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Farming new species and promoting polyculture can enhance aquaculture sustainability. This implies to define the rearing conditions that meet the ecological requirements of a target species and/or to assess if different species can live in the same farming environment. However, there is a large number of rearing conditions and/or taxon combinations that can be considered. In order to minimise cumbersome and expensive empirical trials to explore all possibilities, we introduce a tool, AquaDesign. It is based on a R-script and package which help to determine farming conditions that are most likely suitable for species through in silico assessment. We estimate farming conditions potentially suitable for an aquatic organism by considering the species niche. We define the species n-dimensional niche hypervolume using a correlative approach in which the species niche is estimated by relating distribution data to environmental conditions. Required input datasets are mined from several public databases. The assistant tool allows users to highlight (i) abiotic conditions that are most likely suitable for species and (ii) combinations of species potentially able to live in the same abiotic environment. Moreover, it offers the possibility to assess if a particular set of abiotic conditions or a given farming location is potentially suitable for the monoculture or the polyculture of species of interest. Our tool provides useful pieces of information to develop freshwater aquacultures. Using the large amount of biogeographic and abiotic information available in public databases allows us to propose a pragmatic and operational tool even for species for which abiotic requirements are poorly or not available in literature such as currently non-produced species. Overall, we argue that the assistant tool can act as a stepping stone to promote new aquatic productions which are required to enhance aquaculture sustainability.

Farming new species and promoting polyculture can enhance aquaculture sustainability. This implies to define the rearing conditions that meet the ecological requirements of a target species and/or to assess if different species can live in the same farming environment. However, there is a large number of rearing conditions and/or taxon combinations that can be considered. In order to minimise cumbersome and expensive empirical trials to explore all possibilities, we introduce a tool, AquaDesign. It is based on a R-script and package which help to determine farming conditions that are most likely suitable for species through in silico assessment. We estimate farming conditions potentially suitable for an aquatic organism by considering the species niche. We define the species n-dimensional niche hypervolume using a correlative approach in which the species niche is estimated by relating distribution data to environmental conditions. Required input datasets are mined from several public databases. The assistant tool allows users to highlight (i) abiotic conditions that are most likely suitable for species and (ii) combinations of species potentially able to live in the same abiotic environment. Moreover, it offers the possibility to assess if a particular set of abiotic conditions or a given farming location is potentially suitable for the monoculture or the polyculture of species of interest. Our tool provides useful pieces of information to develop freshwater aquacultures. Using the large amount of biogeographic and abiotic information available in public databases allows us to propose a pragmatic and operational tool even for species for which abiotic requirements are poorly or not available in literature such as currently non-produced species. Overall, we argue that the assistant tool can act as a stepping stone to promote new aquatic productions which are required to enhance aquaculture sustainability.

Phytoplankton, with an estimated 30 000 to 1 000 000 species clustered in 12 phyla, presents a high taxonomic and ecophysiological diversity, reflected by the complex distribution of pigments among the different algal classes. High performance liquid chromatography is the gold standard method for qualitative and quantitative analysis of phytoplankton pigments in seawater and culture samples, but only a few pigments can be used as robust chemotaxonomic markers. A major challenge is thus to identify new ones, characteristic of a strain, species, class or taxon that cannot be currently identified on the basis of its pigment signature. Using an optimized extraction process coupled to a HPLC de-replication strategy, we examined the pigment composition of 37 microalgae strains, representative of the broad taxonomic diversity of marine and freshwater species (excluding cyanobacteria). For each species, the major pigments already described were unambiguously identified. We also observed the presence of several minor unidentified pigments in each chromatogram. The global analysis of pigment compositions revealed a total of 124 pigments, including 98 pigments or derivatives unidentified using the standards. Absorption spectra indicated that 35 corresponded to chlorophyll/porphyrin derivatives, 57 to carotenoids and six to derivatives having both spectral signatures. Sixty-one of these unidentified or new carotenoids and porphyrin derivatives were characteristic of particular strains or species, indicating their possible use as highly specific chemotaxonomic markers capable of identifying one strain out of the 37 selected. We developed a graphical analysis using Gephi software to give a clear representation of pigment communities among the various phytoplankton strains, and to reveal strain-characteristic and shared pigments. This made it possible to reconstruct the taxonomic evolution of microalgae classes, on the basis of the conservation, loss, and/or appearance of pigments.

Temperature is the main abiotic factor that influences the life cycle of poikilotherms. The present study investigated the thermal tolerance and phenotypic plasticity of several parameters (development time, morphometric measures, bioenergetics) for both embryos and fry of a cold stenothermal fish species, brown trout (Salmo trutta L.) in order to allow for a holistic evaluation of the potential effects of temperature. Five temperatures (4°C, 6°C, 8°C, 10°C, and 12°C) were tested, and the effects of temperature were analyzed at three stages: hatching, emergence, and first food intake. A mean of 5,440 (S.E. ± 573) eggs, coming from seven females and seven males (seven families) captured close to Linkebeek (Belgium), were used for each temperature. Maximum survival of well-formed fry at first food intake and better use of energy budget were found at 6°C and 8°C, temperatures at which the possible contribution to the next generation should therefore be greatest. At 12°C, the experimental population fell dramatically (0.9% survival rate for well-formed fry at first food intake), and fry had almost no yolk sac at first food intake. The present results on survival at 12°C are in accordance with predictions of a sharp decrease in brown trout numbers in France over the coming decades according to climate change projections (1°C to 5°C temperature rise by 2100 for France). At 10°C, there was also a lower survival rate (55.4% at first food intake). At 4°C, the survival rate was high (76.4% at first food intake), but the deformity rate was much higher (22% at first food intake) than at 6°C, 8°C, and 10°C. The energetic budget showed that at the two extreme temperatures (4°C and 12°C) there was less energy left in the yolk sac at first food intake, suggesting a limited ability to survive starvation.

Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms.

Randomised controlled trials evaluating perinatal home-visiting programs are frequently confronted with the problem of high attrition rates. The aim of the present study is to identify predictors of study attrition in a trial evaluating a perinatal home-visiting program in France.CAPEDP is a French randomized trial comparing a perinatal home-visiting program using psychologists versus usual care (N = 440). The first assessment was at inclusion into the trial at the 27th week of pregnancy and the final assessment when the child reached the age of two. Attrition rates were calculated at 3 and 24 months postpartum. Stepwise logistic regression was used to identify predictors of early (between inclusion and 3 months postpartum) and later (between 3 and 24 months postpartum) attrition among social, psychological and parenting factors.Attrition rates were 17% and 63% at 3 and 24 months respectively. At 24 months, there was significantly more attrition in the control arm (70.6%) compared to the intervention arm (55.2%). Five independent predictors of early attrition were identified: having already had an abortion; having greater attachment insecurity as measured with the Vulnerable Attachment Style Questionnaire (VASQ); having lower global severity of psychiatric symptoms as assessed with the Symptom Check-List (SCL-90) at inclusion, being neither currently employed nor studying; and declaring no tobacco consumption during pregnancy. Being randomized into the control arm, having undergone early parental loss before age 11 and having lower global severity of psychiatric symptoms (SCL-90) at 3 months postpartum were the only variables associated with later attrition.This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program.

The social valorisation of overweight in African populations could promote high-risk eating behaviours and therefore become a risk factor of obesity. However, existing scales to assess body image are usually not accurate enough to allow comparative studies of body weight perception in different African populations. This study aimed to develop and validate the Body Size Scale (BSS) to estimate African body weight perception.Anthropometric measures of 80 Cameroonians and 81 Senegalese were used to evaluate three criteria of adiposity: body mass index (BMI), overall percentage of fat, and endomorphy (fat component of the somatotype). To develop the BSS, the participants were photographed in full face and profile positions. Models were selected for their representativeness of the wide variability in adiposity with a progressive increase along the scale. Then, for the validation protocol, participants self-administered the BSS to assess self-perceived current body size (CBS), desired body size (DBS) and provide a "body self-satisfaction index." This protocol included construct validity, test-retest reliability and convergent validity and was carried out with three independent samples of respectively 201, 103 and 1115 Cameroonians.The BSS comprises two sex-specific scales of photos of 9 models each, and ordered by increasing adiposity. Most participants were able to correctly order the BSS by increasing adiposity, using three different words to define body size. Test-retest reliability was consistent in estimating CBS, DBS and the "body self-satisfaction index." The CBS was highly correlated to the objective BMI, and two different indexes assessed with the BSS were consistent with declarations obtained in interviews.The BSS is the first scale with photos of real African models taken in both full face and profile and representing a wide and representative variability in adiposity. The validation protocol proved its reliability for estimating body weight perception in Africans.

Soil invertebrates are known to be much involved in soil behaviour and therefore in the provision of ecosystem services. Functional trait-based approaches are methodologies which can be used to understand soil invertebrates' responses to their environment. They (i) improve the predictions and (ii) are less dependent on space and time. The way traits have been used recently has led to misunderstandings in the integration and interpretation of data. Trait semantics are especially concerned. The aim of this paper is to propose a thesaurus for soil invertebrate trait-based approaches. T-SITA, an Internet platform, is the first initiative to deal with the semantics of traits and ecological preferences for soil invertebrates. It reflects the agreement of a scientific expert community to fix semantic properties (e.g. definition) of approximately 100 traits and ecological preferences. In addition, T-SITA has been successfully linked with a fully operational database of soil invertebrate traits. Such a link enhances data integration and improves the scientific integrity of data.

Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL). Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearson's correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, p = 0.46). Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s) as compared to controls (6.3±0.8 m/s; p = 0.01, after Framingham score adjustment) and correlated with internal carotid wall thickness (p = 0.0017). In multivariable analysis, only systolic blood pressure (p = 0.0005) and cumulative dose of glucocorticoids (p = 0.01) were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy.

It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129). Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.

Chronic myeloid leukemia disease (CML) found effective therapy by treating patients with tyrosine kinase inhibitors (TKI), which suppress the BCR-ABL1 oncogene activity. However, the majority of patients achieving remission with TKI still have molecular evidences of disease persistence. Various mechanisms have been proposed to explain the disease persistence and recurrence. One of the hypotheses is that the primitive leukemic stem cells (LSCs) can survive in the presence of TKI. Understanding the mechanisms leading to TKI resistance of the LSCs in CML is a critical issue but is limited by availability of cells from patients. We generated induced pluripotent stem cells (iPSCs) derived from CD34⁺ blood cells isolated from CML patients (CML-iPSCs) as a model for studying LSCs survival in the presence of TKI and the mechanisms supporting TKI resistance. Interestingly, CML-iPSCs resisted to TKI treatment and their survival did not depend on BCR-ABL1, as for primitive LSCs. Induction of hematopoietic differentiation of CML-iPSC clones was reduced compared to normal clones. Hematopoietic progenitors obtained from iPSCs partially recovered TKI sensitivity. Notably, different CML-iPSCs obtained from the same CML patients were heterogeneous, in terms of BCR-ABL1 level and proliferation. Thus, several clones of CML-iPSCs are a powerful model to decipher all the mechanisms leading to LSC survival following TKI therapy and are a promising tool for testing new therapeutic agents.

Postnatal maternal depression (PND) is a significant risk factor for infant mental health. Although often targeted alongside other factors in perinatal home-visiting programs with vulnerable families, little impact on PND has been observed.This study evaluates the impact on PND symptomatology of a multifocal perinatal home-visiting intervention using psychologists in a sample of women presenting risk factors associated with infant mental health difficulties.440 primiparous women were recruited at their seventh month of pregnancy. All were future first-time mothers, under 26, with at least one of three additional psychosocial risk factors: low educational level, low income, or planning to raise the child without the father. The intervention consisted of intensive multifocal home visits through to the child's second birthday. The control group received care as usual. PND symptomatology was assessed at baseline and three months after birth using the Edinburgh Postnatal Depression Scale (EPDS).At three months postpartum, mean (SD) EPDS scores were 9.4 (5.4) for the control group and 8.6 (5.4) for the intervention group (p = 0.18). The difference between the mean EPDS scores was 0.85 (95% CI: 0.35; 1.34). The intervention group had significantly lower EPDS scores than controls in certain subgroups: women with few depressive symptoms at inclusion (EPDS

Transgenic crops expressing Bacillus thuringiensis (Bt) toxins have been adopted worldwide, notably in developing countries. In spite of their success in controlling target pests while allowing a substantial reduction of insecticide use, the sustainable control of these pest populations is threatened by the evolution of resistance. The implementation of the "high dose/refuge" strategy for managing insect resistance in transgenic crops aims at delaying the evolution of resistance to Bt crops in pest populations by promoting survival of susceptible insects. However, a crucial condition for the "high dose/refuge" strategy to be efficient is that the inheritance of resistance should be functionally recessive. Busseolafusca developed high levels of resistance to the Bt toxin Cry 1Ab expressed in Bt corn in South Africa. To test whether the inheritance of B. fusca resistance to the Bt toxin could be considered recessive we performed controlled crosses with this pest and evaluated its survival on Bt and non-Bt corn. Results show that resistance of B. fusca to Bt corn is dominant, which refutes the hypothesis of recessive inheritance. Survival on Bt corn was not lower than on non-Bt corn for both resistant larvae and the F1 progeny from resistant × susceptible parents. Hence, resistance management strategies of B. fusca to Bt corn must address non-recessive resistance.

Recent studies suggest that early modifications in metabolic pathways and behaviour, leading to energy conservation and reduced linear growth, could represent adaptations to nutritional constraints during foetal life and infancy. Impaired fat oxidation, low resting energy expenditure and reduced physical activity, resulting from these adaptations, could facilitate fat storage and development of overweight in growth-retarded children that consume more energy-dense food. This study aims at assessing whether: (1) dual-burden preschool children (simultaneously stunted and overweight) of Yaounde (Cameroon) have low birth-weight (indicator of foetal undernutrition) and reductions in fat oxidation, resting energy expenditure (REE) and physical activity, (2) fat oxidation, REE and physical activity are associated with foetal growth.162 children (24-72 months) were considered: 22 stunted-overweight (SO), 40 stunted (S), 41 overweight (O), and 59 non stunted-non overweight (NSNO). Nutritional status and body composition were assessed using anthropometry and multifrequency bioimpedance analysis. Fasting respiratory quotient (RQ) and REE were measured by indirect calorimetry. Physical activity was determined using accelerometers, food questionnaires were used for diet assessment and birth-weight was noted. Mean RQs and REE (weight adjusted) did not differ between stunted children (SO and S) and non-stunted children (O and NSNO). SO and S children spent more time in sedentary activities than O children (p = 0.01 and p = 0.02, respectively) and less time in moderate-to-vigorous activities than NSNO children (p = 0.05 and p = 0.04, respectively). SO children's diet was less diverse (p = 0.01) with less animal products (p = 0.006). Multiple linear regressions model revealed that birth-weight is predictive of RQ (β = 0.237, p

The New Zealand Thrush, or Piopio, is an extinct passerine that was endemic to New Zealand. It has often been placed in its own family (Turnagridae), unresolved relative to other passerines, but affinities with thrushes, Australaian magpies, manucodes, whistlers, birds-of-paradise and bowerbirds has been suggested based on morphological data. An affinity with the bowerbirds was also indicated in an early molecular study, but low statistical support make this association uncertain. In this study we use sequence data from three nuclear introns to examine the phylogenetic relationships of the piopios. All three genes independently indicate an oriole (Oriolidae) affinity of the piopios, and the monophyly of the typical orioles (Oriolus), figbirds (Sphecotheres), and the piopios is strongly supported in the Bayesian analysis of the concatenated data set (posterior probability = 1.0). The exact placement of the piopios within Oriolidae is, however, more uncertain but in the combined analysis and in two of the gene trees the piopios are placed basal to the typical orioles while the third gene suggest a sister relationship with the figbirds. This is the first time an oriole affinity has been proposed for the piopios. Divergence time estimates for the orioles suggest that the clade originated ca 20 million years ago, and based on these estimates it is evident that the piopios must have arrived on New Zealand by dispersal across the Tasman Sea and not as a result of vicariance when New Zealand separated from Gondwana in the late Cretaceous.

To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire.We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16).cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs.

BackgroundEvolutionary theories that account for the unusual socio-ecological traits and life history features of group-living prosimians, compared with other primates, predict behavioral and physiological mechanisms to conserve energy. Low energy output and possible fattening mechanisms are expected, as either an adaptive response to drastic seasonal fluctuations of food supplies in Madagascar, or persisting traits from previously nocturnal hypometabolic ancestors. Free ranging ring-tailed lemurs (Lemur catta) and brown lemurs (Eulemur sp.) of southern Madagascar have different socio-ecological characteristics which allow a test of these theories: Both gregarious primates have a phytophagous diet but different circadian activity rhythms, degree of arboreality, social systems, and slightly different body size.Methodology and resultsDaily total energy expenditure and body composition were measured in the field with the doubly labeled water procedure. High body fat content was observed at the end of the rainy season, which supports the notion that individuals need to attain a sufficient physical condition prior to the long dry season. However, ring-tailed lemurs exhibited lower water flux rates and energy expenditure than brown lemurs after controlling for body mass differences. The difference was interpreted to reflect higher efficiency for coping with seasonally low quality foods and water scarcity. Daily energy expenditure of both species was much less than the field metabolic rates predicted by various scaling relationships found across mammals.DiscussionWe argue that low energy output in these species is mainly accounted for by low basal metabolic rate and reflects adaptation to harsh, unpredictable environments. The absence of observed sex differences in body weight, fat content, and daily energy expenditure converge with earlier investigations of physical activity levels in ring-tailed lemurs to suggest the absence of a relationship between energy constraints and the evolution of female dominance over males among lemurs. Nevertheless, additional seasonal data are required to provide a definitive conclusion.

BACKGROUND: The amount of inosine monophosphate dehydrogenase (IMPDH), a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP), is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA) are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA-mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL-overexpressing cells). All tested cells remained sensitive to MPA-mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers. CONCLUSIONS/SIGNIFICANCE: These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells.