Changes in movement patterns in relation to sun conditions and spatial scales in wild western gorillas.

For most primates living in tropical forests, food resources occur in patchworks of different habitats that vary seasonally in quality and quantity. Efficient navigation (i.e., spatial memory-based orientation) towards profitable food patches should enhance their foraging success. The mechanisms underpinning primate navigating ability remain nonetheless mostly unknown. Using GPS long-term tracking (596 days) of one group of wild western lowland gorillas (Gorilla gorilla gorilla), we investigated their ability to navigate at long distances, and tested for how the sun was used to navigate at any scale by improving landmark visibility and/or by acting as a compass. Long episodic movements ending at a distant swamp, a unique place in the home range where gorillas could find mineral-rich aquatic plants, were straighter and faster than their everyday foraging movements relying on spatial memory. This suggests intentional targeting of the swamp based on long-distance navigation skills, which can thus be efficient over a couple of kilometres. Interestingly, for both long-distance movements towards the swamp and everyday foraging movements, gorillas moved straighter under sunlight conditions even under a dense vegetation cover. By contrast, movement straightness was not markedly different when the sun elevation was low (the sun azimuth then being potentially usable as a compass) or high (so providing no directional information) and the sky was clear or overcast. This suggests that gorillas navigate their home range by relying on visual place recognition but do not use the sun azimuth as a compass. Like humans, who rely heavily on vision to navigate, gorillas should benefit from better lighting to help them identify landmarks as they move through shady forests. This study uncovers a neglected aspect of primate navigation. Spatial memory and vision might have played an important role in the evolutionary success of diurnal primate lineages.

Vicia sativa subsp. sativa native to the Middle East comprises Pea Albumin1 b-like homologs: A promising natural biopesticide.

The extensive and indiscriminate use of chemical pesticides in agriculture has led to adverse effects on human health, environmental pollution, and the emergence of pesticide-resistant pests. To mitigate these challenges, the development of environmentally friendly alternatives is crucial, with biopesticides emerging as promising solutions such as peptides. Legume seeds naturally contain diverse insecticidal peptides or proteins to combat pest attacks. One such peptide is PA1b (Pea Albumin 1, subunit b), a 37 amino acid extracted from pea seeds (Pisum sativum). PA1b has shown significant potential in controlling cereal weevils (Sitophilus spp.), a major pest of stored cereals. Here, we screened PA1b-like peptides in five wild seeds of vetches (Vicia sativa subsp. sativa) from the Middle East. Using a comprehensive set of biochemical, biological, and molecular techniques, we characterized different PA1b homologs and assessed their toxicity and expression profiles. Our results reveal that PA1b homolog from Vicia sativa subsp. sativa originating from turkey displays outstanding insecticidal activity against Sitophilus oryzae through binding to the receptor site found in the midgut of the insect. Moreover, it exhibits a strong cytotoxic effect against Sf9 cells. This cysteine-rich peptide shows sequence identity and the same hydrophobic pole as AG41, a tenfold more toxic isoform of PA1b from Medicago truncatula. Such observations pave the way for the development of bioinsecticides, with PA1b-like peptides as lead compounds.

Three-dimensional random walk models of individual animal movement and their application to trap counts modelling.

BACKGROUND: Random walks (RWs) have proved to be a powerful modelling tool in ecology, particularly in the study of animal movement. An application of RW concerns trapping which is the predominant sampling method to date in insect ecology and agricultural pest management. A lot of research effort has been directed towards modelling ground-dwelling insects by simulating their movement in 2D, and computing pitfall trap counts, but comparatively very little for flying insects with 3D elevated traps. METHODS: We introduce the mathematics behind 3D RWs and present key metrics such as the mean squared displacement (MSD) and path sinuosity, which are already well known in 2D. We develop the mathematical theory behind the 3D correlated random walk (CRW) which involves short-term directional persistence and the 3D Biased random walk (BRW) which introduces a long-term directional bias in the movement so that there is an overall preferred movement direction. In this study, we focus on the geometrical aspects of the 3D trap and thus consider three types of shape; a spheroidal trap, a cylindrical trap and a rectangular cuboidal trap. By simulating movement in 3D space, we investigated the effect of 3D trap shapes and sizes and of movement diffusion on trapping efficiency. RESULTS: We found that there is a non-linear dependence of trap counts on the trap surface area or volume, but the effect of volume appeared to be a simple consequence of changes in area. Nevertheless, there is a slight but clear hierarchy of trap shapes in terms of capture efficiency, with the spheroidal trap retaining more counts than a cylinder, followed by the cuboidal type for a given area. We also showed that there is no effect of short-term persistence when diffusion is kept constant, but trap counts significantly decrease with increasing diffusion. CONCLUSION: Our results provide a better understanding of the interplay between the movement pattern, trap geometry and impacts on trapping efficiency, which leads to improved trap count interpretations, and more broadly, has implications for spatial ecology and population dynamics.

