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Article: Genome comparisons provide insights into the role of secondary metabolites in the pathogenic phase of the Photorhabdus life cycle

SHARMA, RAHUL

BMC genomics, 17:537

2016

Abstract: BACKGROUND: Bacteria within the genus Photorhabdus maintain mutualistic symbioses with nematodes in complicated lifecycles that also involves insect pathogenic phases. Intriguingly, these bacteria are rich in biosynthetic gene clusters that produce ... ...

Institution	Senckenberg Biodiversität und Klima Forschungszentrum
Abstract	BACKGROUND: Bacteria within the genus Photorhabdus maintain mutualistic symbioses with nematodes in complicated lifecycles that also involves insect pathogenic phases. Intriguingly, these bacteria are rich in biosynthetic gene clusters that produce compounds with diverse biological activities. As a basis to better understand the life cycles of Photorhabdus we sequenced the genomes of two recently discovered representative species and performed detailed genomic comparisons with five publically available genomes. RESULTS: Here we report the genomic details of two new reference Photorhabdus species. By then conducting genomic comparisons across the genus, we show that there are several highly conserved biosynthetic gene clusters. These clusters produce a range of bioactive small molecules that support the pathogenic phase of the integral relationship that Photorhabdus maintain with nematodes. CONCLUSIONS: Photorhabdus contain several genetic loci that allow them to become specialist insect pathogens by efficiently evading insect immune responses and killing the insect host.
Keywords	Secondary metabolites ; Sequencing ; Symbiosis ; Photorhabdus
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article: Genome analyses of the sunflower pathogen Plasmopara halstedii provide insights into effector evolution in downy mildews and Phytophthora

SHARMA, RAHUL

BMC genomics, 16:741

2015

Abstract: BACKGROUND: Downy mildews are the most speciose group of oomycetes and affect crops of great economic importance. So far, there is only a single deeply-sequenced downy mildew genome available, from Hyaloperonospora arabidopsidis. Further genomic ... ...

Institution	Senckenberg Biodiversität und Klima Forschungszentrum
Abstract	BACKGROUND: Downy mildews are the most speciose group of oomycetes and affect crops of great economic importance. So far, there is only a single deeply-sequenced downy mildew genome available, from Hyaloperonospora arabidopsidis. Further genomic resources for downy mildews are required to study their evolution, including pathogenicity effector proteins, such as RxLR effectors. Plasmopara halstedii is a devastating pathogen of sunflower and a potential pathosystem model to study downy mildews, as several Avr-genes and R-genes have been predicted and unlike Arabidopsis downy mildew, large quantities of almost contamination-free material can be obtained easily. RESULTS: Here a high-quality draft genome of Plasmopara halstedii is reported and analysed with respect to various aspects, including genome organisation, secondary metabolism, effector proteins and comparative genomics with other sequenced oomycetes. Interestingly, the present analyses revealed further variation of the RxLR motif, suggesting an important role of the conservation of the dEER-motif. Orthology analyses revealed the conservation of 28 RxLR-like core effectors among Phytophthora species. Only six putative RxLR-like effectors were shared by the two sequenced downy mildews, highlighting the fast and largely independent evolution of two of the three major downy mildew lineages. This is seemingly supported by phylogenomic results, in which downy mildews did not appear to be monophyletic. CONCLUSIONS: The genome resource will be useful for developing markers for monitoring the pathogen population and might provide the basis for new approaches to fight Phytophthora and downy mildew pathogens by targeting core pathogenicity effectors.
Keywords	Comparative genomics ; Core effectors ; Downy mildew ; Evolution ; Oomycetes ; Obligate biotroph ; Microsatellites ; Phytohormones ; Plant pathogen ; Promoters ; RxLR effectors
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article: The genome of the basal agaricomycete Xanthophyllomyces dendrorhous provides insights into the organization of its acetyl-CoA derived pathways and the evolution of Agaricomycotina

SHARMA, RAHUL

BMC genomics, 16:233

2015

Abstract: BACKGROUND: Xanthophyllomyces dendrorhous is a basal agaricomycete with uncertain taxonomic placement, known for its unique ability to produce astaxanthin, a carotenoid with antioxidant properties. It was the aim of this study to elucidate the ... ...

