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We present the second NuSTAR and XMM-Newton extragalactic survey of the JWST north ecliptic pole (NEP) time-domain field (TDF). The first NuSTAR NEP-TDF survey had 681 ks total exposure time executed in NuSTAR cycle 5 in 2019 and 2020. This second survey, acquired from 2020 to 2022 in cycle 6, adds 880 ks of NuSTAR exposure time. The overall NuSTAR NEP-TDF survey is the most sensitive NuSTAR extragalactic survey to date, and a total of 60 sources were detected above the 95% reliability threshold. We constrain the hard X-ray number counts, $\mathrm{log}N$ – $\mathrm{log}S$ , down to 1.7 × 10 ^−14 erg cm ^−2 s ^−1 at 8–24 keV and detect an excess of hard X-ray sources at the faint end. About 47% of the NuSTAR-detected sources are heavily obscured ( N _H > 10 ^23 cm ^−2 ), and ${18}_{-8}^{+20}$ % of the NuSTAR-detected sources are Compton-thick ( N _H > 10 ^24 cm ^−2 ). These fractions are consistent with those measured in other NuSTAR surveys. Four sources presented >2 σ variability in the 3 yr survey. In addition to NuSTAR, a total of 62 ks of XMM-Newton observations were taken during NuSTAR cycle 6. The XMM-Newton observations provide soft X-ray (0.5–10 keV) coverage in the same field and enable more robust identification of the visible and infrared counterparts of the NuSTAR-detected sources. A total of 286 soft X-ray sources were detected, out of which 214 XMM-Newton sources have secure counterparts from multiwavelength catalogs.

Reconocer el carácter híbrido, complejo y sistémico del agua desde los estudios hidrosociales, implicó entender que esta circula en un proceso continuo entre los diversos actores en diferentes periodos históricos. En la cuenca del río Dagua, las profundas transformaciones que han alterado o modificado naturalmente la dinámica ecológica de la cuenca, están estrechamente vinculadas a la forma de apropiación social que cada uno de los actores que allí confluyen realizan, no solo del agua sino del territorio, creando y recreando territorios hidrosociales. Con una metodología interdisciplinaria y descriptiva, a través del análisis documental y del trabajo etnográfico con talleres, entrevistas semiestructuras y trabajo de campo, se reconoció que la apropiación social del agua está determinada por la cultura, es flexible y depende de cada contexto ontológico, geográfico e histórico, en el que se suscribe. El documento abarca desde el periodo precolombino hasta la actualidad y permitió mostrar que la apropiación social del agua no es excluyente ni en tiempo ni espacio. Puede darse simultáneamente, lo que sugiere que, en algunos momentos históricos, coexiste y puede estar inscrita a sociedades diferentes, con modos de vida y diferentes visiones-nociones y acciones de construir territorios hidrosociales, a lo largo del tiempo.

Our contribution focuses on revisiting the theme of maize and the regenerative traditional agricultural system called milpa (corn-beans-squash) in its cosmogonic, cognitive, and practical context within the Mesoamerican agricultural tradition. The milpa crop fields are seen as a historical and current result of ten thousand years of civilization during which biocultural efforts have been revolving around agriculture. This extensive territory where maize – which today constitutes the staple food in Mexican and Central American kitchens – finds its origin has become a symbolic point of reference, forming the core nucleus of a cosmic matrix. Growing maize has unceasingly sculpted heterogeneous landscapes, providing meaning to the systems of knowledge about non-human living beings and their intricate cycles. The study of a Purhépecha community from Central Mexico, focusing on the study of their way of thinking and knowledge associated with maize cultivation practices, demonstrates the biocultural existence, adaptation, and resilience of this sacred-plant. It also reveals the meanings it acquires within the complex interpretation of its multiple relationships with other life entities within the community’s ontology. Through an ethnoecological approach, this example - along with many others - reveals the inseparable relationships between existing beings from the Mesoamerican world (Kosmos), the cognitive systems that organize reality (Corpus), and practices resulting from a thousand-year-old experience surrounding corn cultivation (Praxis). This active and concentrated biocultural memory belongs to the peoples who are made of maize.

