzyme Complexes ; Peptides ; degradosome ; RNA (63231-63-0) ; Polyribonucleotide Nucleotidyltransferase (EC 2.7.7.8) ; Endoribonucleases (EC 3.1.-) ; ribonuclease E (EC 3.1.4.-) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2019-12-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkz1152
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Zs.A 1067: Show issues

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Article ; Online: Correction for Nandineni et al., "Osmosensitivity Associated with Insertions in

Nandineni, Madhusudan R / Laishram, Rakesh S / Gowrishankar, J

Journal of bacteriology

2020 Volume 202, Issue 9

Language	English
Publishing date	2020-04-09
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00077-20
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Article ; Online: Granger Geweke Causality reveals information exchange during physical interaction is modulated by task difficulty.

Colomer, Clémentine / Dhamala, Mukesh / Ganesh, Gowrishankar / Lagarde, Julien

Human movement science

2023 Volume 92, Page(s) 103139

Abstract: The haptic sense is an important mode of communication during physical interactions, and it is known to enable humans to estimate key features of their partner's behavior. It is proposed that such estimations are based upon the exchange of information ... ...

Abstract	The haptic sense is an important mode of communication during physical interactions, and it is known to enable humans to estimate key features of their partner's behavior. It is proposed that such estimations are based upon the exchange of information mediated by the interaction forces, resulting in role distribution and coordination between partners. In the present study, we examined whether the information exchange is functionally modified to adapt to the task, or whether it is a fixed process, leaving the adaptation to individual's behaviors. We analyzed the forces during an empirical dyadic interaction task using Granger-Geweke causality analysis, which allowed us to quantify the causal influence of each individual's forces on their partner's. The dynamics of relative phase were also examined. We observed an increase of inter-partner influence with an increase in the spatial accuracy required by the task, demonstrating an adaptation of information flow to the task. This increase of exchange with the spatial accuracy constraint was accompanied by an increase of errors and of the variability of the relative phase between forces. The influence was dominated by participants in a specific role, showing a clear role division as well as task division between the dyad partners. Moreover, the influence occurred in the [2.15-7] Hz frequency band, demonstrating its importance as a frequency band of interest during cooperation involving haptic interaction. Several interpretations are introduced, ranging from sub-division of motion control to phase-amplitude coupling.
MeSH term(s)	Humans ; Causality ; Communication
Language	English
Publishing date	2023-09-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	601851-8
ISSN	1872-7646 ; 0167-9457
ISSN (online)	1872-7646
ISSN	0167-9457
DOI	10.1016/j.humov.2023.103139
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