Regulation of Sp1 by cell cycle related proteins

Sp1 transcription factor regulates the expression of multiple genes, including the Sp1 gene itself. We analyzed the ability of different cell cycle regulatory proteins to interact with Sp1 and to affect Sp1 promoter activity. Using an antibody array, we observed that CDK4, SKP2, Rad51, BRCA2 and p21 could interact with Sp1 and we confirmed these interactions by co-immunoprecipitation. CDK4, SKP2, Rad51, BRCA2 and p21 also activated the Sp1 promoter. Among the known Sp1-interacting proteins, E2F-DP1, Cyclin D1, Stat3 and Rb activated the Sp1 promoter, whereas p53 and NFκB inhibited it. The proteins that regulated Sp1 gene expression were shown by positive chromatin immunoprecipitation to be bound to the Sp1 promoter. Moreover, SKP2, BRCA2, p21, E2F-DP1, Stat3, Rb, p53 and NFκB had similar effects on an artificial promoter containing only Sp1 binding sites. Transient transfections of CDK4, Rad51, E2F-DP1, p21 and Stat3 increased mRNA expression from the endogenous Sp1 gene in HeLa cells whereas overexpression of NFκB, and p53 decreased Sp1 mRNA levels. p21 expression from a stably integrated inducible promoter in HT1080 cells activated Sp1 expression at the promoter and mRNA levels, but at the same time it decreased Sp1 protein levels due to the activation of Sp1 degradation. The observed multiple effects of cell cycle regulators on Sp1 suggest that Sp1 may be a key mediator of cell cycle associated changes in gene expression

TRIP6 functions in brain ciliogenesis

TRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion compo- nent. Trip6 deletion in the mouse, reported here, reveals a function in the brain: ependymal and choroid plexus epithelial cells are carrying, unexpectedly, fewer and shorter cilia, are poorly differentiated, and the mice develop hydrocephalus. TRIP6 carries numerous protein interaction domains and its functions require homodimerization. Indeed, TRIP6 disruption in vitro (in a choroid plexus epithelial cell line), via RNAi or inhibition of its homodimerization, confirms its function in ciliogenesis. Using super-resolution microscopy, we demonstrate TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localiza- tion along the axoneme, and its co-localization with other cilia components suggest a scaf- fold/co-transporter function for TRIP6 in cilia. Thus, this work uncovers an essential role of a LIM-domain protein assembly factor in mammalian ciliogenesis

Boletín Económico Regional : Costa Caribe, II trimestre de 2022

Atlántico, Bolívar, Cesar, Córdoba, La Guajira, Magdalena, San Andrés y Providencia, Sucre En el segundo trimestre de 2022, la economía de la región Caribe mantuvo su crecimiento anual. Este comportamiento se atribuyó en buena medida a la base comparativa que estuvo marcada por el paro nacional el año anterior. Los resultados más destacados fueron la industria, el comercio interno y externo, la venta de vivienda nueva, el transporte de pasajeros y la actividad agropecuaria, con excepción de la comercialización de ganado vacuno. Por su parte, la tasa de desempleo se redujo de la mano de un aumento en el número de ocupados y una oferta laboral estable; mientras la inflación mantuvo la tendencia alcista iniciada un año atrás

Traducción y análisis traductológico de artículos científicos en alemán

En este trabajo de fin de grado se lleva a cabo la traducción de dos artículos científicos en lengua alemana publicados en el Boletín Epidemiológico (Epidemiologisches Bulletin) del Instituto Robert Koch. Los textos van dirigidos a los profesionales sanitarios y tratan sobre medidas de prevención ante la pandemia de COVID-19. En el primer texto, se comenta el uso de mascarillas en los espacios públicos y en el segundo, los diferentes tipos de desinfectantes para manos. Ambos textos se caracterizan por un lenguaje directo y sin adornos y por el uso de terminología especializada. Mediante el análisis de la traducción de esta tipología textual en alemán, se pretenden mostrar ejemplos de problemas de traducción que pueden surgir durante el proceso de traducción científica del alemán al español y de posibles estrategias para resolverlos.This final degree project focuses on the translation of two scientific articles in German language published in the Epidemiologic Bulletin (Epidemiologisches Bulletin) of the Robert Koch Institute. The texts are aimed at healthcare professionals and address preventive measures against the COVID-19 pandemic. The use of face masks in public spaces is discussed in the first text and the different types of hand disinfectants are summarized in the second. Both texts are characterized by direct and unadorned language and by the use of specialized terminology. By means of analyzing the translation of this textual typology in German, the aim of this project is to show examples of problems that may arise during the process of scientific translation from German to Spanish and of possible strategies to solve them.En aquest treball de fi de grau es duu a terme la traducció de dos articles científics en llengua alemanya publicats en el Butlletí Epidemiològic (Epidemiologisches Bulletin) de l'Institut Robert Koch. Els textos van dirigits als professionals sanitaris i tracten sobre mesures de prevenció davant la pandèmia de COVID-19. En el primer text, es comenta l'ús de màscares en els espais públics i en el segon, els diferents tipus de desinfectants per a mans. Tots dos textos es caracteritzen per un llenguatge directe i sense adorns i per l'ús de terminologia especialitzada. Mitjançant l'anàlisi de la traducció d'aquesta tipologia textual en alemany, es pretenen mostrar exemples de problemes de traducció que poden sorgir durant el procés de traducció científica de l'alemany a l'espanyol i de possibles estratègies per a resoldre'ls

Regulació del promotor de "Sp3"

[cat] Sp1 i Sp3 pertanyen a la família de factors de transcripció Sp que controla la transcripció de gens implicats en gairebé tots els processos cel.lulars. Estudis previs al nostre grup van estudiar la regulació del promotor del gen Sp1 i van demostrar que la transcripció de Sp1 estava regulada principalment de forma positiva per Sp1 i NF-Y, i que Sp3 era capaç de contrarrestar l'activació produïda per Sp1 sobre el seu propi promotor. Donat que la relació Sp1/Sp3 a la cèl·lula és important per a la regulació dels gens diana, en aquest treball ens vam proposar estudiar la regulació del promotor de Sp3. Vam clonar una regió de 546 bp que corresponia al promotor de Sp3 i vam procedir a la seva caracterització. Sp3 presenta múltiples inicis de transcripció localitzats entre les posicions -132 i -70 respecte de l'inici de traducció i la seva màxima activitat promotora es localitza a la regió fins a -281bp respecte de l'inici de traducció. Mitjançant les tècniques de retardament de la movilitat electroforètica (EMSA) i Immunoprecipitació de la Cromatina (ChIP) hem demostrat la unió dels factors Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb i c-Jun al promotor de Sp3. D'altra banda hem estudiat l'efecte de la sobreexpressió i la inhibició d'aquestes proteïnes sobre l'activitat d'aquest promotor utilitzant assajos d'activitat luciferasa, i sobre els nivells endògens de mRNA utilitzant RT-Real Time-PCR. Sp3 activa la transcripció del seu propi promotor. El promotor de Sp3 també és activat de forma més potent per Sp1, Sp3 i NF-Y; tot i que NF-1, c-Myb, B-Myb, c-Jun i c-Fos també poden activar aquest promotor. Un altre fet remarcable és que E2F1 es comporta com a repressor del promotor de Sp3. Tots els resultats observats a nivell de l'activitat del promotor es van confirmar amb la mesura dels nivells endogens de mRNA per Sp3. Addicionalment, s'ha estudiat la interacció de Sp1 amb diferents proteïnes implicades en la regulació del cicle cel·lular i s'ha caracteritzat l'efecte de la seva sobreexpressió sobre l'activitat del promotor de Sp1, ja que està regulat per Sp1. Utilitzant un array d'anticossos, es va fer un cribatge de proteïnes que poguessin interaccionar amb Sp1, i algunes d'elles es van confirmar per co-immunoprecipitació. Això ens va permetre demostrar que Sp1 és capaç d'interaccionar amb CDK4, p21, SKP2 i BRCA2. Posteriorment, vam analitzar l'efecte d'aquestes i altres proteïnes que interaccionen amb Sp1 sobre el promotor de Sp1, i vam observar que el promotor de Sp1 és regulat de forma positiva per la sobreexpressió de CDK4, SKP2, BRCA2, Ciclina D1, E2F1/DP1 i Stat3; mentre que és reprimit per la sobreexpressió de p53 i NFB. Per tal d'analitzar si hi havia una correlació entre els efectes sobre el promotor de Sp1 i una alteració dels nivells endogens de Sp1, vam confirmar tots els efectes observats a nivell de l'activitat del promotor tot emprant la tècnica de RT-Real Time-PCR. A més, els efectes sobre el promotor de Sp1 es produeixen mentre aquestes proteïnes estan unides, directa o indirectament, al promotor tal com van demostrar els assajos de ChIP. També vam estudiar l'efecte de la sobreexpressió d'aquestes proteïnes sobre un promotor que només contenia caixes Sp1 i, en general, vam observar efectes equivalents als observats per al promotor de Sp1. La interacció entre Sp1-p21 va ser objecte d'estudi en més detall i vam determinar que l'expressió de p21 en cèl·lules de fibrosarcoma indueix el promotor de Sp1 així com els nivells de mRNA, però, al mateix temps, indueix la degradació de Sp1. Com a conclusió final, hem vist que el procés de transcripció és un mecanisme molt complex que involucra un gran número de factors de transcripció, així com d'altres proteïnes que puguin interaccionar amb aquests factors.[eng] Sp1 and Sp3 belong to the Sp family of transcription factors that controls transcription of genes involved in almost all processes in the cell. We performed a detailed analysis of the promoter region of the Sp3 transcription factor, including the identification of its transcriptional start sites and the putative binding sites for transcription factors. Multiple transcriptional starts sites were located at position sranging from -70 to -132 relative to the translational start of the gene. We defined the minimal promoter region cooresponding to 281 bp relative to the translational start. Along the promoter sequence we demonstrated the binding of Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb and c-Jun. Moreover, we studied the effect of the overexpression or knocking down of these factors on the Sp3 promoter activity and the endogenous mRNA levels. Sp3 is positively autoregulated and it is also activated by Sp1, NF-Y, Myb, AP-1 and NF-1. On the contrary, Sp3 transcription is repressed by E2F/DP1 overexpression. Additionally, we studied the interaction of Sp1 with other proteins involved in the cell cycle regulation and we characterized the effect the overexpression of these proteins on the Sp1promoter activity, given that this promoter is regulated by Sp1. Sp1 is able to interact with CDK4, p21, SKP2 and BRCA2. The Sp1 promoter is positively regulated by the overexpression of CDK4, SKP2, BRCA2, Ciclina D1, E2F1/DP1 and Stat3 whereas the overepression of p53 and NFB represses the promoter. The effects of all these proteins were also analyzed at the Sp1 mRNA level and by using an artificial promoter containing only Sp1 binding sites. The interaction between Sp1 and p21 was further analyzed and we demonstrated that, in fibrosarcoma cells, p21 induces the Sp1 promoter and its mRNA expression but, at the same time, it induces the degradation of Sp1 protein. The process of transcription is a very complex mechanism that involves a great number of transcription factors and other proteins interacting with these factors

