The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Understanding the Dynamics of Mycorrhizal Communities in Plant Successions. Part 2: Potential for Application to Forest Ecosystem Remediation (Bibliographical Review)

The dynamics of mycorrhizal communities during the stages of the plant colonisation successions leads to an increase in the wealth of species and the diversity of the mycorrhizal community through the gradual establishment of late-stage fungi and the decrease in the number of multi-stage fungi. This brings about, amongst other things, a modification in the structure of the mycorrhizal networks, which has a direct impact on the stability of the plant community and on forest stands. Due to the specialisation of some interactions, the recruitment of new fungi has either direct or feedback effects on the diversity and productivity of the plant community. By taking into account the natural dynamics of the mycorrhizal community, the process of ecological remediation can be speeded up by inoculating the appropriate fungi or introducing suitable mycorrhizal communities by means of nurse plants.La dynamique de la communauté mycorhizienne au cours de la succession végétale se traduit par une augmentation de la richesse spécifique et de la diversité de la communauté due à l’établissement progressif de champignons de stade tardif et à la diminution du nombre de champignons pluristades. Cela provoque notamment une modification de la structure des réseaux mycorhiziens qui impacte directement la stabilité de la communauté végétale et des peuplements forestiers. Du fait de la spécificité de certaines interactions, le recrutement de nouveaux champignons influence, directement ou après des rétroactions, la diversité et la productivité de la communauté végétale. La prise en compte de la dynamique naturelle de la communauté mycorhizienne avec la succession végétale permet d’accélérer le processus de restauration écologique par l’inoculation de champignons appropriés ou par l’apport d’une communauté mycorhizienne adaptés à l’aide de plantes nurses

Understanding the dynamics of mycorrhizal communities in plant successions. Part I - study methods, characterisations and function (bibliographic review)

In a natural environment, major disturbances cause the destruction of the vegetation as well as of soil microorganisms such as mycorrhizal fungi. Plant and mycorrhizal fungus communities are independent and so it is important to understand the dynamics of mycorrhizal communities during the stages in plant colonisation successions that generate a forest canopy. These successions go along with an increase in the wealth of species and the diversity of the mycorrhizal community through the gradual establishment of late-stage fungi and the decrease in the number of multi-stage fungi. Plant-fungus interactions become specialised as the plant succession runs its course or as the population ages. These dynamics of mycorrhizal communities can be explained by differences in the life history traits between species of fungi, but also by a change in the characteristics of the plant community and the soil over timeEn milieu naturel, les perturbations importantes conduisent à la destruction de la végétation mais aussi des microorganismes du sol comme les champignons mycorhiziens. Les communautés de plantes et de champignons mycorhiziens étant interdépendantes, il est important de comprendre la dynamique des communautés mycorhiziennes au cours des stades des successions de colonisation végétale, qui débouchent sur un couvert forestier. Ces successions s’accompagnent d’une augmentation de la richesse spécifique et de la diversité de la communauté mycorhizienne par l’établissement progressif de champignons de stade tardif et la diminution du nombre de champignons pluristades. Les interactions plantes-champignons se spécialisent au cours de la succession végétale ou du vieillissement d’un peuplement. Cette dynamique des communautés mycorhiziennes s’explique par des différences de traits d’histoire de vie entre les espèces de champignons, mais aussi par une modification des caractéristiques de la communauté végétale et du sol avec le temp

Beaugeard2018_Data_FeatherCort_HouseSparrow_juv_4sites

Data of juvenile house sparrows captured in 4 sites in France. Data include the date of capture (2 formats), the site of capture, the urbanization score of the site, the feather corticosterone level expressed either in ng/mg or in ng/mm, the sex, the Scaled Mass Index (SMI), the tarsus length, the body mass, and the levels of baseline and stress-induced corticosterone in plasma

Data from: Does urbanization cause stress in wild birds during development? insights from feather corticosterone levels in juvenile house sparrows (Passer domesticus)

Urban landscapes are associated with abiotic and biotic environmental changes that may result in potential stressors for wild vertebrates. Urban exploiters have physiological, morphological and behavioral adaptations to live in cities. However, there is increasing evidence that urban exploiters themselves can suffer from urban conditions, especially during specific life-history stages. We looked for a link between the degree of urbanization and the level of developmental stress in an urban exploiter (the house sparrow, Passer domesticus), which has recently been declining in multiple European cities (e.g. London, UK). Specifically, we conducted a large-scale study and sampled juvenile sparrows in 11 urban and rural sites to evaluate their feather corticosterone (CORT) levels. We found that juvenile feather CORT levels were positively correlated with the degree of urbanization, supporting the idea that developing house sparrows may suffer from urban environmental conditions. However, we did not find any correlation between juvenile feather CORT levels and body size, mass, or body condition. This suggests either that the growth and condition of urban sparrows are not impacted by elevated developmental CORT levels, or that urban sparrows may compensate for developmental constraints once they have left the nest. Although feather CORT levels were not correlated with baseline CORT levels, we found that feather CORT levels were slightly and positively correlated with the CORT stress response in juveniles. This suggests that urban developmental conditions may potentially have long-lasting effects on stress physiology and stress sensitivity in this urban exploiter

Beaugeard2018_Data_FeatherCort_HouseSparrow_juv_11sites

Data of feathers from juvenile house sparrows captured in 11 sites in France. Data include the date of capture (2 formats), the site of capture, the urbanization score of the site, the level of feather corticosterone expressed either in ng/mg or in ng/mm