EphrinA4 plays a critical role in α4 and αL mediated survival ofhuman CLL cells during extravasation

A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-α activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of α4 and αL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival

Especies forestales y arbustivas asociadas a Maconellicoccus hirsutus (Green) (Hemiptera: Pseudococcidae) en el norte de Nayarit, México

The presence of pink hibiscus mealybug (PHM), Maconellicoccus hirsutus (Green) (Hemiptera: Pseudococcidae), causes environmental and socioeconomic damage in Nayarit, México. Thispest demands studies in order to help develop a management program that includes the knowledge of their hosts. The objectives of this study were to determine the hosts of this pest, such as trees or shrubs, and to know the levels of infestation on them. In 2009 there were selected and sampled 9235 points that included areas such as marginal, urban, agricultural, forestry and nurseries in seven municipalities of northern Nayarit. Also there 37 species were checked as possible host. The insect was present in 1070 points (11.6%), of them 94% presented an infestation at level one (low), to level two 5.6% (medium), and only 0.4% to level three (high). The most infested areas were the marginal (69.3%) and urban (24.9%); the municipalities with higher infestations were Tuxpan, Ruiz, and Rosamorada with an average of 35.2, 22.3, and 12.4%, respectively. About host plants there were recorded 24 species, included in nine botanical families, predominantly those belonging to the family Leguminosae; five of the identified plant species corresponded to new reports with PHM presence in the world. The most abundant and preferred to PHM were three leguminous species; however, the plant species that was present in all municipalities and predominant was Acacia cochliacantha Schlecht & Cham (30.9% infestation), followed by Mimosa pigra L. (19.3%) and Albizia lebbeck (L.) Benth (14.5%).La presencia de cochinilla rosada del hibisco (CRH), Maconellicoccus hirsutus (Green) (Hemiptera: Pseudococcidae), causa serios daños ecológicos y socioeconómicos en Nayarit, México, por lo que demanda la realización de estudios que contribuyan a establecer un programa de manejo de esta plaga, entre los cuales resalta el conocimiento de sus hospederos. Los objetivos del estudio fueronconocer en que especies forestales y arbustivas del norte del estado se presenta este insecto y cuáles son sus niveles de infestación. Durante 2009 se seleccionaron 9235 puntos de muestreo, incluyendoáreas marginales, urbana, agrícola, forestal y viveros en siete municipios del norte de Nayarit; también se inspeccionaron 37 especies vegetales como posibles hospederos. El insecto estuvo presente en 1070 de los puntos muestreados (11.6%) y de ellos el 94% presentó un nivel de infestación 1 (bajo), para el nivel 2 (medio) 5.6% y para el 3 (alto) sólo el 0.4%. Las áreas que presentaron las mayores infestaciones fueron: las marginales (69.3%) y la urbana (24.9%); los municipios más afectados fueron Tuxpan, Ruíz y Rosamorada, con infestaciones promedio de 35.2, 22.3 y 12.4%, respectivamente. Con respecto a las plantas hospederas se registraron 24 especies, mismas que se encuentran incluidas en nueve familias botánicas, con predominio de las Leguminosae; cinco de las especies identificadas correspondieron anuevos registros como hospederos de CRH en el mundo. Tres leguminosas resultaron ser las más abundantes y también de las más preferidas por CRH, Acacia cochliacantha Schlecht & Cham fue la especie  predominante ya que se encontró en todos los municipios (30.9% de infestación), seguida por Mimosa pigra L. (19.3%) y Albizia lebbeck (L.) Benth (14.5%)

Genetic diversity in Pinus remota (Pinaceae) populations of Northeast Mexico: evidences of historical demographic contraction

