Reduction of trimethylamine N-oxide to trimethylamine by the human gut microbiota: supporting evidence for ‘metabolic retroversion’

Dietary sources of methylamines such as choline, trimethylamine (TMA), trimethylamine N-oxide (TMAO), phosphatidylcholine (PC) and carnitine are present in a number of foodstuffs, including meat, fish, nuts and eggs. It is recognized that the gut microbiota is able to convert choline to TMA in a fermentation-like process. Similarly, PC and carnitine are converted to TMA by the gut microbiota. It has been suggested that TMAO is subject to ‘metabolic retroversion’ in the gut (i.e. it is reduced to TMA by the gut microbiota, with this TMA being oxidized to produce TMAO in the liver). Sixty-six strains of human faecal and caecal bacteria were screened on solid and liquid media for their ability to utilize trimethylamine N-oxide (TMAO), with metabolites in spent media profiled by Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy. Enterobacteriaceae produced mostly TMA from TMAO, with caecal/small intestinal isolates of Escherichia coli producing more TMA than their faecal counterparts. Lactic acid bacteria (enterococci, streptococci, bifidobacteria) produced increased amounts of lactate when grown in the presence of TMAO, but did not produce large amounts of TMA from TMAO. The presence of TMAO in media increased the growth rate of Enterobacteriaceae; while it did not affect the growth rate of lactic acid bacteria, TMAO increased the biomass of these bacteria. The positive influence of TMAO on Enterobacteriaceae was confirmed in anaerobic, stirred, pH-controlled batch culture fermentation systems inoculated with human faeces, where this was the only bacterial population whose growth was significantly stimulated by the presence of TMAO in the medium. We hypothesize that dietary TMAO is used as an alternative electron acceptor by the gut microbiota in the small intestine/proximal colon, and contributes to microbial population dynamics upon its utilization and retroversion to TMA, prior to absorption and secondary conversion to TMAO by hepatic flavin-containing monooxygenases. Our findings support the idea that oral TMAO supplementation is a physiologically-stable microbiota-mediated strategy to deliver TMA at the gut barrier

T-cell intracellular antigens in health and disease

T-cell intracellular antigen 1 (TIA1) and TIA1-related/like protein (TIAR/TIAL1) are 2 proteins discovered in 1991 as components of cytotoxic T lymphocyte granules. They act in the nucleus as regulators of transcription and pre-mRNA splicing. In the cytoplasm, TIA1 and TIAR regulate and/or modulate the location, stability and/or translation of mRNAs. As knowledge of the different genes regulated by these proteins and the cellular/biological programs in which they are involved increases, it is evident that these antigens are key players in human physiology and pathology. This review will discuss the latest developments in the field, with physiopathological relevance, that point to novel roles for these regulators in the molecular and cell biology of higher eukaryotes.Ministry Economic Affairs and Competitiveness through FEDER funds (BFU2008–00354, BFU2011–29653 and BFU2014–57735-R). The CBMSO receives an institutional grant from Fundación Ramón Areces.Peer Reviewe

Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota

Background: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes. Results: A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture. Conclusions: Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota

Anatomía radiológica y realidad aumentada: metodología basada en la ludificación para su aprendizaje

[ES] En los últimos años, la ludificación en el aula ha pasado de ser usada exclusivamente en el ámbito escolar hast a llegar a la universidad. El presente trabajo muestra y compara una experiencia de ludificación llevada a cabo en alumnado perteneciente tanto a Educación Superior universitaria como no universitaria. Se trata de un juego tipo quizz basado en casos clínicos reales de Radiología y Anatomía Radiológica, en los que el estudiante va avanzando a medida que acierta la respuesta mostrada a través de realidad aumentada. Tras el juego, se analizaron los conocimientos teórico-prácticos adquiridos y se observaron mejoras estadísticamente significativas. Por último, las encuestas de satisfacción indican que ambos perfiles de alumnado prefieren usar herramientas de ludificación en su aprendizaje y en el desarrollo de sus competencias.[EN] In recent years, gamification in the classroom has gone from being used primarily in the school environments to also being used at universities. The present work shows and compares a gamification experience carried out in students belonging to both higher education and non-university higher education. It is a questionnaire-type game based on real clinical cases of Radiology and Radiological Anatomy, in which the student advances as the answer shown through augmented reality is correct. After playing, the theoretical-practical knowledge acquired will be analyzed and statistically significant improvements will be observed. Finally, satisfaction surveys indicate that both student profiles prefer to use gamification tools in their learning and the development of their skills.Dugnol Menéndez, J.; Jiménez Arberas, E.; Ruiz Fernandez, M.; Fernández Valera, D.; Merayo-Lloves, J. (2021). Anatomía radiológica y realidad aumentada: metodología basada en la ludificación para su aprendizaje. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 128-141. https://doi.org/10.4995/INRED2020.2020.11935OCS12814

Description of a new case of Bohring-Opitz (or Oberklaid-Danks) syndrome

Dismorfología y Genética ClínicaIn 1999, Bohring et al. reported a new syndrome clinically distinguishable from cases with C syndrome or Opitz trigonocephaly. All the patients showed failure to thrive, microcephaly with metopic suture ridging, nevus flammeus over the forehead, thick hair and forehead hirsutism, shallow orbits with prominent eyes, depressed nasal root, anomalous ears, retrognathia, cleft lip and palate, flexion deformities of the upper limbs with radial head dislocation and ulnar deviation of fingers. Patients have severe developmental delay, sucking and swallowing difficulties starting in the prenatal period, as suggested by the usual polyhydramnios. The brain anomalies include hydrocephaly/large ventricles, agenesis/hypoplasia of corpus callosum, Dandy- Walker malformation, myelin abnormalities, and cortical atrophy. Occasional symptoms are a small or closed fontanel at birth, inguinal hernias and cryptorchidism in males, and intestinal malrotation. Most patients die early in childhood because of bradycardia and apnea. Although there is an overlap between C-like syndrome and C syndrome, different manifestations in these patients suggest a different entity. This new syndrome has been called (apart from C-like syndrome) Bohring-Optiz or Oberklaid-Danks syndrome. Recently, it has been associated in some patients to heterozygous de novo nonsense mutations in ASXL1 gene, which is required for maintenance of both activation and silencing of Hox genes, suggesting that the syndrome is genetically heterogeneous. Here we describe the first case of this syndrome identified in the Spanish Collaborative Study of Congenital Malformations (ECEMC) Registry, and possibly in Spain. Therefore, its minimal frequency has been estimated in 1:2,648,286 newborn infants.N

The 2010 Antarctic ozone hole: Observed reduction in ozone destruction by minor sudden stratospheric warmings

Satellite observations show that the 2010 Antarctic ozone hole is characterized by anomalously small amounts of photochemical ozone destruction (40-60% less than the 2005-2009 average). Observations from the MLS instrument show that this is mainly related to reduced photochemical ozone destruction between 20-25 km altitude. Lower down between 15-20 km the atmospheric chemical composition and photochemical ozone destruction is unaffected. The modified chemical composition and chemistry between 20-25 km altitude in 2010 is related to the occurrence of a mid-winter minor Antarctic Sudden Stratospheric Warming (SSW). The measurements indicate that the changes in chemical composition are related to downward motion of air masses rather than horizontal mixing, and affect stratospheric chemistry for several months. Since 1979, years with similar anomalously small amounts of ozone destruction are all characterized by either minor or major SSWs, illustrating that their presence has been a necessary pre-condition for reduced Antarctic stratospheric ozone destruction

Development of Cheaper Embryo Vitrification Device Using the Minimum Volume Method

[EN] This study was designed to compare the efficiency of the Cryotop and Calibrated plastic inoculation loop (CPIL) devices for vitrification of rabbit embryos on in vitro development and implantation rate, offspring rate at birth and embryonic and fetal losses. CPIL is a simple tool used mainly by microbiologists to retrieve an inoculum from a culture of microorganisms. In experiment 1, embryos were vitrified using a Cryotop device and a CPIL device. There were no significant differences in hatched/hatching blastocyst stage rates after 48 h of culture among the vitrified groups (62±4.7% and 62±4.9%, respectively); however, the rates were significantly lower (P<0.05) than those of the fresh group (95±3.4%). In experiment 2, vitrified embryos were transferred using laparoscopic technique. The number of implanted embryos was estimated by laparoscopy as number of implantation sites at day 14 of gestation. At birth, total offspring were recorded. Embryonic and fetal losses were calculated as the difference between implanted embryos and embryos transferred and total born at birth and implanted embryos, respectively. The rate of implantation and development to term was similar between both vitrification devices (56±7.2% and 50±6.8% for implantation rate and 40±7.1% and 35±6.5% for offspring rate at birth); but significantly lower than in the fresh group (78±6.6% for implantation rate and 70±7.2% for offspring rate at birth, P<0.05). Likewise, embryonic losses were similar between both vitrification devices (44±7.2% and 50±6.8%), but significantly higher than in the fresh group (23±6.6%, P < 0.05). However, fetal losses were similar between groups (10±4.4%, 15±4.8% and 8±4.2%, for vitrified, Cryotop or CPIL and fresh, respectively). These results indicate that the CPIL device is as effective as the Cryotop device for vitrification of rabbit embryos, but at a cost of 0.05 per device.This research was supported by the projects Spanish Research project AGL2014-53405-C2-1-P Comision Interministerial de Ciencia y Tecnologia (FMJ, JSV) and Generalitat Valenciana research program (Prometeo II 2014/036, JSV, FMJ).Marco Jiménez, F.; Jiménez Trigos, ME.; Almela-Miralles, V.; Vicente Antón, JS. (2016). Development of Cheaper Embryo Vitrification Device Using the Minimum Volume Method. PLoS ONE. 11(2):1-9. https://doi.org/10.1371/journal.pone.0148661S1911

Calorimetric study of geopolymer binders based on natural pozzolan

This paper investigates the kinetics of geopolymerisation in an inorganic polymeric binder based on a natural pozzolan. The heat released by the exothermic geopolymerisation reaction process is monitored under isothermal temperature conditions, maintained in a differential scanning calorimeter using a water circulation cell. Calorimetric data are obtained isothermally at 65, 75, and 85 °C with various Na2O/Al2O3 and SiO2/Na2O molar ratios and in the presence and absence of small amounts of calcium aluminate cement (used as an efflorescence control admixture in these binder systems). The first stage of reaction, which is rapid and strongly exothermic, is shortened as the temperature increases. The total heat of reaction increases in the mixes containing calcium aluminate cement, but the apparent activation energy calculated using a pseudo-first-order reaction model is lower than without added calcium aluminate cement. At a constant overall SiO2/Na2O molar ratio, the apparent activation energy is decreased as the Na2O/Al2O3 molar ratio increases. Calcium aluminate cement, therefore, reduces the minimum energy required to initiate geopolymerisation reactions of this natural pozzolan and facilitates the progress of the reactions which lead to formation of a cementitious product