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Leguminous plants can establish endosymbiotic relationships with nitrogen-fixing soil rhizobacteria. Bacterial infection and nodule organogenesis are two independent but highly coordinated genetic programs that are active during this interaction. These genetic programs can be regulated along all the stages of gene expression. Most of the studies, for both eukaryotes and prokaryotes, focused on the transcriptional regulation level determining the abundance of mRNAs. However, it has been demonstrated that mRNA levels only sometimes correlate with the abundance or activity of the coded proteins. For this reason, in the past two decades, interest in the role of translational control of gene expression has increased, since the subset of mRNA being actively translated outperforms the information gained only by the transcriptome. In the case of legume-rhizobia interactions, the study of the translatome still needs to be explored further. Therefore, this review aims to discuss the methodologies for analyzing polysome-associated mRNAs at the genome-scale and their contribution to studying translational control to understand the complexity of this symbiotic interaction. Moreover, the Dual RNA-seq approach is discussed for its relevance in the context of a symbiotic nodule, where intricate multi-species gene expression networks occur.
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BACKGROUND: Soybean establishes a mutualistic interaction with nitrogen-fixing rhizobacteria, acquiring most of its nitrogen requirements through symbiotic nitrogen fixation. This crop is susceptible to water deficit; evidence suggests that its nodulation status-whether it is nodulated or not-can influence how it responds to water deficit. The translational control step of gene expression has proven relevant in plants subjected to water deficit. RESULTS: Here, we analyzed soybean roots' differential responses to water deficit at transcriptional, translational, and mixed (transcriptional + translational) levels. Thus, the transcriptome and translatome of four combined-treated soybean roots were analyzed. We found hormone metabolism-related genes among the differentially expressed genes (DEGs) at the translatome level in nodulated and water-restricted plants. Also, weighted gene co-expression network analysis followed by differential expression analysis identified gene modules associated with nodulation and water deficit conditions. Protein-protein interaction network analysis was performed for subsets of mixed DEGs of the modules associated with the plant responses to nodulation, water deficit, or their combination. CONCLUSIONS: Our research reveals that the stand-out processes and pathways in the before-mentioned plant responses partially differ; terms related to glutathione metabolism and hormone signal transduction (2 C protein phosphatases) were associated with the response to water deficit, terms related to transmembrane transport, response to abscisic acid, pigment metabolic process were associated with the response to nodulation plus water deficit. Still, two processes were common: galactose metabolism and branched-chain amino acid catabolism. A comprehensive analysis of these processes could lead to identifying new sources of tolerance to drought in soybean.
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Glycine max , Raíces de Plantas , Transcriptoma , Glycine max/genética , Glycine max/fisiología , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Nodulación de la Raíz de la Planta/genética , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , DeshidrataciónRESUMEN
The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not effectively remove these toxins, posing a potential risk to public health. This study introduces a water treatment approach using nanostructured beads containing magnetic nanoparticles (MNPs) for easy removal from liquid suspension, coated with different adsorbent materials to eliminate cyanotoxins. Thirteen particle types were produced using activated carbon, CMK-3 mesoporous carbon, graphene, chitosan, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidised cellulose nanofibers (TOCNF), esterified pectin, and calcined lignin as an adsorbent component. The particles' effectiveness for detoxification of microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-A (ATX-A) was assessed in an aqueous solution. Two particle compositions presented the best adsorption characteristics for the most common cyanotoxins. In the conditions tested, mesoporous carbon nanostructured particles, P1-CMK3, provide good removal of MC-LR and Merck-activated carbon nanostructured particles, P9-MAC, can remove ATX-A and CYN with high and fair efficacy, respectively. Additionally, in vitro toxicity of water treated with each particle type was evaluated in cultured cell lines, revealing no alteration of viability in human renal, neuronal, hepatic, and intestinal cells. Although further research is needed to fully characterise this new water treatment approach, it appears to be a safe, practical, and effective method for eliminating cyanotoxins from water.
