FUT8-directed core fucosylation of N-glycans is regulated by the glycan structure and protein environment

FUT8 is an essential a-1, 6-fucosyltransferase that fucosylates the innermost GlcNAc of N-glycans, a process called core fucosylation. In vitro, FUT8 exhibits substrate preference for the biantennary complex N-glycan oligosaccharide (G0), but the role of the underlying protein/peptide to which N-glycans are attached remains unclear. Here, we explored the FUT8 enzyme with a series of N-glycan oligosaccharides, N-glycopeptides, and an Asn-linked oligosaccharide. We found that the underlying peptide plays a role in fucosylation of paucimannose (low mannose) and high-mannose N-glycans but not for complex-type N-glycans. Using saturation transfer difference (STD) NMR spectroscopy, we demonstrate that FUT8 recognizes all sugar units of the G0 N-glycan and most of the amino acid residues (Asn-X-Thr) that serve as a recognition sequon for the oligosaccharyltransferase (OST). The largest STD signals were observed in the presence of GDP, suggesting that prior FUT8 binding to GDP-ß-l-fucose (GDP-Fuc) is required for an optimal recognition of N-glycans. We applied genetic engineering of glycosylation capacities in CHO cells to evaluate FUT8 core fucosylation of high-mannose and complex-type N-glycans in cells with a panel of well-characterized therapeutic N-glycoproteins. This confirmed that core fucosylation mainly occurs on complex-type N-glycans, although clearly only at selected glycosites. Eliminating the capacity for complex-type glycosylation in cells (KO mgat1) revealed that glycosites with complex-type N-glycans when converted to high mannose lost the core Fuc. Interestingly, however, for erythropoietin that is uncommon among the tested glycoproteins in efficiently acquiring tetra-antennary N-glycans, two out of three N-glycosites obtained Fuc on the high-mannose N-glycans. An examination of the N-glycosylation sites of several protein crystal structures indicates that core fucosylation is mostly affected by the accessibility and nature of the N-glycan and not by the nature of the underlying peptide sequence. These data have further elucidated the different FUT8 acceptor substrate specificities both in vitro and in vivo in cells, revealing different mechanisms for promoting core fucosylation.

Mechanisms and Kinetics for Sorption of CO2 on Bicontinuous Mesoporous Silica Modified with n-Propylamine

We studied equilibrium adsorption and uptake kinetics and identified molecular species that formed during sorption of carbon dioxide on amine-modified silica. Bicontinuous silicas (AMS-6 and MCM-48) were postsynthetically modified with (3-aminopropyl)triethoxysilane or (3-aminopropyl)methyldiethoxysilane, and amine-modified AMS-6 adsorbed more CO(2) than did amine-modified MCM-48. By in situ FTIR spectroscopy, we showed that the amine groups reacted with CO(2) and formed ammonium carbamate ion pairs as well as carbamic acids under both dry and moist conditions. The carbamic acid was stabilized by hydrogen bonds, and ammonium carbamate ion pairs formed preferably on sorbents with high densities of amine groups. Under dry conditions, silylpropylcarbamate formed, slowly, by condensing carbamic acid and silanol groups. The ratio of ammonium carbamate ion pairs to silylpropylcarbamate was higher for samples with high amine contents than samples with low amine contents. Bicarbonates or carbonates did not form under dry or moist conditions. The uptake of CO(2) was enhanced in the presence of water, which was rationalized by the observed release of additional amine groups under these conditions and related formation of ammonium carbamate ion pairs. Distinct evidence for a fourth and irreversibly formed moiety was observed under sorption of CO(2) under dry conditions. Significant amounts of physisorbed, linear CO(2) were detected at relatively high partial pressures of CO(2), such that they could adsorb only after the reactive amine groups were consumed.authorCount :7</p

Impact of previous tobacco use with or without cannabis on first psychotic experiences in patients with first-episode psychosis

Objective: There is high prevalence of cigarette smoking in individuals with first-episode psychosis (FEP) prior to psychosis onset. The purpose of the study was to determine the impact of previous tobacco use with or without cannabis on first psychotic experiences in FEP and the impact of this use on age of onset of symptoms, including prodromes. Methods: Retrospective analyses from the naturalistic, longitudinal, multicentre, “Phenotype-Genotype and Environmental Interaction. Application of a Predictive Model in First Psychotic Episodes (PEPs)” Study. The authors analysed sociodemographic/clinical data of 284 FEP patients and 231 matched healthy controls, and evaluated first psychotic experiences of patients using the Symptom Onset in Schizophrenia Inventory. Results: FEP patients had significantly higher prevalence of tobacco, cannabis, and cocaine use than controls. The FEP group with tobacco use only prior to onset (N = 56) had more sleep disturbances (42.9% vs 18.8%, P = 0.003) and lower prevalence of negative symptoms, specifically social withdrawal (33.9% vs 58%, P = 0.007) than FEP with no substance use (N = 70), as well as lower prevalence of ideas of reference (80.4% vs 92.4%, P = 0.015), perceptual abnormalities (46.4% vs 67.4%, P = 0.006), hallucinations (55.4% vs 71.5%, P = 0.029), and disorganised thinking (41.1% vs 61.1%, P = 0.010) than FEP group with previous tobacco and cannabis use (N = 144). FEP patients with cannabis and tobacco use had lower age at first prodromal or psychotic symptom (mean = 23.73 years [SD = 5.09]) versus those with tobacco use only (mean = 26.21 [SD = 4.80]) (P = 0.011). Conclusions: The use of tobacco alone was not related to earlier age of onset of a first psychotic experience, but the clinical profile of FEP patients is different depending on previous tobacco use with or without cannabis. © 2021 The Author

Self-Assembly Fabrication of Hollow Mesoporous Silica@Co–Al Layered Double Hydroxide@Graphene and Application in Toxic Effluents Elimination

Here, we propose a self-assembly process to prepare hierarchical HM-SiO2@Co–Al LDH@graphene, with the purpose of combining their outstanding performance. Hollow mesoporous silica was first synthesized as the core, using a novel sonochemical method, followed by a controlled shell coating process and chemical reduction. As a result of the electrostatic potential difference among HM-SiO2, Co–Al LDH, and graphene oxide, the HM-SiO2 spheres were coated by Co–Al LDH and graphene. Subsequently, the HM-SiO2@Co–Al LDH@graphene spheres were introduced into an epoxy resin (EP) matrix for investigation of their toxic effluents capture and elimination effectiveness during combustion. The amount of toxic CO and volatile organic compounds from the epoxy resin decomposition significantly suppressed after incorporating the HM-SiO2@Co–Al LDH@graphene hybrids, implying a reduced toxicity

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Anales de Edafología y Agrobiología Tomo 47 Número 3-4

Suelos. Física. Resistencia del suelo y susceptibilidad a la compactación en terrenos a monte sometidos a pastoreo. Por R. Pérez Moreira y F. Diaz-Fierros Viqueira.-- La reserva de agua útil de los suelos de Galicia. l. Relación con la textura y el contenido de materia orgánica. Por A. M. Martinez Cortizas.-- Química Empleo de aminas alifáticas en el estudio de asociaciones haloisita-esmectita en suelos. Por F. J. Aragoneses, J. Casas, y J. L. Martin de Vidales.-- Quelación por EDDHA de micronutrientes en suelos calizos. Ecuación de límite máximo. Por M. Juárez, J. Sánchez-Andréu, L. Pla y J. Jorda.-- Quelación por EDDHA de micronutrientes en suelos calizos. Ecuación de orden "n ".Por J. Sánchez-Andréu, M. Juarez, L. Pla y J. Jordá.-- Génesis, Clasificación y Cartografía Caracterización de un podsol ferro - húmico en el Puerto de la Quesera (Sierra del Ayllón). Por R. Espejo Serrano, F. Guerrero López y A. Saa Requejo.-- Natrixerales en el Baix Segre (Lleida). Por J. Bech i Borrás, J. Garrigo i Reixach y J. R. Torrento i Marselles.-- Aspectos micromorfológicos del horizonte superior en suelos artificiales (Sorribas) de las Islas Canarias. Por A. Rodríguez Rodríguez y J. M. Ontañón Sánchez.-- Fertilidad Influencia de diferentes factores del suelo sobre su contenido en microelementos asimilables: Mn, Fe, Cu y Zn. Por B. C. Ortega, Ma C. Ortega y J. G. de las Heras.--Incidencia de la salinidad del agua de riego en la mineralización del nitrógeno orgánico en suelos calizos del sureste español. Por J. García-Serna, J. Sánchez Andréu, M. Juárez y J. Mataix.-- Biología Vegetal-Fisiología Efectos de la toxicidad del flúor sobre el ciclo biológico en especies herbáceas dicotiledoneas. Por M. Ibarra, F. López Belmonte y Ma A. Diez.-- Efectos de la toxicidad del flúor sobre el ciclo biológico de especies de monocotiledoneas. Por M. Ibarra, F. López-Belmonte y Mª A . Diez.-- Proteasas ácidas en uvas Vitis vinifera (variedad Macabeo). l. Actividad proteásica durante su maduración. Por J. Marín Expósito, C. Miguel Gordillo, J. l. Maynar Mariño y J. L. Mesias Iglesias.-- Agro biología Efectos de enmiendas calcáreas en suelos fijadores de fósforo. Por S. G. Ramos Hernández y N. Aguilera Herrera.-- III. Trabajo Recapitulativo. Una deriva hacia hemiparasftismo de los líquenes epifitos: Análisis fisiológico de las relaciones con sus fitoforos. Por C. VicentePeer reviewed2019-08.- CopyBook.- Libnova.- Biblioteca IC

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

XVI International Congress of Control Electronics and Telecommunications: "Techno-scientific considerations for a post-pandemic world intensive in knowledge, innovation and sustainable local development"

Este título, sugestivo por los impactos durante la situación de la Covid 19 en el mundo, y que en Colombia lastimosamente han sido muy críticos, permiten asumir la obligada superación de tensiones sociales, políticas, y económicas; pero sobre todo científicas y tecnológicas. Inicialmente, esto supone la existencia de una capacidad de la sociedad colombiana por recuperar su estado inicial después de que haya cesado la perturbación a la que fue sometida por la catastrófica pandemia, y superar ese anterior estado de cosas ya que se encontraban -y aún se encuentran- muchos problemas locales mal resueltos, medianamente resueltos, y muchos sin resolver: es decir, habrá que rediseñar y fortalecer una probada resiliencia social existente - producto del prolongado conflicto social colombiano superado parcialmente por un proceso de paz exitoso - desde la tecnociencia local; como lo indicaba Markus Brunnermeier - economista alemán y catedrático de economía de la Universidad de Princeton- en su libro The Resilient Society…La cuestión no es preveerlo todo sino poder reaccionar…aprender a recuperarse rápido.This title, suggestive of the impacts during the Covid 19 situation in the world, and which have unfortunately been very critical in Colombia, allows us to assume the obligatory overcoming of social, political, and economic tensions; but above all scientific and technological. Initially, this supposes the existence of a capacity of Colombian society to recover its initial state after the disturbance to which it was subjected by the catastrophic pandemic has ceased, and to overcome that previous state of affairs since it was found -and still is find - many local problems poorly resolved, moderately resolved, and many unresolved: that is, an existing social resilience test will have to be redesigned and strengthened - product of the prolonged Colombian social conflict partially overcome by a successful peace process - from local technoscience; As Markus Brunnermeier - German economist and professor of economics at Princeton University - indicates in his book The Resilient Society...The question is not to foresee everything but to be able to react...learn to recover quickly.Bogot

Automated contact time apparatus and measurement procedure for bubble-particle interaction analysis

The novel Automated Contact Time Apparatus (ACTA) presented in this paper serves as a diagnostic tool that allows the detection of changes in bubble-particle attachment probability and therefore floatability caused by alterations in the chemical environment and particle properties. The apparatus consists of six identical capillaries where bubbles with defined size are produced simultaneously in a measurement chamber. The bubbles at the needle tips are placed in contact with the submerged particle bed for specific time periods, controlled with the help of automatic actuators. The advantage of the instrument is that hundreds of bubble-particle contacts can be measured automatically within a short time period. Microscopy pictures of each measured bubble are taken while recording the movement of the bubble before, during and after contact with the solid particles. The recorded pictures can be used to determine the actual bubble size and its corresponding deviation, and to detect the attachment of particles. The attached particles are collected in a detachable chamber for subsequent characterization. Furthermore, the device is portable and can be taken to the mineral processing plants for quick evaluation of particle-bubble attachment efficiency with particles and process water sampled directly from real processes.Peer reviewe