Inhibition of NOX1 mitigates blood pressure increases in elastin insufficiency

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include th

Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion

Funding Information No funding information provided. aThese authors contributed equally to this work

Search for top-down and bottom-up drivers of latitudinal trends in insect herbivory in oak trees in Europe

International audienceAim: The strength of species interactions is traditionally expected to increase toward the Equator. However, recent studies have reported opposite or inconsistent latitudinal trends in the bottom-up (plant quality) and top-down (natural enemies) forces driving herbivory. In addition, these forces have rarely been studied together thus limiting previous attempts to understand the effect of large-scale climatic gradients on herbivory. Location: Europe. Time period: 2018–2019. Major taxa studied: Quercus robur. Methods: We simultaneously tested for latitudinal variation in plant–herbivore–natural enemy interactions. We further investigated the underlying climatic factors associated with variation in herbivory, leaf chemistry and attack rates in Quercus robur across its complete latitudinal range in Europe. We quantified insect leaf damage and the incidence of specialist herbivores as well as leaf chemistry and bird attack rates on dummy caterpillars on 261 oak trees. Results: Climatic factors rather than latitude per se were the best predictors of the large-scale (geographical) variation in the incidence of gall-inducers and leaf-miners as well as in leaf nutritional content. However, leaf damage, plant chemical defences (leaf phenolics) and bird attack rates were not influenced by climatic factors or latitude. The incidence of leaf-miners increased with increasing concentrations of hydrolysable tannins, whereas the incidence of gall-inducers increased with increasing leaf soluble sugar concentration and decreased with increasing leaf C : N ratios and lignins. However, leaf traits and bird attack rates did not vary with leaf damage. Main conclusions: These findings help to refine our understanding of the bottom-up and top-down mechanisms driving geographical variation in plant–herbivore interactions, and indicate the need for further examination of the drivers of herbivory on trees

Search for top-down and bottom-up drivers of latitudinal trends in insect herbivory in oak trees in Europe

AimThe strength of species interactions is traditionally expected to increase toward the Equator. However, recent studies have reported opposite or inconsistent latitudinal trends in the bottom‐up (plant quality) and top‐down (natural enemies) forces driving herbivory. In addition, these forces have rarely been studied together thus limiting previous attempts to understand the effect of large‐scale climatic gradients on herbivory.LocationEurope.Time period2018–2019.Major taxa studiedQuercus robur.MethodsWe simultaneously tested for latitudinal variation in plant–herbivore–natural enemy interactions. We further investigated the underlying climatic factors associated with variation in herbivory, leaf chemistry and attack rates in Quercus robur across its complete latitudinal range in Europe. We quantified insect leaf damage and the incidence of specialist herbivores as well as leaf chemistry and bird attack rates on dummy caterpillars on 261 oak trees.ResultsClimatic factors rather than latitude per se were the best predictors of the large‐scale (geographical) variation in the incidence of gall‐inducers and leaf‐miners as well as in leaf nutritional content. However, leaf damage, plant chemical defences (leaf phenolics) and bird attack rates were not influenced by climatic factors or latitude. The incidence of leaf‐miners increased with increasing concentrations of hydrolysable tannins, whereas the incidence of gall‐inducers increased with increasing leaf soluble sugar concentration and decreased with increasing leaf C : N ratios and lignins. However, leaf traits and bird attack rates did not vary with leaf damage.Main conclusionsThese findings help to refine our understanding of the bottom‐up and top‐down mechanisms driving geographical variation in plant–herbivore interactions, and indicate the need for further examination of the drivers of herbivory on trees.</p

Copper-Binding Domain Variation in a Novel Murine Lysyl Oxidase Model Produces Structurally Inferior Aortic Elastic Fibers Whose Failure Is Modified by Age, Sex, and Blood Pressure

Lysyl oxidase (LOX) is a copper-binding enzyme that cross-links elastin and collagen. The dominant LOX variation contributes to familial thoracic aortic aneurysm. Previously reported murine Lox mutants had a mild phenotype and did not dilate without drug-induced provocation. Here, we present a new, more severe mutant, Loxb2b370.2Clo (c.G854T; p.Cys285Phe), whose mutation falls just N-terminal to the copper-binding domain. Unlike the other mutants, the C285F Lox protein was stably produced/secreted, and male C57Bl/6J Lox+/C285F mice exhibit increased systolic blood pressure (BP; p p p p = 2.8 × 10−8 for breaks by histology) that become increasingly disrupted with age (p p = 6.8 × 10−4). Aortic dilation was amplified in males vs. females (p p = 9.83 × 10−30) and TGFβ-responsive genes (p = 7.42 × 10−29), and aortas from older C57Bl/6J Lox+/C285F mice showed both enhanced susceptibility to elastase (p p Lox+/C285F mutants produce dysfunctional elastic fibers that show increased susceptibility to proteolytic damage. Over time, the progressive weakening of the connective tissue, modified by sex and blood pressure, leads to worsening aortic disease

Organizational determinants of hospital stay: establishing the basis of a widespread action on more efficient pathways in medical units

Numico G, Bellini R, Zanelli C, et al. Organizational determinants of hospital stay: establishing the basis of a widespread action on more efficient pathways in medical units. Internal and Emergency Medicine . 2020;15(6):1011-1019.Given the high hospital costs, the increasing clinical complexity and the overcrowding of emergency departments, it is crucial to improve the efficiency of medical admissions. We aimed at isolating organizational drivers potentially targetable through a widespread improvement action. We studied all medical admissions in a large tertiary referral hospital from January 1st to December 31st, 2018. Data were retrieved from the administrative database. Available information included age, sex, type (urgent or elective) and Unit of admission, number of internal transfers, main ICD-9 diagnosis, presence of cancer among diagnoses, surgical or medical code, type of discharge, month, day and hour of admission and discharge. National Ministry of Health database was used for comparisons. 8099 admissions were analyzed. Urgent admissions (80.5% of the total) were responsible for longer stays and were the object of the multivariate analysis. The variables most influencing length-of-stay (LOS) were internal transfers and assisted discharge: they contributed, respectively, to 62% and 40% prolongation of LOS. Also, the daily and weekly kinetics of admission accounted for a significant amount of variation in LOS. Long admissions (>= 30 days) accounted for the 15.5% of total bed availability. Type of discharge and internal transfers were again among the major determinants. A few factors involved in LOS strictly depend on the organizational environment and are potentially modifiable. Re-engineering should be focused on making more efficient internal and external transitions and at ensuring continuity of the clinical process throughout the day and the week

Le développement : vicissitudes d’une idée structurante

Après une certaine éclipse, les concepts de « développement » et de « développementalisme » ont regagné une place centrale dans les champs politique, économique et académique de l’Amérique latine. À partir de l’an 2000, des courants et des voix diverses, souvent opposées, prônent le « développement durable », le « développement soutenable », le « néodéveloppementisme » ou le « néodéveloppementisme indigéniste ». Parallèlement, s’est déployée une nouvelle trame discursive « post-développementiste ». Plus ou moins radical, ce discours critique est aussi force de propositions avec des concepts telles que « le bien vivre » (sumak kawsay en Équateur, suma qamaña en Bolivie). D’autre part, les courants néolibéraux ne cessent de redéfinir le concept de développement. Ce dossier cartographie et analyse ces nouveaux discours en Amérique Latine en les situant dans l’histoire et par rapport aux pratiques économiques et politiques actuelles. Les débats, intenses, autour du concept de développement sont l'indice d’une nouvelle charnière dans l’histoire régionale