Gender discrimination and growth: theory and evidence from India

Gender inequality is an acute and persistent problem, especially in developing countries. This paper argues that gender discrimination is an inefficient practice. We model gender discrimination as the complete exclusion of females from the labor market or as the exclusion of females from managerial positions. The distortions in the allocation of talent between managerial and unskilled positions, and in human capital investment, are analyzed. It is found that both types of discrimination lower economic growth; and that the former also implies a reduction in per capita GDP, while the latter distorts the allocation of talent. Both types of discrimination imply lower female-to-male schooling ratios. We discuss the sustainability of social norms or stigma that can generate discrimination in the form described in this paper. We present evidence based on panel-data regressions across Indian states over 1961-1991 that is consistent with the model¿s predictions

Gender Discrimination and Growth: Theory and Evidence from India

Gender inequality is an acute and persistent problem, especially in developing countries. This paper argues that gender discrimination is an inefficient practice. We model gender discrimination as the complete exclusion of females from the labor market or as the exclusion of females from managerial positions. The distortions in the allocation of talent between managerial and unskilled positions, and in human capital investment, are analyzed. It is found that both types of discrimination lower economic growth; and that the former also implies a reduction in per capita GDP, while the latter distorts the allocation of talent. Both types of discrimination imply lower female-to-male schooling ratios. We discuss the sustainability of social norms or stigma that can generate discrimination in the form described in this paper. We present evidence based on panel-data regressions across Indian states over 1961-1991 that is consistent with the model¿s predictions.Growth, gender discrimination, labor market, allocation of talent, India.

Gender and social norms in economic development.

Gender and social norms in economic development' analyses gender related issues throughout the development process from an economics point of view. Different issues are examined for countries at different stages of the development process. The issues examined here have a gender component and have to do with participation and social norms. In some cases, the motivation for this differential participation or inequality is the focus of the study; in others, we focus on the economic consequences of this differential participation. In the first chapter, we investigate participation in dowry in a very poor area, namely rural Bangladesh. In that chapter we explore the different possible economic motivations for dowries using household survey information from the Matlab area in rural Bangladesh spanning 1930-1996. We find that dowry participation in the area has increased in recent decades. We also find that religion, coupled with social norms, seems to be an important component in explaining the evolution of dowry. In the second chapter we examine the economic consequences of different participation by gender in the labour market in a poor country - India. We develop a model that suggests distortions in the allocation of talent which we then test with aggregate information by sector using panel data from India's states over 1961-1991. Results suggest that even though implications are different by sector, gender inequality in labour participation in several categories hinders development. In the third chapter, we indirectly study participation of women in top level positions, by analising the different hiring by gender in Spanish public exams. The analysis constitutes a relevant randomised experiment with implications for gender parity rules, or gender quotas. We use information about 75,000 candidates to the judiciary over 1995-2004 who were randomly allocated to evaluating committees. Contrary to expectations behind gender parity rules, we find that recruitment committees with a higher share of women hire fewer women than committees with a higher share of men, suggesting that taste discrimination is not behind the low numbers of women in top level positions

Avances en el conocimiento de los mecanismos moleculares que regulan la síntesis y acumulación de carotenoides durante la maduración y conservación de frutos cítricos

El color de los frutos cítricos es un importante atributo de calidad y un factor decisivo en la aceptación por los consumidores. La coloración de los frutos cítricos se debe al contenido y composición en carotenoides, que constituyen una amplia familia de pigmentos isoprenoides con gran importancia nutricional y para la salud, ya que algunos de ellos son los precursores de la vitamina A. Los estudios sobre el contenido y la composición en carotenoides en diferentes especies y variedades de cítricos ha sido objeto de interés en el pasado. Sin embargo, se dispone de escasa información sobre los mecanismos moleculares que controlan la síntesis y acumulación de carotenoides en los frutos cítricos. La comprensión de estos procesos y entender las bases moleculares que determinan la pigmentación característica de los frutos de las diferentes variedades, así como los cambios durante su vida postcosecha, han sido objetivos prioritarios de nuestros proyectos de investigación. Para ello, en nuestro laboratorio hemos aislado cDNAs de longitud completa o parcial de 10 genes implicados en la biosíntesis de carotenoides de frutos cítricos y 3 genes de las etapas tempranas de la síntesis de isoprenoides en plastidios (ruta MEP), que son precursores de los carotenoides, cubriendo así la práctica totalidad de la ruta. Los genes aislados de la biosíntesis de carotenoides corresponden a las etapas tempranas de la ruta (fitoeno sintasa y desaturasa, z-caroteno desaturasa y una oxidasa terminal de plastidios), a la ciclación de licopeno (b- y elicopeno ciclasas), y a la biosíntesis de xantofilas (b- y e- caroteno hidroxilasas y zeaxantina epoxidasa), que son los carotenoides más abundantes en frutos coloreados de naranjas y mandarinas. El análisis de expresión de estos genes en el flavedo y la pulpa de frutos cítricos y su correlación con los cambios cuantitativos y cualitativos en carotenoides nos está permitido establecer las etapas reguladoras limitantes de la biosíntesis de carotenoides, así como identificar nuevos genes de la ruta que codifican enzimas con un papel clave en la composición de carotenoides. En esta comunicación haremos una revisión de los principales avances en estos estudios en los frutos cítricos, con especial atención a la comparación entre frutos de variedades con distinto grado de pigmentación (pomelos blancos y rojos, naranjas y mandarinas), así como a los cambios durante situaciones de interés en la postcosecha de los frutos cítricos, como el tratamiento con etileno o diferentes temperaturas de conservación

Nationwide COVID-19-EII Study: Incidence, Environmental Risk Factors and Long-Term Follow-Up of Patients with Inflammatory Bowel Disease and COVID-19 of the ENEIDA Registry

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

Glycolysis; Melanomas; Targeted therapyGlucólisis; Melanomas; Terapia dirigidaGlucòlisi; Melanomes; Teràpia dirigidaNRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.This work was funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “A way to make Europe”/“Investing in your future”) PI14/0375-Fondos FEDER J.A.R., PI17/00043-Fondos FEDER; J.A.R., PI20/0384-Fondos FEDER; J.A.R., Euronanomed2-ISCIII (AC16/00019)-Fondos FEDER; J.A.R., Asociación Española Contra el Cancer (AECC-GCB15152978SOEN) (supported P.G.M., K.M.); J.A.R., Ramón Areces Foundation (supported K.M. and research); J.A.R. (PI17/00412)-Fondos FEDER; R.B., A.M., A.N.S. We thank A. Zorzano’s laboratory for technical assistance and performance of Seahorse technology

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRAS(Q61)-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRAS(Q61) mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRAS(Q61)-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib. Targeted therapeutic options for NRAS-mutant melanoma are limited. Here, the authors show that under metabolic stress NRAS-mutant melanoma cells activate a BRAF-dependent glycolysis pathway for survival, leading to improve efficacy of sorafenib when combined with glycolysis inhibitors

Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab

Rituximab; Viral reactivation; CD20Rituximab; Reactivació viral; CD20Rituximab; Reactivación viral; CD20The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.This study was supported by the American National Institutes of Health (grant R21AI118411 to M.B.), the Spanish Secretariat of Science and Innovation and FEDER funds (grant SAF2015-67334-R [MINECO/FEDER]), the Spanish "Ministerio de Economia y Competitividad, Instituto de Salud Carlos III" (ISCIII, PI17/01470), GeSIDA and the Spanish AIDS network Red Tematica Cooperativa de Investigacion en SIDA (RD16/0025/0007). M.B. is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). M.G. is supported by the "Pla estrategic de recerca i innovacio en salut" (PERIS), from the Catalan Government

Development of a Novel Anti-CD19 Chimeric Antigen Receptor : A Paradigm for an Affordable CAR T Cell Production at Academic Institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc Il2rd/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients

Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdcscid Il2rdtm1Wjl/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients