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Article: Selecting an appropriate method for expressing

Ashkani, Jahanshah / Rees, D J G

Biotechnology reports (Amsterdam, Netherlands)

2017 Volume 15, Page(s) 41–47

Abstract: A single locus ( ...

Abstract	A single locus (
Language	English
Publishing date	2017-06-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2801018-8
ISSN	2215-017X
ISSN	2215-017X
DOI	10.1016/j.btre.2017.06.005
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Article ; Online: Meta-analysis suggests evidence of novel stress-related pathway components in Orsay virus - Caenorhabditis elegans viral model.

Mishra, Priyanka / Ngo, Jessica / Ashkani, Jahanshah / Pio, Frederic

Scientific reports

2019 Volume 9, Issue 1, Page(s) 4399

Abstract: The genetic model organism, Caenorhabditis elegans (C. elegans), shares many genes with humans and is the best-annotated of the eukaryotic genome. Therefore, the identification of new genes and pathways is unlikely. Nevertheless, host-pathogen ... ...

Abstract	The genetic model organism, Caenorhabditis elegans (C. elegans), shares many genes with humans and is the best-annotated of the eukaryotic genome. Therefore, the identification of new genes and pathways is unlikely. Nevertheless, host-pathogen interaction studies from viruses, recently discovered in the environment, has created new opportunity to discover these pathways. For example, the exogenous RNAi response in C. elegans by the Orsay virus as seen in plants and other eukaryotes is not systemic and transgenerational, suggesting different RNAi pathways between these organisms. Using a bioinformatics meta-analysis approach, we show that the top 17 genes differentially-expressed during C. elegans infection by Orsay virus are functionally uncharacterized genes. Furthermore, functional annotation using similarity search and comparative modeling, was able to predict folds correctly, but could not assign easily function to the majority. However, we could identify gene expression studies that showed a similar pattern of gene expression related to toxicity, stress and immune response. Those results were strengthened using protein-protein interaction network analysis. This study shows that novel molecular pathway components, of viral innate immune response, can be identified and provides models that can be further used as a framework for experimental studies. Whether these features are reminiscent of an ancient mechanism evolutionarily conserved, or part of a novel pathway, remain to be established. These results reaffirm the tremendous value of this approach to broaden our understanding of viral immunity in C. elegans.
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans/virology ; Host-Pathogen Interactions ; Immunity, Innate/physiology ; Nodaviridae/pathogenicity ; RNA Interference/physiology
Language	English
Publishing date	2019-03-13
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-40762-9
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Article ; Online: The Critical Role Of VP1 In Forming The Necessary Cavities For Receptor-mediated Entry Of FMDV To The Host Cell.

Ashkani, Jahanshah / Rees, D J G

Scientific reports

2016 Volume 6, Page(s) 27140

Abstract: The antigenic inconsistency of the foot-and-mouth disease virus (FMDV) is very broad, such that a vaccine made from one isolate will not offer protection against infection with other isolates from the same serotype. Viral particles (VPs) or surface ... ...

Abstract	The antigenic inconsistency of the foot-and-mouth disease virus (FMDV) is very broad, such that a vaccine made from one isolate will not offer protection against infection with other isolates from the same serotype. Viral particles (VPs) or surface exposed capsid proteins, VP1-VP3, of FMDV determine both the antigenicity of the virus and its receptor-mediated entry into the host cell. Therefore, modifications of these structural proteins may alter the properties of the virus. Here we show putative cavities on the FMDV-SAT1 (FMDV Southern African Territories1) capsid as possible binding sites for the receptor-mediated viral entry into the host cell. We identified three possible cavities on the FMDV capsid surface, from which the largest one (C2) is shaped in the contact regions of VP1-VP3. Our results demonstrate the significance of VP1, in the formation of FMDV-SAT1 surface cavities, which is the main component in all the identified cavities. Our findings can have profound implications in the protein engineering of FMDV in the contact region of VP1-VP3 found to be embedded in several cavities. Such information is of great significance in the context of vaccine design, as it provides the ground for future improvement of synthetic vaccines to control FMD caused by FMDV-SAT1 serotypes.
Language	English
Publishing date	2016-06-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep27140
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Article ; Online: Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes.

Ashkani, Jahanshah / Naidoo, Kevin J

Scientific reports

2016 Volume 6, Page(s) 26451

Abstract: Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural ... ...

Abstract	Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.
Language	English
Publishing date	2016-05-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep26451
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Article ; Online: A Comprehensive Study of Molecular Evolution at the Self-Incompatibility Locus of Rosaceae.