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Toxinas Bacterianas , Toxinas de Cianobacterias , Toxinas Marinas , Microcistinas , Purificación del Agua , Toxinas de Cianobacterias/química , Humanos , Microcistinas/toxicidad , Microcistinas/química , Microcistinas/aislamiento & purificación , Toxinas Marinas/toxicidad , Toxinas Marinas/química , Toxinas Marinas/aislamiento & purificación , Purificación del Agua/métodos , Adsorción , Toxinas Bacterianas/toxicidad , Toxinas Bacterianas/química , Toxinas Bacterianas/aislamiento & purificación , Alcaloides/química , Alcaloides/toxicidad , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidad , Tropanos/química , Tropanos/toxicidad , Tropanos/aislamiento & purificación , Nanoestructuras/química , Nanoestructuras/toxicidad , Uracilo/análogos & derivados , Uracilo/química , Uracilo/toxicidad , Cianobacterias/química , Supervivencia Celular/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/químicaRESUMEN
Gnomoniopsis smithogilvyi (Gnomoniaceae, Diaporthales) is the main causal agent of chestnut brown rot on sweet chestnut worldwide. The rotting of nuts leads to alterations in the organoleptic qualities and decreased fruit production, resulting in significant economic losses. In 2021, there was an important outbreak of chestnut rot in southern Galicia (Spanish northwest). The profile of secondary metabolites from G. smithogilvyi was studied, especially to determine its capability for producing mycotoxins, as happens with other rotting fungi, due to the possible consequences on the safety of chestnut consumption. Secondary metabolites produced by isolates of G. smithogilvyi growing in potato dextrose agar (PDA) medium were identified using liquid chromatography coupled with high-resolution mass spectrometry. Three metabolites with interesting pharmacological and phyto-toxicological properties were identified based on their exact mass and fragmentation patterns, namely adenosine, oxasetin, and phytosphingosine. The capacity of G. smithogilvyi to produce adenosine in PDA cultures was assessed, finding concentrations ranging from 176 to 834 µg/kg. Similarly, the production of mycotoxins was ruled out, indicating that the consumption of chestnuts with necrotic lesions does not pose a health risk to the consumer in terms of mycotoxins.
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Ascomicetos , Micotoxinas , Nueces , Adenosina , Medios de CultivoRESUMEN
Fundamento: la proteína C reactiva de alta sensibilidad (PCR-as) y la homocisteína (Hci) parecen relacionarse con la enfermedad cerebrovascular isquémica, pero sus hallazgos sobre el riesgo y pronóstico de esta enfermedad resultan controversiales y no concluyentes. Objetivo caracterizar la proteína C reactiva de alta sensibilidad y homocisteína en pacientes con enfermedad cerebrovascular isquémica. Métodos: se realizó un estudio descriptivo y retrospectivo de corte transversal en pacientes con enfermedad cerebrovascular isquémica, ingresados en el Servicio de Ictus del Instituto de Neurología y Neurocirugía entre 2016 y 2019. Se recogieron variables demográficas, manifestaciones clínicas, tiempo de evolución, etiología y localización del infarto y factores riesgo. Se cuantificaron la PCR-as (riesgo cardiovascular) y la Hci. Resultados las medias de PCR-as (7,0±8,3 mg/L) y Hci (17,1±7,3 µM) fueron elevadas. El riesgo cardiovascular moderado y alto se presentaron en igual proporción (46,8 %). Hubo diferencias estadísticas en la relación entre el riesgo cardiovascular y la edad (p=0,00); pero ni el tiempo de evolución ni los factores de riesgo de la enfermedad mostraron este comportamiento. Los pacientes con riesgo cardiovascular alto (PCR-as >3 mg/L) y elevada Hci (>15 (M) exhibieron mayores frecuencias de etiologías aterotrombótica o cardioembólica. Conclusiones el riesgo cardiovascular aumenta en la medida que se incrementa la edad de pacientes con enfermedad cerebrovascular isquémica. Las características demográficas, clínicas y neurológicas no mostraron relación con el alto riesgo cardiovascular y los valores elevados de Hci, aunque se encontró una tendencia asociativa de la etiología aterotrombótica con el incremento de PCR-as y Hci.