Institution	Senckenberg Forschungsinstitut und Naturmuseum Frankfurt Senckenberg Biodiversität und Klima Forschungszentrum
Abstract	BACKGROUND: Xanthophyllomyces dendrorhous is a basal agaricomycete with uncertain taxonomic placement, known for its unique ability to produce astaxanthin, a carotenoid with antioxidant properties. It was the aim of this study to elucidate the organization of its CoA-derived pathways and to use the genomic information of X. dendrorhous for a phylogenomic investigation of the Basidiomycota. RESULTS: The genome assembly of a haploid strain of Xanthophyllomyces dendrorhous revealed a genome of 19.50 Megabases with 6385 protein coding genes. Phylogenetic analyses were conducted including 48 fungal genomes. These revealed Ustilaginomycotina and Agaricomycotina as sister groups. In the latter a well-supported sister-group relationship of two major orders, Polyporales and Russulales, was inferred. Wallemia occupies a basal position within the Agaricomycotina and X. dendrorhous represents the basal lineage of the Tremellomycetes, highlighting that the typical tremelloid parenthesomes have either convergently evolved in Wallemia and the Tremellomycetes, or were lost in the Cystofilobasidiales lineage. A detailed characterization of the CoA-related pathways was done and all genes for fatty acid, sterol and carotenoid synthesis have been assigned. CONCLUSIONS: The current study ascertains that Wallemia with tremelloid parenthesomes is the most basal agaricomycotinous lineage and that Cystofilobasidiales without tremelloid parenthesomes are deeply rooted within Tremellomycetes, suggesting that parenthesomes at septal pores might be the core synapomorphy for the Agaricomycotina. Apart from evolutionary insights the genome sequence of X. dendrorhous will facilitate genetic pathway engineering for optimized astaxanthin or oxidative alcohol production.
Keywords	Agaricomycotina ; Astaxanthin Synthase ; Fatty acid metabolism ; Fungal evolution ; Phylogeny ; Xanthophyllomyces dendrorhous
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article ; Online: Harnessing Endogenous T-Regulatory Cells in Acute Kidney Injury.

Sharma, Rahul

Nephron

2020 Volume 144, Issue 12, Page(s) 626–628

Abstract: Acute kidney injury (AKI) affects 20-50% of hospitalized and intensive care patients, with a sizable proportion progressing to ESRD or death (https://www.kidney.org/atoz/content/AcuteKidneyInjury). Since inflammation contributes to the pathogenesis of ... ...

Abstract	Acute kidney injury (AKI) affects 20-50% of hospitalized and intensive care patients, with a sizable proportion progressing to ESRD or death (https://www.kidney.org/atoz/content/AcuteKidneyInjury). Since inflammation contributes to the pathogenesis of AKI, studies on T-regulatory cells (Tregs), which suppress inflammation are important. Here, we highlight advances that utilize Tregs for intervention in AKI and were presented at the 25th International Conference on Advances in Critical Care Nephrology and UAB/UCSD O'Brien Center AKI & CRRT 2020.
MeSH term(s)	Acute Kidney Injury/immunology ; Humans ; T-Lymphocytes, Regulatory/immunology
Language	English
Publishing date	2020-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000508503
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Article: The genome sequence of the commercially cultivated mushroom Agrocybe aegerita reveals a conserved repertoire of fruiting-related genes and a versatile suite of biopolymer-degrading enzymes

Rühl, Martin / SHARMA, RAHUL / Thines, Marco

BMC genomics, 19:48

2018

Abstract: BACKGROUND: Agrocybe aegerita is an agaricomycete fungus with typical mushroom features, which is commercially cultivated for its culinary use. In nature, it is a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood in forests of ...

Institution	Senckenberg Biodiversität und Klima Forschungszentrum
Abstract	BACKGROUND: Agrocybe aegerita is an agaricomycete fungus with typical mushroom features, which is commercially cultivated for its culinary use. In nature, it is a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood in forests of warm and mild climate. The ease of cultivation and fructification on solidified media as well as its archetypal mushroom fruit body morphology render A. aegerita a well-suited model for investigating mushroom developmental biology. RESULTS: Here, the genome of the species is reported and analysed with respect to carbohydrate active genes and genes known to play a role during fruit body formation. In terms of fruit body development, our analyses revealed a conserved repertoire of fruiting-related genes, which corresponds well to the archetypal fruit body morphology of this mushroom. For some genes involved in fruit body formation, paralogisation was observed, but not all fruit body maturation-associated genes known from other agaricomycetes seem to be conserved in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses suggest a versatile arsenal of biopolymer-degrading enzymes that likely account for the flexible life style of this species. Regarding the amount of genes encoding CAZymes relevant for lignin degradation, A. aegerita shows more similarity to white-rot fungi than to litter decomposers, including 18 genes coding for unspecific peroxygenases and three dye-decolourising peroxidase genes expanding its lignocellulolytic machinery. CONCLUSIONS: The genome resource will be useful for developing strategies towards genetic manipulation of A. aegerita, which will subsequently allow functional genetics approaches to elucidate fundamentals of fruiting and vegetative growth including lignocellulolysis.
Keywords	Comparative genomics ; Carbohydrate active enzymes ; Agaricales ; Basidiomycetes ; Developmental biology ; Fruit body ; Mushroom ; White-rot
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article ; Online: Disulfide bond in SUN2 regulates dynamic remodeling of LINC complexes at the nuclear envelope.

Sharma, Rahul / Hetzer, Martin W

Life science alliance

2023 Volume 6, Issue 8

Abstract: The LINC complex tethers the cell nucleus to the cytoskeleton to regulate mechanical forces during cell migration, differentiation, and various diseases. The function of LINC complexes relies on the interaction between highly conserved SUN and KASH ... ...

Abstract	The LINC complex tethers the cell nucleus to the cytoskeleton to regulate mechanical forces during cell migration, differentiation, and various diseases. The function of LINC complexes relies on the interaction between highly conserved SUN and KASH proteins that form higher-order assemblies capable of load bearing. These structural details have emerged from in vitro assembled LINC complexes; however, the principles of in vivo assembly remain obscure. Here, we report a conformation-specific SUN2 antibody as a tool to visualize LINC complex dynamics in situ. Using imaging, biochemical, and cellular methods, we find that conserved cysteines in SUN2 undergo KASH-dependent inter- and intra-molecular disulfide bond rearrangements. Disruption of the SUN2 terminal disulfide bond compromises SUN2 localization, turnover, LINC complex assembly in addition to cytoskeletal organization and cell migration. Moreover, using pharmacological and genetic perturbations, we identify components of the ER lumen as SUN2 cysteines redox state regulators. Overall, we provide evidence for SUN2 disulfide bond rearrangement as a physiologically relevant structural modification that regulates LINC complex functions.
MeSH term(s)	Cytoskeleton/metabolism ; Disulfides/metabolism ; Microtubules/metabolism ; Nuclear Envelope/metabolism ; Nuclear Proteins/metabolism ; Mice ; Animals
Chemical Substances	Disulfides ; Nuclear Proteins ; Sun2 protein, mouse
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302031
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Article ; Online: An NLP-based technique to extract meaningful features from drug SMILES.

Sharma, Rahul / Saghapour, Ehsan / Chen, Jake Y

iScience

2024 Volume 27, Issue 3, Page(s) 109127

Abstract: NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language ... ...

Abstract	NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language texts, special characters in drug SMILES have specific meanings and cannot be ignored. We introduce a novel NLP-based method that extracts interpretable sequences and essential features from drug SMILES notation using N-grams. Our method compares these features to Morgan fingerprint bit-vectors using UMAP-based embedding, and we validate its effectiveness through two personalized drug screening (PSD) case studies. Our NLP-based features are sparse and, when combined with gene expressions and disease phenotype features, produce better ML models for PSD. This approach provides a new way to analyze drug molecule structures represented as SMILES notation, which can help accelerate drug discovery efforts. We have also made our method accessible through a Python library.
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109127
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Article ; Online: Safe and sustainable food packaging: Argemone albiflora mediated green synthesized silver-carrageenan nanocomposite films.

Kumari, Shilpa / Kumari, Asha / Sharma, Rahul

International journal of biological macromolecules

2024 Volume 264, Issue Pt 1, Page(s) 130626

Abstract: Silver-Carrageenan (Ag/Carr) nanocomposite film for food packing application by the green method using Argemone albiflora leaf extract has been developed in this study. Different plant parts of Argemone albiflora (blue stem prickly poppy) are used all ... ...

