Multiple facets of diversity effects on plant productivity: species richness, functional diversity, species identity and intraspecific competition

International audienc

Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement

Background: The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in TTC7A have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. Objectives: This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. Methods: Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. Results: We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. Conclusions: These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.</p

Human papillomavirus infection in “young” versus “old” patients with squamous cell carcinoma of the head and neck

Background Human papillomavirus (HPV) represents a potential risk factor for squamous cell cancer of the head and neck (SCCHN). We evaluated the prevalence of HPV DNA in patients with SCCHN diagnosed at the University of Michigan from 1994–1996. Methods Patients were stratified by age at diagnosis as “young” (50 years; median, 66). Fourteen “young” and 14 “old” were matched for tumor site, and 4 additional “old” patients were included. Specimens were analyzed by polymerase chain reaction for HPV DNA using 2 sets of consensus primers. HPV sequences were confirmed by Southern blot hybridization and typed with type-specific probes. Results Overall, 15 of 32 (46.9%) samples contained HPV sequences. HPV 16 was detected in 9 of 15 (60%), HPV-18 in 1 of 15 (6.6%), and 5 of 15 (33.3%) remained untyped by multiple methods. When stratified, 7 of 14 (50%) “young” were HPV-positive compared with 8 of 18 (44.4%) “old” ( p = .76). Survival in patients with HPV-positive SCCHN was significantly longer than that for HPV-negative patients. Conclusions The incidence of HPV in “young” versus “old” is not significantly different, suggesting similar roles for both groups. Patients with HPV-positive tumors may have a survival advantage relative to patients with HPV-negative tumors. © 2000 John Wiley & Sons, Inc. Head Neck 22: 649–657, 2000.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35115/1/2_ftp.pd

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

How robust is the link between working memory for serial order and lexical skills in children?

The link between verbal working memory (WM) and vocabulary development has been explored extensively. At the same time, the vast majority of studies in this field used lexical tasks that generally involved a high WM demands, leading to an unclear understanding of this link. The present study re-explored the link between WM for serial order, WM for item information and lexical abilities by administering, to 92 children aged 4-to-6 years, both standard receptive vocabulary tasks with a high WM demands and single picture naming tasks with minimal WM demands. Analyses provided strong evidence for a specific link between serial order WM and both vocabulary measures, with a particularly important link with the rare noun subtask and the absence of link with verbs. These results suggest that the link between lexical abilities and verbal WM in young children is robust and not inflated by the WM demands of specific vocabulary tasks

Serum Albumin Kinetics in Major Ovarian, Gastrointestinal, and Cervico Facial Cancer Surgery

Hypoalbuminemia in major cancer surgery can lead to postoperative short and long-term complications. Our study was designed to detect albumin variations in three major cancer surgeries: ovarian debulking (DBK), major abdominal gastrointestinal surgery (ABD), and major cervico-facial, or ear, nose and throat cancer surgery (ENT). Single-center prospective study inclusion criteria were non-emergency procedures scheduled to last at least five hours. We performed hourly perioperative monitoring of the patients&rsquo; albuminemia and hemoglobinemia. Electronic charts were followed for at least five years for survival analysis. Sixty-three patients were analyzed: 30 in the DBK group, 13 in the ABD group, and 20 in the ENT group. There was a significant difference in albumin decrease between the ENT group and the two others (&minus;19% at six hours in the ENT group versus -49% in the debulking group and &minus;31% in the ABD group (p &lt; 0.05). There was no significant difference between the DBK and ABD groups. The decrease in hemoglobin was not significantly different between the groups, and no significant difference was observed in long-term survival. DBK and ABD surgery yielded significant hypoalbuminemia. Therefore, the extent of decrease in serum albumin is probably not the only etiology of the specific postoperative complications of these major surgeries. No significant difference was noticed in five-year mortality, and no correlation was found in relation to the degree of intraoperative albumin kinetics

Neural evidence for a separation of semantic and phonological control processes.

peer reviewedThere remain major doubts about the nature and domain specificity of inhibitory control processes, both within and between cognitive domains. This study examined inhibitory processes within the language domain, by contrasting semantic versus phonological inhibitory control. In an fMRI experiment, elderly participants performed phonological and semantic inhibitory control tasks involving resistance to highly or weakly interfering stimuli. In the semantic domain, inhibitory control effects, contrasting high vs. low interference control levels, were observed at univariate and multivariate levels in all fronto-parieto-temporal region-of-interests. In the phonological domain, inhibitory control effects were observed only at multivariate levels, and were restricted to the pars triangularis of the bilateral inferior frontal gyrus and to the left middle temporal gyrus. Critically, no reliable multivariate cross-domain prediction of neural patterns associated with inhibitory control was observed. This study supports a functional dissociation of the neural substrates associated with inhibitory control for phonological vs. semantic domains

La précision des représentations neuronales sous-tendant la mémoire de travail auditivo-verbale

Working memory (WM) precision is defined as the quality with which representations are stored in WM, and has to be distinguished from WM capacity, which is the quantity of information that can be maintained in WM. This study is the first to assess the neural precision of WM traces for auditory-verbal information, using a functional magnetic resonance imaging (fMRI) approach. In this experiment, we asked 27 young adults to actively maintain 4-syllable nonwords during a 7-second interval. The nonwords were highly similar or dissimilar at the phonological level. Using multivariate voxel pattern analysis (MVPA), we explored the neural patterns associated with each nonword. We hypothesized that if auditory-verbal WM precision is limited, as indicated by the well-established phonological similarity effect in the WM literature, then dissimilar but not similar nonwords should be associated with distinctive neural patterns during WM maintenance. Using Bayesian one sample t-tests on whole-brain classification accuracies, we observed that neural decoding of similar nonwords was at chance level, while neural decoding of dissimilar nonwords was clearly above chance during the maintenance stage. Searchlight analyses showed that the informative neural patterns were located in the dorsal language pathway known to support phonological processing. These results provide evidence for the neural basis of the phonological similarity effect in WM and the limited precision of phonological coding in WM.Precision as a novel index of verbal working memory performanc

La précision des codes neuraux impliqués dans le stockage d'informations phonologiques en mémoire de travail

Working memory (WM) precision is defined as the quality with which representations are stored in WM, and has to be distinguished from WM capacity, which is the quantity of information that can be maintained in WM. This study is the first to assess the neural precision of WM traces for auditory-verbal information, using a functional magnetic resonance imaging (fMRI) approach. In this experiment, we asked 27 young adults to actively maintain 4-syllable nonwords during a 7-second interval. The nonwords were highly similar or dissimilar at the phonological level. Using multivariate voxel pattern analysis (MVPA), we explored the neural patterns associated with each nonword. We hypothesized that if auditory-verbal WM precision is limited, as indicated by the well-established phonological similarity effect in the WM literature, then dissimilar but not similar nonwords should be associated with distinctive neural patterns during WM, especially during the maintenance stage. Using Bayesian one sample t-tests on whole-brain classification accuracies, we observed that neural decoding of similar nonwords was at chance level, while neural decoding of dissimilar nonwords was clearly above chance during the maintenance stage. Searchlight analyses showed that the informative neural patterns were located in the dorsal language pathway known to support phonological processing. These results provide evidence for the neural basis of the phonological similarity effect in WM and the limited precision of phonological coding in WM.Precision as a novel index of verbal working memory performanc