Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts.

BACKGROUND: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. METHODS: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. RESULTS: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. CONCLUSIONS: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.

Visceral adipose of obese mice inhibits endothelial inwardly rectifying K+ channels in a CD36-dependent fashion.

Obesity imposes deficits on adipose tissue and vascular endothelium, yet the role that distinct adipose depots play in mediating endothelial dysfunction in local arteries remains unresolved. We recently showed that obesity impairs endothelial Kir2.1 channels, mediators of nitric oxide production, in arteries of visceral adipose tissue (VAT), while Kir2.1 function in subcutaneous adipose tissue (SAT) endothelium remains intact. Therefore, we determined if VAT versus SAT from lean or diet-induced obese mice affected Kir2.1 channel function in vitro. We found that VAT from obese mice reduces Kir2.1 function without altering channel expression whereas AT from lean mice and SAT from obese mice had no effect on Kir2.1 function as compared to untreated control cells. As Kir2.1 is well known to be inhibited by fatty acid derivatives and obesity is strongly associated with elevated circulating fatty acids, we next tested the role of the fatty acid translocase CD36 in mediating VAT-induced Kir2.1 dysfunction. We found that the downregulation of CD36 restored Kir2.1 currents in endothelial cells exposed to VAT from obese mice. In addition, endothelial cells exposed to VAT from obese mice exhibited a significant increase in CD36-mediated fatty acid uptake. The importance of CD36 in obesity-induced endothelial dysfunction of VAT arteries was further supported in ex vivo pressure myography studies where CD36 ablation rescued the endothelium-dependent response to flow via restoring Kir2.1 and endothelial nitric oxide synthase function. These findings provide new insight into the role of VAT in mediating obesity-induced endothelial dysfunction and suggest a novel role for CD36 as a mediator of endothelial Kir2.1 impairment.NEW & NOTEWORTHY Our findings suggest a role for visceral adipose tissue (VAT) in the dysfunction of endothelial Kir2.1 in obesity. We further reveal a role for CD36 as a major contributor to VAT-mediated Kir2.1 and endothelial dysfunction, suggesting that CD36 offers a potential target for preventing the early development of obesity-associated cardiovascular disease.

The MAPK homolog, Smk1, promotes assembly of the glucan layer of the spore wall in S. cerevisiae.

Smk1 is a MAPK homolog in the yeast Saccharomyces cerevisiae that controls the postmeiotic program of spore wall assembly. During this program, haploid cells are surrounded by a layer of mannan and then a layer of glucan. These inner layers of the spore wall resemble the vegetative cell wall. Next, the outer layers consisting of chitin/chitosan and then dityrosine are assembled. The outer layers are spore-specific and provide protection against environmental stressors. Smk1 is required for the proper assembly of spore walls. However, the protective properties of the outer layers have limited our understanding of how Smk1 controls this morphogenetic program. Mutants lacking the chitin deacetylases, Cda1 and Cda2, form spores that lack the outer layers of the spore wall. In this study, cda1,2∆ cells were used to demonstrate that Smk1 promotes deposition of the glucan layer of the spore wall through the partially redundant glucan synthases Gsc2 and Fks3. Although Gsc2 is localized to sites of spore wall assembly in the wild type, it is mislocalized in the mother cell cytoplasm in the smk1∆ mutant. These findings suggest that Smk1 controls assembly of the spore wall by regulating the localization of Gsc2 during sporogenesis.

Maintenance of Certification-The Value to Patients and Physicians.

This Viewpoint discusses the ABIM's continuing efforts to innovate and streamline maintenance of certification, including the recently launched Longitudinal Knowledge Assessment (LKA), to better accommodate physicians' schedules and desires for flexibility.

Melatonin: the placental antioxidant and anti-inflammatory.

Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm. Interestingly, recent studies have shown that melatonin is an important and essential hormone during pregnancy, specifically in the placenta. This is primarily due to the placenta's ability to synthesize its own melatonin rather than depending on the pineal gland. During pregnancy, melatonin acts as an antioxidant and anti-inflammatory, which is necessary to ensure a stable environment for both the mother and the fetus. It is an essential antioxidant in the placenta because it reduces oxidative stress by constantly scavenging for free radicals, i.e., maintain the placenta's integrity. In a healthy pregnancy, the maternal immune system is constantly altered to accommodate the needs of the growing fetus, and melatonin acts as a key anti-inflammatory by regulating immune homeostasis during early and late gestation. This literature review aims to identify and summarize melatonin's role as a powerful antioxidant and anti-inflammatory that reduces oxidative stress and inflammation to maintain a favorable homeostatic environment in the placenta throughout gestation.

Delayed Burr Hole Evacuation Compared With Acute Craniotomy for Acute Subdural Hematoma in Older Patients With Low-Energy Trauma.

Background Acute subdural hematomas commonly require emergent surgical decompression by craniotomy. There is currently limited research on alternative surgical strategies in the elderly population. This study investigates delayed surgical intervention for stable patients with low-energy trauma presenting with acute subdural hematomas. Methodology In this retrospective chart review, 45 patients over the age of 55 presenting with acute subdural hematomas with a Glasgow Coma Scale score greater than or equal to 13 in the setting of low-energy trauma were selected. Additionally, included patients had a maximal hematoma thickness of >10 mm and/or a midline shift size of >5 mm per the current Brain Trauma Foundations guidelines for surgical intervention of subdural hematomas. The study was performed at a large tertiary care center, with records being examined from 1995 to 2020. Comparison groups were immediate craniotomy (within 24 hours) or delayed burr hole (minimum of 48 hours passing since the initial presentation). Primary outcomes included minor complications, major complications, any complications, and any complications with mortality excluded. There was no significant difference in mortality between the two cohorts. Results The immediate craniotomy group consisted of 16 patients, while the delayed burr hole group consisted of 29 patients. The results demonstrated a statistically significant increase in the incidence of any complication including mortality (relative risk (RR) = 3.17, 95% confidence interval (CI) = 1.71-5.88, p < 0.0001), major complications (RR = 2.33, 95% CI = 1.07-5.07, p = 0.031), and minor complications (RR = 2.42, 95% CI = 1.02-5.74, p = 0.041) in the immediate craniotomy group compared to the delayed burr hole group. Conclusions Our study demonstrates the decreased risk of major and minor complications for delayed burr hole evacuation in stable patients >55 years old presenting with low-energy trauma and subdural hematoma. The results suggest that for this population of patients, it appears to be beneficial to delay surgery if the patient's clinical situation allows.

Ecosystem dynamics and services of a paired Neotropical montane forest and pine plantation / Dinámica y servicios del ecosistema en un bosque montano neotropical y un pinar sembrado

Abstract Montane forests are one of the most decimated of Neotropical biomes even though they provide a suite of valuable ecosystem services such as provision of water to lowland settlements and prevention of erosion and mudslides. In some instances, to restore these and other ecosystem services, degraded montane forests are replaced by exotic tree plantations, which cover sizeable areas in several countries. Despite their importance for assessment of ecological services and for intrinsic ecological value, comparative studies of paired native montane forest and conifer plantation are scarce along the Northern Andean Cordillera. Additionally, extrapolations are challenging because each pair of communities is highly site specific due to environmental setting, age and density of plantation, and reforestation species. Here, we assess and compare structure, biogeochemistry and ecosystem services provided by closely positioned native forest and pine plantation from a protected montane area in Venezuela. Soil nutrients and soil carbon content were 60 and 54 % respectively higher in the forest. As consequence of pine' growth form and leaf biochemistry, aboveground biomass and litter mass, as well as nutrient content and carbon stocks, were higher in the plantation. This results in the plantation storing 30 % more MgC ha-1 than the nearby forest. Canopy structure and litter properties influence the hydrology of both ecosystems through differences in rain throughfall. Most of the ecosystem services itemized are superior in the native forest, with exception that the younger plantation sequesters more carbon. An additional service provided by plantations might be that of ecological corridors that connect fragmented native forests. Our study, a specific case of nutrient and carbon cycling dynamics in paired montane forests and pine plantations, provides another set of data for the design of policy and management of considerable areas in the Neotropics with established conservation plantations.(AU)

Resumen Los bosques montanos son uno de los biomas más devastados del Neotrópico aunque proporcionan valiosos servicios ecológicos al suministrar agua a los asentamientos humanos y proteger contra la erosión y los deslaves. En algunas instancias, para mantener esos servicios ecológicos, los bosques destruidos son reemplazados por plantaciones forestales en áreas considerables de varios países. Aunque existen unos pocos estudios comparativos en a lo largo del norte de la Cordillera Andina, las extrapolaciones son difíciles debido a que estos son altamente específicos debido al entorno ambiental, edad de las plantaciones, y a la especie de conífera dominante. Nosotros analizamos y comparamos la diversidad y estructura de la vegetación, la biogeoquímica y los servicios ecológicos proporcionados por un bosque montano y una plantación de pino adyacente en un área protegida de Venezuela. Los suelos del bosque nativo contienen 60 % más de nitrógeno y 54 % más de carbono que los de la plantación. Como consecuencia de la forma de vida de los pinos y de su composición foliar, la biomasa aérea y el contenido de nutrientes en la hojarasca seca son mayores en la plantación dando como resultado que la plantación contiene 30 % MgC ha-1 más que el bosque. La estructura del dosel influencia la hidrología de ambos ecosistemas mediante diferencias en la penetración del agua de lluvia. La mayoría de los servicios son de menor valor ecológico en la plantación de pino. Sin embargo, esta ofrece servicios que no existirían en su ausencia. En regiones montañosas, las plantaciones de coníferas fueron establecidas para mejorar la provisión de agua y estabilizar los suelos. Sin embargo, nuestros resultados sugieren que las plantaciones pueden proporcionar corredores ecológicos que conecten bosques nativos fragmentados. Nuestro estudio, al proveer un ejemplo adicional de dinámica ecológica comparada, expone las diferencias en servicios ecológicos proporcionados por un bosque montano y una plantación de pino y proporciona información para establecer políticas de conservación y manejo de recursos naturales en extensas áreas neotropicales.(AU)

What deters plant colonization in a tropical pine plantation? / ¿Cuáles son los factores que limitan la colonización vegetal en una plantación de pino tropical?

AbstractPine plantations in the tropics are often employed to recondition eroded slopes from mudslides, as the Pinus caribaea plantation that shields the Universidad Simón Bolívar campus in Caracas (Venezuela). However, mismanagement of this plantation has led to its rapid degradation. The best option to maintain the protective service is to restore the plantation and direct its successional trajectory towards the neighbouring montane forest. Through experimental manipulation, we aimed to determine which factors block secondary succession and to investigate their effects. Within the experimental constraints imposed by the plantation small area, we analysed the effects of light and fertility limitation, litter accumulation and access to seed on plantation restoration. Light availability was manipulated by clearing and thinning three 800 m2 main plots. Fertilization and litter removal was applied to sub-plots within the light plots. Soils were analysed, microclimate was monitored and, for four years, stem density, species richness and basal area were tallied. Our results showed that light accessibility was the main factor deterring the successional trajectory of the plots, with varying grades of interaction with the sub-treatments. By the end of the fourth year, the cleared plot showed the largest responses in all traits (triplicating stem density and basal area and >20 times higher species richness). The main colonizers were Croton megalodendron, Ocoteafendleri, and Clusia spp. all dominant trees in the nearby native forest. We concluded that the results of this pioneer study, showed that small clearings, repeated in 3-4 year cycles are appropriate for similar restoration schemes. This procedure would create a mosaic of vegetation patches at different successional stages while protecting the slopes from erosion and increasing local biodiversity. Rev. Biol. Trop. 64 (2): 461-471. Epub 2016 June 01.

ResumenEn los trópicos, las plantaciones de pino se emplean comúnmente para proteger laderas erosionadas. Este es el caso de la plantación de Pinus caribaea que resguarda el campus de la Universidad Simón Bolívar en Caracas (Venezuela) de los deslaves de lodo. Sin embargo, el inadecuado manejo de la plantación está conduciendo a su rápido deterioro. La opción más adecuada para mantener el papel protector de la plantación es la restauración dirigida hacia una sucesión similar a la del bosque montano vecino. Mediante manipulaciones experimentales nos proponemos determinar cuáles son los factores que bloquean la sucesión secundaria e investigar sus efectos específicos. Dentro de las limitaciones impuestas por el reducido tamaño de la plantación y su rol protector, aquí analizamos los efectos de la reducida radiación solar y fertilidad del suelo, la acumulación de acículas de pino y el acceso a la fuente de semillas para la restauración. La disponibilidad de radiación solar se varió cortando y entresacando los pinos de parcelas de 800 m2. Los tratamientos de fertilidad y la remoción de acículas (por fuego y manualmente) se realizaron en subparcelas replicadas dentro de las parcelas principales. Los suelos se analizaron fisicoquímicamente, se monitoreo el microclima y, durante 4 años, se censó la densidad, el área basal y la riqueza de especies de los elementos leñosos en las parcelas. Los resultados muestran que el acceso a la radiación solar fue el factor principal que influyó sobre la colonización y crecimiento de nuevos individuos en las parcelas con diversos grados de interacción con los sub-tratamientos. Al finalizar el cuarto año, la parcela totalmente deforestada mostró las respuestas más elevadas (tres veces superior en cuanto a densidad y área basal y hasta veinte veces mayor en cuanto a riqueza de especies) comparada con las parcelas control y parcialmente deforestada. Las principales especies leñosas colonizadoras fueron: Croton megalodendron, Ocotea fendleri y Clusia spp., todas ellas dominantes en el bosque montano vecino. Concluimos que este estudio pionero muestra que el aclareo total de parcelas pequeñas, repetido en ciclos de 3-4 años es apropiado para proyectos de restauración similares. Así se obtendría un mosaico de vegetación en diferentes estadios sucesionales que mantienen el papel protector de la cubierta vegetal e incrementando la biodiversidad local.

