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  1. Article: Efficient gene knockout and genetic interactions: the IN4MER CRISPR/Cas12a multiplex knockout platform.

    Anvar, Nazanin Esmaeili / Lin, Chenchu / Ma, Xingdi / Wilson, Lori L / Steger, Ryan / Sangree, Annabel K / Colic, Medina / Wang, Sidney H / Doench, John G / Hart, Traver

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Genetic interactions mediate the emergence of phenotype from genotype, but initial technologies for combinatorial genetic perturbation in mammalian cells suffer from inefficiency and are challenging to scale. Recent focus on paralog synthetic lethality ... ...

    Abstract Genetic interactions mediate the emergence of phenotype from genotype, but initial technologies for combinatorial genetic perturbation in mammalian cells suffer from inefficiency and are challenging to scale. Recent focus on paralog synthetic lethality in cancer cells offers an opportunity to evaluate different approaches and improve on the state of the art. Here we report a meta-analysis of CRISPR genetic interactions screens, identifying a candidate set of background-independent paralog synthetic lethals, and find that the Cas12a platform provides superior sensitivity and assay replicability. We demonstrate that Cas12a can independently target up to four genes from a single guide array, and we build on this knowledge by constructing a genome-scale library that expresses arrays of four guides per clone, a platform we call 'in4mer'. Our genome-scale human library, with only 49k clones, is substantially smaller than a typical CRISPR/Cas9 monogenic library while also targeting more than four thousand paralog pairs, triples, and quads. Proof of concept screens in four cell lines demonstrate discrimination of core and context-dependent essential genes similar to that of state-of-the-art CRISPR/Cas9 libraries, as well as detection of synthetic lethal and masking/buffering genetic interactions between paralogs of various family sizes, a capability not offered by any extant library. Importantly, the in4mer platform offers a fivefold reduction in the number of clones required to assay genetic interactions, dramatically improving the cost and effort required for these studies.
    Language English
    Publishing date 2023-09-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.03.522655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Association between polymorphisms in Interleukin-16 gene and risk of late-onset Alzheimer's disease.

    Anvar, Nazanin Esmaeili / Saliminejad, Kioomars / Ohadi, Mina / Kamali, Koorosh / Daneshmand, Parvaneh / Khorshid, Hamid Reza Khorram

    Journal of the neurological sciences

    2015  Volume 358, Issue 1-2, Page(s) 324–327

    Abstract: Cytokines play important roles in the inflammation pathways. Alzheimer's disease (AD) is an inflammatory disease, and it is suggested that cytokines are able to influence AD. We investigated the association between IL16 polymorphisms and risk of AD in an ...

    Abstract Cytokines play important roles in the inflammation pathways. Alzheimer's disease (AD) is an inflammatory disease, and it is suggested that cytokines are able to influence AD. We investigated the association between IL16 polymorphisms and risk of AD in an Iranian population. The case group consisted of 144 individuals with AD and the control group included 173 healthy individuals. Genotyping of the IL16 rs4072111 C>T and rs1131445 T>C polymorphisms was determined using PCR-RFLP method. The frequency of rs4072111 CT genotype was significantly lower (P=0.007; OR=0.5, 95% CI: 0.3-0.8) in the patients (17.3%) than the control group (30%). The rs4072111 T allele was significantly lower (P=0.008; OR=0.5, 95% CI: 0.3-0.9) in the cases (8.6%) compared with the control group (15.6%). The IL16 rs4072111 polymorphism may be associated with susceptibility to AD and the T allele may have a protective role in the progression of AD in an Iranian population.
    MeSH term(s) Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Interleukin-16/genetics ; Iran ; Male ; Polymorphism, Genetic
    Chemical Substances Interleukin-16
    Language English
    Publishing date 2015-11-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80160-4
    ISSN 1878-5883 ; 0022-510X ; 0374-8642
    ISSN (online) 1878-5883
    ISSN 0022-510X ; 0374-8642
    DOI 10.1016/j.jns.2015.09.344
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 308: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  3. Article ; Online: BMP2 and BMP4 variations and risk of non-syndromic cleft lip and palate.