Foundation: High-sensitivity C-reactive protein and homocysteine seem to be related to ischemic cerebrovascular disease, but their findings on the risk and prognosis of this disease are controversial and inconclusive. Objective: to characterize high sensitivity C-reactive protein and homocysteine in patients with ischemic cerebrovascular disease. Methods: a descriptive and retrospective cross-sectional study was carried out in patients with ischemic cerebrovascular disease, admitted to the Stroke Service of the Neurology and Neurosurgery Institute between 2016 and 2019. Demographic variables, clinical manifestations, time of evolution, etiology and infarction location, risk factors. High-sensitivity C-reactive protein (cardiovascular risk) and homocysteine were quantified. Results: the means of C-reactive protein (7.0±8.3 mg/L) and homocysteine (17.1±7.3 µM) were high. Moderate and high cardiovascular risk occurred in equal proportions (46.8%). There were statistical differences in the relationship between cardiovascular risk and age (p=0.00); but neither the time of evolution nor the risk factors of the disease showed this behavior. Patients with high cardiovascular risk (hs-CRP >3 mg/L) and high homocysteine (>15 (M), exhibited higher frequencies of atherothrombotic or cardioembolic etiologies. Conclusions: cardiovascular risk increases as the age of patients with ischemic cerebrovascular disease increases. Demographic, clinical and neurological characteristics did not show a relationship with high cardiovascular risk and high homocysteine values, although an associative trend of atherothrombotic etiology was found with increased high-sensitivity C-reactive protein and homocysteine.
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In the original publication [...].
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ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3'UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.
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Enfermedad de Alzheimer , Anciano de 80 o más Años , Humanos , Proteínas ADAM/metabolismo , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas del Líquido Cefalorraquídeo/análisis , Proteínas del Líquido Cefalorraquídeo/metabolismoRESUMEN
Soybean (Glycine max (L.) Merr.) establishes symbiosis with rhizobacteria, developing the symbiotic nodule, where the biological nitrogen fixation (BNF) occurs. The redox control is key for guaranteeing the establishment and correct function of the BNF process. Plants have many antioxidative systems involved in ROS homeostasis and signaling, among them a network of thio- and glutaredoxins. Our group is particularly interested in studying the differential response of nodulated soybean plants to water-deficit stress. To shed light on this phenomenon, we set up an RNA-seq experiment (for total and polysome-associated mRNAs) with soybean roots comprising combined treatments including the hydric and the nodulation condition. Moreover, we performed the initial identification and description of the complete repertoire of thioredoxins (Trx) and glutaredoxins (Grx) in soybean. We found that water deficit altered the expression of a greater number of differentially expressed genes (DEGs) than the condition of plant nodulation. Among them, we identified 12 thioredoxin (Trx) and 12 glutaredoxin (Grx) DEGs, which represented a significant fraction of the detected GmTrx and GmGrx in our RNA-seq data. Moreover, we identified an enriched network in which a GmTrx and a GmGrx interacted with each other and associated through several types of interactions with nitrogen metabolism enzymes.
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The aim of this protocol is to provide a strategy for studying the eukaryotic translatome of the soybean (Glycine max) symbiotic nodule. This paper describes methods optimized to isolate plant-derived polyribosomes and their associated mRNAs to be analyzed using RNA-sequencing. First, cytoplasmic lysates are obtained through homogenization in polysome- and RNA-preserving conditions from whole, frozen soybean nodules. Then, lysates are cleared by low-speed centrifugation, and 15% of the supernatant is used for total RNA (TOTAL) isolation. The remaining cleared lysate is used to isolate polysomes by ultracentrifugation through a two-layer sucrose cushion (12% and 33.5%). Polysome-associated mRNA (PAR) is purified from polysomal pellets after resuspension. Both TOTAL and PAR are evaluated by highly sensitive capillary electrophoresis to meet the quality standards of sequencing libraries for RNA-seq. As an example of a downstream application, after sequencing, standard pipelines for gene expression analysis can be used to obtain differentially expressed genes at the transcriptome and translatome levels. In summary, this method, in combination with RNA-seq, allows the study of the translational regulation of eukaryotic mRNAs in a complex tissue such as the symbiotic nodule.