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study.

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

Milk fat globule--epidermal growth factor--factor VIII (MFGE8)/lactadherin promotes bladder tumor development.

Milk fat globule-epidermal growth factor-factor VIII (MFGE8), also called lactadherin or SED1, is a secreted integrin-binding protein that promotes elimination of apoptotic cells by phagocytes leading to tolerogenic immune responses, and vascular endothelial growth factor (VEGF)-induced angiogenesis: two important processes for cancer development. Here, by transcriptomic analysis of 228 biopsies of bladder carcinomas, we observed overexpression of MFGE8 during tumor development, correlated with expression of genes involved in cell adhesion or migration and in immune responses, but not in VEGF-mediated angiogenesis. To test whether MFGE8 expression was instrumental in bladder tumor development, or a simple consequence of this development, we used genetic ablation in a mouse model of carcinogen-induced bladder carcinoma. We showed that Mfge8 was also upregulated in mouse carcinoma, and that in its absence, Mfge8-deficient animals developed less advanced tumors. Angiogenesis was similar in carcinogen-treated Mfge8-expressing or -deficient bladders, thus ruling out a major role of the proangiogenic function of Mfge8 for its protumoral role. By contrast, the tumor-promoting role of Mfge8 was not observed anymore in mice devoid of adaptive immune system, and human tumors overexpressing MFGE8 where invaded with macrophages and regulatory T cells, thus suggesting that MFGE8/lactadherin favors development of bladder tumors at least partly by an immune system-dependent mechanism. Our observations suggest future use of MFGE8-inhibiting molecules as therapies of bladder carcinomas, and of a limited number of other human cancers, in which our analysis of public databases also revealed overexpression of MFGE8.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors.

BACKGROUND: Radiotherapy of the left breast is associated with higher cardiovascular mortality linked to cardiotoxic effect of irradiation. Radiotherapy of inner quadrants can be associated with greater heart irradiation, but no study has evaluated the effect of inner-quadrant irradiation on cardiovascular mortality. PATIENTS AND METHODS: We identified 1245 women, the majority with breast-conserving surgery, irradiated for primary node-negative breast cancer from 1980 to 2004 registered at the Geneva Cancer Registry. We compared breast cancer-specific and cardiovascular mortality between inner-quadrant (n = 393) versus outer-quadrant tumors (n = 852) by multivariate Cox regression analysis. RESULTS: After a mean follow-up of 7.7 years, 28 women died of cardiovascular disease and 91 of breast cancer. Patients with inner-quadrant tumors had a more than doubled risk of cardiovascular mortality compared with patients with outer-quadrant tumors (adjusted hazard ratio 2.5; 95% confidence interval 1.1-5.4). Risk was particularly increased in the period with higher boost irradiation. Patients with left-sided breast cancer had no excess of cardiovascular mortality compared with patients with right-sided tumors. CONCLUSIONS: Radiotherapy of inner-quadrant breast cancer is associated with an important increase of cardiovascular mortality, a possible result of higher irradiation of the heart. For patients with inner-quadrant tumors, the heart should be radioprotected.

Impact of a positive family history on diagnosis, management, and survival of breast cancer: different effects across socio-economic groups.

BACKGROUND: This study aims to investigate whether increased awareness of breast cancer, due to a positive family history (FH), reduces diagnostic, therapeutic, and survival differences between women of low versus high socio-economic status (SES). METHODS: All breast cancer patients registered between 1990 and 2005 at the population-based Geneva Cancer Registry were included. With multivariate logistic and Cox regression analysis, we estimated the impact of SES and FH on method of detection, treatment, and mortality from breast cancer. RESULTS: SES discrepancies in method of detection and suboptimal treatment, as seen among women without a FH, disappeared in the presence of a positive FH. SES differences in stage and survival remained regardless of the presence of a positive FH. Overall, positive FH was associated with better survival. This effect was the strongest in women of high SES (age-adjusted Hazard Ratio [HR(ageadj)] 0.54 [0.3-1.0]) but less pronounced in women of middle (0.77 [0.6-1.0]), and absent in women of low SES (0.80 [0.5-1.2]). CONCLUSION: A positive FH of breast cancer may reduce SES differences in access to screening and optimal treatment. However, even with better access to early detection and optimal treatment, women of low SES have higher risks of death from their disease than those of high SES.

Overexpression of matrix metalloproteinase 1 in dermal fibroblasts from DNA repair-deficient/cancer-prone xeroderma pigmentosum group C patients.

Xeroderma pigmentosum (XP) is a rare, recessively inherited genetic disease characterized by skin cancer proneness and premature aging in photoexposed area. The disease results from defective nucleotide excision repair of ultraviolet (UV)-induced DNA lesions. Reconstruction of group C (XP-C) skin in vitro previously suggested that patients' dermal fibroblasts might be involved in promoting skin cancer development, as they elicited microinvasions of both control and XP-C keratinocytes within dermal equivalents. Here we show that in the absence of UV exposure XP-C fibroblasts exhibit aged-like features such as an elongated and dendritic shape. We analysed the repertoire of expression of matrix metalloproteinases (MMPs) involved in skin aging and cancer. All XP-C fibroblasts tested in this study overexpressed specifically and significantly MMP1. MMP1 expression was also found increased in the dermis of XP-C skin sections suggesting the active contribution of XP-C mesenchymal cells to skin aging and exacerbated carcinogenesis. Increased MMP1 expression in cultured XP-C fibroblasts resulted from MMP1 mRNA accumulation and enhanced transcriptional activity of the MMP1 gene promoter. Deletion analysis revealed the essential role of AP-1 activation in constitutive MMP1 overexpression in XP-C primary fibroblasts. In parallel, levels of reactive oxygen species and FOSB DNA-binding activity were found increased in XP-C fibroblasts. Altogether, these observations suggest that beyond its role in nucleotide excision repair the XPC protein may be important in cell metabolism and fate in the absence of UV.

Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers.

BACKGROUND: Non-small-cell lung cancer arising in never-smokers is usually of adenocarcinoma subtype. The oncogenic pathway of such tumors is poorly understood. To better define the biological characteristics of these tumors, we have compared the expression of a panel of epidermal growth factor receptor (EGFR)-related biomarkers in lung adenocarcinomas from smokers versus those in never-smokers. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed EGFR, pAKT, PTEN, Ki-67, p27 and hTERT expression in specimens from 190 patients with completely resected lung adenocarcinomas (43 never-smokers and 147 smokers). These analyses were performed on tissue microarrays. RESULTS: EGFR expression was higher in tumors from smokers (P < 0.01), while pAKT was overexpressed mainly in tumors from never-smokers (P = 0.01). As expected, the tumors from smokers presented a higher expression of Ki-67 and a more frequent loss of expression of p27 (P < 0.01). In a multivariate model, two biological factors (p27 and Ki-67) and two clinical factors (age and sex) showed independent significant correlation with never-smoking status. CONCLUSIONS: Lung adenocarcinomas in never-smokers have a very distinct immunohistochemical expression profile of EGFR-related biomarkers as compared with lung adenocarcinomas in smokers. High levels of EGFR and Ki-67 are observed in smokers, while never-smokers are characterized by high levels of pAKT and p27.

Orientation in the wandering albatross: interfering with magnetic perception does not affect orientation performance.

After making foraging flights of several thousands of kilometers, wandering albatrosses (Diomedea exulans) are able to pinpoint a specific remote island where their nests are located. This impressive navigation ability is highly precise but its nature is mysterious. Here we examined whether albatrosses rely on the perception of the Earth's magnetic field to accomplish this task. We disturbed the perception of the magnetic field using mobile magnets glued to the head of nine albatrosses and compared their performances with those of 11 control birds. We then used satellite telemetry to monitor their behavior. We found that the ability of birds to home specific nest sites was unimpaired by this manipulation. In particular, experimental and control birds did not show significant differences with respect to either foraging trip duration, or length, or with respect to homing straightness index. Our data suggest that wandering albatrosses do not require magnetic cues to navigate back to their nesting birds.

Association of metabolic gene polymorphisms with alcohol consumption in controls.

The objectives were to study the association between metabolic genes involved in alcohol metabolism (CYP2E1 RsaI, CYP2E1 DraI, ADH1C, NQO1) and alcohol consumption in a large sample of healthy controls. Healthy subjects were selected from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Subjects with information on both alcohol consumption and at least one of the studied polymorphisms were included in the analysis (n=2224). Information on the amount of alcohol consumption was available for a subset of subjects (n=844). None of the studied genes was significantly associated with drinking habits. A significant heterogeneity with age was observed when studying the association between CYP2E1 RsaI and alcohol drinking. CYP2E1 RsaI polymorphism was significantly associated with being a never drinker at older ages (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-4.8; at ages above 68 years), while the association was reversed at ages below 47 years (OR 0.5, 95% CI 0.2-1.4). For subjects with detailed information on alcohol intake, no association between alcohol quantity and polymorphisms in metabolic genes was observed; subjects carrying the NQO1 polymorphism tended to drink more than subjects carrying the wild-type alleles. Therefore, no significant association between CYP2E1 RsaI, CYP2E1 DraI, ADH1C, NQO1 polymorphisms and alcohol consumption was observed in healthy controls.

Set-up of a population-based familial breast cancer registry in Geneva, Switzerland: validation of first results.

BACKGROUND: This article evaluates the accuracy of family history of breast and ovarian cancer among first-degree relatives of breast cancer patients, retrospectively collected during the setting up of a population-based family breast cancer registry. PATIENTS AND METHODS: Family histories of cancer for all women with breast cancer recorded at the Geneva Cancer Registry from 1990 to 1999 were retrospectively extracted from medical files. The accuracy of these family histories was validated among Swiss women born in Geneva: all 119 with a family history of breast (n = 110) or ovarian (n = 9) cancer and a representative sample of 100 women with no family history of breast or ovarian cancer. We identified the first-degree relatives of these women with information from the Cantonal Population Office. All first-degree relatives, resident in Geneva from 1970 to 1999, were linked to the cancer registry database for breast and ovarian cancer occurrence. Sensitivity, specificity and level of overall agreement (kappa) were calculated. RESULTS: Among 310 first-degree relatives identified, 61 had breast cancer and six had ovarian cancer recorded at the Geneva Cancer Registry. The sensitivity, specificity and kappa of the reported family histories of breast cancer were 98%, 97% and 0.97, respectively. For ovarian cancer, the sensitivity, specificity and kappa were 67%, 99%, and 0.66, respectively. CONCLUSIONS: This study indicates that retrospectively obtained family histories are very accurate for breast cancer. For ovarian cancer, family histories are less precise and may need additional verification.

Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years.

BACKGROUND: A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. METHODS: The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and

Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients.

BACKGROUND: Prophylactic cranial irradiation (PCI) has a beneficial effect on overall survival in patients with small-cell lung cancer (SCLC) in complete remission as shown in a worldwide meta-analysis. The current analysis aimed to evaluate PCI effects on patterns of failure in this patient category. PATIENTS AND METHODS: The Institut Gustave-Roussy coordinated two parallel randomized studies including a total of 511 patients with SCLC. Patients were randomly assigned to either PCI (24 Gy in eight fractions and 12 days) or no PCI. Patterns of failure were analyzed according to (i) total event rates and (ii) isolated first site of relapse using a competing risk approach. RESULTS: Five hundred and five patients were analyzed. The 5-year cumulative rate of brain metastasis as an isolated first site of relapse was 37% in the control group and 20% in the PCI group (P < 0.001). The overall 5-year rates of brain metastasis were 59% and 43%, respectively [relative risk (RR) 0.50; P < 0.001]. The 5-year overall survival rates were 15% in the control group and 18% in the PCI group (RR 0.84; P = 0.06). CONCLUSIONS: PCI decreased significantly the risk of brain metastasis. Other events were not influenced. The relative death risk reduction was of borderline significance. Results reported as isolated first cause of failure and subsequent competing events may explain why a major treatment effect on brain metastases rate has a rather moderate effect on survival.