Lysine Acetylation and Deacetylation in Brain Development and Neuropathies

Embryonic development is critical for the final functionality and maintenance of the adult brain. Brain development is tightly regulated by intracellular and extracellular signaling. Lysine acetylation and deacetylation are posttranslational modifications that are able to link extracellular signals to intracellular responses. A wealth of evidence indicates that lysine acetylation and deacetylation are critical for brain development and functionality. Indeed, mutations of the enzymes and cofactors responsible for these processes are often associated with neurodevelopmental and psychiatric disorders. Lysine acetylation and deacetylation are involved in all levels of brain development, starting from neuroprogenitor survival and proliferation, cell fate decisions, neuronal maturation, migration, and synaptogenesis, as well as differentiation and maturation of astrocytes and oligodendrocytes, to the establishment of neuronal circuits. Hence, fluctuations in the balance between lysine acetylation and deacetylation contribute to the final shape and performance of the brain. In this review, we summarize the current basic knowledge on the specific roles of lysine acetyltransferase (KAT) and lysine deacetylase (KDAC) complexes in brain development and the different neurodevelopmental disorders that are associated with dysfunctional lysine (de)acetylation machineries

HAT cofactor TRRAP modulates microtubule dynamics via SP1 signaling to prevent neurodegeneration

Brain homeostasis is regulated by the viability and functionality of neurons. HAT (histone acetyltransferase) and HDAC (histone deacetylase) inhibitors have been applied to treat neurological deficits in humans; yet, the epigenetic regulation in neurodegeneration remains elusive. Mutations of HAT cofactor TRRAP (transformation/transcription domain-associated protein) cause human neuropathies, including psychosis, intellectual disability, autism, and epilepsy, with unknown mechanism. Here we show that Trrap deletion in Purkinje neurons results in neurodegeneration of old mice. Integrated transcriptomics, epigenomics, and proteomics reveal that TRRAP via SP1 conducts a conserved transcriptomic program. TRRAP is required for SP1 binding at the promoter proximity of target genes, especially microtubule dynamics. The ectopic expression of Stathmin3/4 ameliorates defects of TRRAP-deficient neurons, indicating that the microtubule dynamics is particularly vulnerable to the action of SP1 activity. This study unravels a network linking three well-known, but up-to-date unconnected, signaling pathways, namely TRRAP, HAT, and SP1 with microtubule dynamics, in neuroprotection

Study protocol for pragmatic trials of Internet-delivered guided and unguided cognitive behavior therapy for treating depression and anxiety in university students of two Latin American countries: the Yo Puedo Sentirme Bien study

Background: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent among university students and predict impaired college performance and later life role functioning. Yet most students do not receive treatment, especially in low-middle-income countries (LMICs). We aim to evaluate the effects of expanding treatment using scalable and inexpensive Internet-delivered transdiagnostic cognitive behavioral therapy (iCBT) among college students with symptoms of MDD and/or GAD in two LMICs in Latin America (Colombia and Mexico) and to investigate the feasibility of creating a precision treatment rule (PTR) to predict for whom iCBT is most effective. Methods: We will first carry out a multi-site randomized pragmatic clinical trial (N = 1500) of students seeking treatment at student mental health clinics in participating universities or responding to an email offering services. Students on wait lists for clinic services will be randomized to unguided iCBT (33%), guided iCBT (33%), and treatment as usual (TAU) (33%). iCBT will be provided immediately whereas TAU will be whenever a clinic appointment is available. Short-term aggregate effects will be assessed at 90 days and longer-term effects 12 months after randomization. We will use ensemble machine learning to predict heterogeneity of treatment effects of unguided versus guided iCBT versus TAU and develop a precision treatment rule (PTR) to optimize individual student outcome. We will then conduct a second and third trial with separate samples (n = 500 per arm), but with unequal allocation across two arms: 25% will be assigned to the treatment determined to yield optimal outcomes based on the PTR developed in the first trial (PTR for optimal short-term outcomes for Trial 2 and 12-month outcomes for Trial 3), whereas the remaining 75% will be assigned with equal allocation across all three treatment arms. Discussion: By collecting comprehensive baseline characteristics to evaluate heterogeneity of treatment effects, we will provide valuable and innovative information to optimize treatment effects and guide university mental health treatment planning. Such an effort could have enormous public-health implications for the region by increasing the reach of treatment, decreasing unmet need and clinic wait times, and serving as a model of evidence-based intervention planning and implementation. Trial status: IRB Approval of Protocol Version 1.0; June 3, 2020. Recruitment began on March 1, 2021. Recruitment is tentatively scheduled to be completed on May 30, 2024. Trial registration: ClinicalTrials.govNCT04780542. First submission date: February 28, 2021

Predictors of dental visits for routine check-ups and for the resolution of problems among preschool children

OBJECTIVE: To estimate the prevalence of dental visits among preschool children and determine the factors associated with using dental services. METHODS: A cross-sectional study was conducted with 1,129 fi ve-year-old children from the Pelotas Birth Cohort Study in Pelotas (Southern Brazil) 2004, from September 2009 to January 2010. Use of dental services at least once in the child’s life and the reason for the child’s fi rst dental visit were recorded. The categories assigned for the fi rst dental visit were: routine checkup, resolution of a problem, or never saw a dentist. The oral examinations and interviews were performed in the children’s homes. Socioeconomic aspects and independent variables related to the mother and child were analyzed using multivariable logistic regression. RESULTS: The prevalence of dental visits (both categories combined) was 37.0%. The main predictors for a routine visit were higher economic status, mothers with more schooling, and mothers who had received guidance about prevention. Major predictors for a visit because of a problem were having felt pain in the previous six months, mothers with higher education level, and mothers who had received guidance about prevention. Approximately 45.0% of mothers received information about how to prevent cavities, usually from the dentist. Children of mothers who adhered to health programs were more likely to have had a routine dental visit. CONCLUSIONS: The rate of preschool visits to dental services was lower than the rate for medical appointments (childcare). In addition to income and education, maternal behavior plays an important role in routine visits. Pain reported in the last six months and a high number of teeth affected by tooth decay, independent of other factors, were associated with visits for a specific problem. It is important to integrate oral health instruction into maternal and child health programs.Maria Beatriz Junqueira Camargo, Aluísio J D Barros, Paulo Frazão, Alicia Matijasevich, Iná S Santos, Marco Aurélio Peres, Karen Glazer Pere

Laboratorio pedagógico : institución educativa Héctor Abad Gómez, sede Darío Londoño Cardona

En algunos momentos de la cotidianidad laboral, el horizonte de lo que estamos haciendo desaparece por la adversidad que nos toca percibir en las instituciones educativas que están ancladas en un contexto de alta vulnerabilidad social; en estos espacios, la pobreza, la desprotección y la indefensión campean por todas las calles como parte del panorama social. Al llegar a estas instituciones, se pueden ver y escuchar una, dos, tres, cuatro, cinco y más historias, todas en relación con las necesidades de la población escolar