Una reflexión sobre el aprendizaje de la matemática fuera del espacio escolar

Desde hace aproximadamente 25 años, los resultados en matemáticas, según la Agencia de la Calidad de la Educación en Chile, confirman la amplia brecha existente entre los estudiantes más favorecidos socioeconómicamente y los menos favorecidos. Lo anterior nos lleva a reflexionar sobre la visión sociopolítica de la enseñanza de la matemática escolar. Algunas premisas que se analizan al respecto son: la matemática como asignatura de la excelencia; la educación matemática como un dispositivo de poder; el sistema escolar como monopolio de la enseñanza de las matemáticas; restarse en el mundo de la matemática; y la matemática necesaria fuera del espacio escolar. El objetivo de este artículo es reflexionar sobre tales premisas, ubicando el escenario chileno en ellas, para entender los mecanismos por los que se reproducen desigualdades desfavorables para los estudiantes más vulnerables de nuestra sociedad y con ello identificar directrices para contribuir con la justicia social desde el ámbito educativo

Generation of new tools to fight/counteract protein aggregation.

Cells need to eliminate unfolded, damaged, or aged protein in order to maintain protein homeostasis, a mechanism known as proteostasis. Whereas molecular chaperones contribute to proteostasis by promoting correct protein folding, the proteasome, and autophagy are the main proteolytic machinery for the selective elimination of these proteins.¹ Mutation in components of these systems or stress situations that overwhelm these proteostasis mechanisms results in the accumulation of damaging protein aggregates that in humans cause neurodegenerative diseases. Furthermore, during aging, there is an overall decrease in the activity of these proteins’ clearance machinery which generates a state of chronic proteostasis stress that eventually leads to cell death.²In this project, we aim to build different genetic tools to assay proteolytic activities in S. pombe cells and determine the relative level of protein aggregation. These tools will allow us to characterize in more detail both, the stress-induced protein aggregations and the activity and relative level of aggregation in different proteasome mutants. In addition, using different molecular biology techniques, we will develop genetic tools to induce proteotoxicity through the expression of human proteins prone to aggregation, and hallmarks of neurodegenerative diseases.Finally, it is known that molecular chaperones prevent protein aggregation by interacting and blocking aggregation-prone domains. In this context, using both, a mutant of the proteasome which accumulates protein aggregates and mimics an aged cell, and some of the tools generated.., we will screen compounds that function as chemical chaperones and decrease proteotoxicity. These chemical chaperones might help to develop new treatments for neurodegenerative diseases and aging.

Effects of the microtubule nucleator Mto1 on chromosomal movement, DNA repair, and sister chromatid cohesion in fission yeast.

Although the function of microtubules (MTs) in chromosomal segregation during mitosis is well characterized, much less is known about the role of MTs in chromosomal functions during interphase. In the fission yeast Schizosaccharomyces pombe, dynamic cytoplasmic MT bundles move chromosomes in an oscillatory manner during interphase via linkages through the nuclear envelope (NE) at the spindle pole body (SPB) and other sites. Mto1 is a cytoplasmic factor that mediates the nucleation and attachment of cytoplasmic MTs to the nucleus. Here, we test the function of these cytoplasmic MTs and Mto1 on DNA repair and recombination during interphase. We find that mto1Δ cells exhibit defects in DNA repair and homologous recombination (HR) and abnormal DNA repair factory dynamics. In these cells, sister chromatids are not properly paired, and binding of Rad21 cohesin subunit along chromosomal arms is reduced. Our findings suggest a model in which cytoplasmic MTs and Mto1 facilitate efficient DNA repair and HR by promoting dynamic chromosomal organization and cohesion in the nucleus.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness BFU2011-15216-E, P09-CTS-4697, and PGC2018-099849-B-100 to R.R.D.; National Institutes of Health (NIH) R01, GM067690, and GM115185 to F.C.; and NIH grants R01-GM085145 and R35-GM126910 to S.J

Regulation of Fission Yeast Morphogenesis by PP2A Activator pta2

Cell polarization is key for the function of most eukaryotic cells, and regulates cell shape, migration and tissue architecture. Fission yeast, Schizosaccharomyces pombe cells are cylindrical and polarize cell growth to one or both cell tips dependent on the cell cycle stage. Whereas microtubule cytoskeleton contributes to the positioning of the growth sites by delivering polarity factors to the cell ends, the Cdc42 GTPase polarizes secretion via actin-dependent delivery and tethering of secretory vesicles to plasma membrane. How growth is restricted to cell tips and how re-initiation of tip growth is regulated in the cell cycle remains poorly understood. In this work we investigated the function of protein phosphatase type 2A (PP2A) in S. pombe morphogenesis by deleting the evolutionary conserved PTPA-type regulatory subunit that we named pta2. pta2-deleted cells showed morphological defects and altered growth pattern. Consistent with this, actin patches and active Cdc42 were mislocalized in the pta2 deletion. These defects were additive to the lack of Cdc42-GAP Rga4. pta2Δ cells show upregulated Cdc42 activity and pta2 interacts genetically with polarisome components Tea1, Tea4 and For3 leading to complete loss of cell polarity and rounded morphology. Thus, regulation of polarity by PP2A requires the polarisome and involves Pta2-dependent control of Cdc42 activity

PDRs4All III: JWST's NIR spectroscopic view of the Orion Bar

(Abridged) We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the HII region to the atomic PDR (crossing the ionisation front (IF)), and the subsequent transition to the molecular PDR (crossing the dissociation front (DF)). We use high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science Program. The NIRSpec data reveal a forest of lines including, but not limited to, HeI, HI, and CI recombination lines, ionic lines, OI and NI fluorescence lines, Aromatic Infrared Bands (AIBs including aromatic CH, aliphatic CH, and their CD counterparts), CO2 ice, pure rotational and ro-vibrational lines from H2, and ro-vibrational lines HD, CO, and CH+, most of them detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. We observe numerous smaller scale structures whose typical size decreases with distance from Ori C and IR lines from CI, if solely arising from radiative recombination and cascade, reveal very high gas temperatures consistent with the hot irradiated surface of small-scale dense clumps deep inside the PDR. The H2 lines reveal multiple, prominent filaments which exhibit different characteristics. This leaves the impression of a "terraced" transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star- and planet formation as well as galaxy evolution.Comment: 52 pages, 30 figures, submitted to A&

Spatiotemporal control of spindle disassembly in fission yeast

Maintenance of genomic stability during cell division is one of the most important cellular tasks, and it critically depends on the faithful replication of the genetic material and its equal partitioning into daughter cells, gametes, or spores in the case of yeasts. Defective mitotic spindle assembly and disassembly both result in changes in cellular ploidy that ultimately impinge proliferation fitness and might increase tumor malignancy. Although a great progress has been made in understanding how spindles are assembled to orchestrate chromosome segregation, much less is known about how they are disassembled once completed their function. Here, we review two recently uncovered mechanisms of spindle disassembly that operate at different stages of the fission yeast life cycle.This work was supported by the grants BFU2015-70604 and PGC2018-099849-B-100 to R.R. Daga, from the Ministerio de Economía y Competitividad of the Spanish Government.Peer reviewe

Reversible protein aggregation as cytoprotective mechanism against heat stress

© The Author(s) 2021.Temperature fluctuation is one of the most frequent threats to which organisms are exposed in nature. The activation of gene expression programs that trigger the transcription of heat stress-protective genes is the main cellular response to resist high temperatures. In addition, reversible accumulation and compartmentalization of thermosensitive proteins in high-order molecular assemblies are emerging as critical mechanisms to ensure cellular protection upon heat stress. Here, we summarize representative examples of membrane-less intracellular bodies formed upon heat stress in yeasts and human cells and highlight how protein aggregation can be turned into a cytoprotective mechanism.This work was supported by the Ministerio de Ciencia, Innovación y Universidades (Grant: PGC2018-099849-B-I00 to R.R. Daga) and Junta de Andalucía-FEDER-UPO (grant: UPO-1264663 to S.S.P.)

El papel de la proteína TRP Alm1 en el mantenimiento de la integridad genómica

Motivación:La envuelta nuclear es la barrera física que separa el núcleo y el citoplasma en las células eucariotas. Ésta se encuentra atravesada por los complejos del poro nuclear (NPCs). Uno de sus dominios fundamentales es la cesta del poro nuclear, formada por proteínas denominadas TPR (Translocated Promoter Region), que se han asociado a diversas funciones. El objetivo de este proyecto es el estudio de los mecanismos de mantenimiento de la integridad del genoma mediado por SUMOilación, utlizando como organismo modelo Schizosaccharomyces pombe, y como proteína de estudio Alm1.Métodos:Análisis del anclaje dinámico de la SUMO-proteasa Ulp1 a la envuelta nuclear. Se utilizarán técnicas de cultivo celular y microscopía de fluorescencia in vivo.Caracterización de los fenotipos asociados a la localización defectuosa de Ulp1 debidos a la ausencia de alm1, empleando técnicas de cultivo celular, análisis de sensibilidad a diferentes compuestos y microscopía de fluorescencia. Complementación de los fenotipos defectuosos de alm1∆ mediante la restauración de los niveles de Ulp1 a la envuelta nuclear, mediante sobre-expresión controlada de Ulp1 y restauración de la localización de Ulp1 mediante un sistema basados en los epítopos GBP-GFP.Análisis bioquímico del patrón de SUMOilación global en un fondo alm1∆ y comparación cuantitativa de los niveles celulares de Ulp1 en un fondo silvestre y en ausencia de alm1, mediante Western BlotResultados:Los resultados obtenidos hasta el momento evidencian que la dinámica de localición de Ulp1 depende del estadio del ciclo celular, localizando Ulp1 en la envuelta nuclear en interfase y en el nucleoplasma en mitosis. También hemos observado que la ausencia de Ulp1 no es indispensable para la viabilidad celular, pero tiene un papel muy importante en el correcta segregación cromosómica y en la organización nuclear. Además, se ha observado que el anclaje artificial de Ulp1 a la envuelta nuclear aumenta la viabilidad de alm1Δ a alta temperatura, pero su crecimiento empeora a baja temperatura.Conclusiones:En conjunto, los datos obtenidos sugieren que la liberación de Ulp1 al nucleoplasma es importante para prevenir las segregaciones asimétricas. Dada la coincidencia de fenotipos que se observan en ausencia de Alm1 y mutantes de SUMOilación, Alm1 podría participar en la localización dependiente de ciclo celular de Ulp1, regulando su anclaje al NPC y contribuyendo al mantenimiento del equilibrio SUMOilación/deSUMOilación

