Shared apical sorting of anion exchanger isoforms AE2a, AE2b1, and AE2b2 in primary hepatocytes

AE2 (SLC4A2) is the member of the Na(+)-independent anion exchanger (AE) family putatively involved in the secretion of bicarbonate to bile. In humans, three variants of AE2 mRNA have been described: the full-length transcript AE2a (expressed from the upstream promoter in most tissues), and alternative transcripts AE2b(1) and AE2b(2) (driven from alternate promoter sequences in a tissue-restricted manner, mainly in liver and kidney). These transcripts would result in AE protein isoforms with short N-terminal differences. To ascertain their translation, functionality, and membrane sorting, we constructed expression vectors encoding each AE2 isoform fused to GFP at the C-terminus. Transfected HEK293 cells showed expression of functional GFP-tagged AE2 proteins, all three isoforms displaying comparable AE activities. Primary rat hepatocytes transfected with expression vectors and repolarized in a collagen-sandwich configuration showed a microtubule-dependent apical sorting of each AE2 isoform. This shared apical sorting is liver-cell specific, as sorting of AE2 isoforms was basolateral in control experiments on polarized kidney MDCK cells. Hepatocytic apical targeting of AE2 isoforms suggests that they all may participate in the canalicular secretion of bicarbonate to bile

Reducing emergence services arrival time by using vehicular communications and Evolution Strategies

Nowadays, traffic jams in urban areas have become a problem that keeps growing every year since the number of vehicles in our cities is continuously increasing. One of the most common causes producing traffic jams are vehicle accidents. Moreover, the arrival time of the emergency services could be raised due to traffic congestion. Intelligent Transportation Systems (ITS) have a key role in order to reduce or mitigate this problem. In this paper, we propose four different approaches addressing the traffic congestion problem, comparing them to obtain the best solution. Using V2I communications, we are able to accurately estimate the traffic density in a certain area, which represents a key parameter to perform efficient traffic redirection, thereby reducing the emergency services arrival time, and avoiding traffic jams when an accident occurs. Specifically, we propose two approaches based on the Dijkstra algorithm, and two approaches based on Evolution Strategies. Notice that, when an accident occurs, time is a critical issue, and the strategies here proposed contribute to find the optimal solution within a short time period.This work was partially supported by the Ministerio de Ciencia e Innovacion, Spain, under Grant TIN2011-27543-C03-01, as well as by the Fundacion Universitaria Antonio Gargallo, the Obra Social de Ibercaja, under Grant 2013/B010, and by the Government of Aragon and the European Social Fund (T91 Research Group).Barrachina, J.; Garrido, P.; Fogue, M.; Martínez, FJ.; Cano Escribá, JC.; Tavares De Araujo Cesariny Calafate, CM.; Manzoni, P. (2014). Reducing emergence services arrival time by using vehicular communications and Evolution Strategies. Expert Systems with Applications. 41(4):1206-1217. https://doi.org/10.1016/j.eswa.2013.08.004S1206121741

Risk factors for mortality caused by pseudomonas aeruginosa infection in hospitalized patients with oncologic diagnosis in three cities of Colombia

Pseudomonas aeruginosa es una bacteria oportunista Gram negativa particularmente eficiente en la adquisición de mecanismos de resistencia y de alta prevalencia en infecciones nosocomiales en pacientes oncológicos. Objetivo: identificar los factores de riesgo para mortalidad en pacientes oncológicos con aislamiento de P. aeruginosa. Metodología: estudio descriptivo, la población de estudio fueron los casos reportados con aislamiento de P. aeruginosa en el servicio de hospitalización de Oncólogos de Occidente en Pereira, Armenia y Manizales durante el año 2015. Se realizaron análisis univariados y multivariados; la supervivencia se estableció según el método de Kaplan-Meier. Se estableció un valor de p <0.05. Se usó el software STATA. Se tuvo aval de bioética de la Universidad Tecnológica de Pereira. Resultados: se estudió 41 casos confirmados de cultivos positivos de P. aeruginosa. El sexo masculino (46.3%), anemia (46.3%), neutropenia febril (41%), trombocitopenia (29.3%) y haber sido hospitalizado en la unidad de cuidados intensivos (29.3%) fueron asociados estadísticamente con mayor mortalidad (p=0.019); con estos resultados se diseñó una escala de riesgo (alfa de Cronbach =0.72). Los pacientes con cuatro de estas exposiciones mostraron mayor riesgo de mortalidad al egreso hospitalario con una sensibilidad del 68% y especificidad del 90%. La P. aeruginosa presentó resistencia a cefepime (36.6%) y a aztreonam (34.1%), mientras que la letalidad global fue del 26.8%. Conclusión: El sexo masculino, la coexistencia de anemia, trombocitopenia, y neutropenia febril, así como la estancia en la unidad de cuidados intensivos aumentan la mortalidad en los pacientes oncológicos infectados con P. aeruginosa.Pseudomonas aeruginosa is a Gram-negative and rod-shape opportunistic bacterium that is particularly efficient in the acquisition of resistance mechanisms and its high prevalence in nosocomial infections in cancer patients. Objective: To identify risk factors for mortality in cancer patients with P. aeruginosa infection. Methodology: A descriptive study was carried out in patients with P. aeruginosa infection during the hospitalization service of “Oncólogos de Occidente” in Pereira, Armenia and Manizales during 2015. Univariate and multivariate analyzes were performed. The survival analysis was established according to the Kaplan-Meier method. A value of p<0.05 was established for it. The analyses were examined with the STATA software. This study was endorsed by the bioethics committee of the “Universidad Tecnológica de Pereira”. Results: Fourty-one patients with positive culture for P. aeruginosa were studied. Males (46.3%), anemia (46.3%), febrile neutropenia (41%), thrombocytopenia (29.3%) and previous hospitalization in an intensive care unit (29.3%) were associated with higher mortality risk (p = 0.019); a risk scale was designed with these factors (Cronbach´s alpha = 0.72). Patients who presented four of these exposures were at higher risk of mortality with a sensitivity of 68% and specificity of 90% at the moment of discharge. P. aeruginosa showed 36.6% of resistance to cefepime, 34.1% to aztreonam, the mortality rate was 26.8%. Conclusion: Male sex, anemia, thrombocytopenia, febrile neutropenia and previous hospitalization in an intensive care unit increase the mortality rate in patients with cancer who were infected by P. aeruginosa.

Factores de riesgo para mortalidad en la infección por Pseudomonas aeruginosa en pacientes oncológicos hospitalizados en tres ciudades de Colombia

Introduction: Pseudomonas aeruginosa is a Gram-negative and rod-shape opportunistic bacterium that is particularly efficient in the acquisition of resistance mechanisms and its high prevalence in nosocomial infections in cancer patients. Objective: To identify risk factors for mortality in cancer patients with P. aeruginosa infection. Methodology: A descriptive study was carried out in patients with P. aeruginosa infection during the hospitalization service of “Oncólogos de Occidente” in Pereira, Armenia and Manizales during 2015. Univariate and multivariate analyzes were performed. The survival analysis was established according to the Kaplan-Meier method. A value of p<0.05 was established for it. The analyses were examined with the STATA software. This study was endorsed by the bioethics committee of the “Universidad Tecnológica de Pereira”. Results: Fourty-one patients with positive culture for P. aeruginosa were studied. Males (46.3%), anemia (46.3%), febrile neutropenia (41%), thrombocytopenia (29.3%) and previous hospitalization in an intensive care unit (29.3%) were associated with higher mortality risk (p = 0.019); a risk scale was designed with these factors (Cronbach´s alpha = 0.72). Patients who presented four of these exposures were at higher risk of mortality with a sensitivity of 68% and specificity of 90% at the moment of discharge. P. aeruginosa showed 36.6% of resistance to cefepime, 34.1% to aztreonam, the mortality rate was 26.8%. Conclusion: Male sex, anemia, thrombocytopenia, febrile neutropenia and previous hospitalization in an intensive care unit increase the mortality rate in patients with cancer who were infected by P. aeruginosa. Introducción: Pseudomonas aeruginosa es una bacteria oportunista Gram negativa particularmente eficiente en la adquisición de mecanismos de resistencia y de alta prevalencia en infecciones nosocomiales en pacientes oncológicos. Objetivo: identificar los factores de riesgo para mortalidad en pacientes oncológicos con aislamiento de P. aeruginosa. Metodología: estudio descriptivo, la población de estudio fueron los casos reportados con aislamiento de P. aeruginosa en el servicio de hospitalización de Oncólogos de Occidente en Pereira, Armenia y Manizales durante el año 2015. Se realizaron análisis univariados y multivariados; la supervivencia se estableció según el método de Kaplan-Meier. Se estableció un valor de p <0.05. Se usó el software STATA. Se tuvo aval de bioética de la Universidad Tecnológica de Pereira. Resultados: se estudió 41 casos confirmados de cultivos positivos de P. aeruginosa. El sexo masculino (46.3%), anemia (46.3%), neutropenia febril (41%), trombocitopenia (29.3%) y haber sido hospitalizado en la unidad de cuidados intensivos (29.3%) fueron asociados estadísticamente con mayor mortalidad (p=0.019); con estos resultados se diseñó una escala de riesgo (alfa de Cronbach =0.72). Los pacientes con cuatro de estas exposiciones mostraron mayor riesgo de mortalidad al egreso hospitalario con una sensibilidad del 68% y especificidad del 90%. La P. aeruginosa presentó resistencia a cefepime (36.6%) y a aztreonam (34.1%), mientras que la letalidad global fue del 26.8%. Conclusión: El sexo masculino, la coexistencia de anemia, trombocitopenia, y neutropenia febril, así como la estancia en la unidad de cuidados intensivos aumentan la mortalidad en los pacientes oncológicos infectados con P. aeruginosa

Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia

Genomic profiling at diagnosis of B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification and treatment decisions. Patients for which diagnostic screening fails to identify disease defining or risk stratifying lesions are classified as B-other ALL. We screened a cohort of 652 BCP-ALL cases enrolled in UKALL14 to identify and perform whole genome sequencing (WGS) on paired tumor-normal samples. For 52 B-other patients we compared WGS findings to data from clinical and research cytogenetics. WGS identifies a cancer associated event in 51/52 cases, this includes an established subtype defining genetic alteration in 5/52 that were previously missed by standard-of-care genetics. Of the 47 true B-other ALL we identified a recurrent driver in 87% (41). Complex karyotype by cytogenetics emerges as a heterogeneous group, including distinct genetic alterations associated with either favorable (DUX4-r) or poor outcomes (MEF2D-r, IGK::BCL2). For a subset of 31 cases, we integrate findings from RNA-sequencing (RNA-seq) analysis to include fusion gene detection, and classification by gene expression. Compared to RNA-seq, WGS was sufficient to detect and resolve recurrent genetic subtypes, however RNA-seq can provide orthogonal validation of findings. In conclusion, we demonstrate that WGS can identify clinically relevant genetic abnormalities missed by standard-of-care testing and identify leukemia driver events in virtually all cases of B-other ALL

COOL-LAMPS III: Discovery of a 25".9 Separation Quasar Lensed by a Merging Galaxy Cluster

In the third paper from the COOL-LAMPS Collaboration, we report the discovery of COOL J0542-2125, a gravitationally lensed quasar at $z=1.84$, observed as three images due to an intervening massive galaxy cluster at $z=0.61$. The lensed quasar images were identified in a search for lens systems in recent public optical imaging data and have separations on the sky up to 25".9, wider than any previously known lensed quasar. The galaxy cluster acting as a strong lens appears to be in the process of merging, with two sub-clusters separated by $\sim 1$ Mpc in the plane of the sky, and their central galaxies showing a radial velocity difference of $\sim 1000$ km/s. Both cluster cores show strongly lensed images of an assortment of background sources, as does the region between them. A preliminary strong lens model implies masses of $M(<250\ \rm{kpc}) = 1.79^{+0.16} _{-0.01} \times 10^{14} M_{\odot}$and$M(<250\ \rm{kpc}) = 1.48^{+0.04}_{-0.10} \times 10^{14} M_{\odot}$ for the East and West sub-clusters, respectively. This line of sight is also coincident with a ROSAT ALL-sky Survey source, centered between the two confirmed cluster halos reminiscent of other major cluster-scale mergers.Comment: 13 pages, 6 figures. Submitted to Ap

A DIGE study on the effects of salbutamol on the rat muscle proteome - an exemplar of best practice for data sharing in proteomics

BACKGROUND: Proteomic techniques allow researchers to perform detailed analyses of cellular states and many studies are published each year, which highlight large numbers of proteins quantified in different samples. However, currently few data sets make it into public databases with sufficient metadata to allow other groups to verify findings, perform data mining or integrate different data sets. The Proteomics Standards Initiative has released a series of "Minimum Information About a Proteomics Experiment" guideline documents (MIAPE modules) and accompanying data exchange formats. This article focuses on proteomic studies based on gel electrophoresis and demonstrates how the corresponding MIAPE modules can be fulfilled and data deposited in public databases, using a new experimental data set as an example. FINDINGS: We have performed a study of the effects of an anabolic agent (salbutamol) at two different time points on the protein complement of rat skeletal muscle cells, quantified by difference gel electrophoresis. In the DIGE study, a total of 31 non-redundant proteins were identified as being potentially modulated at 24 h post treatment and 110 non redundant proteins at 96 h post-treatment. Several categories of function have been highlighted as strongly enriched, providing candidate proteins for further study. We also use the study as an example of best practice for data deposition. CONCLUSIONS: We have deposited all data sets from this study in public databases for further analysis by the community. We also describe more generally how gel-based protein identification data sets can now be deposited in the PRoteomics IDEntifications database (PRIDE), using a new software tool, the PRIDESpotMapper, which we developed to work in conjunction with the PRIDE Converter application. We also demonstrate how the ProteoRed MIAPE generator tool can be used to create and share a complete and compliant set of MIAPE reports for this experiment and others

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.Peer reviewe