Atf6alpha impacts cell number by influencing survival, death and proliferation

BACKGROUND: A growing body of literature suggests the cell-intrinsic activity of Atf6alpha during ER stress responses has implications for tissue cell number during growth and development, as well as in adult biology and tumorigenesis [1]. This concept is important, linking the cellular processes of secretory protein synthesis and endoplasmic reticulum stress response with functional tissue capacity and organ size. However, the field contains conflicting observations, especially notable in secretory cell types like the pancreatic beta cell. SCOPE OF REVIEW: Here we summarize current knowledge of the basic biology of Atf6alpha, along with the pleiotropic roles Atf6alpha plays in cell life and death decisions and possible explanations for conflicting observations. We include studies investigating the roles of Atf6alpha in cell survival, death and proliferation using well-controlled methodology and specific validated outcome measures, with a focus on endocrine and metabolic tissues when information was available. MAJOR CONCLUSIONS: The net outcome of Atf6alpha on cell survival and cell death depends on cell type and growth conditions, the presence and degree of ER stress, and the duration and intensity of Atf6alpha activation. It is unquestioned that Atf6alpha activity influences the cell fate decision between survival and death, although opposite directions of this outcome are reported in different contexts. Atf6alpha can also trigger cell cycle activity to expand tissue cell number through proliferation. Much work remains to be done to clarify the many gaps in understanding in this important emerging field

Outlier mining in high-dimensional data using the Jensen-Shannon divergence and graph structure analysis

Reliable anomaly/outlier detection algorithms have practical applications in many fields. For instance, anomaly detection allows to filter and clean the data used to train machine learning algorithms, improving their performance. However, outlier mining is challenging when the data is high-dimensional, and different approaches have been proposed for different types of data (temporal, spatial, network, etc). Here we propose a methodology to mine outliers in generic datasets in which it is possible to define a meaningful distance between elements of the dataset. The methodology is based on defining a fully connected, undirected graph, where the nodes are the elements of the dataset and the links have weights that are the distances between the nodes. Outlier scores are defined by analyzing the structure of the graph, in particular, by using the Jensen–Shannon (JS) divergence to compare the distributions of weights of different nodes. We demonstrate the method using a publicly available database of credit-card transactions, where some of the transactions are labeled as frauds. We compare with the performance obtained when using Euclidean distances and graph percolation, and show that the JS divergence leads to performance improvement, but increases the computational cost.Peer ReviewedPostprint (published version

Endoplasmic Reticulum Stress Induced Proliferation Remains Intact in Aging Mouse beta-Cells

Aging is associated with loss of proliferation of the insulin-secreting beta-cell, a possible contributing factor to the increased prevalence of type 2 diabetes in the elderly. Our group previously discovered that moderate endoplasmic reticulum (ER) stress occurring during glucose exposure increases the adaptive beta-cell proliferation response. Specifically, the ATF6alpha arm of the tripartite Unfolded Protein Response (UPR) promotes beta-cell replication in glucose excess conditions. We hypothesized that beta-cells from older mice have reduced proliferation due to aberrant UPR signaling or an impaired proliferative response to ER stress or ATF6alpha activation. To investigate, young and old mouse islet cells were exposed to high glucose with low-dose thapsigargin or activation of overexpressed ATF6alpha, and beta-cell proliferation was quantified by BrdU incorporation. UPR pathway activation was compared by qPCR of target genes and semi-quantitative Xbp1 splicing assay. Intriguingly, although old beta-cells had reduced proliferation in high glucose compared to young beta-cells, UPR activation and induction of proliferation in response to low-dose thapsigargin or ATF6alpha activation in high glucose were largely similar between young and old. These results suggest that loss of UPR-led adaptive proliferation does not explain the reduced cell cycle entry in old beta-cells, and raise the exciting possibility that future therapies that engage adaptive UPR could increase beta-cell number through proliferation even in older individuals

Fur Activates the Expression of Salmonella enterica Pathogenicity Island 1 by Directly Interacting with the hilD Operator In Vivo and In Vitro

Previous studies have established that the expression of Salmonella enterica pathogenicity island 1 (SPI1), which is essential for epithelial invasion, is mainly regulated by the HilD protein. The ferric uptake regulator, Fur, in turn modulates the expression of the S. enterica hilD gene, albeit through an unknown mechanism. Here we report that S. enterica Fur, in its metal-bound form, specifically binds to an AT-rich region (BoxA), located upstream of the hilD promoter (PhilD), at position -191 to -163 relative to the hilD transcription start site. Furthermore, in a PhilD variant with mutations in BoxA, PhilD*, Fur·Mn2+ binding is impaired. In vivo experiments using S. enterica strains carrying wild-type PhilD or the mutant variant PhilD* showed that Fur activates hilD expression, while in vitro experiments revealed that the Fur·Mn2+ protein is sufficient to increase hilD transcription. Together, these results present the first evidence that Fur·Mn2+, by binding to the upstream BoxA sequence, directly stimulates the expression of hilD in S. enterica

Financial Education from school age - analysis in small Municipalities in Colombia / Educação financeira desde a idade escolar - análise em pequenos Municípios da Colômbia

Financial education is an aspect that has acquired great importance in the economic development of countries, and its inclusion in basic and secondary education programs can bring benefits to the society and the economy of a country. This being the case, the financial education should not be an option but a necessary condition in the training processes, even more because we are facing generations that think in a different way, whose priorities have changed compared to those of previous generations. The measurement of the level of competences in finance has acquired such importance that different organizations such as S&P or the OECD have developed instruments for this purpose. Colombia shows a low level of development in these measurements, a fact that justifies this research with which it is sought to establish the real level of basic knowledge in finance on the part of students who are about to graduate from high scholl and enroll higher education or be integrated into the labor world, in the municipalities of Chía and Sopó, near Bogotá, capital of Colombia

An integrated gene regulatory network controls stem cell proliferation in teeth.

Epithelial stem cells reside in specific niches that regulate their self-renewal and differentiation, and are responsible for the continuous regeneration of tissues such as hair, skin, and gut. Although the regenerative potential of mammalian teeth is limited, mouse incisors grow continuously throughout life and contain stem cells at their proximal ends in the cervical loops. In the labial cervical loop, the epithelial stem cells proliferate and migrate along the labial surface, differentiating into enamel-forming ameloblasts. In contrast, the lingual cervical loop contains fewer proliferating stem cells, and the lingual incisor surface lacks ameloblasts and enamel. Here we have used a combination of mouse mutant analyses, organ culture experiments, and expression studies to identify the key signaling molecules that regulate stem cell proliferation in the rodent incisor stem cell niche, and to elucidate their role in the generation of the intrinsic asymmetry of the incisors. We show that epithelial stem cell proliferation in the cervical loops is controlled by an integrated gene regulatory network consisting of Activin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Follistatin within the incisor stem cell niche. Mesenchymal FGF3 stimulates epithelial stem cell proliferation, and BMP4 represses Fgf3 expression. In turn, Activin, which is strongly expressed in labial mesenchyme, inhibits the repressive effect of BMP4 and restricts Fgf3 expression to labial dental mesenchyme, resulting in increased stem cell proliferation and a large, labial stem cell niche. Follistatin limits the number of lingual stem cells, further contributing to the characteristic asymmetry of mouse incisors, and on the basis of our findings, we suggest a model in which Follistatin antagonizes the activity of Activin. These results show how the spatially restricted and balanced effects of specific components of a signaling network can regulate stem cell proliferation in the niche and account for asymmetric organogenesis. Subtle variations in this or related regulatory networks may explain the different regenerative capacities of various organs and animal species

Searching for extragalactic sources in the VISTA variables in the VÍa láctea survey

We search for extragalactic sources in the VISTA Variables in the Vía Láctea survey that are hidden by the Galaxy. Herein, we describe our photometric procedure to find and characterize extragalactic objects using a combination of SExtractor and PSFEx. It was applied in two tiles of the survey: d010 and d115, without previous extragalactic IR detections, in order to obtain photometric parameters of the detected sources. The adopted criteria to define extragalactic candidates include CLASS-STAR 0.002 and the colors: 0.5 0.44 mag. We detected 345 and 185 extragalactic candidates in the d010 and d115 tiles, respectively. All of them were visually inspected and confirmed to be galaxies. In general, they are small and more circular objects, due to the near-IR sensitivity to select more compact objects with higher surface brightness. The procedure will be used to identify extragalactic objects in other tiles of the VVV disk, which will allow us to study the distribution of galaxies and filaments hidden by the Milky Way.Fil: Baravalle, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Alonso, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Castellón, José Luis Nilo. Universidad de La Serena; ChileFil: Beamín, Juan C.. Millennium Institute of Astrophysics; Chile. Universidad de Valparaíso; ChileFil: Minniti, Dante. Universidad Andrés Bello; Chile. Millennium Institute of Astrophysics; Chil

The high schools in Colombia and the creation of a convenient environment for organizational change / As escolas secundárias na Colômbia e a criação de um ambiente conveniente para a mudança organizacional

Research on change management and its impact on organizational performance has become a significant factor for the preservation of organizations that operates in markets with high level of uncertainty.  However, change management cannot be considered as an attribute of the organizations by themselves; it is closely related to the management and leadership skills of the chancellor, principal or school directors. Being the high schools, those organizations that must be at the forefront of the training processes; this research aims to establish the perception of the schools’ directors regarding the creation of an environment conducive to organizational change. To do this, a research instrument was applied to 338 schools throughout the country, extracted from a ranking of the best high schools in Colombia, according to the results of the state tests that are performed on their graduates. The main results indicate the use of proactive language, transmit positive energy and demonstration of gratitude are the most frequent skills to lead positive change in Schools. Likewise, assertive communication becomes a skill to improve and develop change processes in those educational institutions

Diffusion capacity of single and interconnected networks

Understanding diffusive processes in networks is a significant challenge in complexity science. Networks possess a diffusive potential that depends on their topological configuration, but diffusion also relies on the process and initial conditions. This article presents Diffusion Capacity, a concept that measures a node’s potential to diffuse information based on a distance distribution that considers both geodesic and weighted shortest paths and dynamical features of the diffusion process. Diffusion Capacity thoroughly describes the role of individual nodes during a diffusion process and can identify structural modifications that may improve diffusion mechanisms. The article defines Diffusion Capacity for interconnected networks and introduces Relative Gain, which compares the performance of a node in a single structure versus an interconnected one. The method applies to a global climate network constructed from surface air temperature data, revealing a significant change in diffusion capacity around the year 2000, suggesting a loss of the planet’s diffusion capacity that could contribute to the emergence of more frequent climatic events.Research partially supported by Brazilian agencies FAPEMIG, CAPES, and CNPq. P.M.P. acknowledges support from the “Paul and Heidi Brown Preeminent Professorship in ISE, University of Florida”, and RSF 14-41- 00039, Humboldt Research Award (Germany) and LATNA, Higher School of Economics, RF. C.M. acknowledges partial support from Spanish MINECO (PID2021-123994NB-C21) and ICREA ACADEMIA. A.D.- G. knowledges support from the Spanish grants PGC2018-094754-BC22 and PID2021-128005NB-C22, funded by MCIN/AEI/ 10.13039/ 501100011033 and “ERDF A way of making Europe”; and from Generalitat de Catalunya (2021SGR00856). M.G.R acknowledges partial support from FUNDEP.Peer ReviewedPostprint (published version

High energy gamma-ray sources in the VVV survey - II. The AGN counterparts

© 2024 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We identified Active Galactic Nuclei (AGN) candidates as counterparts to unidentified gamma-ray sources (UGS) from the Fermi-LAT Fourth Source Catalogue at lower Galactic latitudes. Our methodology is based on the use of near- and mid-infrared photometric data from the VISTA Variables in the Vía Láctea (VVV) and Wide-field Infrared Survey Explorer (WISE) surveys. The AGN candidates associated with the UGS occupy very different regions from the stars and extragalactic sources in the colour space defined by the VVV and WISE infrared colours. We found 27 near-infrared AGN candidates possibly associated with 14 Fermi-LAT sources using the VVV survey. We also found 2 blazar candidates in the regions of 2 Fermi-LAT sources using WISE data. There is no match between VVV and WISE candidates. We have also examined the Ks light curves of the VVV candidates and applied the fractional variability amplitude (σrms) and the slope of variation in the Ks passband to characterise the near-infrared variability. This analysis shows that more than 85 per cent of the candidates have slopes in the Ks passband \gt;10−4 mag/day and present σrms values consistent with a moderate variability. This is in good agreement with typical results seen from type-1 AGN. The combination of YJHKs colours and Ks variability criteria was useful for AGN selection, including its use in identifying counterparts to Fermi γ-ray sources.Peer reviewe