Defining genetic interaction

Sometimes mutations in two genes produce a phenotype that is surprising in light of each mutation's individual effects. This phenomenon, which defines genetic interaction, can reveal functional relationships between genes and pathways. For example, double mutants with surprisingly slow growth define synergistic interactions that can identify compensatory pathways or protein complexes. Recent studies have used four mathematically distinct definitions of genetic interaction (here termed Product, Additive, Log, and Min). Whether this choice holds practical consequences has not been clear, because the definitions yield identical results under some conditions. Here, we show that the choice among alternative definitions can have profound consequences. Although 52% of known synergistic genetic interactions in Saccharomyces cerevisiae were inferred according to the Min definition, we find that both Product and Log definitions (shown here to be practically equivalent) are better than Min for identifying functional relationships. Additionally, we show that the Additive and Log definitions, each commonly used in population genetics, lead to differing conclusions related to the selective advantages of sexual reproduction.     

Comparison of stress fractures of male and female recruits during basic training in the Israeli anti-aircraft forces

BACKGROUND: In military basic training, stress fractures are a common orthopedic problem. Female recruits have a significantly higher incidence of stress fractures than do male recruits. Because the Israeli Defense Forces opened traditionally male roles in combat units to female recruits, their high risk for stress fractures is of concern. OBJECTIVE: To compare the prevalence of stress fractures during Israeli Defense Forces anti-aircraft basic training among otherwise healthy young male and female recruits, in terms of anatomic distribution and severity. DESIGN: Ten mixed gender batteries, including 375 male recruits and 138 female recruits, carried out basic training in the Israeli anti-aircraft corps between November 1999 and January 2003. Each battery was monitored prospectively for 10 weeks of a basic training course. During that time, recruits who were suspected of having an overuse injury went through a protocol that included an orthopedic specialist physical examination followed by a radionuclide technetium bone scan, which was assessed by consultant nuclear medicine experts. The assessment included the anatomic site and the severity of the fractures, labeled as either high severity or low severity. RESULTS: Stress fractures were significantly more common among female recruits than among male recruits. A total of 42 male (11.2%) and 33 female (23.91%) recruits had positive bone scans for stress fractures (female:male relative ratio, 2.13; p < 0.001). Pelvic, femur, and tibia fractures were significantly more common among female recruits than among male recruits (p < 0.005). Female recruits had significantly more severe fractures in the tibia (p < 0.05). However, there was no significant difference in the severity of stress fractures in the femur or metatarsals between male and female recruits, as assessed by radionuclide uptake. CONCLUSIONS: We recommend that different training programs be assigned according to gender, in which female recruits would have a lower level of target strain or a more moderate incline of strain in the training program throughout basic training.     

Potato Consumption and Risk of Colorectal Cancer in the Norwegian Women and Cancer Cohort

Potatoes are the fourth most plentiful food crop in the world, yet the scientific literature on the health effects of potato consumption is scarce. This study aimed to investigate the association between potato consumption and the risk of colorectal cancer (CRC) among 79,778 women aged 41–70, in the Norwegian Women and Cancer study. Information on diet, lifestyle, and health was collected by questionnaire. CRC cases (n = 912) were identified through registry linkage. Adjusted Cox proportional hazard models were used to estimate the association between potato consumption and the risk of CRC. Results showed that high potato consumption was associated with a higher risk of CRC (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.10, 1.60 for ≥3 potatoes per day versus 0–7 potatoes per week). The same association was found for rectal cancer (HR: 1.68, 95% CI: 1.19, 2.36), and same tendencies were found for colon cancer (HR: 1.20, 95% CI: 0.96, 1.50). When stratified by body mass index (BMI) (<25 and ≥25 kg/m²), significant associations were found with BMI <25 kg/m² for CRC (HR: 1.48, 95% CI: 1.15, 1.89) and rectal cancer (HR: 1.95, 95% CI: 1.25, 3.06). No significant interaction between potato consumption and BMI (P = 0.49) was found.     

The Educational Gradient in Intake of Energy and Macronutrients in the General Adult and Elderly Population: The Tromsø Study 2015–2016

Worldwide, there are socioeconomic inequalities in health and diet. We studied the relationship between education and nutrient intake in 11,302 women and men aged 40–96 years who participated in the seventh survey of the population-based Tromsø Study (2015–2016), Norway (attendance 65%). Diet was assessed using a validated food-frequency questionnaire. We examined the association between education and intake of total energy and macronutrients by sex using linear and logistic regression models adjusted for age, body mass index, leisure time physical activity and smoking. The intake of macronutrients was compared with the Nordic Nutrition Recommendations 2012. There was a positive association between education and intake of fiber and alcohol, and a negative association between education and intake of total carbohydrates and added sugar in both women and men. Participants with long tertiary education had higher odds of being compliant with the recommended intake of fiber and protein and the maximum recommended level for added sugar and had lower odds of being compliant with the recommended intake of total carbohydrates and the maximum recommended level for alcohol, compared to participants with primary education. Overall, we found that participants with higher education were more compliant with the Nordic Nutrition Recommendations 2012.     

The association between meat and fish consumption and bladder cancer risk: a pooled analysis of 11 cohort studies

European Journal of Epidemiology - Evidence on the effects of meat consumption from different sources on the risk of bladder cancer (BC) is limited and controversial. Therefore, this study aimed to...     

In vitro Inhibition of CYP3A4 by the Multiherbal Commercial Product Sambucus Force and its Main Constituents Echinacea purpurea and Sambucus nigra

The multiherbal product Sambucus Force contains Echinacea purpurea and Sambucus nigra as its main constituents. The aims of this study were to evaluate Sambucus Force's inhibition potential and inhibition mechanisms towards CYP3A4, and to evaluate the inhibitory co‐contribution of E. purpurea and S. nigra. Metabolic studies were performed with recombinant human CYP3A4, with testosterone as substrate. Sambucus Force inhibited CYP3A4 activity with a mean (95% confidence interval) half maximal inhibitory concentration (IC₅₀) value of 1192 (1091–1302) µg/mL. The inhibitory potency seems exclusively to be exerted by E. purpurea, implicating an insignificant inhibition by S. nigra. The inhibition by E. purpurea as a single herb was in agreement with mechanism‐based inhibition with heterotropic positive cooperative effects. Echinacea purpurea acted differently in the multiherbal product, which showed a dual inhibition profile with both an uncompetitive (substrate‐dependent) inhibition and a time‐dependent (substrate‐independent) inhibitory mechanism. These mechanistic differences are suggested to be caused by herb–herb interactions in the multiherbal product. The CYP3A4 inhibition of Sambucus Force in vitro is considered relatively weak, but recommended high herbal dosages might enhance the potential for clinical interactions. Copyright © 2012 John Wiley & Sons, Ltd.     

Intake of whole grains from different cereal and food sources and incidence of colorectal cancer in the Scandinavian HELGA cohort

Purpose

A high intake of whole grains has been associated with a lower incidence of colorectal cancer, but few studies are available on the association with whole grains from different cereals, for example, wheat, rye and oats, and none has addressed these separately. The objective of this study was to investigate the association between whole-grain intake and colorectal cancer.

Method

We used data from the large population-based Scandinavian cohort HELGA consisting of 108,000 Danish, Swedish, and Norwegian persons, of whom 1,123 developed colorectal cancer during a median of 11 years of follow-up. Detailed information on daily intake of whole-grain products, including whole-grain bread, crispbread, and breakfast cereals, was available, and intakes of total whole grains and specific whole-grain species (wheat, rye, and oats) were estimated. Associations between these whole-grain variables and the incidence of colorectal cancer were investigated using Cox proportional hazards models. Intake of whole-grain products was associated with a lower incidence of colorectal cancer per 50-g increment (incidence rate ratio [IRR], 0.94; 95 % confidence interval [CI], 0.89, 0.99), and the same tendency was found for total whole-grain intake (IRR pr. 25-g increment, 0.94; 95 % CI, 0.88, 1.01). Intake of whole-grain wheat was associated with a lower incidence of colorectal cancer (IRR for highest versus lowest quartile of intake, 0.66; 95 % CI, 0.51, 0.85), but no statistical significant linear trend was observed (p for trend: 0.18). No significant association was found for whole-grain rye or oats.

Conclusion

Whole-grain intake was associated with a lower incidence of colorectal cancer.     

Cover Picture: Eur. J. Immunol. 5/11

The cover image of this issue consists of a confocal microscopic FRET image showing immunological synapse formation in Jurkat T cells, and is taken from Roszik et al. (pp. 1288–1297). In this article, the authors characterize TCR‐ζ, a heterodimer of TCR‐α and β chains each coupled to complete human CD3ζ, in gene‐engineered T cells and assess whether this receptor is able to interact with surface molecules and drive correct synapse formation in Jurkat T cells. The authors notably demonstrate that TCR‐ζ is able to induce synapse formation upon antigen recognition, and that synapse formation induced by TCR‐ζ is independent of TCR‐CD3.