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Targeted Calcium Influx Boosts Cytotoxic T Lymphocyte Function In The Tumour Microenvironment, Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G. De Rubio, Alan V. Smrcka, Jun Chang-Duk, Jung Woojin, Byeonghak Park, Minsoo Kim, Tae-Il Kim, Minsoo Kim
Targeted Calcium Influx Boosts Cytotoxic T Lymphocyte Function In The Tumour Microenvironment, Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G. De Rubio, Alan V. Smrcka, Jun Chang-Duk, Jung Woojin, Byeonghak Park, Minsoo Kim, Tae-Il Kim, Minsoo Kim
Biology
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to …
5-Azacytidine Induces Transcriptome Changes In Escherichia Coli Via Dna Methylation-Dependent And Dna Methylation-Independent Mechanisms, Kevin T. Militello, Robert D. Simon, Alexandra H. Mandarano, Anthony Dinatale, Stacy M. Hennick, Justine C. Lazatin, Sarah Cantatore
5-Azacytidine Induces Transcriptome Changes In Escherichia Coli Via Dna Methylation-Dependent And Dna Methylation-Independent Mechanisms, Kevin T. Militello, Robert D. Simon, Alexandra H. Mandarano, Anthony Dinatale, Stacy M. Hennick, Justine C. Lazatin, Sarah Cantatore
Biology
Background: Escherichia coli K-12 strains contain DNA cytosine methyltransferase (Dcm), which generates 5-methylcytosine at 5′CCWGG3′ sites. Although the role of 5-methylcytosine in eukaryotic gene expression is relatively well described, the role of 5-methylcytosine in bacterial gene expression is largely unknown. Results: To identify genes that are controlled by 5-methylcytosine in E. coli, we compared the transcriptomes of cells grown in the absence and presence of the DNA methylation inhibitor 5-azacytidine. We observed expression changes for 63 genes. The majority of the gene expression changes occurred at early stationary phase and were up-regulations. To identify gene expression changes due to a …
Spermatogenesis Drives Rapid Gene Creation And Masculinization Of The X Chromosome In Stalk-Eyed Flies (Diopsidae), Richard H. Baker, Apurva Narechania, Rob Desalle, Philip M. Johns, Josephiine A. Reinhardt, Gerald S. Wilkinson
Spermatogenesis Drives Rapid Gene Creation And Masculinization Of The X Chromosome In Stalk-Eyed Flies (Diopsidae), Richard H. Baker, Apurva Narechania, Rob Desalle, Philip M. Johns, Josephiine A. Reinhardt, Gerald S. Wilkinson
Biology
Throughout their evolutionary history, genomes acquire new genetic material that facilitates phenotypic innovation and diversification. Developmental processes associated with reproduction are particularly likely to involve novel genes. Abundant gene creation impacts the evolution of chromosomal gene content and general regulatory mechanisms such as dosage compensation. Numerous studies in model organisms have found complex and, at times contradictory, relationships among these genomic attributes highlighting the need to examine these patterns in other systems characterized by abundant sexual selection. Therefore, we examined the association among novel gene creation, tissue-specific gene expression, and chromosomal gene content within stalk-eyed flies. Flies in this family …
Meiotic Drive Impacts Expression And Evolution Of X-Linked Genes In Stalk-Eyed Flies, Josephine A. Reinhardt, Cara L. Brand, Kimberly A. Paczolt, Philip M. Johns, Richard H. Baker, Gerald S. Wilkinson
Meiotic Drive Impacts Expression And Evolution Of X-Linked Genes In Stalk-Eyed Flies, Josephine A. Reinhardt, Cara L. Brand, Kimberly A. Paczolt, Philip M. Johns, Richard H. Baker, Gerald S. Wilkinson
Biology
Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (X SR ) or a standard X …
Reduced Dntp Binding Affinity Of 3tc-Resistant M184i Hiv-1 Reverse Transcriptase Variants Responsible For Viral Infection Failure In Macrophage, Varuni K. Jamburuthugoda, Jose M. Santos-Velazquez, Mark Skasko, Darwin J. Operario, Vandana Purohit, Pauline Chugh, Erika A. Szymanski, Joseph E. Wedekind, Robert A. Bambara, Baek Kim
Reduced Dntp Binding Affinity Of 3tc-Resistant M184i Hiv-1 Reverse Transcriptase Variants Responsible For Viral Infection Failure In Macrophage, Varuni K. Jamburuthugoda, Jose M. Santos-Velazquez, Mark Skasko, Darwin J. Operario, Vandana Purohit, Pauline Chugh, Erika A. Szymanski, Joseph E. Wedekind, Robert A. Bambara, Baek Kim
Biology
We characterized HIV-1 reverse transcriptase (RT) variants either with or without the (-)-2′,3′-deoxy-3′-thiacytidine-resistant M184I mutation isolated from a single HIV-1 infected patient. First, unlike variants with wild-type M184, M184I RT variants displayed significantly reduced DNA polymerase activity at low dNTP concentrations, which is indicative of reduced dNTP binding affinity. Second, the M184I variant displayed a ∼10- to 13-fold reduction in dNTP binding affinity, compared with the Met-184 variant. However, the kpol values of these two RTs were similar. Third, unlike HIV-1 vectors with wild-type RT, the HIV-1 vector harboring M184I RT failed to transduce cell types containing low dNTP concentrations, …