Cell fate following irradiation of MDA-MB-231 and MCF-7 breast cancer cells pre-exposed to the setrahydroisoquinoline sulfamate microtubule disruptor STX3451

The compound STX3451 is not commercially available.SUPPLEMENTARY MATERIAL : TABLE S1: Data analysis comparing flow cytometric quantification of individual cell cycle phases across 24-h and 48-h timelines. TABLE S2: Data analysis of flow cytometric quantification of the cell cycle distribution in MCF-7 cells exposed to STX3451 and radiation. TABLE S3: Statistical analysis of cell cycle distribution in MCF-7 cells exposed to STX3451 and radiation. TABLE S4: Data analysis comparing flow cytometric quantification of individual cell cycle phases across 24-h and 48-h timelines in MDA-MB-231 cells. TABLE S5: Statistical analysis of cell cycle progression in MDA-MB-231 cells exposed to STX3451 and radiation. TABLE S6: Statistical analysis of cell cycle distribution in MDA-MB-231 cells exposed to STX3451 and radiation. TABLE S7: Annexin-V analysis of MCF-7 cells 48-h. TABLE S8: Annexin-V statistical analysis of MDA-MB-231 48-h. TABLE S9: Colony formation in MCF-7 cells. TABLE S10: Colony formation in MDA-MB-231 cells. TABLE S11: The total number of Mn in MCF-7 cells that were terminated 2- and 24-h after radiation. TABLE S12: The total number of Mn in MDA-MB-231 cells terminated 2- and 24-h after radiation. TABLE S13: Number of Mn per cell in MCF-7 cells terminated 2-h after radiation. TABLE S14: Number of Mn per cell in MCF-7 cells terminated 24-h after radiation. TABLE S15: Number of Mn per cell in MDA-MB-231 cells terminated 2-h after radiation. TABLE S16: The number of Mn per cell in MDA-MB-231 cells that were terminated 24-h after radiation. TABLE S17: Superoxide detection in MCF-7 cells treated with the various modalities. TABLE S18: Superoxide detection in pre-sensitized MDA-MB-231 cells. TABLE S19: Statistical analysis of ATM expression in combination treated MCF-7 and MDA-MB-231 cells 2- and 24-h post-radiation. TABLE S20: Nontumored animal toxicity assay; VIDEO S1: not applicable.Atetrahydroisoquinoline (THIQ) core is able tomimic theAand B rings of 2-methoxyestradiol (2ME2), an endogenous estrogen metabolite that demonstrates promising anticancer properties primarily by disrupting microtubule dynamic instability parameters, but has very poor pharmaceutical properties that can be improved by sulfamoylation. The non-steroidal THIQ-based microtubule disruptor 2-(3-bromo-4,5-dimethoxybenzyl)-7-methoxy-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (STX3451), with enhanced pharmacokinetic and pharmacodynamic profiles, was explored for the first time in radiation biology. We investigated whether 24 h pre-treatment with STX3451 could pre-sensitize MCF-7 and MDA-MB-231 breast cancer cells to radiation. This regimen showed a clear increase in cytotoxicity compared to the individual modalities, results that were contiguous in spectrophotometric analysis, flow cytometric quantification of apoptosis induction, clonogenic studies and microscopy techniques. Drug pre-treatment increased radiation-induced DNA damage, with statistically more double-strand (ds) DNA breaks demonstrated. The latter could be due to the induction of a radiation-sensitive metaphase block or the increased levels of reactive oxygen species, both evident after compound exposure. STX3451 pre-exposure may also delay DNA repair mechanisms, as the DNA damage response element ataxia telangiectasia mutated (ATM) was depressed. These in vitro findings may translate into in vivo models, with the ultimate aim of reducing both radiation and drug doses for maximal clinical effect with minimal adverse effects.The Research Committee of the University of Pretoria, the Struwig-Germeshuysen Trust, the Cancer Association of South Africa (CANSA), the National Research Foundation (NRF) and the Research Development Programme of the University of Pretoria (RDP-UP).https://www.mdpi.com/journal/moleculesam2023Physiolog

Emergence of Skyrme crystal in Gross-Neveu and 't Hooft models at finite density

We study two-dimensional, large $N$ field theoretic models (Gross-Neveu model, 't Hooft model) at finite baryon density near the chiral limit. The same mechanism which leads to massless baryons in these models induces a breakdown of translational invariance at any finite density. In the chiral limit baryonic matter is characterized by a spatially varying chiral angle with a wave number depending only on the density. For small bare quark masses a sine-Gordon kink chain is obtained which may be regarded as simplest realization of the Skyrme crystal for nuclear matter. Characteristic differences between confining and non-confining models are pointed out.Comment: 27 pages, 11 figures, added reference, corrected sig

Search for Exotic Mesons in pi- P Interactions at 18 GeV/c

The recent search for non $q \bar{q}$ mesons in $\pi^{-}p$ interactions at Brookhaven National Laboratory is summarized. Many final states such as $\eta \pi$, $\eta' \pi^{-}$, $a_{0} \pi$, $f_{1} \pi$, $a_{2} \pi$, $b_{1} \pi$, which are favored decay modes of exotics, are under investigation.Comment: 9 pages, PostScript, Presented at the International School of Nuclear Physics, Erice, Sicily, Italy, September 199

Observation of a New J(PC)=1(+-) Isoscalar State in the Reaction Pi- Proton -> Omega Eta Neutron at 18 GeV/c

Results are presented on a partial wave analysis of the Omega Eta final state produced in Pi- Proton interactions at 18 GeVc where Omega -> Pi+ Pi- Pi0, Pi0 -> 2 Gammas, and Eta -> 2 Gammas. We observe the previously unreported decay mode Omega(1650) -> Omega Eta and a new 1(+-) meson state h1(1595) with a mass M=1594(15)(+10)(-60) MeV/c^2 and a width Gamma=384(60)(+70)(-100) MeV/c^2. The h1(1595) state exhibits resonant-like phase motion relative to the Omega(1650).Comment: Submitted to Physics Letters B Eight total pages including 11 figures and 1 tabl

Inheritance of resistance to bacterial spot in tomato

A herança da resistência do tomateiro (Lycopersicon esculentum) à mancha-bacteriana (Xanthomonas campestris pv. vesicatoria, raça T2) foi estudada, em condições de campo, cruzando-se os genótipos resistentes 'Ohio 8245' e 'Hawaii 7998' com os genótipos suscetíveis 'CNPH 401-08' e 'CNPH 416.81.01.02', em um esquema dialélico desconsiderando-se os recíprocos. Foram obtidas cinco famílias, cada uma constituída por seis gerações: Genitor1, Genitor2, F1, F2 e os retrocruzamentos (RC1 e RC2). A família 'Ohio 8245 ' Hawaii 7998' apresentou menor média para severidade da doença, seguida por 'Hawaii 7998 ' CNPH 416.81.01.02' e 'Ohio 8245 ' CNPH 416.81.01.02', as quais, apresentaram maiores estimativas de herdabilidade e de predição de ganho por seleção. Em todas combinações, a herança da resistência genética à mancha-bacteriana foi do tipo quantitativa, com estimativa do número de genes variando de quatro a oito genes, conforme a família analisada. Foi observada segregação transgressiva nas famílias 'Ohio 8245 ' CNPH 401-08', 'Hawaii 7998 ' CNPH 401-08' e 'Hawaii 7998 ' CNPH 416.81.01.02'. Os efeitos gênicos foram do tipo aditivo para todas as famílias e os dados ajustados ao modelo aditivo-dominante, com o componente aditivo apresentando maior magnitude.The inheritance of resistance to bacterial spot (Xanthomonas campestris pv. vesicatoria, race T2) in tomato (Lycopersicon esculentum) was investigated in a field trial. The genotypes 'Ohio 8245' and 'Hawaii 7998' (resistant), 'CNPH 401-08' and 'CNPH 416.81.01.02' (susceptible) were crossed in a diallel scheme without reciprocals. Each cross was labeled as one family, represented by six different generations: Parent1, Parent2, F1, F2 and Backcrosses to parents (BC1 and BC2). The family 'Ohio 8245 ' Hawaii 7998' presented the lowest disease severity, followed by the family 'Hawaii 7998 ' CNPH 416.81.01.02' and by the family 'Ohio 8245 ' CNPH 416.81.01.02'. These last two families showed both higher broad and narrow sense inheritability estimates and the highest prediction of selection gain. The resistance was found to be quantitative, with four to eight genes involved, depending on the family. Transgressive segregation was observed in the 'Ohio 8245 ' CNPH 401-08', the 'Hawaii 7998 ' CNPH 401-08' and the 'Hawaii 7998 ' CNPH 416.81.01.02' families. The relevance of the additive effects was observed and for all the families the data fitted to additive-dominant model, with the additive component showing greater magnitude