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Glycine max , Biosíntesis de Proteínas , Polirribosomas/genética , Polirribosomas/metabolismo , ARN Mensajero/genética , RNA-Seq , Análisis de Secuencia de ARN , Glycine max/genética , Glycine max/metabolismoRESUMEN
About 60% of the nut production of sweet chestnut (Castanea sativa Mill.) in Europe originates in Spain (FAOSTAT, 2022), mostly (91%) in Galicia (NW Spain). In September 2021, premature fall of immature chestnut burrs and nuts of C. sativa was observed in eight orchards of Pontevedra and Ourense (provinces of Galicia). Chestnut green burrs had turned brown and fallen off, and the nuts showed brown lesions in kernels and embryos. Some nuts had become mummified. Symptomatic samples of burrs and nuts, including mummified fruits, were collected. Small pieces of samples were surface-disinfected with 2% sodium hypochlorite, and plated onto potato dextrose agar (PDA) plates. Colonies were creamy white to gray or light brown, and presented a woolly to felty mycelium with a dense development in concentric circles. Brownish to black conidiomata, produced abundantly, were globose to sub-globose. Conidia were hyaline, oval, obovoid, fusoid and multi-guttulate, and 6.6±0.78 [5.07 to 9.01] µm x 3.2±0.43 [2.41 to 4.38] µm in size. These features matched those described for Gnomoniopsis smithogilvyi (Shuttleworth et al. 2012), syn. G. castaneae (Visentin et al. 2012; Shuttleworth et al. 2015). Genomic DNA was extracted from mycelium developed in 22 burrs and nuts, and 30 pure cultures. The rDNA internal transcribed spacer (ITS), fragments of the ß-tubulin (TUB2) and the translation elongation factor-1α (TEF-1α) genes were amplified using ITS1F (Gardes and Bruns 1993) and ITS4 (White et al. 1990), T1/Bt2b (O'Donnell and Cigelnik 1997), and EF1-728F/EF1-986R (Carbone and Kohn 1999) primers, respectively. Two isolates (EFA 924A, EFA962.4A) were deposited in the Spanish Type Culture Collection (Paterna, Valencia), and their sequences submitted to GenBank (accession nos.: ITS: OM319846, OM319848; TUB2: OM417078, OM417080; TEF-1α: OM417081, OM417083). BLASTn analyses showed: for ITS and TEF-1α sequences, ≥99.7% identity to the ex-type of G. smithogilvyi (ITS: JQ910642, 474 matching bp; TEF-1α: JQ910645, 335-338 matching bp), and for TUB2 sequences, ≥99.1% identity to G. castaneae (LN999975, 446-453 matching bp). Pathogenicity tests were carried out on surface disinfected nuts of Castanea sativa `Raigona´. A superficial wound was made in the pericarp of each nut. A 2-mm mycelial plug of a 7-days-old culture of G. smithogilvyiwas then inoculated: twenty nuts with isolate EFA924A and twenty with isolate EFA962.4A. Twenty nuts inoculated with sterile agar were used as control. The holes were sealed with Parafilm®. Nuts were incubated in a moist chamber at 22±2°C. Two replicated tests were carried out. Four inoculated and four control nuts were inspected for the presence and progress of rot symptoms every seven days. Three weeks after inoculation, all remaining inoculated nuts were completely rotted, whereas all control nuts remained healthy. Gnomoniopsis smitholgilvyi was reisolated from all inoculated nuts, and it was not recovered from the controls. This pathogen causes chestnut brown rot on sweet chestnut worldwide (EPPO, 2022), causing also shoot cankers on chestnut (Lione et al, 2019). This is the first report of G. smithogilvyi causing chestnut brown rot on nuts and burrs of C. sativa in Spain. Future studies on the incidence of this pathogen and its impact on chestnut yield should be carried out in the main European producing countries, i.e. Spain, Italy, Portugal and Greece, where the disease has been detected and represents an emerging threat to chestnut production.
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Maize and grass silages are important dietary components for ruminant livestock that influence the quality of animal products for human consumption, such as milk, in many parts of the world. Infection of plants by fungi able to produce mycotoxins, either in the field or post-harvest, can result in a decrease of silage nutritional quality and, consequently, in milk quality. In this study, 45 maize and grass silage samples were collected from 25 dairy farms located in the north of Portugal. The occurrence of fungi was evaluated in samples, the most frequently isolated species being Aspergillus fumigatus, Dipodascus geotrichum, Mucor circinelloides, Penicillium paneum, and Aspergillus flavus. The mycotoxigenic profile of the fungal species was studied using the ultra-high-performance liquid chromatography coupled to mass spectrometry-ion trap-time-of-flight (UHPLC-MS-IT-TOF) detection. In addition, a new method based on a QuEChERS extraction followed by the UHPLC- tandem mass spectrometry (UHPLC-MS/MS) detection was developed for simultaneous analysis of 39 mycotoxins in silage. A high co-occurrence of Fusarium mycotoxins was found, although at low levels of contamination. Deoxynivalenol and beauvericin were found in more than 82% of maize silage samples. It can be highlighted the low occurrence of Penicillium and Aspergillus toxins in the maize and grass silages studied despite the frequent detection of species of both genera.
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Micotoxinas , Animales , Contaminación de Alimentos/análisis , Hongos/genética , Humanos , Micotoxinas/análisis , Portugal , Ensilaje/análisis , Espectrometría de Masas en Tándem , Zea maysRESUMEN
We report a patient with sporadic Alzheimer's disease with onset in his twenties found to carry the de novo Pro436Gln mutation in the presenilin 1 gene (PS1). Clinical phenotype featured a posterior cortical syndrome with severe visual agnosia and mild limb spasticity with brisk reflexes. Brain MRI and FDG-PET scans revealed severe parieto-occipital atrophy/hypometabolism. Cerebrospinal fluid biomarkers showed a decrease in Aß42 level and Aß42/40 ratio, increased phospho-tau, and normal total tau. Amyloid PET identified a very high burden of amyloid-ß neuritic plaques in the posterior cortex. Similarities between this and two previously reported cases with this variant support that this mutation has a very strong impact on the clinical phenotype and is consistently associated with spasticity.
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Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Espasticidad Muscular/etiología , Mutación , Presenilina-1/genética , Adulto , Agnosia/etiología , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Humanos , Imagen por Resonancia Magnética , Masculino , Fragmentos de Péptidos/líquido cefalorraquídeo , Tomografía de Emisión de Positrones , Proteínas tau/líquido cefalorraquídeoRESUMEN
A simple method for the quantification of 40 mycotoxins in milk was developed. This method is based on a QuEChERS extraction followed by the ultra-high liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection, and allows the simultaneous analysis of regulated, emerging, and modified mycotoxins. A sample treatment procedure was optimized to include a concentration step for the analysis of some compounds such as aflatoxin M1. The method was in-house validated in terms of limits of detection (LODs), limits of quantification (LOQs), linearity, recoveries, and precision. LOQs lower than 10 ng/mL were obtained, and recoveries ranged from 61% to 120% with a precision, expressed as the relative standard deviation, lower than 15%. Therefore, acceptable performance characteristics were obtained fulfilling European regulations. The method was successfully applied for the quantification of mycotoxins in raw milk. It can be highlighted high occurrence of beauvericin and enniatins were found in low amounts.
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Leche/química , Micotoxinas/análisis , Animales , Cromatografía Líquida de Alta Presión/métodos , Depsipéptidos/análisis , Depsipéptidos/química , Límite de Detección , Micotoxinas/química , Espectrometría de Masas en Tándem/métodosRESUMEN
Mutations in the Arabidopsis TETRATRICOPEPTIDE THIOREDOXIN-LIKE 1 (TTL1) gene cause reduced tolerance to osmotic stress evidenced by an arrest in root growth and root swelling, which makes it an interesting model to explore how root growth is controlled under stress conditions. We found that osmotic stress reduced the growth rate of the primary root by inhibiting the cell elongation in the elongation zone followed by a reduction in the number of cortical cells in the proximal meristem. We then studied the stiffness of epidermal cell walls in the root elongation zone of ttl1 mutants under osmotic stress using atomic force microscopy. In plants grown in control conditions, the mean apparent elastic modulus was 448% higher for live Col-0 cell walls than for ttl1 (88.1 ± 2.8 vs. 16.08 ± 6.9 kPa). Seven days of osmotic stress caused an increase in the stiffness in the cell wall of the cells from the elongation zone of 87% and 84% for Col-0 and ttl1, respectively. These findings suggest that TTL1 may play a role controlling cell expansion orientation during root growth, necessary for osmotic stress adaptation.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Raíces de Plantas/genética , Estrés Fisiológico/genética , Aclimatación/genética , Adaptación Fisiológica/genética , Anisotropía , Arabidopsis/crecimiento & desarrollo , Pared Celular/genética , Regulación de la Expresión Génica de las Plantas/genética , Meristema/genética , Meristema/crecimiento & desarrollo , Presión Osmótica , Raíces de Plantas/crecimiento & desarrollo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrolloRESUMEN
BACKGROUND: The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive. METHODS: Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPPα and sAPPß peptides. We evaluate variant's pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort. RESULTS: The mutation was absent from public databases and segregated with the disease. CSF Aß42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPPα peptide, both compared to controls, while sAPPß levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα and sAPPß levels resembled those of controls. Therefore, a decreased sAPPα/sAPPß ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened. CONCLUSIONS: This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of α-secretase. This report encourages future research on ADAM10 enhancers.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Proteína ADAM10/genética , Enfermedad de Alzheimer/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Péptidos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Biomarcadores , Codón sin Sentido , Humanos , Proteínas de la Membrana/genética , Fragmentos de PéptidosRESUMEN
Introduction: Several studies investigating blood biomarkers such as C-reactive protein (CRP) in the prognosis and mortality of stroke have not been conclusive. This may be related to the fact that age has not been taken into account for these analyses. Objective: In the present study, we evaluated the possible relationship of blood markers with the age and clinical characteristics of ischemic stroke patients. Methods: Two groups of acute ischemic stroke patients (≤ 55 years and > 55 years of age) who were paired with a control group were included. CRP, alpha 1 antitrypsin (AAT), complements C3 and C4, microalbuminura, ceruloplasmin, glucose, cholesterol, triglycerides, glutamic-piruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT), gamma glutamiltranspeptidase (GGT), creatinine, and uric acid were determined. Other clinical information, including NIH stroke scale was collected. Results: AAT, ceruloplasmin, microalbuminuria, GPT, GOT and GGT were significantly increased with respect to control subjects in both age groups. Nevertheless, CRP was increased only in patients older than 55 years. CRP and age were directly correlated in stroke patients, but not in the control group joint analysis of age and NIHSS revealed a tendency towards even higher CRP values in older patients with more severe neurological impairment. Levels of CRP increased significantly with age according to NIH score. Conclusions: Age should be considered when evaluating the usefulness of CRP and other blood biomarkers as clinical tools for predicting long or short-term neurological outcome or stroke recurrence events in ischemic stroke patients(AU)
Introducción: Los estudios sobre marcadores sanguíneos incluido la proteína C reactiva (PCR) en el pronóstico y mortalidad del ictus no han sido concluyentes, quizás porque en sus análisis no se ha tenido en cuenta la edad los pacientes. Objetivo: Evaluar la relación de los marcadores sanguíneos con la edad y características clínicas de pacientes con ictus isquémico. Métodos: Se incluyeron en el estudio 2 grupos de pacientes con ictus isquémico (( y > 55 años) quienes fueron pareados con grupos controles. Fueron determinados: PCR, alfa 1 antitripsina (AAT), complementos C3 y C4, microalbuminuria, ceruloplasmina, glucosa, colesterol, triglicéridos, transaminasa glutámico-pirúvico (TGP), transaminasa glutámico-oxalacético (TGO), gamma glutamiltranspeptidasa (GGT), creatinina, y ácido úrico. También, se recogió información clínica (escala neurológica, etiología y localización del ictus). Resultados: La AAT, ceruloplasmina, microalbuminuria, TGP, TGO y GGT aumentaron significativamente respecto al grupo control de ambos grupos de estudio. Sin embargo, la PCR se incrementó solamente en pacientes mayores de 55 años. La PCR se correlacionó directamente con la edad de los pacientes, pero no en el grupo control. A su vez, se observó una tendencia hacia el aumento de la PCR en pacientes mayores de 55 años con mayor la severidad neurológica. Los valores de PCR se incrementaron estadísticamente con la edad de acuerdo al déficit neurológico. Conclusiones: La edad debiera ser considerada en la evaluación de la utilidad de la PCR y de otros marcadores como herramientas clínicas para predecir un desenlace neurológico fatal o recurrencia de nuevos eventos en pacientes con ictus isquémico(AU)
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Humanos , Proteína C-Reactiva , Reacción en Cadena de la Polimerasa , Grupos Control , Selección del Sitio de Tratamiento de Residuos , Accidente Cerebrovascular Isquémico , Grupos de Edad , Estudios de Casos y ControlesRESUMEN
Highly porous scaffolds of Si3N4 are fabricated by direct ink writing method (Robocasting) with a pattern of macroporous cavities of 650-700µm. Two different Si3N4 ink compositions regarding the oxide sintering aids (namely, Y2O3, Al2O3, and SiO2) are tried. Both inks reach solid volume fractions of ~0.40 with about 10-12wt% of polymeric additive content that imparts the necessary pseudoplastic characteristics. The printed structures are sintered under controlled N2 atmosphere either in a conventional graphite furnace or by the spark plasma sintering technique. Skeleton of the scaffolds reaches densities above 95% of the theoretical value with ≈18-24% of linear shrinkage. Analysis of the crystalline phases, microstructure and mechanical properties are comparatively done for both compositions. The bioactivity of these structures is addressed by evaluating the ion release rate in simulated body fluid. In parallel, atomic force microscopy is used to determine the effect of the filaments surface roughness on protein adsorption (Bovine Serum Albumin) for assessing the potential application of 3D-Si3N4 scaffolds in bone regeneration.
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Albúmina Sérica Bovina/metabolismo , Compuestos de Silicona/química , Andamios del Tejido/química , Adsorción , Regeneración Ósea , Huesos , Técnicas In Vitro , Tinta , Iones/metabolismo , Ensayo de Materiales , Microscopía de Fuerza Atómica , Porosidad , Impresión Tridimensional , Compuestos de Silicona/farmacología , Propiedades de SuperficieRESUMEN
BACKGROUND: The diagnostic sensitivity of CSF specific oligoclonal bands (OCBs) in multiple sclerosis (MS), using state of the art methods, has been clearly established to be over 95% in patients with a predominantly Caucasian background. This is not the case for other geographical regions, where reports of OCB prevalence can be much lower, and a relationship between OCB frequency and latitude has been suggested. OBJECTIVE: The aim of the present study was to assess the frequency of OCBs in a cohort of MS patients evaluated at the Institute of Neurology and Neurosurgery (Havana, Cuba), and to review the scientific literature in order to investigate the possible relationship between OCB status and latitude in the region of Latin America. METHODS: Fifty-three patients (47 with definite MS and 6 with clinically isolated syndrome - CIS) were included. Isoelectric focusing (IEF) with IgG immunoblotting for OCB analyses, was performed placing paired CSF and serum samples in the same analytical run. PubMed, Scielo and Google Scholar were searched for papers containing information concerning CSF OCB status (employing isoelectric focusing with IgG immunoblotting) in patients with definite MS in Latin America and the Caribbean. RESULTS: In Cuban patients with definite MS, an OCB prevalence of 87% was observed, while the frequency in CIS patients was lower (67%). The prevailing pattern was that of OCBs restricted to the CSF (type 2), which was observed in 71% of definite MS patients and in all CIS patients with intrathecal IgG synthesis. OCB prevalence was slightly lower, but very close to that reported in Caucasian populations. Comparison with other Latin American countries revealed a significant correlation between OCB prevalence and latitude. CONCLUSIONS: A prevalence of CSF restricted OCBs of 87% was observed in definite MS patients, a frequency which was slightly lower, but similar to that reported in Caucasian populations. The analysis of OCB frequency in Latin American countries revealed a possible relationship between OCB prevalence and latitude, but this must be further investigated in more countries and larger samples of patients.
Asunto(s)
Esclerosis Múltiple , Bandas Oligoclonales , Región del Caribe , Estudios de Cohortes , Humanos , América Latina/epidemiología , Esclerosis Múltiple/epidemiologíaRESUMEN
Marine and freshwater toxins contaminate water resources, shellfish and aquaculture products, causing a broad range of toxic effects in humans and animals. Different core-shell nanoparticles were tested as a new sorbent for removing marine and freshwater toxins from liquid media. Water solutions were contaminated with 20 µg/L of marine toxins and up to 50 µg/L of freshwater toxins and subsequently treated with 250 or 125 mg/L of nanoparticles. Under these conditions, carbon nanoparticles removed around 70% of saxitoxins, spirolides, and azaspiracids, and up to 38% of diarrheic shellfish poisoning toxins. In the case of freshwater toxins, the 85% of microcystin LR was eliminated; other cyclic peptide toxins were also removed in a high percentage. Marine toxins were adsorbed in the first 5 min of contact, while for freshwater toxins it was necessary 60 min to reach the maximum adsorption. Toxins were recovered by extraction from nanoparticles with different solvents. Gymnodinium catenatum, Prorocentrum lima, and Microcystis aeruginosa cultures were employed to test the ability of nanoparticles to adsorb toxins in a real environment, and the same efficacy to remove toxins was observed in these conditions. These results suggest the possibility of using the nanotechnology in the treatment of contaminated water or in chemical analysis applications.
Asunto(s)
Toxinas Marinas/química , Nanoestructuras/química , Compuestos de Espiro/química , Purificación del Agua/métodos , Animales , Dinoflagelados , Agua Dulce/química , Humanos , Fenómenos Magnéticos , Toxinas Marinas/análisis , Microcistinas , Microcystis , Saxitoxina , Alimentos Marinos/análisis , Mariscos/análisis , Intoxicación por Mariscos , Compuestos de Espiro/análisisRESUMEN
Gender diversity has been linked to positive business results. Yet limited data exist to characterize the gender landscape in health technology, a field that draws employees from both biomedical engineering and medicine. To better understand the state of gender diversity in this industry, we developed a survey to explore leadership representation and perceptions of workplace equality, job satisfaction, and work-life balance. Data from 400 + health technology professionals revealed that women are significantly underrepresented in senior leadership and that men and women experience the workplace differently. Men believe in greater numbers than females that senior leaders are focused on recruiting and promoting women, promotion criteria are equitable, and the major barrier to leadership roles for women is work/family balance. In contrast, women perceive a less meritocratic and inclusive workplace in which their ability to rise is hampered by exclusion from influential communication networks and stereotyping/bias. Perhaps as a result, more than one-third of female respondents are considering leaving their current jobs, citing dissatisfaction with management and a desire for greater advancement opportunities. This study highlights significant gender perception differences in health technology that require further study and proactive remediation for the field to fully realize the benefits of gender diversity.