Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by the progressive and irreversible loss of vision. We previously found that intraperitoneal administration of ...Adalimumab, a monoclonal anti‐TNFα antibody, slowed down retinal degeneration in the murine model of RP, the rd10 mice. The aims of this study were to improve its neuroprotective effect and to deepen understanding of the molecular mechanisms involved in this effect. We analyzed (i) the in vitro effect of Adalimumab on the TNFα‐mediated cell death in retinal cells; (ii) the effect of a single intravitreal injection of Adalimumab on retinal degeneration in rd10 mice at postnatal day (P) 23. In vitro studies showed that TNFα induced caspase and poly ADP ribose polymerase (PARP) activation, downregulation of (kinase receptor‐interacting protein 1) RIPK1 and upregulation of RIPK3 in retinal cells. Adalimumab reduced cell death probably through the inhibition of caspase 3 activation. In vivo studies suggested that PARP and NLRP3 inflammasome are mainly activated and to a lesser extent caspase‐dependent mechanisms in rd10 retinas at P23. Necroptosis seems to be inhibited by the downregulation of RIPK1. Adalimumab prevented from retinal degeneration without affecting caspase ‐dependent mechanisms but decreasing PARP activation, microglia activation as well as NLRP3 inflammasome.
Inherited retinal dystrophies (IRDs) are a group of retinal disorders that cause progressive and severe loss of vision because of retinal cell death, mainly photoreceptor cells. IRDs include ...retinitis pigmentosa (RP), the most common IRD. IRDs present a genetic and clinical heterogeneity that makes it difficult to achieve proper treatment. The progression of IRDs is influenced, among other factors, by the activation of the immune cells (microglia, macrophages, etc.) and the release of inflammatory molecules such as chemokines and cytokines. Upregulation of tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, is found in IRDs. This cytokine may influence photoreceptor cell death. Different cell death mechanisms are proposed, including apoptosis, necroptosis, pyroptosis, autophagy, excessive activation of calpains, or parthanatos for photoreceptor cell death. Some of these cell death mechanisms are linked to TNFα upregulation and inflammation. Therapeutic approaches that reduce retinal inflammation have emerged as useful therapies for slowing down the progression of IRDs. We focused this review on the relationship between retinal inflammation and the different cell death mechanisms involved in RP. We also reviewed the main anti-inflammatory therapies for the treatment of IRDs.
Yellow lupin (Lupinus luteus L.) is a minor legume crop characterized by its high seed protein content. Although grown in several temperate countries, its orphan condition has limited the generation ...of genomic tools to aid breeding efforts to improve yield and nutritional quality. In this study, we report the construction of 454-expresed sequence tag (EST) libraries, carried out comparative studies between L. luteus and model legume species, developed a comprehensive set of EST-simple sequence repeat (SSR) markers, and validated their utility on diversity studies and transferability to related species.
Two runs of 454 pyrosequencing yielded 205 Mb and 530 Mb of sequence data for L1 (young leaves, buds and flowers) and L2 (immature seeds) EST- libraries. A combined assembly (L1L2) yielded 71,655 contigs with an average contig length of 632 nucleotides. L1L2 contigs were clustered into 55,309 isotigs. 38,200 isotigs translated into proteins and 8,741 of them were full length. Around 57% of L. luteus sequences had significant similarity with at least one sequence of Medicago, Lotus, Arabidopsis, or Glycine, and 40.17% showed positive matches with all of these species. L. luteus isotigs were also screened for the presence of SSR sequences. A total of 2,572 isotigs contained at least one EST-SSR, with a frequency of one SSR per 17.75 kbp. Empirical evaluation of the EST-SSR candidate markers resulted in 222 polymorphic EST-SSRs. Two hundred and fifty four (65.7%) and 113 (30%) SSR primer pairs were able to amplify fragments from L. hispanicus and L. mutabilis DNA, respectively. Fifty polymorphic EST-SSRs were used to genotype a sample of 64 L. luteus accessions. Neighbor-joining distance analysis detected the existence of several clusters among L. luteus accessions, strongly suggesting the existence of population subdivisions. However, no clear clustering patterns followed the accession's origin.
L. luteus deep transcriptome sequencing will facilitate the further development of genomic tools and lupin germplasm. Massive sequencing of cDNA libraries will continue to produce raw materials for gene discovery, identification of polymorphisms (SNPs, EST-SSRs, INDELs, etc.) for marker development, anchoring sequences for genome comparisons and putative gene candidates for QTL detection.
: The purpose of this study was to identify distinct motivational profiles in high school Physical Education students. These motivational profiles were examined in relation to controlling teacher ...behaviors, as well as to various psychological correlates including the perceived importance of physical activity to the student, student intentions to be physically active, psychological need satisfaction and current physical activity levels.
416 high school Physical Education students comprised the sample.
: Cluster analysis and additional multivariate analyses revealed two motivational profiles,
= 0.56,
(7, 431) = 45.50,
< 0.01. The "Self-Determined" profile was characterized by high levels of self-determined motivation; high levels of competence, autonomy and relatedness; importance of physical activity; stronger intentions to engage in physical activity; and greater current actual physical activity involvement. The "Less Self-Determined" profile was associated with the perception of controlling teacher behaviors, and with greater external regulation and amotivation.
: These findings help to provide new insights into the explanation of student motivation in Physical Education and the design of intervention programs.
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•New models for water classification using machine learning and a simulated dataset.•Comparison of these new nonparametric models against the WClassHLR parametric model.•Application ...of the new water multidimensional classification scheme to groundwater samples.
We proposed four new models (WClassCB, WClassVL WClassVP WClassVR) for water classification using Categorical Boosting (CatBoost) and Support Vector Machines (SVM) with three kernels: linear, polynomial, and radial basis function. The new models were compared with the recently proposed WClassHLR (7 hybrid log-ratio) model based on linear discriminant analysis and canonical analysis techniques. A training database (50,000 samples) and another independent validation database (8,000 samples) of ionic charge-balanced concentrations of 4 cations (Ca,Mg,Na, and K) and 4 anions (SO4, Cl, HCO3, and CO3) were generated through Monte Carlo simulations. The initial 16 classes were assigned from the highest cation and anion molar concentrations (GMC criteria, i.e. greater molar concentration model). Seven hybrid log-ratio transformations were used as features for training and external validation of the multidimensional classification models. These models generate probability values for each of the output classes allowing us to determine hybrid water types improving the possible water types to 256. WClassCB model showed the best accuracy values in the training set. However, WClassVL model is the recommended procedure because it generalizes better than other models in the external validation set. The new models outperform the recently proposed WClassHLR with up to a 7% difference. The usefulness of all models (WClassHLR, WClassCB, WClassVL, WClassVP, WClassVR) is illustrated by four applications to groundwater samples from India and Nigeria. All models have difficulties in classifying real samples when there is more than one major cation or anion, but they can recover the classification suggesting hybrid water types. The new computer program WaterClaSys_ML has been developed for applying these new models.
Companies belonging to broadly globalized sectors are looking for keys and guidelines that will allow them to stand out from their competitors in order to win the contracts tendered on a global ...scale. The study conducted in this research has found the importance of following the principles of the standards of Environmental Management (EM; ISO 14001), Corporate Social Responsibility (CSR; ISO 26000), Quality Management (QM; ISO 9001), and Occupational Health and Safety Assessment Series (OSHAS 18001) in the shipbuilding industry and its relationship with firms' performance. This research proposes a new measurement index that evaluates the degree of certification of the industry over time regarding EM, CSR, QM, and Occupational Health, demonstrating a link between the evolution of companies' results (in terms of orderbooks, completions, and new orders) and the implantation of official certifications and their maturity (time elapsed since certification).
Background
The inflammatory response triggered in dogs after laparoscopic ovariectomy (LapOV) or ovariectomy through mini‐celiotomy (COV) has never been compared using the neutrophil‐to‐lymphocyte ...ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and systemic inflammatory index (SII).