Ashkani, Jahanshah / Rees, D J G

Journal of molecular evolution

2016 Volume 82, Issue 2-3, Page(s) 128–145

Abstract: The family Rosaceae includes a range of important fruit trees, most of which have the S-RNase-based self-incompatibility (SI). Several models have been developed to explain how pollen (SLF) and pistil (S-RNase) components of the S-locus interact. It was ... ...

Abstract	The family Rosaceae includes a range of important fruit trees, most of which have the S-RNase-based self-incompatibility (SI). Several models have been developed to explain how pollen (SLF) and pistil (S-RNase) components of the S-locus interact. It was discovered in 2010 that additional SLF proteins are involved in pollen specificity, and a Collaborative Non-Self Recognition model has been proposed for SI in Solanaceae; however, the validity of such model remains to be elucidated for other species. The results of this study support the divergent evolution of the S-locus genes from two Rosaceae subfamilies, Prunoideae/Amygdaloideae and Maloideae, The difference identified in the selective pressures between the two lineages provides evidence for positive selection at specific sites in both the S-RNase and the SLF proteins. The evolutionary findings of this study support the role of multiple SLF proteins leading to a Collaborative Non-Self Recognition model for SI in the Maloideae. Furthermore, the identification of the sites responsible for SI specificity determination and the mapping of these sites onto the modelled tertiary structure of ancestor proteins provide useful information for rational functional redesign and protein engineering for the future engineering of new functional alleles providing increased diversity in the SI system in the Maloideae.
MeSH term(s)	Alleles ; Biological Evolution ; Evolution, Molecular ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; Phylogeny ; Plant Proteins/genetics ; Pollen ; Ribonucleases ; Rosaceae/genetics ; Rosaceae/physiology ; Self-Incompatibility in Flowering Plants/genetics ; Self-Incompatibility in Flowering Plants/physiology
Chemical Substances	Plant Proteins ; Ribonucleases (EC 3.1.-)
Language	English
Publishing date	2016-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120148-7
ISSN	1432-1432 ; 0022-2844
ISSN (online)	1432-1432
ISSN	0022-2844
DOI	10.1007/s00239-015-9726-4
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Article ; Online: A simple, high-throughput modeling approach reveals insights into the mechanism of gametophytic self-incompatibility.

Ashkani, Jahanshah / Rees, D J G

Scientific reports

2016 Volume 6, Page(s) 34732

Abstract: Specificity in the GSI response results from the S-haplotype-specific molecular interaction of S-locus F-box (SLF/SFB) and SRNase proteins in the self-incompatibility locus (S-locus). The answer to the question of how these two components of the S-locus ( ...

Abstract	Specificity in the GSI response results from the S-haplotype-specific molecular interaction of S-locus F-box (SLF/SFB) and SRNase proteins in the self-incompatibility locus (S-locus). The answer to the question of how these two components of the S-locus (SRNase and SLF/SFB) interact has been gathered from several models. Since there is not enough evidence as to which one is the definitive model, none of them can be ruled out. Despite the identification of interacting protein elements, the mechanism by which SLF/SFB and SRNase interact to differently trigger the self-incompatibility among families and subfamilies remain uncertain. The high-throughput modeling approach demonstrates structural visions into the possible existence of a Collaborative Non-Self Recognition model in apple. These findings postulate several prospects for future investigation providing useful information to guide the implementation of breeding strategies.
MeSH term(s)	Binding Sites ; F-Box Proteins/chemistry ; F-Box Proteins/genetics ; F-Box Proteins/metabolism ; Gene Expression Regulation, Plant ; Malus/physiology ; Models, Genetic ; Plant Breeding ; Plant Proteins/chemistry ; Plant Proteins/metabolism ; Protein Binding ; Ribonucleases/chemistry ; Ribonucleases/genetics ; Ribonucleases/metabolism ; Self-Incompatibility in Flowering Plants
Chemical Substances	F-Box Proteins ; Plant Proteins ; Ribonucleases (EC 3.1.-)
Language	English
Publishing date	2016-10-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep34732
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Article: Selecting an appropriate method for expressing S locus F-box-S2 recombinant protein

Ashkani, Jahanshah / D.J.G. Rees

Biotechnology reports. 2017 Sept., v. 15

2017

Abstract: A single locus (S locus) including at least two linked genes (female and male determinants) genetically controls the gametophytic self-incompatibility (GSI) in apple, which has evolved to avoid self-fertilization. There has been extensive work done on ... ...

Abstract	A single locus (S locus) including at least two linked genes (female and male determinants) genetically controls the gametophytic self-incompatibility (GSI) in apple, which has evolved to avoid self-fertilization. There has been extensive work done on the female determinant of self-incompatibility, which has led to the determination of the tertiary structure of S-RNase. However, the tertiary structure of male determinant (S locus F-box, SLF/SFB) remains unresolved, which could mainly be due to difficulties associated with its expression in the recombinant expression systems. In addressing this, we have evaluated several in vivo (prokaryotic and eukaryotic) and in vitro expression systems for their efficiency in the expression of apple SLF2. The most successful expression of SLF2 (1mg/ml) was achieved in E. coli using the synthesized gene in a high salt culture and applying heat shock before induction of culture. We therefore present an approach for the efficient expression of S locus F-box recombinant proteins for future functional and structural studies.
Keywords	apples ; biotechnology ; Escherichia coli ; females ; gametophytes ; genes ; heat stress ; loci ; males ; Malus domestica ; recombinant proteins ; ribonucleases ; selfing
Language	English
Dates of publication	2017-09
Size	p. 41-47.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2801018-8
ISSN	2215-017X
ISSN	2215-017X
DOI	10.1016/j.btre.2017.06.005
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Article ; Online: NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma.

Arora, Rahul / Haynes, Logan / Kumar, Mehul / McNeil, Reid / Ashkani, Jahanshah / Nakoneshny, Steven C / Matthews, T Wayne / Chandarana, Shamir / Hart, Robert D / Jones, Steven J M / Dort, Joseph C / Itani, Doha / Chanda, Ayan / Bose, Pinaki

Cancer gene therapy

2023 Volume 30, Issue 5, Page(s) 752–765

Abstract: There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function ... ...

Abstract	There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck/genetics ; Carcinoma, Squamous Cell/pathology ; Mouth Neoplasms/pathology ; Prognosis ; DNA Copy Number Variations ; Papillomavirus Infections/genetics ; Head and Neck Neoplasms/genetics ; Carcinogenesis/genetics ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212513-1
ISSN	1476-5500 ; 0929-1903
ISSN (online)	1476-5500
ISSN	0929-1903
DOI	10.1038/s41417-022-00578-8
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Zs.A 4125: Show issues

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Article ; Online: An infant with congenital respiratory insufficiency and diaphragmatic paralysis: A novel BICD2 phenotype?

Chin, Hui-Lin / Huynh, Stephanie / Ashkani, Jahanshah / Castaldo, Michael / Dixon, Katherine / Selby, Kathryn / Shen, Yaoqing / Wright, Marie / Boerkoel, Cornelius F / Hendson, Glenda / Jones, Steven J M

American journal of medical genetics. Part A

2021 Volume 188, Issue 3, Page(s) 926–930

Abstract: Monoallelic pathogenic variants in BICD2 are associated with autosomal dominant Spinal Muscular Atrophy Lower Extremity Predominant 2A and 2B (SMALED2A, SMALED2B). As part of the cellular vesicular transport, complex BICD2 facilitates the flow of ... ...

Abstract	Monoallelic pathogenic variants in BICD2 are associated with autosomal dominant Spinal Muscular Atrophy Lower Extremity Predominant 2A and 2B (SMALED2A, SMALED2B). As part of the cellular vesicular transport, complex BICD2 facilitates the flow of constitutive secretory cargoes from the trans-Golgi network, and its dysfunction results in motor neuron loss. The reported phenotypes among patients with SMALED2A and SMALED2B range from a congenital onset disorder of respiratory insufficiency, arthrogryposis, and proximal or distal limb weakness to an adult-onset disorder of limb weakness and contractures. We report an infant with congenital respiratory insufficiency requiring mechanical ventilation, congenital diaphragmatic paralysis, decreased lung volume, and single finger camptodactyly. The infant displayed appropriate antigravity limb movements but had radiological, electrophysiological, and histopathological evidence of myopathy. Exome sequencing and long-read whole-genome sequencing detected a novel de novo BICD2 variant (NM_001003800.1:c.[1543G>A];[=]). This is predicted to encode p.(Glu515Lys); p.Glu515 is located in the coiled-coil 2 mutation hotspot. We hypothesize that this novel phenotype of diaphragmatic paralysis without clear appendicular muscle weakness and contractures of large joints is a presentation of BICD2-related disease.
MeSH term(s)	Contracture ; Humans ; Infant ; Microtubule-Associated Proteins/genetics ; Muscle Weakness ; Mutation ; Pedigree ; Phenotype ; Respiratory Insufficiency/genetics ; Respiratory Paralysis/genetics
Chemical Substances	BICD2 protein, human ; Microtubule-Associated Proteins
Language	English
Publishing date	2021-11-26
Publishing country	United States
Document type	Case Reports
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.62578
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Article ; Online: The genome sequence of the Loggerhead sea turtle,

F1000Research

2023 Volume 12, Page(s) 336

Abstract: We present a genome assembly ... ...

Abstract	We present a genome assembly of
MeSH term(s)	Animals ; Female ; Turtles/genetics ; Reptiles ; Genome ; Genomics
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.131283.2
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