Awn length variation and its effect on dispersal unit burial of Trachypogon spicatus (Poaceae) / Efecto de la variación en longitud de la arista de la unidad dispersante de Trachypogon spicatus (Poaceae) en la profundidad de su entierro

Trachypogon spicatus, formerly known as Trachypogon plumosus, is a dominant grass in some savannas of Northern South America. Its dispersal unit, like many other species of the Andropogoneae tribe, bears a hygroscopic awn which facilitates its establishment in favorable microsites. Some authors have previously proposed that there is a positive correlation between awn length and dispersal unit burial, and that this relationship increases the probability of seed survival in the event of a fire, since soil acts as insulator. In this study we experimentally tested this relationship for T. spicatus. A total of 192 diaspores were placed in randomized blocks, in aluminum trays filled with soil under greenhouse conditions. Diaspores were sprayed with water daily for a month to guarantee awn movement; on the last day of the experiment, they were sprayed with red aerosol paint to determine burial depth. The effects of awn length, presence of caryopses, and presence of a pivot for the passive segment of the awn on diaspore burial were evaluated. Germination viability was tested using a tetrazolium salt test for 35 caryopses. No significant differences in diaspore burial were observed between diaspores with and without caryopses (F(2,126)= 0.034, p=0.853). A positive correlation between awn length and diaspore burial was observed only if the passive awn lacked a pivot (r(66)=0.394, p<0.05). Diaspores whose awns had a pivot point achieved significantly deeper burial distances than their counterparts (F(2,126)=7.063, p=0.005). Viability test found that 0% of caryopses tested were able to germinate; this is possibly due to the time difference between sampling and testing. We considered the presence or absence of caryopsis as an important factor, since previous studies have not yet considered it and the high production of sterile diaspores in grasses. These results suggest that the physical mechanism behind T. spicatus diaspore burial is awn torque. This would explain why our results partially support the hypothesis previously proposed by other authors regarding the effect of awn length upon dispersal unit burial, but would also account for the differences observed in burial depth between diaspores with an available pivot point for the passive awn and diaspores lacking thereof. Rev. Biol. Trop. 62 (1): 321-326. Epub 2014 March 01.

Trachypogon spicatus es una gramínea dominante de algunas sabanas del norte de Suramérica. Su unidad dispersante presenta una arista higroscópica la cual facilita su inserción en irregularidades del suelo, facilitando su ubicación en microhábitats favorables para su establecimiento. Igualmente, se ha sugerido que existe una relación positiva entre la longitud de la arista y la capacidad de entierro de la unidad dispersante. Esta relación incrementa la probabilidad de supervivencia de la semilla ante el fuego al ser el suelo aislante de las altas temperaturas. Se colocaron 192 diásporas de T. spicatus, en bloques aleatorios, en bandejas de sustrato bajo condiciones de invernadero. Luego, se sometieron a cambios de humedad para garantizar el movimiento de la arista y pintaron con aerosol rojo el último día del experimento para determinar la profundidad de entierro. Se evaluó el efecto de la presencia de cariópsis, la longitud de la arista y la presencia de un punto de apoyo para la arista sobre la profundidad de entierro de la diáspora. Se realizó una prueba de sal de Tetrazolio para probar la viabilidad de germinación de 35 cariópsis. No se observaron diferencias significativas en la profundidad de entierro entre diásporas provistas y desprovistas de cariópsis (F(2,126)=0.034, p=0.853). La longitud de la arista parece guardar una relación positiva con la profundidad de entierro únicamente para aquellas unidades dispersantes cuyas aristas no cuentan con un punto de apoyo (r(66)=0.394, p<0.05). Por otro lado, aquellas diásporas cuyas aristas contaban con un punto de apoyo lograron profundidades de entierro significativamente mayores (F(2,126)=7.063, p=0.005). La prueba de viabilidad determinó que 0% de las cariópsis analizadas eran capaces de germinar, esto posiblemente sea debido a la diferencia entre el tiempo de recolección y de prueba. Consideramos que el factor presencia/ausencia de cariópsis era importante ya que había sido ignorado en estudios previos y por la alta producción de diásporas estériles en las gramíneas. Los resultados sugieren que el mecanismo físico que opera sobre la capacidad de entierro de la unidad dispersante de T. spicatus es el torque. Esto explica por qué solo se apoyaron parcialmente las hipótesis propuestas previamente por otros autores, y justifica las diferencias observadas en cuanto a la profundidad de entierro entre unidades dispersantes cuyas aristas contaban o carecían de un punto de apoyo.