This research recovers the collective memory of elderly people who recall experiences lived alongside the Tagus River in the city of Toledo (Spain). The study develops an individual and collective ...narrative story to add to our understanding of the relationship between society and its environment during the years 1950-1970. A qualitative methodology is used through documentary analysis techniques and in-depth interviews. The results obtained from the testimonies reflect the influence that the Tagus River had as a natural heritage on the socialization and emotions of Toledo society. The sociological study carried out is unique, since it is the first in which, through collective memory, a contrast is made between the enjoyment of a natural fluvial environment in good condition compared to its current state of an ecosystem in deterioration.
Porous carbon materials have been prepared from different precursors (anthracite and carbon fibers) by different activation methods (KOH and CO2), obtaining a series of samples with very different ...porous texture and porous structure. Electrochemical impedance spectroscopy has been used to analyze the kinetics of the charge−discharge process during the behavior of these materials as supercapacitors. Capacitance reduction percentages (CRPs) from the starting value (at the lowest frequency of the measurements) to the value at around 0.02 Hz frequency were calculated for all of the samples. The results pointed out that, from a kinetic point of view, porous materials with wider micropore size distribution (MPSD) have a better performance, because porosity is accessible to the electrolyte even at high charge−discharge rates. In addition, quite different behavior between activated carbons (ACs) and activated carbon fibers (ACFs) has been observed when Na2SO4 is used as the electrolyte; a widening of the porosity produces a lower CRP (better kinetic behavior) in ACF than in AC, which is most likely due to the existence of a smaller tortuosity of networks of porosity in ACF than in AC. This different behavior is much less important when H2SO4 is used as the electrolyte, which is due to the higher mobility of proton in solution compared to any other ion. Thus, kinetics of the double-layer formation is improved using (i) samples with wide MPSD, (ii) samples with a porous texture with low tortuosity, and (iii) acidic medium as the electrolyte.
Abstract
Background
The majority of cases of Dent’s disease are caused by pathogenic variants in the
CLCN5
gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal ...tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion
CLCN5
variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity.
Case presentation
A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in
CLCN5
, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant.
Conclusions
The identification of this novel variant in four individuals with features of Dent’s disease, has led to the re-classification of the variant to one of likely pathogenicity.
As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.
During 2000 to 2009, data on people undergoing HIV testing and on those newly diagnosed with HIV were collected in a network of 20 Spanish clinics specialising in sexually transmitted infections ...and/or HIV testing and counselling. The number of tests performed, overall and disaggregated by different variables, was obtained. HIV prevalence among first-time testers and HIV incidence among repeat testers were calculated. To evaluate trends, joinpoint regression models were fitted. In total, 236,939 HIV tests were performed for 165,745 individuals. Overall HIV prevalence among persons seeking HIV testing was 2.5% (95% CI: 2.4 to 2.6). Prevalence was highest in male sex workers who had sex with other men (19.0% (95% CI: 16.7 to 21.4)) and was lowest in female sex workers (0.8% (95% CI: 0.7 to 0.9)). Significant trends in prevalence were observed in men who have sex with men (MSM) (increasing) and heterosexual individuals (decreasing). The incidence analysis included 30,679 persons, 64,104 person-years (py) of follow-up and 642 seroconversions. The overall incidence rate (IR) was 1.0/100 py (95% CI: 0.9/100 to 1.1/100). Incidence was significantly higher in men and transgender females than in women (1.8/100 py (95% CI: 1.6 to 1.9), 1.2/100 py (95% CI: 0.5 to 2.8) and 0.1/100 py (95% CI: 0.09 to 0.2) respectively) and increased with age until 35–39 years. IRs in MSM and people who inject drugs were significantly greater than in heterosexual individuals (2.5/100 py (95% CI: 2.3 to 2.7), 1.6/100 py (95% CI: 1.1 to 2.2) and 0.1/100 py (95% CI: 0.09 to 0.2) respectively), and an upward trend was observed in MSM. Our results call for HIV prevention to be reinforced in MSM and transgender women in Spain.
Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed ...whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was
(
= 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that
,
have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.
The objective of this study was to employ ensemble clustering and tree-based risk model approaches to identify interactions between clinicogenomic features for colorectal cancer using the 100,000 ...Genomes Project.
Among the 2211 patients with colorectal cancer (mean age of diagnosis: 67.7; 59.7% male), 16.3%, 36.3%, 39.0% and 8.4% had stage 1, 2, 3 and 4 cancers, respectively. Almost every patient had surgery (99.7%), 47.4% had chemotherapy, 7.6% had radiotherapy and 1.4% had immunotherapy. On average, tumour mutational burden (TMB) was 18 mutations/Mb and 34.4%, 31.3% and 25.7% of patients had structural or copy number mutations in KRAS, BRAF and NRAS, respectively. In the fully adjusted Cox model, patients with advanced cancer stage 3 hazard ratio (HR) = 3.2; p < 0.001; stage 4 HR = 10.2; p < 0.001 and those who had immunotherapy (HR = 1.8; p < 0.04) or radiotherapy (HR = 1.5; p < 0.02) treatment had a higher risk of dying. The ensemble clustering approach generated four distinct clusters where patients in cluster 2 had the best survival outcomes (1-year: 98.7%; 2-year: 96.7%; 3-year: 93.0%) while patients in cluster 3 (1-year: 87.9; 2-year: 70.0%; 3-year: 53.1%) had the worst outcomes. Kaplan-Meier analysis and log rank test revealed that the clusters were separated into distinct prognostic groups (p < 0.0001). Survival tree or recursive partitioning analyses were performed to further explore risk groups within each cluster. Among patients in cluster 2, for example, interactions between cancer stage, grade, radiotherapy, TMB, BRAF mutation status were identified. Patients with stage 4 cancer and TMB ≥ 1.6 mutations/Mb had 4 times higher risk of dying relative to the baseline hazard in that cluster.
•Transglutaminases (TGases) are enzymes of a great importance in biological processes that regulate protein cross-linking using different substrates. There are much studied in animals, humans and ...microorganisms. One of the most studied is the Factor XIII of blood coagulation.•Plant TGases are scarcely known. Only maize (TGZ) and, recently, rice TGase (TGO) had been cloned until present (both in our research group).•In the present work, some plastidial TGO-related proteins are identified for the first time by means of a proteomic in vitro system.•The Dynamic Platform Fluidigm™ was used for transcriptomic in vivo analyses of 30 different plastidial genes. The use of this Platform is very new. This is the first time that it has been used to analyze relative mRNA expression of plant leaf genes in different environmental conditions.•The results revealed that TGO is light dependent, regulated by the illumination period, and related to plastidial proteins specially that implicated in photoprotection and in thylakoid electrochemical gradient. These relationships seem to be also connected with the day/night cycling of gene expression, suggesting that tgo expression might be regulated in a similar manner as other circadian genes, perhaps by the mRNA expression of its own substrates.
The recently cloned rice transglutaminase gene (tgo) is the second plant transglutaminase identified to date (Campos et al. Plant Sci. 205–206 (2013) 97–110). Similarly to its counterpart in maize (tgz), this rice TGase was localized in the chloroplast, although in this case not exclusively. To further characterise plastidial tgo functionality, proteomic and transcriptomic studies were carried out to identify possible TGO-related proteins. Some LHCII antenna proteins were identified as TGO related using an in vitro proteomic approach, as well as ATPase and some PSII core proteins by mass spectrometry. To study the relationship between TGO and other plastidial proteins, a transcriptomic in vivo Dynamic Array (Fluidigm™) was used to analyse the mRNA expression of 30 plastidial genes with respect to that of tgo, in rice plants subjected to different periods of continuous illumination. The results indicated a gene-dependent tendency in the expression pattern that was related to tgo expression and to the illumination cycle. For certain genes, including tgo, significant differences between treatments, principally at the initiation and/or at the end of the illumination period, connected with the day/night cycling of gene expression, were observed. The tgo expression was especially related to plastidial proteins involved in photoprotection and the thylakoid electrochemical gradient.
Abstract
The aim of this study was to investigate coenzyme Q10 (CoQ
10
) biosynthesis pathway defects in inherited retinal dystrophy. Individuals affected by inherited retinal dystrophy (IRD) ...underwent exome or genome sequencing for molecular diagnosis of their condition. Following negative IRD gene panel analysis, patients carrying biallelic variants in CoQ
10
biosynthesis pathway genes were identified. Clinical data were collected from the medical records. Haplotypes harbouring the same missense variant were characterised from family genome sequencing (GS) data and direct Sanger sequencing. Candidate splice variants were characterised using Oxford Nanopore Technologies single molecule sequencing. The CoQ
10
status of the human plasma was determined in some of the study patients. 13 individuals from 12 unrelated families harboured candidate pathogenic genotypes in the genes:
PDSS1, COQ2, COQ4
and
COQ5
. The
PDSS1
variant c.589 A > G was identified in three affected individuals from three unrelated families on a possible ancestral haplotype. Three variants (
PDSS1
c.468-25 A > G,
PDSS1
c.722-2 A > G,
COQ5
c.682-7 T > G) were shown to lead to cryptic splicing. 6 affected individuals were diagnosed with non-syndromic retinitis pigmentosa and 7 had additional clinical findings. This study provides evidence of CoQ
10
biosynthesis pathway gene defects leading to non-syndromic retinitis pigmentosa in some cases. Intronic variants outside of the canonical splice-sites represent an important cause of disease. RT-PCR nanopore sequencing is effective in characterising these splice defects.
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