Membrane protein Oca3 is essential to keep structural integrity of mitochondria and endoplasmic reticulum

Mitochondrial function is tightly conserved through evolution since it becomes essential for the fitness of any eukaryotic cell. Defective function of this organelle represents the cellular basis of some severe diseases in humans. Thus, the characterization of genes involved in the correct mitochondrial structure and function is critical to understand and treating these diseases. In our laboratory, using the fission yeast as a model, we are characterising the function of oca3 gene, the ortholog of EMC2 gene in human. This gene is predicted to be a member of the ER membrane protein complex involved in the mitochondrion-endoplasmic reticulum membrane tethering1. We find the protein in the non-aqueous phase in cell extracts and Oca3-mCherry tagging actually decorates most cell membranes. Oca3 over-expression cause lethality2 and the gene deletion becomes cold-sensitive. In both situations aberrant mitochondria aggregations are observed and endoplasmic reticulum seems disorganised. Interestingly, addition of Tween20 restores the viability of oca3 deletion at low temperature. This result suggests that Oca3 may have a role in membrane fluidity homeostasis. In addition to this, we will analyse different gene interaction between some of the EMC complex members to clarify both, the importance of Oca3 for the complex and the importance of the complex itself for the cell

Extending the Schizosaccharomyces pombe molecular genetic toolbox

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Targeted alteration of the genome lies at the heart of the exploitation of S. pombe as a model system. The rate of analysis is often determined by the efficiency with which a target locus can be manipulated. For most loci this is not a problem, however for some loci, such as fin1+, rates of gene targeting below 5% can limit the scope and scale of manipulations that are feasible within a reasonable time frame. We now describe a simple modification of transformation procedure for directing integration of genomic sequences that leads to a 5-fold increase in the transformation efficiency when antibiotic based dominant selection markers are used. We also show that removal of the pku70+ and pku80+ genes, which encode DNA end binding proteins required for the non-homologous end joining DNA repair pathway, increases the efficiency of gene targeting at fin1+ to around 75-80% (a 16-fold increase). We describe how a natMX6/rpl42+ cassette can be used for positive and negative selection for integration at a targeted locus. To facilitate the evaluation of the impact of a series of mutations on the function of a gene of interest we have generated three vector series that rely upon different selectable markers to direct the expression of tagged/untagged molecules from distinct genomic integration sites. pINTL and pINTK vectors use ura4+ selection to direct disruptive integration of leu1+ and lys1+ respectively, while pINTH vectors exploit nourseothricin resistance to detect the targeted disruption of a hygromycin B resistance conferring hphMX6 cassette that has been integrated on chromosome III. Finally, we have generated a series of multi-copy expression vectors that use resistance to nourseothricin or kanamycin/G418 to select for propagation in prototrophic hosts. Collectively these protocol modifications and vectors extend the versatility of this key model system.Swiss National Science Foundation (www.snf.ch). École polytechnique fédérale de Lausanne (www.epfl.ch). Cancer Research UK [CRUK] C147/A6058.Peer Reviewe

Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast

PMCID: PMC3549529.-- et al.Activation of mitosis-promoting factor (MPF) drives mitotic commitment. In human cells active MPF appears first on centrosomes. We show that local activation of MPF on the equivalent organelle of fission yeast, the spindle pole body (SPB), promotes Polo kinase activity at the SPBs long before global MPF activation drives mitotic commitment. Artificially promoting MPF or Polo activity at various locations revealed that this local control of Plo1 activity on G2 phase SPBs dictates the timing of mitotic commitment. Cytokinesis of the rod-shaped fission yeast cell generates a naive, new, cell end. Growth is restricted to the experienced old end until a point in G2 phase called new end take off (NETO) when bipolar growth is triggered. NETO coincided with MPF activation of Plo1 on G2 phase SPBs (ref. 4). Both MPF and Polo activities were required for NETO and both induced NETO when ectopically activated at interphase SPBs. NETO promotion by MPF required polo. Thus, local MPF activation on G2 SPBs directs polo kinase to control at least two distinct and temporally separated, cell-cycle transitions at remote locations.This work was supported by Cancer Research UK (CRUK) grant number C147/A6058. V.S. and A.K. were supported by the Swiss National Science Foundation and EPFL.Peer reviewe

