Resultados de investigación

Appendix B. Coinvestigators - The Jain COS Consortium., Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R2 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R2 0.18). EK scores were strongly associated with PUL (Pseudo R2 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R2 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy., Peer reviewed

The available data contains: sky images before, during, and after the flash, event file, corresponding ARF and RMF, light-curves. See README file for further information., Peer reviewed

Figure S1. Distribution of z-scores for individual items across patients grouped by major domains (i.e., each count represents the score of one item in one of the patients’ assessment) Values less than 0 indicate items where brain tumour patients showed lower performance than healthy controls. Table S1. Individual cognitive tests included in the OCS-Bridge assessment and the traditional neuropsychology battery. Table S2. Combined domains across neuropsychological testing and OCS-Bridge testing. Table S3. OCS-Bridge screening and neuropsychological assessments completed by each participant. Table S4. Average total number of cognitive deficits and standard deviations across patients for each domain and assessment. A positive T value indicates a larger number of deficits detected by traditional neuropsychology compared with OCS-BRIDGE., Peer reviewed

1 table. -- Real activity (measured at physiological conditions) and total activity (measured at optimal enzymatic conditions) of the major digestive enzymes in the stomach (pepsin) and pyloric caeca (trypsin, chymotrypsin, leucine aminopeptidase and lipase) of S. dumerili., The study of fish digestive biochemistry is essential to understand factors that affect the net efficiency of food transformation and growth, and therefore aquaculture profitability. The aim of the present study was to assess the activity and functional characteristics of key digestive enzymes in juveniles of greater amberjack (Seriola dumerili), as well as the possible modulation of their relative importance by water temperature. For that, a combination of biochemical assays and substrate-SDS-PAGE were used. Under physiological conditions pepsin activity was negligible. Chymotrypsin was the most active enzyme in the digestive tract of the greater amberjack, while lipase was the enzyme with lower activity, though both enzymes in addition to trypsin were responsive to water temperature as revealed by discriminant analysis. Seriola dumerili showed to have pH-sensitive and, except for chymotrypsin, thermally robust proteases. Inhibition assays showed the major importance of serine proteases and revealed inverse trypsin and chymotrypsin responses to environmental temperature, with higher trypsin contribution in 26°C-fish while higher chymotrypsin contribution in 18°C-fish. Zymograms revealed three isotrypsin and three isochymotrypsin enzymes, with no variation in the presence of particular isoforms among rearing temperatures. However, they confirmed the role of chymotrypsin activity in providing digestive plasticity, with one of the isoforms being more active at lower temperatures. Thus, results indicate that variation in the relative contribution of chymotrypsin isoenzymes to a particular environmental temperature occurs due to different physic-chemical features of isoforms as a source of functional flexibility. This study assessed for the first time the effects of rearing temperature on greater amberjack digestive enzymes, increasing the knowledge on its digestive biochemistry, and aiding in the improvement of management practices for this species industrialization., Peer reviewed

The extreme currents matrix E and the explicite xtreme currents of KNS-LES, KNSCI and KNSCI-LES models., Peer reviewed

1 figure. -- Effect of Ph on the stability of trypsin (TRY), chymotripsin (CHY), leucine aminopeptidase (LAP), lipase (LIP) and pepsin (PP) activities from pyloric caeca and stomach of S. Dumerili adapted to different rearing temperatures (18, 22 and 26º C)., The study of fish digestive biochemistry is essential to understand factors that affect the net efficiency of food transformation and growth, and therefore aquaculture profitability. The aim of the present study was to assess the activity and functional characteristics of key digestive enzymes in juveniles of greater amberjack (Seriola dumerili), as well as the possible modulation of their relative importance by water temperature. For that, a combination of biochemical assays and substrate-SDS-PAGE were used. Under physiological conditions pepsin activity was negligible. Chymotrypsin was the most active enzyme in the digestive tract of the greater amberjack, while lipase was the enzyme with lower activity, though both enzymes in addition to trypsin were responsive to water temperature as revealed by discriminant analysis. Seriola dumerili showed to have pH-sensitive and, except for chymotrypsin, thermally robust proteases. Inhibition assays showed the major importance of serine proteases and revealed inverse trypsin and chymotrypsin responses to environmental temperature, with higher trypsin contribution in 26°C-fish while higher chymotrypsin contribution in 18°C-fish. Zymograms revealed three isotrypsin and three isochymotrypsin enzymes, with no variation in the presence of particular isoforms among rearing temperatures. However, they confirmed the role of chymotrypsin activity in providing digestive plasticity, with one of the isoforms being more active at lower temperatures. Thus, results indicate that variation in the relative contribution of chymotrypsin isoenzymes to a particular environmental temperature occurs due to different physic-chemical features of isoforms as a source of functional flexibility. This study assessed for the first time the effects of rearing temperature on greater amberjack digestive enzymes, increasing the knowledge on its digestive biochemistry, and aiding in the improvement of management practices for this species industrialization., Peer reviewed

