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Robert D Kuchta - One of the best experts on this subject based on the ideXlab platform.
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Arg304 of human DNA primase is a Key Contributor to catalysis and NTP binding: primase and the family X polymerases share significant sequence homology.
Biochemistry, 1999Co-Authors: Brian W. Kirk, Robert D KuchtaAbstract:Comparison of the amino acid sequences of eucaryotic DNA primase and the family X polymerases indicates that primase shares significant sequence homology with this family. With the use of DNA polymerase β (pol β) as a paradigm for family X polymerases, these homologies include both the catalytic core domain/subunit of each enzyme (31 kDa domain of pol β and p49 subunit of primase) as well as the accessory domain/subunit (8 kDa domain of pol β and p58 subunit of primase). To further explore these homologies as well as provide insights into the mechanism of primase, we generated three mutants (R304K, R304Q, and R304A) of the p49 subunit at an arginine that is highly conserved between primase and the eukaryotic family X polymerases. These mutations significantly decreased the rate of primer synthesis, due primarily to a decreased rate of initiation, and the extent of impairment correlated with the severity of the mutation (A > Q > K). R304 also contributes to efficient utilization of the NTP that will become...
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arg304 of human dna primase is a Key Contributor to catalysis and ntp binding primase and the family x polymerases share significant sequence homology
Biochemistry, 1999Co-Authors: Brian W. Kirk, Robert D KuchtaAbstract:Comparison of the amino acid sequences of eucaryotic DNA primase and the family X polymerases indicates that primase shares significant sequence homology with this family. With the use of DNA polym...
Brian W. Kirk - One of the best experts on this subject based on the ideXlab platform.
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Arg304 of human DNA primase is a Key Contributor to catalysis and NTP binding: primase and the family X polymerases share significant sequence homology.
Biochemistry, 1999Co-Authors: Brian W. Kirk, Robert D KuchtaAbstract:Comparison of the amino acid sequences of eucaryotic DNA primase and the family X polymerases indicates that primase shares significant sequence homology with this family. With the use of DNA polymerase β (pol β) as a paradigm for family X polymerases, these homologies include both the catalytic core domain/subunit of each enzyme (31 kDa domain of pol β and p49 subunit of primase) as well as the accessory domain/subunit (8 kDa domain of pol β and p58 subunit of primase). To further explore these homologies as well as provide insights into the mechanism of primase, we generated three mutants (R304K, R304Q, and R304A) of the p49 subunit at an arginine that is highly conserved between primase and the eukaryotic family X polymerases. These mutations significantly decreased the rate of primer synthesis, due primarily to a decreased rate of initiation, and the extent of impairment correlated with the severity of the mutation (A > Q > K). R304 also contributes to efficient utilization of the NTP that will become...
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arg304 of human dna primase is a Key Contributor to catalysis and ntp binding primase and the family x polymerases share significant sequence homology
Biochemistry, 1999Co-Authors: Brian W. Kirk, Robert D KuchtaAbstract:Comparison of the amino acid sequences of eucaryotic DNA primase and the family X polymerases indicates that primase shares significant sequence homology with this family. With the use of DNA polym...
Don Jellyman - One of the best experts on this subject based on the ideXlab platform.
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obituary: Bob McDowall (September 1939 ‐ February 2011): a Key Contributor to our understanding of Southern Hemisphere biogeography and the significance of marine dispersal
Frontiers of biogeography, 2012Co-Authors: Christopher Paul Burridge, Don JellymanAbstract:ISSN 1948‐6596 profiles obituary Bob McDowall (September 1939 ‐ February 2011): a Key Contributor to our understanding of Southern Hemisphere biogeography and the sig‐ nificance of marine dispersal It is with great sadness that I report the loss of Dr Robert (“Bob”) Montgomery McDowall, on Febru‐ ary 19 th , 2011. Bob was a Key figure in the study of Southern Hemisphere biogeography and marine dispersal. After a childhood of fishing and freshwater activities with his parents, both of whom were also scientists, Bob completed a MSc on the ecol‐ ogy of redfin bully (Gobiomorphus huttoni) at Vic‐ toria University, Wellington, in 1962. Bob subse‐ quently joined the Fisheries Laboratory of the New Zealand Marine Department in 1963, study‐ ing Galaxias maculatus, the dominant Contributor to the New Zealand whitebait fishery, and a spe‐ cies that probably ignited his interest in biogeog‐ raphy, much as its distribution had earlier in‐ trigued the likes of Charles Darwin. Bob was soon awarded a National Research Fellowship to study overseas, and started a PhD on galaxiid systemat‐ ics at Harvard University in 1965, in an environ‐ ment that included some of the foremost evolu‐ tionary biologists (Mayr) and biogeographers (Darlington) of the time. Bob completed his PhD in 3 years, a timeframe to be much admired even in this age, which enabled him to return to New Zea‐ land via Chile—for galaxiid collections, of course! Back in New Zealand, Bob became New Zealand’s foremost freshwater fisheries scientist, outlasting the names of several Government departments, prior to “retiring” from the National Institute of Water and Atmosphere Research (NIWA) in March 2000. However, like many a great scientist, retire‐ ment freed Bob from administrative burdens such