Methods
Bitches underwent LapOV (n = 25) or COV (n = 25). NLR, PLR and SII were calculated 1 hour before ovariectomy (T0) and 2−3, 6−8 and 20−24 hours (T1−T3) after surgery.
Results
Surgical time was longer in the LapOV group. Changes over time were observed in the NLR, PLR and SII in both groups (p < 0.001). PLR at baseline and T1 (p = 0.03 and 0.01) and NLR, PLR and SII at T2 (p = 0.01, 0.01 and 0.009) were higher in the LapOV group than in the COV group, but they did not differ at T3.
Limitations
The overrepresentation of Greyhounds in the LapOV group and the short‐term follow‐up are the study's main limitations.
Conclusion
Although an inflammatory peak was observed 6−8 hours after COV or LapOV, it was higher after the laparoscopy. However, there was no difference in the bitches' inflammatory status 24 hours after surgery.
Caveolin-1 (CAV1) is a scaffolding protein with a controversial role in cancer. This review will initially discuss earlier studies focused on the role as a tumor suppressor before elaborating ...subsequently on those relating to function of the protein as a promoter of metastasis. Different mechanisms are summarized illustrating how CAV1 promotes such traits upon expression in cancer cells (intrinsic mechanisms). More recently, it has become apparent that CAV1 is also a secreted protein that can be included into exosomes where it plays a significant role in determining cargo composition. Thus, we will also discuss how CAV1 containing exosomes from metastatic cells promote malignant traits in more benign recipient cells (extrinsic mechanisms). This ability appears, at least in part, attributable to the transfer of specific cargos present due to CAV1 rather than the transfer of CAV1 itself. The evolution of how our perception of CAV1 function has changed since its discovery is summarized graphically in a time line figure.
This article draws on existing debates on standardization versus adaptation to propose two possible pathways for digital servitization. On the one hand, the standardization pathway posits that ...digital transformation enables servitized firms to make their service-based business model more standardized, and as a result, scalable. On the other hand, the adaptation pathway advocates that servitization enables highly digitalized firms to make their digital offerings more adaptable to heterogeneous customer needs, and as a result, customizable. We investigate which of these two paths integrates more effectively, and which one is thus likely to prevail in the long run. We use a purpose-built survey of 127 Spanish product firms to test these relationships using partial least squares structural equation modelling (PLS-SEM), and test single- and multi-mediation models. The results corroborate the existence of both pathways, but also suggest that the standardization pathway contributes more to performance than the adaptation pathway. This is consistent with historical transitions in adoption (services existed before digital transformation) and services being dependent on digital technologies delivered remotely. These findings suggest the benefits of customization in digital servitization are lower than previous studies seem to imply, and provide important managerial implications.
Copy number variants (CNVs) are intermediate-scale structural variants containing copy number changes involving DNA fragments of between 1 kb and 5 Mb. Although known to account for a significant ...proportion of the genetic burden in human disease, the role of CNVs (especially small CNVs) is often underestimated, as they are undetectable by traditional Sanger sequencing. Since the development of next-generation sequencing (NGS) technologies, several research groups have compared depth of coverage (DoC) patterns between samples, an approach that may facilitate effective CNV detection. Most CNV detection tools based on DoC comparisons are designed to work with whole-genome sequencing (WGS) or whole-exome sequencing (WES) data. However, few methods developed to date are designed for custom/commercial targeted NGS (tg-NGS) panels, the assays most commonly used for diagnostic purposes. Moreover, the development and evaluation of these tools is hindered by (i) the scarcity of thoroughly annotated data containing CNVs and (ii) a dearth of simulation tools for WES and tg-NGS that mimic the errors and biases encountered in these data. Here, we review DoC-based CNV detection methods described in the current literature, assess their performance with simulated tg-NGS data, and discuss their strengths and weaknesses when integrated into the daily laboratory workflow. Our findings suggest that the best methods for CNV detection in tg-NGS panels are DECoN, ExomeDepth, and ExomeCNV. Regardless of the method used, there is a need to make these programs more user-friendly to enable their use by diagnostic laboratory staff who lack bioinformatics training.
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