eAppendix. Additional acknowledgments eMethods. eFigure 1. Flowchart describing the number of individuals remaining at each filtering steps eFigure 2. V236E and R251G are associated with decreased AD risk across dataset in APOE-stratified sensitivity analyses eFigure 3. APOE ε3/ε3[V236E] individuals have a lower AD risk than APOE ε2/ε3 individuals and APOE ε3/ε4[R251G] have a risk equivalent to ε2/ε3 carriers despite carrying 1 ε4 allele, regardless of the EUR ancestry cutoff for admixed Europeans and Europeans eTable 1. Queried cohort overview to identify admixed and European ancestry individuals in the ADSP discovery and ADGC internal replication eTable 2. Overview of ADSP studies with whole-exome sequencing (WES) and/or whole-genome sequencing (WGS) available at NIAGADS DSS (NG00067) eTable 3. Demographic characteristics of the cohorts queried for discovery and internal replication samples eTable 4. Missense variants on the APOE canonical transcript reported in gnomADv.3.1 eTable 5. Demographic characteristics per cohort in ADSP discovery and ADGC internal replication after ancestry selection, quality control, and duplicates removal eTable 6. APOE missense variants rs769452-C (APOE[L28P]), rs199768005-A (APOE[V236E]), and rs267606661-G (APOE[R251G]) allelic breakdown by APOE main genotype eTable 7. V236E and R251G association in primary and secondary analyses, nonstratified and APOE stratified eTable 8. Nonstratified sensitivity analyses at various European ancestry cutoffs eTable 9. Sensitivity analysis, including all dementia in the CCHS and CGPS data set, slightly strengthens the V236E and R251G associations with decreased AD risk eTable 10. Sensitivity analysis, excluding the UK Biobank proxy-AD phenotype from the meta-analysis, results in slight worsening of the P values of the V236E and R251G associations with decreased AD risk eReferences. Supplemental Online Content: Nonauthor Collaborators., Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging., Peer reviewed

1 figure. -- Effect of Ph on the stability of trypsin (TRY), chymotripsin (CHY), leucine aminopeptidase (LAP), lipase (LIP) and pepsin (PP) activities from pyloric caeca and stomach of S. Dumerili adapted to different rearing temperatures (18, 22 and 26º C)., The study of fish digestive biochemistry is essential to understand factors that affect the net efficiency of food transformation and growth, and therefore aquaculture profitability. The aim of the present study was to assess the activity and functional characteristics of key digestive enzymes in juveniles of greater amberjack (Seriola dumerili), as well as the possible modulation of their relative importance by water temperature. For that, a combination of biochemical assays and substrate-SDS-PAGE were used. Under physiological conditions pepsin activity was negligible. Chymotrypsin was the most active enzyme in the digestive tract of the greater amberjack, while lipase was the enzyme with lower activity, though both enzymes in addition to trypsin were responsive to water temperature as revealed by discriminant analysis. Seriola dumerili showed to have pH-sensitive and, except for chymotrypsin, thermally robust proteases. Inhibition assays showed the major importance of serine proteases and revealed inverse trypsin and chymotrypsin responses to environmental temperature, with higher trypsin contribution in 26°C-fish while higher chymotrypsin contribution in 18°C-fish. Zymograms revealed three isotrypsin and three isochymotrypsin enzymes, with no variation in the presence of particular isoforms among rearing temperatures. However, they confirmed the role of chymotrypsin activity in providing digestive plasticity, with one of the isoforms being more active at lower temperatures. Thus, results indicate that variation in the relative contribution of chymotrypsin isoenzymes to a particular environmental temperature occurs due to different physic-chemical features of isoforms as a source of functional flexibility. This study assessed for the first time the effects of rearing temperature on greater amberjack digestive enzymes, increasing the knowledge on its digestive biochemistry, and aiding in the improvement of management practices for this species industrialization., Peer reviewed

1 figure. -- 13% substrate SDS-PAGE showing caseinolysc activity bands in pyloric caeca extracts of individual S. dumerili adapted to different rearing temperatures (18, 22 and 26º C). Get incubation temperature 37º C., The study of fish digestive biochemistry is essential to understand factors that affect the net efficiency of food transformation and growth, and therefore aquaculture profitability. The aim of the present study was to assess the activity and functional characteristics of key digestive enzymes in juveniles of greater amberjack (Seriola dumerili), as well as the possible modulation of their relative importance by water temperature. For that, a combination of biochemical assays and substrate-SDS-PAGE were used. Under physiological conditions pepsin activity was negligible. Chymotrypsin was the most active enzyme in the digestive tract of the greater amberjack, while lipase was the enzyme with lower activity, though both enzymes in addition to trypsin were responsive to water temperature as revealed by discriminant analysis. Seriola dumerili showed to have pH-sensitive and, except for chymotrypsin, thermally robust proteases. Inhibition assays showed the major importance of serine proteases and revealed inverse trypsin and chymotrypsin responses to environmental temperature, with higher trypsin contribution in 26°C-fish while higher chymotrypsin contribution in 18°C-fish. Zymograms revealed three isotrypsin and three isochymotrypsin enzymes, with no variation in the presence of particular isoforms among rearing temperatures. However, they confirmed the role of chymotrypsin activity in providing digestive plasticity, with one of the isoforms being more active at lower temperatures. Thus, results indicate that variation in the relative contribution of chymotrypsin isoenzymes to a particular environmental temperature occurs due to different physic-chemical features of isoforms as a source of functional flexibility. This study assessed for the first time the effects of rearing temperature on greater amberjack digestive enzymes, increasing the knowledge on its digestive biochemistry, and aiding in the improvement of management practices for this species industrialization., Peer reviewed

14 pages. -- Supplementary description of methods: 1.1. Chemical analysis of pesticides: extraction procedure and LC-MS/MS analysis; 1.2. Acetylcholinesterase (AChE) activity. -- Table S1. MRM conditions used in UPLC-MS/MS determination of pesticides selected. Two transitions (precursor ion →product ion) of each compound were analyzed. -- Table S2. Ranges of nominal and quantified concentrations in μg/L for the two pesticides used and the metabolite analyzed in the colonization assays. -- Table S3. Results of the Chi-square test to check statistically significant differences between the percentage of colonization achieved by the organisms in each chamber at 48h in the pesticide experiments and the expected value (100%). -- Table S4. Results of the within-group Kruskal-Wallis test to check statistically significant differences between chambers (source of variation) for the percentage of colonization of D. magna achieved at 48h in each pesticide experiment, together with the significant results of the pairwise post hoc test. -- Table S5. Results of the between-group Kruskal-Wallis test to check statistically significant differences between colonization experiments and chambers (sources of variation) for the percentage of colonization of D. magna at 48h, together with the significant results of the pairwise post hoc test. -- Table S6. Mean, standard error (SE), maximum and minimum values obtained for the mobility variables analyzed in D. magna after 48 h of exposure to the different study treatments. -- Table S7. Results of PERMANOVA ONE-WAY test to check statistically significant differences between study treatments for the mobility variables evaluated, together with the significant results of the pairwise post hoc test. -- Table S8. Results of Kruskal-Wallis test to check statistically significant differences between study treatments for the average vertical speed (study variable with non-normal distribution according to Shapiro-Wilk test), together with the significant results of the pairwise post hoc test and Dunn´s multiple comparisons test (specific comparisons with the control treatment). -- Table S9. One-way ANOVA test to check statistically significant differences among treatments for the remaining mobility variables evaluated, together with the significant results of the pairwise post hoc test and Dunnett´s multiple comparisons test (specific comparisons with the control treatment). -- Table S10. Mean, standard error (SE), maximum and minimum values obtained for the AChE activity in D. magna after 48 h of exposure to the different study treatments. -- Table S11. One-way ANOVA test to check statistically significant differences among treatments for the acetylcholinesterase (AChE) activity, together with the significant results of the pairwise post hoc test. -- Fig. S1. HeMHAS – Heterogeneous Multi-Habitat Assay System (version #3) used in the colonization experiments. -- Fig. S2. Detail of one of the compartments of the HeMHAS together with two gates that connect it to the adjacent chambers throughout a rotary locking system. -- Fig. S3. Picture of D. magna individually disposed in four wells of culture plates for analysis of horizontal swimming behavior. -- Fig. S4. Percentage of organisms (A) and colonization response (B) achieved in each chamber in the control test at 48h with ±SE of four replicates. -- Fig. S5. PCA analysis of the responses obtained for the mobility variables analysed in D. magna exposed to the different study treatments., Peer reviewed