Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats.

The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period characterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)-treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk occurring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 µL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 transcriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter.

Role of Presurgical Gut Microbial Diversity in Roux-en-Y Gastric Bypass Weight-Loss Response: A Cohort Study.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) substantially alters the gut microbial composition which could be associated with the metabolic improvements seen after surgery. Few studies have been conducted in Latin American populations, such as Mexico, where obesity prevalence is above 30% in the adult population. Thus, the aim of this study was to characterize the changes in the gut microbiota structure in a Mexican cohort before and after RYGB and to explore whether surgery-related changes in the microbial community were associated with weight loss. METHODS: Biological samples from patients who underwent RYGB were examined before and 12 months after surgery. Fecal microbiota characterization was performed through 16S rRNA sequencing. RESULTS: Twenty patients who underwent RYGB showed a median excess weight loss of 66.8% 12 months after surgery. Surgery increased alpha diversity estimates (Chao, Shannon index, and observed operational taxonomic units, p < 0.05) and significantly altered gut microbiota composition. Abundance of four genera was significantly increased after surgery: Oscillospira, Veillonella, Streptococcus, and an unclassified genus from Enterobacteriaceae family (PFDR < 0.1). The change in Veillonella abundance was associated with lower excess weight loss (rho = -0.446, p = 0.063) and its abundance post-surgery with a greater BMI (rho = 0.732, p = 5.4 × 10-4). In subjects without type 2 diabetes, lower bacterial richness and diversity before surgery were associated with a greater Veillonella increase after surgery (p < 0.05), suggesting that a lower bacterial richness before surgery could favor the bloom of certain oral-derived bacteria that could negatively impact weight loss. CONCLUSION: Presurgical microbiota profile may favor certain bacterial changes associated with less successful results.

Effective Mechanisms for Improving Seed Oil Production in Pennycress (Thlaspi arvense L.) Highlighted by Integration of Comparative Metabolomics and Transcriptomics.

Pennycress is a potentially lucrative biofuel crop due to its high content of long-chain unsaturated fatty acids, and because it uses non-conventional pathways to achieve efficient oil production. However, metabolic engineering is required to improve pennycress oilseed content and make it an economically viable source of aviation fuel. Research is warranted to determine if further upregulation of these non-conventional pathways could improve oil production within the species even more, which would indicate these processes serve as promising metabolic engineering targets and could provide the improvement necessary for economic feasibility of this crop. To test this hypothesis, we performed a comparative biomass, metabolomic, and transcriptomic analyses between a high oil accession (HO) and low oil accession (LO) of pennycress to assess potential factors required to optimize oil content. An evident reduction in glycolysis intermediates, improved oxidative pentose phosphate pathway activity, malate accumulation in the tricarboxylic acid cycle, and an anaplerotic pathway upregulation were noted in the HO genotype. Additionally, higher levels of threonine aldolase transcripts imply a pyruvate bypass mechanism for acetyl-CoA production. Nucleotide sugar and ascorbate accumulation also were evident in HO, suggesting differential fate of associated carbon between the two genotypes. An altered transcriptome related to lipid droplet (LD) biosynthesis and stability suggests a contribution to a more tightly-packed LD arrangement in HO cotyledons. In addition to the importance of central carbon metabolism augmentation, alternative routes of carbon entry into fatty acid synthesis and modification, as well as transcriptionally modified changes in LD regulation, are key aspects of metabolism and storage associated with economically favorable phenotypes of the species.

Sustained Energy Deficit Following Perinatal Asphyxia: A Shift towards the Fructose-2,6-bisphosphatase (TIGAR)-Dependent Pentose Phosphate Pathway and Postnatal Development.

Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H2O2 than those from CS animals. Several therapeutic strategies are discussed, including hypothermia; N-acetylcysteine; memantine; nicotinamide, and intranasally administered mesenchymal stem cell secretomes, promising clinical translation.

Ski Is Required for Tri-Methylation of H3K9 in Major Satellite and for Repression of Pericentromeric Genes: Mmp3, Mmp10 and Mmp13, in Mouse Fibroblasts.

Several mechanisms directing a rapid transcriptional reactivation of genes immediately after mitosis have been described. However, little is known about the maintenance of repressive signals during mitosis. In this work, we address the role of Ski in the repression of gene expression during M/G1 transition in mouse embryonic fibroblasts (MEFs). We found that Ski localises as a distinct pair of dots at the pericentromeric region of mitotic chromosomes, and the absence of the protein is related to high acetylation and low tri-methylation of H3K9 in pericentromeric major satellite. Moreover, differential expression assays in early G1 cells showed that the presence of Ski is significantly associated with repression of genes localised nearby to pericentromeric DNA. In mitotic cells, chromatin immunoprecipitation assays confirmed the association of Ski to major satellite and the promoters of the most repressed genes: Mmp3, Mmp10 and Mmp13. These genes are at pericentromeric region of chromosome 9. In these promoters, the presence of Ski resulted in increased H3K9 tri-methylation levels. This Ski-dependent regulation is also observed during interphase. Consequently, Mmp activity is augmented in Ski-/- MEFs. Altogether, these data indicate that association of Ski with the pericentromeric region of chromosomes during mitosis is required to maintain the silencing bookmarks of underlying chromatin.

Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?

Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult.PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD+ exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1ß and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss evidence showing that (i) inhibition of PARP-1 overactivation by nicotinamide and (ii) inhibition of extrasynaptic NMDA receptor overactivation by memantine can prevent the short- and long-term consequences of PA. These hypotheses have been evaluated in a rat preclinical model of PA, aiming to identify the metabolic cascades responsible for the long-term consequences induced by the insult, also assessing postnatal vulnerability to recurrent oxidative insults. Thus, we present and discuss evidence demonstrating that PA induces long-term changes in metabolic pathways related to energy and oxidative stress, priming vulnerability of cells with both the neuronal and the glial phenotype. The effects induced by PA are region dependent, the substantia nigra being particularly prone to cell death. The issue of short- and long-term consequences of PA provides a framework for addressing a fundamental issue referred to plasticity of the CNS, since the perinatal insult triggers a domino-like sequence of events making the developing individual vulnerable to recurrent adverse conditions, decreasing his/her coping repertoire because of a relevant insult occurring at birth.

Effect of liquefied petroleum gas on ozone formation in Guadalajara and Mexico City.

Leakages of liquefied petroleum gas (LPG) are suspected to contribute greatly to ozone (O3) formation in Mexico City. We tested such a hypothesis by outdoor captive-air irradiation (CAI) experiments in the two largest Mexican metropolitan areas: Guadalajara (GMA) in 1997 and Mexico City (MCMA) in 2000. O3 was monitored in each city for 20 days (8:00 a.m.-6:00 p.m.) in smog chambers containing unaltered morning air or morning air enriched with either commercial LPG or LPG synthetic mixture 60/40 (propane and butane). Tested additions of both components were 35% (by volume) in GMA and 60% (by volume) in MCMA. The addition effects on O3 (max) were compared with effects from diluting LPG components or total nonmethane hydrocarbons (tNMHCs) by 50%. Diluting tNMHCs had the greatest absolute effect at both cities: it lowered O3 (max) by 24% in GMA and 55% in MCMA. Adding commercial LPG increased O3 (max) by 6% in GMA and 28% in MCMA; whereas adding LPG synthetic mixture 60/40 caused a similar increase in O3 (max), 4 and 21% in GMA and MCMA, respectively. Compared with dilution of tNMHCs, dilution of LPG-associated compounds had a smaller decreasing effect on O3 (max), only 4% in GMA and 15% in MCMA. These results show that commercial LPG and LPG synthetic mixture 60/40 affect O3 formation to a lesser extent than estimated previously.

La televisión comunitaria en el oriente antioqueño: un ejercicio de construcción de tejido social y paz / The community television system in the eastern region in antioquia: an exercise of construction of the social fabric and peace

El presente artículo resultado de investigación, expone las diversas realidades que atraviesan los canales comunitarios del Oriente Antioqueño (Colombia). Para presentar los resultados el texto relaciona tres momentos: primero, aspectos jurídicos que en Colombia rigen la Televisión Comunitaria, normativas que ha regido a la televisión pública en el país y sus incidencias en el desarrollo de la televisión comunitaria local; dos, se ahonda en la necesidad de entender los modos de organización como asociaciones económicas y sus acciones colectivas (Actividades en Red) como estrategias co-operativas para el trabajo y tres, plantea el papel de la televisión comunitaria como órgano de expresión de las comunidades de esta subregión golpeada por la violencia, la exclusión y la impuesta llegada del desarrollo.

This current article, the result of a piece of research, introduces the various situations that the community channels, in the eastern region in Antioquia (Colombia), have to go through. In order to present the results, the text relates three moments: firstly, legal aspects governing the community television system, regulations that have controlled the public television in the country and its effects on the development of the local community television system; in Colombia; secondly, it delves into the need to understand modes of organization such as economic associations and their collective actions (Network Activities) as co-operative strategies for the work, and thirdly, it raises the role of the community television system as an organ of expression of the communities in this sub-region, struck by violence, exclusion, and the imposed arrival of development.