that he was able to focus entirely on research. While predominantly employed as a fisher‐ ies biologist, Bob somehow managed to regularly publish biogeographic research. In this context, Bob focussed on the Southern Hemisphere “Gondwanan” distribution of galaxiid fishes, and also the influence of diadromy (migration be‐ tween the ocean and freshwaters) on species dis‐ tributions. In the period following the acceptance The late Bob McDowall in December 2010. Picture by Ainslie McDowall of plate tectonics, Bob was a dominant protago‐ nist for the retention of oceanic dispersal as a valid biogeographic hypothesis (McDowall 1978), particularly in taxa such as his diadromous Galax‐ ias maculatus, where conspecific populations broadly occupy temperate lowland catchments throughout the Southern Hemisphere, and larvae have been recorded 100’s of km out to sea (McDowall et al. 1975). Bob argued his point against several notable opponents within the dis‐ cipline: Nelson, Rosen, Platnick, Croizat. Much subsequent research has supported Bob’s position on oceanic dispersal, with many examples from terrestrial, freshwater, and nearshore marine fau‐ nas and floras (McDowall 2002; Sanmartin and Ronquist 2004; de Queiroz 2005). But while Bob could easily be considered a strong proponent of oceanic dispersal, it perhaps best reflects his at‐ tention to balanced approaches of scientific in‐ quiry, and in recent correspondence he was keen to highlight that Gondwanan vicariance should not be forgotten (fearing that the pendulum was now swinging too far the other way). Bob was a frenetic publisher, with (at last count) 267 scientific papers and 232 reports and popular articles. His papers spanned a variety of journals, including those not immediately within frontiers of biogeography 3.1, 2011 — © 2011 the authors; journal compilation © 2011 The International Biogeography Society
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obituary bob mcdowall september 1939 february 2011 a Key Contributor to our understanding of southern hemisphere biogeography and the significance of marine dispersal
Frontiers of biogeography, 2012Co-Authors: Christopher Paul Burridge, Don JellymanAbstract:ISSN 1948‐6596 profiles obituary Bob McDowall (September 1939 ‐ February 2011): a Key Contributor to our understanding of Southern Hemisphere biogeography and the sig‐ nificance of marine dispersal It is with great sadness that I report the loss of Dr Robert (“Bob”) Montgomery McDowall, on Febru‐ ary 19 th , 2011. Bob was a Key figure in the study of Southern Hemisphere biogeography and marine dispersal. After a childhood of fishing and freshwater activities with his parents, both of whom were also scientists, Bob completed a MSc on the ecol‐ ogy of redfin bully (Gobiomorphus huttoni) at Vic‐ toria University, Wellington, in 1962. Bob subse‐ quently joined the Fisheries Laboratory of the New Zealand Marine Department in 1963, study‐ ing Galaxias maculatus, the dominant Contributor to the New Zealand whitebait fishery, and a spe‐ cies that probably ignited his interest in biogeog‐ raphy, much as its distribution had earlier in‐ trigued the likes of Charles Darwin. Bob was soon awarded a National Research Fellowship to study overseas, and started a PhD on galaxiid systemat‐ ics at Harvard University in 1965, in an environ‐ ment that included some of the foremost evolu‐ tionary biologists (Mayr) and biogeographers (Darlington) of the time. Bob completed his PhD in 3 years, a timeframe to be much admired even in this age, which enabled him to return to New Zea‐ land via Chile—for galaxiid collections, of course! Back in New Zealand, Bob became New Zealand’s foremost freshwater fisheries scientist, outlasting the names of several Government departments, prior to “retiring” from the National Institute of Water and Atmosphere Research (NIWA) in March 2000. However, like many a great scientist, retire‐ ment freed Bob from administrative burdens such that he was able to focus entirely on research. While predominantly employed as a fisher‐ ies biologist, Bob somehow managed to regularly publish biogeographic research. In this context, Bob focussed on the Southern Hemisphere “Gondwanan” distribution of galaxiid fishes, and also the influence of diadromy (migration be‐ tween the ocean and freshwaters) on species dis‐ tributions. In the period following the acceptance The late Bob McDowall in December 2010. Picture by Ainslie McDowall of plate tectonics, Bob was a dominant protago‐ nist for the retention of oceanic dispersal as a valid biogeographic hypothesis (McDowall 1978), particularly in taxa such as his diadromous Galax‐ ias maculatus, where conspecific populations broadly occupy temperate lowland catchments throughout the Southern Hemisphere, and larvae have been recorded 100’s of km out to sea (McDowall et al. 1975). Bob argued his point against several notable opponents within the dis‐ cipline: Nelson, Rosen, Platnick, Croizat. Much subsequent research has supported Bob’s position on oceanic dispersal, with many examples from terrestrial, freshwater, and nearshore marine fau‐ nas and floras (McDowall 2002; Sanmartin and Ronquist 2004; de Queiroz 2005). But while Bob could easily be considered a strong proponent of oceanic dispersal, it perhaps best reflects his at‐ tention to balanced approaches of scientific in‐ quiry, and in recent correspondence he was keen to highlight that Gondwanan vicariance should not be forgotten (fearing that the pendulum was now swinging too far the other way). Bob was a frenetic publisher, with (at last count) 267 scientific papers and 232 reports and popular articles. His papers spanned a variety of journals, including those not immediately within frontiers of biogeography 3.1, 2011 — © 2011 the authors; journal compilation © 2011 The International Biogeography Society
Jane Fisher - One of the best experts on this subject based on the ideXlab platform.
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sexual violence as a Key Contributor to poor mental health among japanese women subjected to intimate partner violence
Journal of Womens Health, 2017Co-Authors: Tomoko Honda, Karen Wynter, Jinko Yokota, Thach Duc Tran, Yuri Ujiie, Madoka Niwa, Michi Nakayama, Fumie Ito, Yoshiharu Kim, Jane FisherAbstract:Abstract Objectives: The aim of this study was to examine the impact of sexual intimate partner violence (IPV) on mental health among Japanese women and to explore to what extent sexual IPV is an important Contributor to the severity of mental health problems in comparison with physical and psychological IPV. Materials and Methods: A cross-sectional analysis was conducted of the medical records of participants during psychiatric consultation at the Institute of Women's Health, Tokyo Women's Medical University, including 62 women who experienced IPV without sexual violence and 83 women who experienced IPV with sexual violence. Mental health problems were compared, including anxiety, depression, suicidality, post-traumatic stress disorder (PTSD), and dissociative experiences. Results: The results demonstrated a higher incidence and severity of somatic symptoms, insomnia, social dysfunction, severe depression and suicidality, PTSD, and dissociative experiences among women in the sexual IPV group than in the ...
Astin Powers - One of the best experts on this subject based on the ideXlab platform.
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target deconvolution of a multikinase inhibitor with antimetastatic properties identifies taok3 as a Key Contributor to a cancer stem cell like phenotype
Molecular Cancer Therapeutics, 2019Co-Authors: Yansong Bian, Yaroslav Teper, Lesley Mathews A Griner, Taylor Aiken, Vivek Shukla, Rajarshi Guha, Paul Shinn, Hongwu Xin, Holger Pflicke, Astin PowersAbstract:Pancreatic cancer remains an incurable condition. Its progression is driven, in part, by subsets of cancer cells that evade the cytotoxic effects of conventional chemotherapies. These cells are often low-cycling, multidrug resistant, and adopt a stem cell–like phenotype consistent with the concept of cancer stem cells (CSC). To identify drugs impacting on tumor-promoting CSCs, we performed a differential high-throughput drug screen in pancreatic cancer cells cultured in traditional (2D) monolayers versus three-dimensional (3D) spheroids which replicate Key elements of the CSC model. Among the agents capable of killing cells cultured in both formats was a 1H-benzo[d]imidazol-2-amine–based inhibitor of IL2-inducible T-cell kinase (ITK; NCGC00188382, inhibitor #1) that effectively mediated growth inhibition and induction of apoptosis in vitro, and suppressed cancer progression and metastasis formation in vivo. An examination of this agent9s polypharmacology via in vitro and in situ phosphoproteomic profiling demonstrated an activity profile enriched for mediators involved in DNA damage repair. Included was a strong inhibitory potential versus the thousand-and-one amino acid kinase 3 (TAOK3), CDK7, and aurora B kinases. We found that cells grown under CSC-enriching spheroid conditions are selectively dependent on TAOK3 signaling. Loss of TAOK3 decreases colony formation, expression of stem cell markers, and sensitizes spheroids to the genotoxic effect of gemcitabine, whereas overexpression of TAOK3 increases stem cell traits including tumor initiation and metastasis formation. By inactivating multiple components of the cell-cycle machinery in concert with the downregulation of Key CSC signatures, inhibitor #1 defines a distinctive strategy for targeting pancreatic cancer cell populations.