The S. pombe mitotic regulator Cut12 promotes spindle pole body activation and integration into the nuclear envelope

The fission yeast spindle pole body (SPB) comprises a cytoplasmic structure that is separated from an ill-defined nuclear component by the nuclear envelope. Upon mitotic commitment, the nuclear envelope separating these domains disperses as the two SPBs integrate into a hole that forms in the nuclear envelope. The SPB component Cut12 is linked to cell cycle control, as dominant cut12.s11 mutations suppress the mitotic commitment defect of cdc25.22 cells and elevated Cdc25 levels suppress the monopolar spindle phenotype of cut12.1 loss of function mutations. We show that the cut12.1 monopolar phenotype arises from a failure to activate and integrate the new SPB into the nuclear envelope. The activation of the old SPB was frequently delayed, and its integration into the nuclear envelope was defective, resulting in leakage of the nucleoplasm into the cytoplasm through large gaps in the nuclear envelope. We propose that these activation/integration defects arise from a local deficiency in mitosis-promoting factor activation at the new SPB

Open partial nephrectomy in renal cancer: a feasible good standard technique

Recommended by J. Rubio Introduction. Partial nephrectomy (PN) is playing an increasingly important role in localized renal cell carcinoma (RCC) as a true alternative to radical nephrectomy. With the greater experience and expertise of surgical teams, it has become an alternative to radical nephrectomy in young patients when the tumor diameter is 4 cm or less in almost all hospitals since cancer-specific survival outcomes are similar to those obtained with radical nephrectomy

Los órganos de los sentidos y el sistema nervioso en los libros de texto de primaria

Esta investigación se basa en la elaboración de mapas conceptuales para analizar el contenido sobre el sistema nervioso y los órganos del sentido en los libros de texto de primaria de México. El análisis de contenido se basa en la propuesta de Thagard de identificar las relaciones que aparecen en el texto en función de si son de clase, de parte, de ejemplo, de propiedad y de regla. Nuestro análisis pone de manifiesto los puntos débiles y los puntos fuertes de los textos, por ejemplo, permite identificar cuando el modelo aparece con sus regularidades (cosa que permitirá poder transferir la explicación a otro fenómeno) o cuando sólo aparece como descripción. Los resultados permiten manifestar implicaciones relacionadas con el potencial de los análisis de texto para ayudar a los profesores y a los alumnos en la elaboración de explicaciones y argumentaciones científicas

Los órganos de los sentidos y el sistema nervioso en los libros de texto de primaria

Esta investigación se basa en la elaboración de mapas conceptuales para analizar el contenido sobre el sistema nervioso y los órganos del sentido en los libros de texto de primaria de México. El análisis de contenido se basa en la propuesta de Thagard de identificar las relaciones que aparecen en el texto en función de si son de clase, de parte, de ejemplo, de propiedad y de regla. Nuestro análisis pone de manifiesto los puntos débiles y los puntos fuertes de los textos, por ejemplo, permite identificar cuando el modelo aparece con sus regularidades (cosa que permitirá poder transferir la explicación a otro fenómeno) o cuando sólo aparece como descripción. Los resultados permiten manifestar implicaciones relacionadas con el potencial de los análisis de texto para ayudar a los profesores y a los alumnos en la elaboración de explicaciones y argumentaciones científicas