The atoms in molecule theory shows that the spiropentadiene dication has a planar tetracoordinate carbon (ptC) atom stabilized mainly through the bonds and this atom has a negative charge. The bonds to the ptC atom have less covalent character than the central carbon from neutral spiropentadiene. The total positive charge is spread along the structure skeleton. The analysis of the potential energy surface shows that the dication spiropentadiene has a 2.3 kcal/mol activation barrier for ring opening. [ABSTRACT FROM AUTHOR]

A importância da administração de recursos humanos nas organizações é determinada pela necessidade e valor atribuído pelos gestores a essa função. Atualmente se estuda as mesmas políticas e técnicas de recursos humanos que há dez anos, mas com uma nova visão, com gestão estratégica de recursos humanos voltada para práticas e políticas estratégicas atualizadas. Esse trabalho de pesquisa teve como objetivo contextualizar o desenvolvimento de recrutamento e seleção em uma empresa do setor alimentício na região da grande Dourados, MS. A metodologia empregada foi o estudo de caso, usando como instrumentos de pesquisa questionários e entrevistas semiestruturadas. A técnica utilizada para aplicação do questionário foi a escala de Likert, com uma abordagem quantitativa e qualitativa. Foi usada a pesquisa bibliográfica descritiva para o embasamento teórico do estudo. A pesquisa identificou notada relevância em relação ao desenvolvimento das políticas de recrutamento e seleção na empresa, pois o capital humano é o diferencial no processo produtivo. Após a realização de análises, foi possível identificar a visão dos colaboradores do setor de Recursos Humanos, bem como a visão dos supervisores de produção em relação ao desenvolvimento das políticas de Recrutamento e Seleção.

A partir del concepto de paisaje y bajo los enfoques de la geografía cultural y la ecología política se hizo la zonificación participativa de la cuenca del río Huámito, Michoacán, México, a fin de analizar el papel del agua dentro de la cultura local en términos de percepciones, perspectivas, discursos y roles de poder de los diversos grupos sociales locales.Con este ejercicio metodológico se logró una descripción de las complejas relaciones sociales y espacialidades en el uso de los recursos naturales. La geografía cultural y las metodologías de investigación participativa, como enfoques complementarios, fueron herramientas que permitieron realizar una aproximación a la integración conceptual interdisciplinaria con la ecología política.

El objetivo es mostrar una asociación entre las notas propias de un discurso populista típico y los rasgos del perfil psicológico de una población propensa a ser objeto de ese discurso. El discurso es una dimensión decisiva donde se forja el vínculo líder idealizado - Pueblo. Ese vínculo resulta más estructurante para la práctica política y social que las instituciones. El método de trabajo se basa en los tipos ideales de Max Weber no obstante los rasgos descritos del perfil psicológico de la población se apoya en múltiples investigaciones empíricas realizadas en el marco de los Proyectos UBACyT desde 1998 y particularmente desde el 2002 a la fecha.The aim is to show an association between the notes of a populist discourse and the typical features of the psychological profile of a population likely to be the subject of that discourse. The speech is a crucial dimension of the populist regime. The link idealized leader - people became more crucial for the practice of political institutions. The working method is based on the ideal types of Max Weber, however the features described in the psychological profile of the population is based on multiple empirical research carried out under the Project UBACyT since 1998 and in particular since 2002.

Sobre todo desde los trabajos de Daniel Kahneman y Amos Tversky, la psicología económica se consolida como disciplina. Esos autores muestran que la racionalidad económica con frecuencia no se cumple a cabalidad. Resultado de esas constataciones se plantea si dado que el sujeto puede perjudicarse con sus decisiones le corresponde al Estado decidir por él. Esta cuestión acarrea la discusión de si el paternalismo de Estado, aún el blando, no menoscaba la libertad y por ende el desarrollo mismo de un sujeto responsable ¹ . En este trabajo ubicamos algunos ejemplos y los términos de la discusión. En las conclusiones planteamos que es la propia dinámica del mercado, al pasar de una etapa a otra, más que una iniciativa individual, la que corrige esas irracionalidades. Por último analizamos en que condiciones la intervención del Estado no socava la libertad del individuo o incluso puede fortalecer las posibilidades de un sujeto responsable.Behavioral economics has now become a major new field in economic. Daniel Kahneman and Amos Tversky backed up by a large amount of experiments; show that rationality in standard economy is not always accomplished by the decision maker. Due to these experiments the discussion is the following: if the individual can harm himself by making his own decision, then should the State make the decision on what is best for the individual? This subject matter leads to the controversy on paternalism: Does it diminish freedom as a value and so the development of the responsible citizen? In this paper we will set some examples of the discussion currently held in the academic world. Last we will show how the historic market dynamic can modify the irrational behavior. We will also set some precision on when not only the state intervention doesn't diminish freedom but also can enforce the experience of consumption of the responsible citizen.