A new role for the nuclear basket network

Our view of the nuclear pore complexes (NPCs) as gateways between the nuclear and cytoplasmic compartments has been largely expanded in recent years. NPCs have now demonstrated roles in genome regulation and maintenance from single cells to multicellular organisms. Both NPC proteins as well as components of the NPC basket act as dynamic scaffolds for silencing factors, and chromatin and cell cycle regulators. Components of the NPC basket also couple mRNA production and export, and prevent the exit of unprocessed mRNAs from the nucleus. Our recent work describes a novel function of the fission yeast nuclear basket component – the translocated promoter region (TPR) nucleoporin Alm1 – in proper localization of the proteasome to the nuclear envelope. Here we discuss how regulation of proteasome localization to the nuclear envelope by Alm1 is key to maintain kinetochores homeostasis and proper chromosome segregation

Alm1p se requiere para la correcta captura de los cromosomas en S. pombe

Resumen del póster presentado al XXXVII Congreso de la Sociedad Española de Genética, celebrado en Torremolinos (Málaga) del 29 de septiembre al 2 de octubre de 2009.Alm1 es una proteína de alto peso molecular que pertenece a la familia de las TPR. La proteínas tipo TPR son proteínas que forman parte del complejo del poro nuclear (NPC) en células eucariotas y cuya estructura terciaria está organizada en regiones tipo >coiled-coil” implicadas, normalmente, en interacción proteína-proteína. Se han descrito distintas funciones de los miembros de esta familia en diversos procesos tales como el mantenimiento del SPB (spindle pole body, o centrosoma), organización de cromatina, retención de mRNA mal procesados, etc. En Schizosaccharomyces pombe existen dos miembros de esta familia; Nup211, que está implicado en el transporte núcleo-citoplasma y Alm1, cuya función no está caracterizada. La deleción de Alm1 (Alm1D) es viable aunque presenta un cierta tasa de muerte celular. Un análisis detallado mediante microscopia nos ha permitido demostrar que Alm1 activa el mecanismo de supervivencia del ensamblaje del huso mitótico (spindle assembly check-point o SAC) presentando un retraso en la transición Metafase-Anafase. En general, este check-point se activa cuando el huso esta mal ensamblado y/o no se ha producido la captura de todos los cinetocoros. Este retraso es dependiente de la proteína quinasa Bub1p. Consistente con esta observacion, la falta de función de alm1 es extremadamente sensible en un fondo genético delecionado en varios componentes clave del SAC, como Mph1, Bub1, Bub3 y Mad2. Para caracterizar si el mecanismo de captura de cromosomas durante mitosis estaba alterado en el cepa Alm1D se marcaron los cinetocoros y los SPB con distintos marcadores y se realizó la filmación de estas células a intervalos de 1 minuto. En estas condiciones, se observó que la segregación de las cromátidas durante mitosis era a menudo asimétrica, produciendose un reparto desigual entre ambas células hijas. Además, en la cepa delecionada para alm1 era muy frecuente la presencia de >lagging chromosomes> o cromosomas retrasados durante la separación del huso durante anafase B. Esto suele ser indicativo de un defecto en la captura de los cromosomas. Alm1-GFP localiza en el complejo del poro nuclear y co-localiza parcialmente con el SPB. Alm1 colocaliza en el poro nuclear con Mad2 durante interfase y es necesario para la correcta localización de este componente del check-point del huso en los NPC durante interfase. Nuestros datos son consistentes con un modelo en el que la falta de función de Alm1 produce defectos estructurales en los SPBs que hacen muy ineficiente la captura de cromosomas. Alternativamente una fracción de Alm1, indetectable con la metodología empleada, podría localizar en los cinetocoros para asistir en la captura de los mismos.Peer Reviewe