Abstract	Silver-Carrageenan (Ag/Carr) nanocomposite film for food packing application by the green method using Argemone albiflora leaf extract has been developed in this study. Different plant parts of Argemone albiflora (blue stem prickly poppy) are used all over the world for the treatment of microbial infections, jaundice, skin diseases etc. GC-MS analysis was used to examine the phytochemical found in the Argemone albiflora leaf extract which reduces the metal ions to nanoscale. The biopolymer employed in the synthesis of nanocomposite film was carrageenan, a natural carbohydrate (polysaccharide) extracted from edible red seaweeds. We developed a food packing that is biodegradable, eco-friendly, economical and free from harmful chemicals. These films possess better UV barrier and mechanical and antimicrobial properties with 1 mM AgNO
MeSH term(s)	Carrageenan/chemistry ; Silver/chemistry ; Argemone ; Food Packaging ; Metal Nanoparticles/chemistry ; Escherichia coli ; Staphylococcus aureus ; Anti-Infective Agents/pharmacology ; Anti-Infective Agents/chemistry ; Nanocomposites/chemistry ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry
Chemical Substances	Carrageenan (9000-07-1) ; Silver (3M4G523W1G) ; Anti-Infective Agents ; Plant Extracts ; Anti-Bacterial Agents
Language	English
Publishing date	2024-03-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.130626
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Book ; Thesis: Auswertung der Qualitätssicherungsmaßnahmen nach Einführung eines Qualitätsmanagementsystems nach DIN EN ISO 9001:2000 am Interdisziplinären Uveitiszentrum Heidelberg

Sharma, Rahul

2005

Author's details	vorgelegt von Rahul Sharma
Language	German
Size	III, 91, 78 Bl. : graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Heidelberg, Univ., Diss., 2005
HBZ-ID	HT014648140
Database	Catalogue ZB MED Medicine, Health

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2006 E 228	order for loan	Magazin

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Article: Community barcoding reveals little effect of ocean acidification on the composition of coastal plankton communities: Evidence from a long-term mesocosm study in the Gullmar Fjord, Skagerrak

Langer, Julia / SHARMA, RAHUL / Thines, Marco

PLOS ONE, 12(4):e0175808

2017

Abstract: The acidification of the oceans could potentially alter marine plankton communities with consequences for ecosystem functioning. While several studies have investigated effects of ocean acidification on communities using traditional methods, few have ... ...

Institution	Senckenberg Biodiversität und Klima Forschungszentrum
Abstract	The acidification of the oceans could potentially alter marine plankton communities with consequences for ecosystem functioning. While several studies have investigated effects of ocean acidification on communities using traditional methods, few have used genetic analyses. Here, we use community barcoding to assess the impact of ocean acidification on the composition of a coastal plankton community in a large scale, in situ, long-term mesocosm experiment. High-throughput sequencing resulted in the identification of a wide range of planktonic taxa (Alveolata, Cryptophyta, Haptophyceae, Fungi, Metazoa, Hydrozoa, Rhizaria, Straminipila, Chlorophyta). Analyses based on predicted operational taxonomical units as well as taxonomical compositions revealed no differences between communities in high CO2 mesocosms (~ 760 μatm) and those exposed to present-day CO2 conditions. Observed shifts in the planktonic community composition were mainly related to seasonal changes in temperature and nutrients. Furthermore, based on our investigations, the elevated CO2 did not affect the intraspecific diversity of the most common mesozooplankter, the calanoid copepod Pseudocalanus acuspes. Nevertheless, accompanying studies found temporary effects attributed to a raise in CO2. Differences in taxa composition between the CO2 treatments could, however, only be observed in a specific period of the experiment. Based on our genetic investigations, no compositional long-term shifts of the plankton communities exposed to elevated CO2 conditions were observed. Thus, we conclude that the compositions of planktonic communities, especially those in coastal areas, remain rather unaffected by increased CO2.
Keywords	Copepods ; Carbon dioxide ; Mesocosms ; Sequence databases ; Polymerase chain reaction ; Phytoplankton ; Plankton ; Taxonomy
Language	English
Document type	Article
Database	Repository for Life Sciences

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