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  • Open Access English
    Authors: 
    Ivano Baronchelli; G. Rodighiero; Harry I. Teplitz; Claudia Scarlata; Alberto Franceschini; S. Berta; Laia Barrufet; Mattia Vaccari; Matteo Bonato; Laure Ciesla; +15 more
    Publisher: HAL CCSD
    Countries: France, Italy, United States
    Project: EC | HELP (607254)

    For a sample of star forming galaxies in the redshift interval 0.15$<$z$<$0.3, we study how both the relative strength of the AGN infra-red emission, compared to that due to the star formation (SF), and the numerical fraction of AGNs, change as a function of the total stellar mass of the hosting galaxy group (M$^{*}_{\mathrm{group}}$), between $10^{10.25}$ and $10^{11.9}$M$_{\odot}$. Using a multi-component SED fitting analysis, we separate the contribution of stars, AGN torus and star formation to the total emission at different wavelengths. This technique is applied to a new multi-wavelength data-set in the SIMES field (23 not redundant photometric bands), spanning the wavelength range from the UV (GALEX) to the far-IR (Herschel) and including crucial AKARI and WISE mid-IR observations (4.5 \mu m$<\lambda<$24 \mu m), where the BH thermal emission is stronger. This new photometric catalog, that includes our best photo-z estimates, is released through the NASA/IPAC Infrared Science Archive (IRSA). Groups are identified through a friends of friends algorithm ($\sim$62% purity, $\sim$51% completeness). We identified a total of 45 galaxies requiring an AGN emission component, 35 of which in groups and 10 in the field. We find BHAR$\propto ($M$^{*}_{\mathrm{group}})^{1.21\pm0.27}$ and (BHAR/SFR)$\propto ($M$^{*}_{\mathrm{group}})^{1.04\pm0.24}$ while, in the same range of M$^{*}_{\mathrm{group}}$, we do not observe any sensible change in the numerical fraction of AGNs. Our results indicate that the nuclear activity (i.e. the BHAR and the BHAR/SFR ratio) is enhanced when galaxies are located in more massive and richer groups. Comment: 31 pages, 23 figures

  • Publication . Article . 2020
    Open Access English
    Authors: 
    Sher Bahadur Poudel; Manisha Dixit; Maria Neginskaya; Karthik Nagaraj; Evgeny Pavlov; Haim Werner; Shoshana Yakar;
    Publisher: MDPI AG

    The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

  • Open Access English
    Authors: 
    Golan Miller; Avital Beery; Prashant Kumar Singh; Fengde Wang; Rotem Zelingher; Etel Motenko; Michal Lieberman-Lazarovich;
    Publisher: Oxford University Press
    Country: France

    Abstract Climate change is causing temperature increment in crop production areas worldwide, generating conditions of heat stress that negatively affect crop productivity. Tomato (Solanum lycopersicum), a major vegetable crop, is highly susceptible to conditions of heat stress. When tomato plants are exposed to ambient day/night temperatures that exceed 32 °C/20 °C, respectively, during the reproductive phase, fruit set and fruit weight are reduced, leading to a significant decrease in yield. Processing tomato cultivars are cultivated in open fields, where environmental conditions are not controlled; therefore, plants are exposed to multiple abiotic stresses, including heat stress. Nonetheless, information on stress response in processing tomatoes is very limited. Understanding the physiological response of modern processing tomato cultivars to heat stress may facilitate the development of thermotolerant cultivars. Here, we compared two tomato processing cultivars, H4107 and H9780, that we found to be constantly differing in yield performance. Using field and temperature-controlled greenhouse experiments, we show that the observed difference in yield is attributed to the occurrence of heat stress conditions. In addition, fruit set and seed production were significantly higher in the thermotolerant cultivar H4107, compared with H9780. Despite the general acceptance of pollen viability as a measure of thermotolerance, there was no difference in the percentage of viable pollen between H4107 and H9780 under either of the conditions tested. In addition to observations of similar pollen germination and bud abscission rates, our results suggest that processing tomato cultivars may present a particular case, in which pollen performance is not determining reproductive thermotolerance. Our results also demonstrate the value of combining controlled and uncontrolled experimental settings, in order to validate and identify heat stress-related responses, thus facilitating the development of thermotolerant processing tomato cultivars. Our paper deals with the response of tomato plants to high temperatures. Tomato is an important crop, and tomato plants are very sensitive to high temperatures. Therefore, the increase in temperatures due to climate change poses a threat to tomato production. We found that a specific tomato cultivar is heat stress-tolerant, with better productivity under high temperatures. Usually, such tolerance is linked with pollen grains viability. Interestingly, in our case, pollen characteristics were eliminated as a causal factor for heat stress tolerance, meaning that other factors are involved. Follow-up studies are performed towards the development of heat-tolerant tomato.

  • Open Access English
    Authors: 
    Omer Edhan; Ziv Hellman; Ilan Nehama;
    Publisher: The Royal Society
    Country: United Kingdom

    AbstractWe consider genotypic convergence of populations and show that under fixed fitness asexual and haploid sexual populations attain monomorphic convergence (even under genetic linkage between loci) to basins of attraction with locally exponential convergence rates; the same convergence obtains in single locus diploid sexual reproduction but to polymorphic populations. Furthermore, we show that there is a unified underlying theory underlying these convergences: all of them can be interpreted as instantiations of players in a potential game implementing a multiplicative weights updating algorithm to converge to equilibrium, making use of the Baum–Eagon Theorem. To analyse varying environments, we introduce the concept of ‘virtual convergence’, under which, even if fixation is not attained, the population nevertheless achieves the fitness growth rate it would have had under convergence to an optimal genotype. Virtual convergence is attained by asexual, haploid sexual, and multi-locus diploid reproducing populations, even if environments vary arbitrarily. We also study conditions for true monomorphic convergence in asexually reproducing populations in varying environments.

  • Open Access English
    Authors: 
    Fred J. Vermolen; R. P. van der Meijden; M. van Es; Amit Gefen; Daphne Weihs;
    Publisher: Springer
    Country: Netherlands

    A phenomenological model is formulated to model the early stages of tumor formation. The model is based on a cell-based formalism, where each cell is represented as a circle or sphere in two-and three dimensional simulations, respectively. The model takes into account constituent cells, such as epithelial cells, tumor cells, and T-cells that chase the tumor cells and engulf them. Fundamental biological processes such as random walk, haptotaxis/chemotaxis, contact mechanics, cell proliferation and death, as well as secretion of chemokines are taken into account. The developed formalism is based on the representation of partial differential equations in terms of fundamental solutions, as well as on stochastic processes and stochastic differential equations. We also take into account the likelihood of seeding of tumors. The model shows the initiation of tumors and allows to study a quantification of the impact of various subprocesses and possibly even of various treatments.

  • Publication . Article . Preprint . 2017
    Open Access English
    Authors: 
    Kyle Kawagoe; Greg Huber; Marc Pradas; Michael Wilkinson; Alain Pumir; Eli Ben-Naim;

    We investigate statistical properties of trails formed by a random process incorporating aggregation, fragmentation, and diffusion. In this stochastic process, which takes place in one spatial dimension, two neighboring trails may combine to form a larger one and also, one trail may split into two. In addition, trails move diffusively. The model is defined by two parameters which quantify the fragmentation rate and the fragment size. In the long-time limit, the system reaches a steady state, and our focus is the limiting distribution of trail weights. We find that the density of trail weight has power-law tail $P(w) \sim w^{-\gamma}$ for small weight $w$. We obtain the exponent $\gamma$ analytically, and find that it varies continuously with the two model parameters. The exponent $\gamma$ can be positive or negative, so that in one range of parameters small-weight tails are abundant, and in the complementary range, they are rare. Comment: 8 pages, 8 figures

  • Open Access English
    Authors: 
    Adam J. Bass; Michael S. Lawrence; Lear E. Brace; Alex H. Ramos; Yotam Drier; Kristian Cibulskis; Carrie Sougnez; Douglas Voet; Gordon Saksena; Andrey Sivachenko; +30 more
    Country: United States

    Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma1 and have surveyed exons of protein-coding genes for mutations in 11 affected individuals2,3. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin4 in colorectal carcinogenesis5,6, the fusion lacks the TCF4 β-catenin–binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.

  • Open Access English
    Authors: 
    Adi Lahiani; Dikla Haham-Geula; David Lankri; Susan Cornell-Kennon; Erik Schaefer; Dmitry Tsvelikhovsky; Philip Lazarovici;
    Publisher: American Chemical Society

    Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathies. In a recent study, we synthesized and established the methylene-cycloalkylacetate (MCAs) pharmacophore as a lead for the development of a neurotropic drug (inducing neurite/axonal outgrowth) using the PC12 neuronal model. In the present study we extended the characterizations of the in vitro neurotropic effect of the derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid (MCA-13) on dorsal root ganglia and spinal cord neuronal cultures and analyzed its safety properties using blood biochemistry and cell counting, acute toxicity evaluation in mice and different in vitro "off-target" pharmacological evaluations. This MCA derivative deserves further preclinical mechanistic pharmacological characterizations including therapeutic efficacy in in vivo animal models of polyneuropathies, toward development of a clinically relevant neurotropic drug.

  • Open Access English
    Authors: 
    Oye Gureje; Bibilola D. Oladeji; Irving Hwang; W. T. Chiu; Ronald C. Kessler; Nancy A. Sampson; Jordi Alonso; Laura Helena Andrade; Annette L. Beautrais; Guilherme Borges; +18 more
    Publisher: Springer Nature
    Countries: Spain, Spain, United States
    Project: NIH | Trauma, Stress, and Menta... (7R01MH059575-08), NIH | Lebanon-Epidemiology: The... (1R03TW006481-01A1), NIH | World Mental Health Conso... (5R13MH066849-03), NIH | CROSS-NATIONAL STUDIES OF... (5R01DA016558-06), NIH | Prevalence of and Risk an... (5R01MH077883-03), NIH | EPIDEMIOLOGY-- NATIONAL C... (3U01MH060220-05S1), NIH | Social Role Disability an... (1R01MH069864-01), NIH | Risk Factors for Psychopa... (3R01MH070884-02S1)

    Previous research suggests that parental psychopathology predicts suicidal behavior among offspring; however, the more fine-grained associations between specific parental disorders and distinct stages of the pathway to suicide are not well understood. We set out to test the hypothesis that parental disorders associated with negative mood would predict offspring suicide ideation, whereas disorders characterized by impulsive aggression (for example, antisocial personality) and anxiety/agitation (for example, panic disorder) would predict which offspring act on their suicide ideation and make a suicide attempt. Data were collected during face-to-face interviews conducted on nationally representative samples (N=55 299; age 18+) from 21 countries around the world. We tested the associations between a range of parental disorders and the onset and persistence over time (that is, time since most recent episode controlling for age of onset and time since onset) of subsequent suicidal behavior (suicide ideation, plans and attempts) among offspring. Analyses tested bivariate and multivariate associations between each parental disorder and distinct forms of suicidal behavior. Results revealed that each parental disorder examined increased the risk of suicide ideation among offspring, parental generalized anxiety and depression emerged as the only predictors of the onset and persistence (respectively) of suicide plans among offspring with ideation, whereas parental antisocial personality and anxiety disorders emerged as the only predictors of the onset and persistence of suicide attempts among ideators. A dose-response relation between parental disorders and respondent risk of suicide ideation and attempt was also found. Parental death by suicide was a particularly strong predictor of persistence of suicide attempts among offspring. These associations remained significant after controlling for comorbidity of parental disorders and for the presence of mental disorders among offspring. These findings should inform future explorations of the mechanisms of intergenerational transmission of suicidal behavior. These activities were supported by the United States National Institute of Mental Health (R01MH070884, R01MH077883), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204-3. The ESEMeD project is funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123), the Piedmont Region (Italy), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP). The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H). The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575). The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the Robert Wood Johnson Foundation (RWJF; Grant 044708).

  • Open Access English
    Authors: 
    M. D. Petrović; Goran Gligorić; Aleksandra Maluckov; Lj. Hadžievski; Boris A. Malomed;
    Country: Serbia
    Project: MESTD | Photonics of micro and na... (45010)

    Existence, stability and dynamics of soliton complexes, centered at the site of a single transverse link connecting two parallel 2D (two-dimensional) lattices, are investigated. The system with the on-site cubic self-focusing nonlinearity is modeled by the pair of discrete nonlinear Schr\"{o}dinger equations linearly coupled at the single site. Symmetric, antisymmetric and asymmetric complexes are constructed by means of the variational approximation (VA) and numerical methods. The VA demonstrates that the antisymmetric soliton complexes exist in the entire parameter space, while the symmetric and asymmetric modes can be found below a critical value of the coupling parameter. Numerical results confirm these predictions. The symmetric complexes are destabilized via a supercritical symmetry-breaking pitchfork bifurcation, which gives rise to stable asymmetric modes. The antisymmetric complexes are subject to oscillatory and exponentially instabilities in narrow parametric regions. In bistability areas, stable antisymmetric solitons coexist with either symmetric or asymmetric ones. Comment: 9 figures

Advanced search in
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arrow_drop_down
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Include:
63,257 Research products, page 1 of 6,326
  • Open Access English
    Authors: 
    Ivano Baronchelli; G. Rodighiero; Harry I. Teplitz; Claudia Scarlata; Alberto Franceschini; S. Berta; Laia Barrufet; Mattia Vaccari; Matteo Bonato; Laure Ciesla; +15 more
    Publisher: HAL CCSD
    Countries: France, Italy, United States
    Project: EC | HELP (607254)

    For a sample of star forming galaxies in the redshift interval 0.15$<$z$<$0.3, we study how both the relative strength of the AGN infra-red emission, compared to that due to the star formation (SF), and the numerical fraction of AGNs, change as a function of the total stellar mass of the hosting galaxy group (M$^{*}_{\mathrm{group}}$), between $10^{10.25}$ and $10^{11.9}$M$_{\odot}$. Using a multi-component SED fitting analysis, we separate the contribution of stars, AGN torus and star formation to the total emission at different wavelengths. This technique is applied to a new multi-wavelength data-set in the SIMES field (23 not redundant photometric bands), spanning the wavelength range from the UV (GALEX) to the far-IR (Herschel) and including crucial AKARI and WISE mid-IR observations (4.5 \mu m$<\lambda<$24 \mu m), where the BH thermal emission is stronger. This new photometric catalog, that includes our best photo-z estimates, is released through the NASA/IPAC Infrared Science Archive (IRSA). Groups are identified through a friends of friends algorithm ($\sim$62% purity, $\sim$51% completeness). We identified a total of 45 galaxies requiring an AGN emission component, 35 of which in groups and 10 in the field. We find BHAR$\propto ($M$^{*}_{\mathrm{group}})^{1.21\pm0.27}$ and (BHAR/SFR)$\propto ($M$^{*}_{\mathrm{group}})^{1.04\pm0.24}$ while, in the same range of M$^{*}_{\mathrm{group}}$, we do not observe any sensible change in the numerical fraction of AGNs. Our results indicate that the nuclear activity (i.e. the BHAR and the BHAR/SFR ratio) is enhanced when galaxies are located in more massive and richer groups. Comment: 31 pages, 23 figures

  • Publication . Article . 2020
    Open Access English
    Authors: 
    Sher Bahadur Poudel; Manisha Dixit; Maria Neginskaya; Karthik Nagaraj; Evgeny Pavlov; Haim Werner; Shoshana Yakar;
    Publisher: MDPI AG

    The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

  • Open Access English
    Authors: 
    Golan Miller; Avital Beery; Prashant Kumar Singh; Fengde Wang; Rotem Zelingher; Etel Motenko; Michal Lieberman-Lazarovich;
    Publisher: Oxford University Press
    Country: France

    Abstract Climate change is causing temperature increment in crop production areas worldwide, generating conditions of heat stress that negatively affect crop productivity. Tomato (Solanum lycopersicum), a major vegetable crop, is highly susceptible to conditions of heat stress. When tomato plants are exposed to ambient day/night temperatures that exceed 32 °C/20 °C, respectively, during the reproductive phase, fruit set and fruit weight are reduced, leading to a significant decrease in yield. Processing tomato cultivars are cultivated in open fields, where environmental conditions are not controlled; therefore, plants are exposed to multiple abiotic stresses, including heat stress. Nonetheless, information on stress response in processing tomatoes is very limited. Understanding the physiological response of modern processing tomato cultivars to heat stress may facilitate the development of thermotolerant cultivars. Here, we compared two tomato processing cultivars, H4107 and H9780, that we found to be constantly differing in yield performance. Using field and temperature-controlled greenhouse experiments, we show that the observed difference in yield is attributed to the occurrence of heat stress conditions. In addition, fruit set and seed production were significantly higher in the thermotolerant cultivar H4107, compared with H9780. Despite the general acceptance of pollen viability as a measure of thermotolerance, there was no difference in the percentage of viable pollen between H4107 and H9780 under either of the conditions tested. In addition to observations of similar pollen germination and bud abscission rates, our results suggest that processing tomato cultivars may present a particular case, in which pollen performance is not determining reproductive thermotolerance. Our results also demonstrate the value of combining controlled and uncontrolled experimental settings, in order to validate and identify heat stress-related responses, thus facilitating the development of thermotolerant processing tomato cultivars. Our paper deals with the response of tomato plants to high temperatures. Tomato is an important crop, and tomato plants are very sensitive to high temperatures. Therefore, the increase in temperatures due to climate change poses a threat to tomato production. We found that a specific tomato cultivar is heat stress-tolerant, with better productivity under high temperatures. Usually, such tolerance is linked with pollen grains viability. Interestingly, in our case, pollen characteristics were eliminated as a causal factor for heat stress tolerance, meaning that other factors are involved. Follow-up studies are performed towards the development of heat-tolerant tomato.

  • Open Access English
    Authors: 
    Omer Edhan; Ziv Hellman; Ilan Nehama;
    Publisher: The Royal Society
    Country: United Kingdom

    AbstractWe consider genotypic convergence of populations and show that under fixed fitness asexual and haploid sexual populations attain monomorphic convergence (even under genetic linkage between loci) to basins of attraction with locally exponential convergence rates; the same convergence obtains in single locus diploid sexual reproduction but to polymorphic populations. Furthermore, we show that there is a unified underlying theory underlying these convergences: all of them can be interpreted as instantiations of players in a potential game implementing a multiplicative weights updating algorithm to converge to equilibrium, making use of the Baum–Eagon Theorem. To analyse varying environments, we introduce the concept of ‘virtual convergence’, under which, even if fixation is not attained, the population nevertheless achieves the fitness growth rate it would have had under convergence to an optimal genotype. Virtual convergence is attained by asexual, haploid sexual, and multi-locus diploid reproducing populations, even if environments vary arbitrarily. We also study conditions for true monomorphic convergence in asexually reproducing populations in varying environments.

  • Open Access English
    Authors: 
    Fred J. Vermolen; R. P. van der Meijden; M. van Es; Amit Gefen; Daphne Weihs;
    Publisher: Springer
    Country: Netherlands

    A phenomenological model is formulated to model the early stages of tumor formation. The model is based on a cell-based formalism, where each cell is represented as a circle or sphere in two-and three dimensional simulations, respectively. The model takes into account constituent cells, such as epithelial cells, tumor cells, and T-cells that chase the tumor cells and engulf them. Fundamental biological processes such as random walk, haptotaxis/chemotaxis, contact mechanics, cell proliferation and death, as well as secretion of chemokines are taken into account. The developed formalism is based on the representation of partial differential equations in terms of fundamental solutions, as well as on stochastic processes and stochastic differential equations. We also take into account the likelihood of seeding of tumors. The model shows the initiation of tumors and allows to study a quantification of the impact of various subprocesses and possibly even of various treatments.

  • Publication . Article . Preprint . 2017
    Open Access English
    Authors: 
    Kyle Kawagoe; Greg Huber; Marc Pradas; Michael Wilkinson; Alain Pumir; Eli Ben-Naim;

    We investigate statistical properties of trails formed by a random process incorporating aggregation, fragmentation, and diffusion. In this stochastic process, which takes place in one spatial dimension, two neighboring trails may combine to form a larger one and also, one trail may split into two. In addition, trails move diffusively. The model is defined by two parameters which quantify the fragmentation rate and the fragment size. In the long-time limit, the system reaches a steady state, and our focus is the limiting distribution of trail weights. We find that the density of trail weight has power-law tail $P(w) \sim w^{-\gamma}$ for small weight $w$. We obtain the exponent $\gamma$ analytically, and find that it varies continuously with the two model parameters. The exponent $\gamma$ can be positive or negative, so that in one range of parameters small-weight tails are abundant, and in the complementary range, they are rare. Comment: 8 pages, 8 figures

  • Open Access English
    Authors: 
    Adam J. Bass; Michael S. Lawrence; Lear E. Brace; Alex H. Ramos; Yotam Drier; Kristian Cibulskis; Carrie Sougnez; Douglas Voet; Gordon Saksena; Andrey Sivachenko; +30 more
    Country: United States

    Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma1 and have surveyed exons of protein-coding genes for mutations in 11 affected individuals2,3. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin4 in colorectal carcinogenesis5,6, the fusion lacks the TCF4 β-catenin–binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.

  • Open Access English
    Authors: 
    Adi Lahiani; Dikla Haham-Geula; David Lankri; Susan Cornell-Kennon; Erik Schaefer; Dmitry Tsvelikhovsky; Philip Lazarovici;
    Publisher: American Chemical Society

    Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathies. In a recent study, we synthesized and established the methylene-cycloalkylacetate (MCAs) pharmacophore as a lead for the development of a neurotropic drug (inducing neurite/axonal outgrowth) using the PC12 neuronal model. In the present study we extended the characterizations of the in vitro neurotropic effect of the derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid (MCA-13) on dorsal root ganglia and spinal cord neuronal cultures and analyzed its safety properties using blood biochemistry and cell counting, acute toxicity evaluation in mice and different in vitro "off-target" pharmacological evaluations. This MCA derivative deserves further preclinical mechanistic pharmacological characterizations including therapeutic efficacy in in vivo animal models of polyneuropathies, toward development of a clinically relevant neurotropic drug.

  • Open Access English
    Authors: 
    Oye Gureje; Bibilola D. Oladeji; Irving Hwang; W. T. Chiu; Ronald C. Kessler; Nancy A. Sampson; Jordi Alonso; Laura Helena Andrade; Annette L. Beautrais; Guilherme Borges; +18 more
    Publisher: Springer Nature
    Countries: Spain, Spain, United States
    Project: NIH | Trauma, Stress, and Menta... (7R01MH059575-08), NIH | Lebanon-Epidemiology: The... (1R03TW006481-01A1), NIH | World Mental Health Conso... (5R13MH066849-03), NIH | CROSS-NATIONAL STUDIES OF... (5R01DA016558-06), NIH | Prevalence of and Risk an... (5R01MH077883-03), NIH | EPIDEMIOLOGY-- NATIONAL C... (3U01MH060220-05S1), NIH | Social Role Disability an... (1R01MH069864-01), NIH | Risk Factors for Psychopa... (3R01MH070884-02S1)

    Previous research suggests that parental psychopathology predicts suicidal behavior among offspring; however, the more fine-grained associations between specific parental disorders and distinct stages of the pathway to suicide are not well understood. We set out to test the hypothesis that parental disorders associated with negative mood would predict offspring suicide ideation, whereas disorders characterized by impulsive aggression (for example, antisocial personality) and anxiety/agitation (for example, panic disorder) would predict which offspring act on their suicide ideation and make a suicide attempt. Data were collected during face-to-face interviews conducted on nationally representative samples (N=55 299; age 18+) from 21 countries around the world. We tested the associations between a range of parental disorders and the onset and persistence over time (that is, time since most recent episode controlling for age of onset and time since onset) of subsequent suicidal behavior (suicide ideation, plans and attempts) among offspring. Analyses tested bivariate and multivariate associations between each parental disorder and distinct forms of suicidal behavior. Results revealed that each parental disorder examined increased the risk of suicide ideation among offspring, parental generalized anxiety and depression emerged as the only predictors of the onset and persistence (respectively) of suicide plans among offspring with ideation, whereas parental antisocial personality and anxiety disorders emerged as the only predictors of the onset and persistence of suicide attempts among ideators. A dose-response relation between parental disorders and respondent risk of suicide ideation and attempt was also found. Parental death by suicide was a particularly strong predictor of persistence of suicide attempts among offspring. These associations remained significant after controlling for comorbidity of parental disorders and for the presence of mental disorders among offspring. These findings should inform future explorations of the mechanisms of intergenerational transmission of suicidal behavior. These activities were supported by the United States National Institute of Mental Health (R01MH070884, R01MH077883), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204-3. The ESEMeD project is funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123), the Piedmont Region (Italy), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP). The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H). The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575). The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the Robert Wood Johnson Foundation (RWJF; Grant 044708).

  • Open Access English
    Authors: 
    M. D. Petrović; Goran Gligorić; Aleksandra Maluckov; Lj. Hadžievski; Boris A. Malomed;
    Country: Serbia
    Project: MESTD | Photonics of micro and na... (45010)

    Existence, stability and dynamics of soliton complexes, centered at the site of a single transverse link connecting two parallel 2D (two-dimensional) lattices, are investigated. The system with the on-site cubic self-focusing nonlinearity is modeled by the pair of discrete nonlinear Schr\"{o}dinger equations linearly coupled at the single site. Symmetric, antisymmetric and asymmetric complexes are constructed by means of the variational approximation (VA) and numerical methods. The VA demonstrates that the antisymmetric soliton complexes exist in the entire parameter space, while the symmetric and asymmetric modes can be found below a critical value of the coupling parameter. Numerical results confirm these predictions. The symmetric complexes are destabilized via a supercritical symmetry-breaking pitchfork bifurcation, which gives rise to stable asymmetric modes. The antisymmetric complexes are subject to oscillatory and exponentially instabilities in narrow parametric regions. In bistability areas, stable antisymmetric solitons coexist with either symmetric or asymmetric ones. Comment: 9 figures

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