La adquisición de competencias profesionales es posible si el aprendiz controla su propio proceso. Este artículo muestra las competencias desde un punto de vista metacognitivo aplicado a organizaciones y empresas. También se señalan los pasos a dar en cuanto a definición de necesidades y diseño. Por último se presenta un mapa para la auto-evaluación de competencias metacognitivas en la empresa

En este trabajo se analiza la relación entre: perfil cultural, actitudes políticas y económicas, y comportamiento electoral. Se trabaja con una muestra de 1253 estudiantes de 4 universidades nacionales. Los ítems estudiados fueron: funciones del Estado; evaluación del Gobierno Nacional y de los partidos políticos; importancia asignada al mercado, a la propiedad privada y a las inversiones económicas; intención de voto para las elecciones legislativas del 23/10/05 y razones; actividades culturales realizadas en el tiempo libre. Se analizan los resultados obtenidos y la relación entre perfil cultural e intención de voto.This work analyzed the relationship between: cultural profile, political and economic attitudes, and electoral behaviour, with a sample of 1253 students of 4 national universities. The studied issues were: State functions; National Government and political parties' evaluation; value assigned to the market, to private property and economic investments; vote intention for 10/23/05 legislative elections and reasons; cultural activities carried out during free time. The obtained results and the relationship between cultural profile and vote intention are analyzed.

Se trata de un estudio descriptivo que busca verificar diferencias entre grupos de estudiantes universitarios a partir de una muestra intencional de 1070 sujetos voluntarios. El objetivo era conocer la conceptualización que realizan de la democracia, la evaluación que efectúan del actual funcionamiento de las instituciones cívico-políticas en Argentina y la valoración que presentan del desarrollo individual. Respecto a la calidad actual de la democracia, la mayoría de las respuestas se acercan al polo negativo del continuo de evaluación. Se detectan diferencias en las respuestas en función del tipo de carrera que estudian: presentan una mayor valoración quienes estudian carreras técnico-económicas. Se destaca que los estudiantes de carreras técnico-económicas en general y quienes estudian en universidades privadas presentan una mejor valoración de la iniciativa individual y de la capacitación recibida en sus carreras, así como una percepción más positiva de la relación entre iniciativa privada e interés social.It is a descriptive study that looks forward to verify differences between college students' groups from an intentional sample of 1070 voluntaries. The objective was to know what they understand about democracy, the evaluation they make of the current functioning of the civic-political institutions in Argentina and the valuation they present of the individual development. In relation with the current quality of democracy, most of the answers come closer to the negative pole of the continuous of evaluation. Differences are detected in the answers in function of the career type they study: those studying technician-economic careers present a higher valuation. It is notable that students of technician-economic careers in general and those studying in private universities present a better valuation of the individual initiative and of their careers, as well as a more positive perception of the relationship between private initiative and social interest.

O artigo revela uma maneira de valorizar os conhecimentos milenares sobre a natureza dos povos indígenas e rurais do planeta. Esta valorização se denomina Etnoecologia, nova disciplina híbrida, transdisciplinar e pós-normal. Distinguem-se as duas tradições intelectuais que elaboraram uma compreensão sobre a natureza: a ocidental, forjadora da ciência moderna e a que aglutina diversas formas de compreensão sobre o mundo natural, denominada a experiência tradicional. Assim, é possível distinguir duas ecologias e não só aquela que organiza a ciência moderna e que tornou invisível as ecologias das 7.000 culturas indígenas que resistem à expansão do mundo industrial, e que sustentam os ecossistemas planetários. Torná-las visíveis requer um pensamento crítico que oferece o olhar etnoecológico. Discutem-se os traços principais do conhecimento tradicional. Quem são os sujeitos sociais que o animam. Como se transmite e pratica. Quais são seus resultados simbólicos e práticos. O que nos ensina e como a Etnoecologia revela sua complexidade mediante o estudo do complexo k-c-p, que sintetiza a teorização, representação e produção do mundo sócio-natural dos outros. Este jogo duplo que potencia o diálogo de saberes permite ao etnoecologista analisar o mundo dos outros e oferece seu próprio escrutínio sobre esses mundos. Isso permite reinventar possíveis futuros. Finalmente, discute-se por que a Etnoecologia tem a singular tarefa de decifrar a “memória de nossa espécie”, isto é, a memória bio-cultural, reivindicando e revalorizando a quem a mantêm em vez de aprofundar a crítica sobre o mundo moderno e sua racionalidade intelectual.

El objetivo de este trabajo ha sido indagar sobre la situación laboral y el grado de integración socio-afectiva de la población migratoria latina en la Región de Castilla La Mancha-España en las condiciones de un mundo crecientemente globalizado. Esta investigación se llevó a cabo sobre la base de dos encuestas, utilizando un Diseño Exploratorio. Una, la principal, a los inmigrantes latinoamericanos que viven en municipios de Castilla-La Mancha y la otra, a sus familias residentes en los países de origen - en esta fase sólo con los residentes en Argentina-. Para aplicar el cuestionario a la población inmigrante en Castilla-La Mancha se trabajó con una muestra no probabilística, intencional, de 206 casos. Los resultados muestran que esta población ha obtenido una rápida inserción laboral y sobre esa base ha generado una actitud favorable para con la integración hacia la sociedad receptora y en suma un cierto optimismo para con su proyecto migratorio en ese país.This research was conducted on the basis of two surveys, using an Exploratory Design. One, the main, Latin American immigrants living in towns of Castilla-La Mancha and the other, their families residing in the countries of origin - at this stage only residents in Argentina. To implement the questionnaire to the immigrant population in Castilla-La Mancha was worked with a sample, intentional, with 206 cases. The results show that this population has obtained a rapid entry into the labour market and on that basis has created a favourable attitude towards integration into the host society and a certain amount of optimism for his proposed immigration in this country.

La anomia es un fenómeno que no sólo afecta a la convivencia sino que incide en la calidad de las instituciones y, tal cual lo estudiara el neo-institucionalismo económico, por ende, en las posibilidades del desarrollo económico. Hasta el presente el tratamiento de ese fenómeno proviene, predominantemente, de la vertiente sociológica. En ese sentido, en este trabajo se reconocen aportes de Emile Durkheim y Robert Merton agregando, por la perspicacia de sus observaciones sobre el comportamiento del argentino, precisiones realizadas por Carlos Nino en particular lo que él denominara "anomia boba". Luego, lo que hace al objetivo principal de este trabajo, describimos lo que estimamos es la configuración psicológica básica de una población en que la anomia no es percibida como disvalor.The anomie is a phenomenon which not only affects the living daily but as the quality of institutions and therefore, as is the study of the economic neo-institutionalism, the possibilities of economic development. So far the treatment of this phenomenon comes predominantly from the sociological theory. In this paper we recognize some contributions of Emile Durkheim and Robert Merton adding, by the perspicacity of his comments on the behaviour of the Argentine details by Carlos Nino in particular what he called "anomie boba." Then, what makes the main purpose of this article is to describe what we believe is the basic psychological con- figuration of a population in which the anomie is not perceived as a negative value.

El objetivo principal es analizar las diferencias entre las nociones de sociedad y comunidad y los tipos de sujetos implicados. Se sostiene que existe una cercanía entre la noción de comunidad y el concepto de masa así como una asociación entre la noción de sociedad con la de individuo. Según Weber la diferencia es que en el concepto de sociedad la actitud de los actores se basa en una "compensación de intereses" por motivos racionales; en tanto en la comunidad la actitud se apoya en el "sentimiento subjetivo" de los integrantes de constituir un todo. Para este análisis se toman aportes de pensadores socio-políticos como Durkheim y Kornhauser. Pero sustantivamente para considerar los tipos de sujetos implicados nos apoyamos en los desarrollos que al respecto realizara Sigmund Freud. En particular en lo referente al concepto de masa y al vinculo con el líder. Por ultimo, se muestra como la noción de "comunidad"-tomada como reemplazo de "sociedad"- y el vinculo libidinal líder-masa, son características de los regimenes políticos populistas. Esto es que en el Populismo el sujeto no es propiamente el ciudadano en el sentido dado por Aristóteles.El sujeto en el populismo más bien tiende a ser el de pueblo en el sentido de un comportamiento más cercano a lo definible desde el psicoanálisis como Masa.The aim of this work is to analyze the differences between the notions of community and society, and the type of subject they imply. Relations are established between community and mass, society and individual. According to Weber, the attitudes of the diverse subjects in a society are oriented towards a compensation of interests based on rational motives, whereas in a community, their attitudes rely on the sense of being part of a whole. The social and political theories of authors such as Durkheim and Kornhauser are also relevant to this study, but Freud's theoretical developments constitute the basis for the proposed analysis, especially those related to the concept of mass and its bond to the leader. It is suggested that the features included in the notion of community -as replacement for that of society- and the libidinal bond between leader and mass are characteristic of populist regimes, in which the subject is not the citizen in the classical Aristotelian sense, but rather "the people" displaying behavior close to that characteristic of a mass as defined in psychoanalytic terms.

En este artículo se analiza la medida en que la naturaleza del material audiovisual influye en la estructura del mensaje y el carácter de organizadores previos que tienen los recursos tecnológicos de los mensajes escritos y sus imágenes, planteándose la necesidad de mantener abiertas las líneas de investigación existentes en cuanto a modelos de construcción de programas cognitivos de metacomprensión.

The Caenorhabditis elegans Integrator complex is a set of at least 13 evolutionarily conserved proteins that binds the C-terminal domain of RNA polymerase II to regulate snRNA 3'-end processing and gene expression. Here we show that the Integrator subunit 6 intervenes in the DNA damage response in C. elegans . We find that upon X-ray radiation, INTS-6 is necessary for RAD-51 foci formation. In addition, CDK-1 Tyr-15 phosphorylation depends on the presence of INTS-6 . This work adds a new piece to elucidate the Integrator complex mechanism of action in DNA repair., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Several studies indicate that some cognitive changes occur after COVID-19. Visuospatial alterations have been reported in 24-40 %. These alterations may be useful as early biomarkers of neurodegenerative disease. Thus, we can emphasize the importance of visuospatial processes in cognition through quantitative and qualitative analysis of performance on the Clock Test (CDT) and the Rey-Osterrieth Complex Figure (FCRO). Our objective was to describe the performance of post COVID 19 patients in visuospatial tests, with different degrees of respiratory impairment and to perform a qualitative analysis of the performance to check its relationship with alterations in attention and executive functions. This will allow highlighting the executive component of the performance of the CDT and ROCF and differentiate patients with possible cognitive impairment. 77 patients with SARS-CoV-2 infection were evaluated (3 months post-infection) with a complete neuropsychological battery and MRI. Overall, there is a significant difference between FCRO and CDT, with FCRO having only 9 % change and CDT having 51.9 % change. Regarding the correlations observed between groups (VM Inv, VM non I and non hospitalized) the highest correlations were observed between Boston with FCRO copy (r=0.497; p=0.001) and with FCRO memory (r=0.429; p=0.001). Comparing the performance between groups by severity, significant differences were observed only in the TMT A (13.706 p=0.001) and B (9.583 p=0.008) tests and in the phonological fluency letter A (13.445 p=0.001), we observed that the group of non-hospitalized patients had a better performance. Neuropsychological deficits often have a direct impact on daily life by affecting the ability to learn and adapt. Thus, a useful strategy for the neuropsychological characterization of post-COVID-19 patients is the qualitative analysis of visuospatial abilities in conjunction with executive functions that cannot be analyzed in isolation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

While androgen deprivation therapy (ADT) has been the standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC), recent strategies like intensification of systemic treatment (Rozet et al., 2020) (i.e. adding another treatment to ADT) and radiotherapy have improved overall survival. PROFILE, a national retrospective multicentric real-world study, involved patients with mCSPC recruited by medical oncologists, urologists, and radiation oncologists, and who started treatment between November 2020 and May 2021. Patients by sites were included consecutively. Data were collected from medical records. Primary objectives were to: (1) describe retrospectively the characteristics of whole population of patients with mCSPC as well as subgroups defined by prognostic factors in France at diagnosis; (2) identify current practices for managing mCSPC in a real-life clinical setting. Among the 416 patients with mCSPC included in the PROFILE study, 315 (76%) were synchronous (metastasis at the initial diagnosis) and 101 (24%) were metachronous patients (metastasis diagnosed post-progression). A majority (83% of synchronous and 73% of metachronous patients) received an intensified systemic treatment (ADT plus ARSI [androgen-receptor signaling inhibitors]±chemotherapy±primary tumour radiotherapy±metastasis-directed therapy [MDT]), while only 40% of low-volume patients received prostate radiotherapy. This study depicts the standardization of new therapeutic strategies for patients with mCSPC in France with most of them receiving an intensified treatment, mainly with ADT+ARSI (64% of synchronous intensified patients and 76% of metachronous intensified patients). Most of patients were assessed using conventional imaging (CT scan and/or bone scan). Overall, PROFILE results are in line with French and European guidelines for diagnosis, management, and follow-up of such patients (Rozet et al., 2020; Cornford et al., 2021)., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies evaluating antiangiogenic agents. Few data are available regarding immune checkpoint inhibitors (ICI) in patients with bone metastatic RCC. NIVOREN is a multicentre prospective study in which patients were treated with nivolumab after the failure of antiangiogenic agents. We aim to assess the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients enrolled in the NIVOREN trial., Materials and Methods: All patients with BM at inclusion were included in our study. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE)., Results: Among 720 patients treated with nivolumab, 194 presented BM at inclusion. The median follow-up was 23.9 months. Median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (p = 0.0023). The difference was not statistically significant after adjustment (p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, p = 0.0045), as well as the ORR (14.8% versus 23.3%). SRE occurred for 36% of patients with BM. A post-hoc analysis evaluating the impact of bone-targeting agents (BTA) on SRE incidence showed a significant benefit of BTA on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895])., Conclusion: Nivolumab is associated with shorter PFS, and lower ORR in RCC patients with BM. Our study suggests that BTA in association with immunotherapy decreases the incidence of SRE., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MaudVELEV, Cecile Dalban, Florence Joly, Mathieu Laramas, Berangère Narciso, Jean-François BERDAH, Victoria FERRARI, Quentin Dominique THOMAS, Cecile Mione, Florence Tantot and Sylvie Chabaud have nothing to disclose. Christine Chevreau: consulting or advisory role – BMS; Ipsen; Novartis; Pfizer. Travel, accommodations, and expenses – AstraZeneca, BMS, Pfysez-Ipsen. Gwenaelle Gravis: AstraZeneca (Inst); Bayer (Inst); BMS (Inst); IPSEN (Inst); Janssen (Inst); MSD Oncology (Inst); Pfizer (Inst); Sanofi/Aventis (Inst). Speaker's: Amgen (Inst); Astellas Pharma (Inst); BMS (Inst); Ipsen (Inst); Janssen Oncology (Inst); MSD Oncology (Inst); Sanofi/Aventis (Inst), Research Funding: BMS. Sylvie Negrier: Honoraria: Bristol-Myers Squibb; Ipsen; MSD Oncology; Novartis; Pfizer. Consulting or advisory role – Bristol-Myers Squibb; Ipsen; MSD Oncology; Novartis; Pfizer. Research Funding: IPSEN (Inst); Pfizer (Inst). Travel, accommodations, and expenses – Bristol-Myers Squibb; IPSEN; Novartis; Pfizer. Brigitte Laguerre: Honoraria: Astellas Pharma; AstraZeneca; Ipsen; Ipsen; Ipsen; Janssen-Cilag; MSD Oncology. Travel, accommodations, and expenses – Astellas Pharma; Janssen; Janssen Oncology; Novartis; Pfizer. Marine Gross-Goupil: consulting or advisory role – Amgen; Astellas Medivation; AstraZeneca; Bayer/Onyx; Bristol-Myers Squibb; Ipsen; Janssen-Cilag; MSD Oncology; Pfizer; Roche; Sanofi. Research Funding – AstraZeneca (Inst); AstraZeneca (Inst); BMS (Inst); Ipsen (Inst); Janssen-Cilag (Inst); Merck (Inst); MSD Oncology (Inst); Pfizer (Inst); Roche (Inst). Sylvain Ladoire: Expert testimony – Astellas Pharma; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Lilly; Novartis; Pfizer; Roche; Sanofi. Travel, accommodations, and expenses – Astellas Pharma; AstraZeneca; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Novartis; Pfizer; Sanofi. Delphine Borchiellini has received consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Novartis, Pfizer, and Sanofi; research funding from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Janssen, MSD, and Roche; and travel and accommodations expenses from Bristol-Myers Squibb, Janssen, Pfizer, and Roche. Lionnel Geoffrois: Honoraria: BMS; Ipsen; Merck serono; Pfizer. Consulting or advisory role – Ipsen. Frank Priou: consulting or advisory role – AstraZeneca. Philippe Barthélémy: Honoraria Astellas Pharma; BMS; IPSEN; Janssen-Cilag; Merck KGaA; MSD; Novartis; Pfizer. Consulting or advisory role – Amgen; AstraZeneca; BMS; Eisai; Ipsen; Janssen-Cilag; Merck KGaA; MSD Oncology; Pfizer. Travel, accommodations, and expenses – Astellas Pharma; BMS; IPSEN; Janssen-Cilag; MSD; Pfizer. Antoine Thiery-Vuillemin has received honoraria from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi; research funding from Pfizer; and travel and accommodations expenses from AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Pfizer, and Roche. Hubert Curcio: Honoraria or consultation fees: Bristol Myers Squibb. Stephane Oudard has received honoraria from Astellas Pharma, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD Oncology, Novartis, Pfizer, Roche, Roche, and Sanofi; research funding from Ipsen and Sanofi; and travel and accommodation expenses from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, MSD Oncology, Novartis, Pfizer, and Roche. Bernard Escudier: Honoraria Bristol-Myers Squibb; Ipsen; Oncorena; Pfizer. Consulting or Advisory Role – AVEO; Bristol-Myers Squibb; Ipsen; Oncorena; Pfizer. Research Funding - BMS France (Inst). Travel, accommodations, and expenses - Bristol-Myers Squibb; Ipsen; MSD. Laurence Albiges: consulting or advisory role – Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Corvus Pharmaceuticals (Inst); Exelixis (Inst); Ipsen (Inst); Janssen (Inst); Merck (Inst); MSD (Inst); Novartis (Inst); Peloton therapeutics (Inst); Pfizer (Inst); Roche (Inst). Research Funding – Bristol-Myers Squibb (Inst). Travel, accommodations, and expenses – Bristol-Myers Squibb; MSD. Constance Thibault: consulting or advisory role – Astellas/Agensys; AstraZeneca; Bristol-Myers Squibb; Ipsen; Janssen; Merck; MSD; Pfizer; Sanofi. Travel, accommodations, and expenses - Astellas/Agensys; Janssen; Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The ZFP36 family of RNA-binding proteins acts post-transcriptionally to repress translation and promote RNA decay. Studies of genes and pathways regulated by the ZFP36 family in CD4 + T cells have focussed largely on cytokines, but their impact on metabolic reprogramming and differentiation is unclear. Using CD4 + T cells lacking Zfp36 and Zfp36l1, we combined the quantification of mRNA transcription, stability, abundance and translation with crosslinking immunoprecipitation and metabolic profiling to determine how they regulate T cell metabolism and differentiation. Our results suggest that ZFP36 and ZFP36L1 act directly to limit the expression of genes driving anabolic processes by two distinct routes: by targeting transcription factors and by targeting transcripts encoding rate-limiting enzymes. These enzymes span numerous metabolic pathways including glycolysis, one-carbon metabolism and glutaminolysis. Direct binding and repression of transcripts encoding glutamine transporter SLC38A2 correlated with increased cellular glutamine content in ZFP36/ZFP36L1-deficient T cells. Increased conversion of glutamine to α-ketoglutarate in these cells was consistent with direct binding of ZFP36/ZFP36L1 to Gls (encoding glutaminase) and Glud1 (encoding glutamate dehydrogenase). We propose that ZFP36 and ZFP36L1 as well as glutamine and α-ketoglutarate are limiting factors for the acquisition of the cytotoxic CD4 + T cell fate. Our data implicate ZFP36 and ZFP36L1 in limiting glutamine anaplerosis and differentiation of activated CD4 + T cells, likely mediated by direct binding to transcripts of critical genes that drive these processes., (© 2022. The Author(s).)