Publications by authors named "D M Kirkpatrick"
Histone tail phosphorylation has diverse effects on a myriad of cellular processes, including cell division, and is highly conserved throughout eukaryotes. Histone H3 phosphorylation at threonine 3 (H3T3) during mitosis occurs at the inner centromeres and is required for proper biorientation of chromosomes on the mitotic spindle. While H3T3 is also phosphorylated during meiosis, a possible role for this modification has not been tested.
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- 5-fluorouracil (5-FU) is an important cancer treatment that mostly works by blocking a specific enzyme, leading to DNA damage, but clinical trials show it doesn't work well with certain other drugs for colorectal cancer.
- Research indicates that 5-FU actually kills colorectal cancer cells by targeting RNA during the process of making ribosomes, rather than mainly causing DNA damage, which some cancer types are more sensitive to.
- Strategies that increase ribosome production may enhance the effectiveness of 5-FU, suggesting that combining treatments that focus on this aspect could improve outcomes in cancer therapy.
Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is an invasive pest which feeds on numerous economically significant crops. Many integrated pest management strategies for this species rely on effective season-long monitoring for H. halys populations, including attract-and-kill and threshold-based insecticide sprays.
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- Ribosomes are influenced by ubiquitination and deubiquitination processes, with the deubiquitinase OTUD6 playing a key role in protein translation in Drosophila by modifying the RPS7 subunit of the 40S ribosome.
- Research shows that OTUD6 interacts specifically with the free 40S ribosomes and that several proteins, including RACK1 and E3 ligases like CNOT4 and RNF10, are involved in regulating this interaction and responding to cellular stress.
- The levels of OTUD6 can change due to aging and stress, suggesting it helps control the initiation of protein translation by affecting the recycling of the 40S ribosomes.
With the finalization of the ICH Q14 Analytical Procedure Development guideline, how to apply enhanced approaches (such as analytical quality by design (AQbD)) to develop an analytical procedure, and to propose Established Conditions (ECs) and corresponding reporting categories, is increasingly being discussed. To gain practical experience in applying an enhanced approach for method development and identifying ECs, we developed, validated, and implemented an analytical procedure for a nitrosamine drug substance-related impurity (NDSRI). Here, as an example of the application of Q12 Lifecycle Management guideline principles in regards to analytical procedures, we briefly elaborate how: 1) the principles documented in the ICH Q14 guideline for analytical procedure development were applied, with the focus on identifying an Analytical Target Profile (ATP), knowledge management and risk assessment; 2) analytical procedure robustness according to the recommendations in ICH Q2(R2) Validation of Analytical Procedure guideline and Q14, were evaluated; and 3) mass spectrometry ECs and associated proposed reporting categories were proposed.
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