CompreHensive geriAtRician-led MEdication Review (CHARMER): protocol for a feasibility study of a hospital deprescribing behaviour change intervention

Introduction Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation. Methods and analysis A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken. Ethics and dissemination Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations

Calibrating and adjusting expectations in life: A grounded theory on how elderly persons with somatic health problems maintain control and balance in life and optimize well-being

Aim: This study aims at exploring the main concern for elderly individuals with somatic health problems and what they do to manage this. Method: In total, 14 individuals (mean = 74.2 years; range = 68–86 years) of both gender including hospitalized and outpatient persons participated in the study. Open interviews were conducted and analyzed according to grounded theory, an inductive theory-generating method. Results: The main concern for the elderly individuals with somatic health problems was identified as their striving to maintain control and balance in life. The analysis ended up in a substantive theory explaining how elderly individuals with somatic disease were calibrating and adjusting their expectations in life in order to adapt to their reduced energy level, health problems, and aging. By adjusting the expectations to their actual abilities, the elderly can maintain a sense of that they still have the control over their lives and create stability. The ongoing adjustment process is facilitated by different strategies and result despite lower expectations in subjective well-being. The facilitating strategies are utilizing the network of important others, enjoying cultural heritage, being occupied with interests, having a mission to fulfill, improving the situation by limiting boundaries and, finally, creating meaning in everyday life. Conclusion: The main concern of the elderly with somatic health problems was to maintain control and balance in life. The emerging theory explains how elderly people with somatic health problems calibrate their expectations of life in order to adjust to reduced energy, health problems, and aging. This process is facilitated by different strategies and result despite lower expectation in subjective well-being

Preface paper to the Semi-Arid Land-Surface-Atmosphere (SALSA) Program special issue

The Semi-Arid Land-Surface-Atmosphere Program (SALSA) is a multi-agency, multi-national research effort that seeks to evaluate the consequences of natural and human-induced environmental change in semi-arid regions. The ultimate goal of SALSA is to advance scientific understanding of the semi-arid portion of the hydrosphere–biosphere interface in order to provide reliable information for environmental decision making. SALSA approaches this goal through a program of long-term, integrated observations, process research, modeling, assessment, and information management that is sustained by cooperation among scientists and information users. In this preface to the SALSA special issue, general program background information and the critical nature of semi-arid regions is presented. A brief description of the Upper San Pedro River Basin, the initial location for focused SALSA research follows. Several overarching research objectives under which much of the interdisciplinary research contained in the special issue was undertaken are discussed. Principal methods, primary research sites and data collection used by numerous investigators during 1997–1999 are then presented. Scientists from about 20 US, five European (four French and one Dutch), and three Mexican agencies and institutions have collaborated closely to make the research leading to this special issue a reality. The SALSA Program has served as a model of interagency cooperation by breaking new ground in the approach to large scale interdisciplinary science with relatively limited resources

Taxonomy based on science is necessary for global conservation

Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat