Anger problems and posttraumatic stress disorder in male and female National Guard and Reserve Service members

Anger is a common problem among veterans and has been associated with posttraumatic stress disorder (PTSD). This study aimed to improve understanding of how anger and PTSD co-occur by examining gender differences and differences by whether the triggering traumatic event is deployment-related vs. civilian-related in current service members. A representative cohort of Reserve and National Guard service personnel (n = 1293) were interviewed to assess for deployment- or civilian-related traumas, PTSD, and anger. The prevalence of self-reported anger problems was estimated among male (n = 1036) and female (n = 257) service members. Log Poisson regression models with robust standard errors were used to estimate the associations of problems with anger with PTSD and PTSD symptom severity for men and women. Self-reported anger problems were common among male (53.0%) and female (51.3%) service members. Adjusted prevalence ratios (PR) showed associations between anger and PTSD connected to both civilian- and deployment-related traumas (PR were 1.77 (95% CI 1.52–2.05) and 1.85 (95% CI 1.62–2.12), respectively). PTSD symptom severity was also associated with anger. This study was cross-sectional and so a causal relationship between PTSD and anger cannot be established. Problems with anger are common among male and female current Guard and Reserve members. These findings suggest that anger treatment should be made available to current service members and that clinicians should assess anger problems irrespective of gender. Future research should examine the effectiveness of anger treatment protocols by gender

Evolution of Resistance to Aurora Kinase B Inhibitors in Leukaemia Cells

Aurora kinase inhibitors are new mitosis-targeting drugs currently in clinical trials for the treatment of haematological and solid malignancies. However, knowledge of the molecular factors that influence sensitivity and resistance remains limited. Herein, we developed and characterised an in vitro leukaemia model of resistance to the Aurora B inhibitor ZM447439. Human T-cell acute lymphoblastic leukaemia cells, CCRF-CEM, were selected for resistance in 4 µM ZM447439. CEM/AKB4 cells showed no cross-resistance to tubulin-targeted and DNA-damaging agents, but were hypersensitive to an Aurora kinase A inhibitor. Sequencing revealed a mutation in the Aurora B kinase domain corresponding to a G160E amino acid substitution. Molecular modelling of drug binding in Aurora B containing this mutation suggested that resistance is mediated by the glutamate substitution preventing formation of an active drug-binding motif. Progression of resistance in the more highly selected CEM/AKB8 and CEM/AKB16 cells, derived sequentially from CEM/AKB4 in 8 and 16 µM ZM447439 respectively, was mediated by additional defects. These defects were independent of Aurora B and multi-drug resistance pathways and are associated with reduced apoptosis mostly likely due to reduced inhibition of the catalytic activity of aurora kinase B in the presence of drug. Our findings are important in the context of the use of these new targeted agents in treatment regimes against leukaemia and suggest resistance to therapy may arise through multiple independent mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

GenBank at Los Alamos: User manual, training guide, and reference manual for the OPEN LOOK[trademark] AWB

The GenBank project at Los Alamos collects nucleotide sequence submissions from the biological research community. This work includes the processing of data received in several different forms as well as maintenance and quality control on those submissions. This manual explains the procedures involved in that work for both Los Alamos GenBank staff and off-site users. The GenBank database stores annotated DNA sequences. This manual contains the procedures for depositing these sequences into the database. There are two ways to do this. Either the sequence arrives at GenBank as a submission and is entered by the database staff or the sequence is directly entered by an off-site user. The Annotator's WorkBench (AWB), which is a database browsing and editing tool, is used in both cases. This manual is for GenBank staff and off-site users of the GenBank database at the Los Alamos National Laboratory. It contains an introduction and tutorials for AWB, as well as procedures for entering sequences either as submissions or as data directly deposited by an off-site user. Instructions for all of these are found in Chapters 2 through 4. The introduction to AWB is in Chapter 2. Instructions for submission handling are in Chapter 3. Instructions for entering sequence information are in Chapter 4. Off-site users should look at section 4.3 for instructions on entering a sequence. In addition, the manual describes various in-house curatorial tasks that are part of maintaining the database, as well as the procedures and conventions for annotating sequences. The procedures for annotation and review are in Chapters 5 and 6. The description of in-house curator's tasks is in Chapter 7. The appendices contain: Annotation conventions, two reference chapters on AWB and other utility programs, a complete list of all the forms, fields, and commands in AWB and descriptions of other (non-AWB) software utilities used by database staff

GenBank at Los Alamos: User manual, training guide, and reference manual for the ASCII AWB

The GenBank project at Los Alamos collects nucleotide sequence submissions from the biological research community. This work includes the processing of data received in several different forms as well as maintenance and quality control on those submissions. This manual explains the procedures involved in that work for both Los Alamos GenBank staff and off-site users. The GenBank database stores annotated DNA sequences. This manual contains the procedures for depositing these sequences into the database. There are two ways to do this. Either the sequence arrives at GenBank as a submission and is entered by the database staff or the sequence is directly entered by an off-site user. The Annotator's WorkBench (AWB), which is a database browsing and editing tool, is used in both cases. This manual is for GenBank staff and off-site users of the GenBank database at the Los Alamos National Laboratory. It contains an introduction and tutorials for AWB, as well as procedures for entering sequences either as submissions or as data directly deposited by an off-site user. Instructions for all of these are found in Chapters 2 through 4. The introduction to AWB is in Chapter 2. Instructions for submission handling are in Chapter 3. Instructions for entering sequence information are in Chapter 4. Off-site users should look at section 4.3 for instructions on entering a sequence. In addition, the manual describes various in-house curatorial tasks that are part of maintaining the database, as well as the procedures and conventions for annotating sequences. The procedures for annotation and review are in Chapters 5 and 6. The description of in-house curator's tasks is in Chapter 7. The appendices contain: Annotation conventions, two reference chapters on AWB and other utility programs, a complete list of all the forms, fields, and commands in AWB and descriptions of other (non-AWB) software utilities used by database staff

GenBank

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 85,000,000 nucleotides in 67,000 entries from a total of 3,000 organisms. The input stream of data coming into the database is primarily as direct submissions from the scientific community on electronic media, with little or no data being keyboarded from the printed page by the databank staff. The data are maintained in a relational database management system and are made available in flatfile form through on-line access, and through various network and off-line computer-readable media. The data are also distributed in relational form through satellite copies at a number of institutions in the U.S. and elsewhere. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service