The PAU survey: Ly α intensity mapping forecast

In this work, we explore the application of intensity mapping to detect extended Ly$\alpha$ emission from the IGM via cross-correlation of PAUS images with Ly$\alpha$ forest data from eBOSS and DESI. Seven narrow-band (FWHM=13nm) PAUS filters have been considered, ranging from 455 to 515 nm in steps of 10 nm, which allows the observation of Ly$\alpha$ emission in a range $2.7<z<3.3$. The cross-correlation is simulated first in an area of 100 deg$^2$ (PAUS projected coverage), and second in two hypothetical scenarios: a deeper PAUS (complete up to $i_{\rm AB}<24$ instead of $i_{\rm AB}<23$, observation time x6), and an extended PAUS coverage of 225 deg$^2$ (observation time x2.25). A hydrodynamic simulation of size 400 Mpc/h is used to simulate both extended Ly$\alpha$ emission and absorption, while the foregrounds in PAUS images have been simulated using a lightcone mock catalogue. Using an optimistic estimation of uncorrelated PAUS noise, the total probability of a non-spurious detection is estimated to be 1.8\% and 4.5\% for PAUS-eBOSS and PAUS-DESI , from a run of 1000 simulated cross-correlations with different realisations of instrumental noise and quasar positions. The hypothetical PAUS scenarios increase this probability to 15.3\% (deeper PAUS) and 9.0\% (extended PAUS). With realistic correlated noise directly measured from PAUS images, these probabilities become negligible. Despite these negative results, some evidences suggest that this methodology may be more suitable to broad-band surveys.Comment: 18 pages, 14 figures, 6 tables. Accepted in MNRA

The PAU Survey: Photometric redshifts using transfer learning from simulations

In this paper we introduce the \textsc{Deepz} deep learning photometric redshift (photo-$z$) code. As a test case, we apply the code to the PAU survey (PAUS) data in the COSMOS field. \textsc{Deepz} reduces the $\sigma_{68}$ scatter statistic by 50\% at $i_{\rm AB}=22.5$ compared to existing algorithms. This improvement is achieved through various methods, including transfer learning from simulations where the training set consists of simulations as well as observations, which reduces the need for training data. The redshift probability distribution is estimated with a mixture density network (MDN), which produces accurate redshift distributions. Our code includes an autoencoder to reduce noise and extract features from the galaxy SEDs. It also benefits from combining multiple networks, which lowers the photo-$z$ scatter by 10 percent. Furthermore, training with randomly constructed coadded fluxes adds information about individual exposures, reducing the impact of photometric outliers. In addition to opening up the route for higher redshift precision with narrow bands, these machine learning techniques can also be valuable for broad-band surveys.Comment: Accepted versio

EV-Associated miRNAs from Peritoneal Lavage are a Source of Biomarkers in Endometrial Cancer

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is responsible for more than 89,000 deaths every year. Mortality is associated with presence of poor prognostic factors at diagnosis, i.e., diagnosis at an advanced stage, with a high grade and/or an aggressive histology. Development of novel approaches that would permit us to improve the clinical management of EC patients is an unmet need. In this study, we investigate a novel approach to identify highly sensitive and specific biomarkers of EC using extracellular vesicles (EVs) isolated from the peritoneal lavage of EC patients. EVs of peritoneal lavages of 25 EC patients were isolated and their miRNA content was compared with miRNAs of EVs isolated from the ascitic fluid of 25 control patients. Expression of the EV-associated miRNAs was measured using the Taqman OpenArray technology that allowed us to detect 371 miRNAs. The analysis showed that 114 miRNAs were significantly dysregulated in EC patients, among which eight miRNAs, miRNA-383-5p, miRNA-10b-5p, miRNA-34c-3p, miRNA-449b-5p, miRNA-34c-5p, miRNA-200b-3p, miRNA-2110, and miRNA-34b-3p, demonstrated a classification performance at area under the receiver operating characteristic curve (AUC) values above 0.9. This finding opens an avenue for the use of EV-associated miRNAs of peritoneal lavages as an untapped source of biomarkers for EC