    Saket, Mitra / Saliminejad, Kioomars / Kamali, Koorosh / Moghadam, Fatemeh Aghakhani / Anvar, Nazanin Esmaeili / Khorram Khorshid, Hamid Reza

    Archives of oral biology

    2016  Volume 72, Page(s) 134–137

    Abstract: Objective: Non-syndromic cleft lip with or without cleft palate (CL/P) is one of the most common congenital anomalies and arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association ... ...

    Abstract Objective: Non-syndromic cleft lip with or without cleft palate (CL/P) is one of the most common congenital anomalies and arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association between the BMP2 (bone morphogenetic protein 2) and BMP4 (bone morphogenetic protein 4) polymorphisms with non-syndromic CL/P to clarify the potential role of these genes in the etiology of CL/P in Iranian population.
    Design: The allelic and genotypic frequencies of BMP2 rs235768 A>T and BMP4 rs17563 T>C polymorphisms were determined in 107 unrelated Iranian subjects with non-syndromic CL/P and 186 control subjects using PCR and RFLP methods, and the results were compared with healthy controls. A p-value of <0.05 was considered statistically significant.
    Results: The BMP2 rs235768 AT genotype was significantly higher (P=0.009, OR=3, 95% CI=1.3-7.0) in the CL/P (59.8%) than the control group (33.3%). Similarly, the BMP4 rs17563 TC genotype were significantly higher (P=0.008, OR=3.7, 95% CI=1.4-9.9) in the CL/P (70.0%) than the control group (44.6%).
    Conclusion: The BMP2 rs235768 A>T and BMP4 rs17563 T>C polymorphisms could be considered as the risk factor for non-syndromic CL/P in Iranian population.
    MeSH term(s) Alleles ; Bone Morphogenetic Protein 2/genetics ; Bone Morphogenetic Protein 4/genetics ; Case-Control Studies ; Cleft Lip/genetics ; Cleft Palate/genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant, Newborn ; Iran ; Polymorphism, Single Nucleotide ; Risk Factors
    Chemical Substances BMP2 protein, human ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Protein 4
    Language English
    Publishing date 2016-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 80227-x
    ISSN 1879-1506 ; 0003-9969
    ISSN (online) 1879-1506
    ISSN 0003-9969
    DOI 10.1016/j.archoralbio.2016.08.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ul III Zs.151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: The androgen receptor is a therapeutic target in desmoplastic small round cell sarcoma.

    Lamhamedi-Cherradi, Salah-Eddine / Maitituoheti, Mayinuer / Menegaz, Brian A / Krishnan, Sandhya / Vetter, Amelia M / Camacho, Pamela / Wu, Chia-Chin / Beird, Hannah C / Porter, Robert W / Ingram, Davis R / Ramamoorthy, Vandhana / Mohiuddin, Sana / McCall, David / Truong, Danh D / Cuglievan, Branko / Futreal, P Andrew / Velasco, Alejandra Ruiz / Anvar, Nazanin Esmaeili / Utama, Budi /
    Titus, Mark / Lazar, Alexander J / Wang, Wei-Lien / Rodriguez-Aguayo, Cristian / Ratan, Ravin / Livingston, J Andrew / Rai, Kunal / MacLeod, A Robert / Daw, Najat C / Hayes-Jordan, Andrea / Ludwig, Joseph A

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 3057

    Abstract: Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. ... ...

    Abstract Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the C-terminal partner of the pathognomonic fusion protein) and FOXF1. Additionally, AR occupied enhancer sites that regulate the Wnt pathway, neural differentiation, and embryonic organ development, implicating AR in dysfunctional cell lineage commitment. Our findings have direct clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.
    MeSH term(s) Androgen Receptor Antagonists/pharmacology ; Androgens ; Animals ; Cell Line, Tumor ; Desmoplastic Small Round Cell Tumor/genetics ; Humans ; Male ; Oligonucleotides, Antisense/pharmacology ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Xenograft Model Antitumor Assays
    Chemical Substances Androgen Receptor Antagonists ; Androgens ; Oligonucleotides, Antisense ; Receptors, Androgen
    Language English
    Publishing date 2022-06-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30710-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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