Métodos: El estudio se realizó en siete poblaciones representativas de su distribución natural en México, con muestras de acículas de 112 árboles analizadas con cinco microsatélites de núcleo. Los datos se evaluaron con parámetros de la genética de poblaciones y métodos de aproximación Bayesiana. Resultados clave: La heterocigosidad promedio esperada (He=0.557) fue más alta que la observada (Ho=0.375). Las poblaciones no se encuentran en equilibro Hardy-Weinberg, con una endogamia significativa (FIS=0.259) y tamaños efectivos reducidos (Ne entre 375-425); están estructuradas en tres grupos genéticos (FST=0.158), con valores altos del índice Mc (0.186-0.283), sugiriendo eventos de declinamiento demográfico ancestral (entre 11,910 y 23,820 años atrás), asociados con los cambios climáticos del Pleistoceno. Conclusiones: El estudio demuestra que P. remota contiene una variación genética considerable, pero estructurada espacialmente y asociada a cuellos de botella ancestrales. Además, se confirma que P. catarinae es su sinónimo. La especie ha sido capaz de subsistir y adaptarse a condiciones ambientales locales. Con este conocimiento se plantean estrategias para la conservación de las poblaciones remanentes de la especie.Background and Aims: The decrease and fragmentation of populations result in the loss of variation and increase in genetic differentiation. Pinus remota is an arboreal-shrubby species of restricted distribution with scattered and fragmented populations. The objectives of the present study were: to evaluate the levels of genetic variation, inbreeding and the effective size of the populations, to test the hypothesis of the existence of bottlenecks associated with the reduction of the genetic variation of the populations, and to analyze the genetic structure and its association with the geographic distribution of populations. Methods: The study was carried out in seven representative populations of their natural distribution in Mexico, by screening a total of 112 trees with five nuclear microsatellites. The data were evaluated with parameters of population genetics and Bayesian approach methods. Key results: The average expected heterozygosity (He=0.557) was higher than the observed heterozygosity (Ho=0.375). The populations are not in Hardy-Weinberg equilibrium, with significant inbreeding levels (FIS=0.259) and small effective sizes (Ne between 375-425). These are structured in three genetic groups (FST=0.158), with high values of the Mc index (0.186-0.283), suggesting ancestral demographic decline events (between 11,910 to 23,820 years ago), associated with the Pleistocene climate changes. Conclusions: The study showed that P. remota contains a considerable genetic variation, which is spatially structured and associated with ancestral bottlenecks. Moreover, it is confirmed that P. catarinae is its synonym. The species has been able to survive and adapt to local environmental conditions. With this knowledge conservation strategies for the remaining populations of the species are proposed

Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs

BackgroundDiabetes mellitus is characterized by chronic hyperglycemia with loss of β-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce β-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets.Methods and findingsRat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1β, IL1β+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1β and vitamin D in β-cells. These include Ri-lnc1, which is enriched in mature β-cells.ConclusionsOur results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on β-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic β-cells and downregulated by IL1β treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in β-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes

Thermal degradation assessment of Kraft paper in power transformers insulated with natural esters

Kraft paper in combination with dielectric oil is the most common as insulation system used in power transformers. The most used oil in power transformers is mineral oil. However, dielectric oils based on natural esters possess some advantages in comparison with mineral oil such as higher biodegradability, fire safety and availability. Therefore, they might be the most ideal substitute for mineral oil. The introduction of a new material requires the evaluation of its degradation rate because this determines transformers’ life span. In order to assess the performance of new insulating systems based on vegetable oils, simulations to obtain the hot-spot temperatures in power transformers using vegetable oils and controlled laboratory experiments of ageing were carried out. The reason is that hot spot temperature inside windings of the oil-immersed power transformers is one of the main manifestations of the thermal stress which leads to aging of insulation systems.The research leading to these results has received funding from multiple sources during years but we would specifically like to acknowledge the support received in the later stages from the Spanish Plan Estatal de I+D under the grant agreement DPI2013- 43897-P

Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17–44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors

Long-term thermal sensitivity of Earth’s tropical forests

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (−9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth’s climate

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality