Cystic fibrosis transmembrane conductance regulator (CFTR): beyond cystic fibrosis

Abstract Background The cystic fibrosis transmembrane conductance regulator (CFTR) gene has been traditionally linked to cystic fibrosis (CF) inheritance in an autosomal recessive manner. Advances in molecular biology and genetics have expanded our understanding of the CFTR gene and its encoding products expressed in different tissues. Aim The study's aim consists of reviewing the different pathological CF phenotypes using the existing literature. We know that alterations of the CFTR protein's structure may result in different pathological phenotypes. Methods Open sources such as PubMed and Science Direct databases have been used for this review. We focused our selection on articles published within the last 15 years. Critical terms related to the CFTR protein have been used: "CFTR AND cancer," "CFTR AND celiac disease," "CFTR AND pancreatitis," "children," "adults," "genotype," "phenotype," "correlation," "mutation," "CFTR," "diseases," "disorders," and "no cystic fibrosis." Results We analyzed 1,115 abstracts in total. Moreover, only 189 were suitable for the topic. We focused on the role of CFTR in cancer, gastrointestinal disorders, respiratory diseases, reproductive system, and systemic hypertension. Conclusions Mutations in CFTR gene are often associated with CF. In this review, we highlighted the broad spectrum of alterations reported for this gene, which may be involved in the pathogenesis of other diseases. The importance of these new insights in the role of CFTR relies on the possibility of considering this protein/gene as a novel therapeutic target for CF- and CFTR-related diseases

modality independent encoding of individual concepts in the left parietal cortex

Abstract The organization of semantic information in the brain has been mainly explored through category-based models, on the assumption that categories broadly reflect the organization of conceptual knowledge. However, the analysis of concepts as individual entities, rather than as items belonging to distinct superordinate categories, may represent a significant advancement in the comprehension of how conceptual knowledge is encoded in the human brain. Here, we studied the individual representation of thirty concrete nouns from six different categories, across different sensory modalities (i.e., auditory and visual) and groups (i.e., sighted and congenitally blind individuals) in a core hub of the semantic network, the left angular gyrus, and in its neighboring regions within the lateral parietal cortex. Four models based on either perceptual or semantic features at different levels of complexity (i.e., low- or high-level) were used to predict fMRI brain activity using representational similarity encoding analysis. When controlling for the superordinate component, high-level models based on semantic and shape information led to significant encoding accuracies in the intraparietal sulcus only. This region is involved in feature binding and combination of concepts across multiple sensory modalities, suggesting its role in high-level representation of conceptual knowledge. Moreover, when the information regarding superordinate categories is retained, a large extent of parietal cortex is engaged. This result indicates the need to control for the coarse-level categorial organization when performing studies on higher-level processes related to the retrieval of semantic information

Bacterial Diversity in a Dynamic and Extreme Sub-Arctic Watercourse (Pasvik River, Norwegian Arctic)

Microbial communities promptly respond to the environmental perturbations, especially in the Arctic and sub-Arctic systems that are highly impacted by climate change, and fluctuations in the diversity level of microbial assemblages could give insights on their expected response. 16S rRNA gene amplicon sequencing was applied to describe the bacterial community composition in water and sediment through the sub-Arctic Pasvik River. Our results showed that river water and sediment harbored distinct communities in terms of diversity and composition at genus level. The distribution of the bacterial communities was mainly affected by both salinity and temperature in sediment samples, and by oxygen in water samples. Glacial meltwaters and runoff waters from melting ice probably influenced the composition of the bacterial community at upper and middle river sites. Interestingly, marine-derived bacteria consistently accounted for a small proportion of the total sequences and were also more prominent in the inner part of the river. Results evidenced that particular conditions occurring at sampling sites (such as algal blooms, heavy metal contamination and anaerobiosis) may select species at local scale from a shared bacterial pool, thus favoring certain bacterial taxa. Conversely, the few phylotypes specifically detected in some sites are probably due to localized external inputs introducing allochthonous microbial groups

Benthic Microbial Communities in a Seasonally Ice-Covered Sub-Arctic River (Pasvik River, Norway) Are Shaped by Site-Specific Environmental Conditions

The Pasvik River experiences chemical, physical, and biological stressors due to the direct discharges of domestic sewage from settlements located within the catchment and runoff from smelter and mine wastes. Sediments, as a natural repository of organic matter and associated contaminants, are of global concern for the possible release of pollutants in the water column, with detrimental effects on aquatic organisms. The present study was aimed at characterizing the riverine benthic microbial community and evaluating its ecological role in relation to the contamination level. Sediments were sampled along the river during two contrasting environmental periods (i.e., beginning and ongoing phases of ice melting). Microbial enzymatic activities, cell abundance, and morphological traits were evaluated, along with the phylogenetic community composition. Amplified 16S rRNA genes from bacteria were sequenced using a next-generation approach. Sediments were also analyzed for a variety of chemical features, namely particulate material characteristics and concentration of polychlorobiphenyls, polycyclic aromatic hydrocarbons, and pesticides. Riverine and brackish sites did not affect the microbial community in terms of main phylogenetic diversity (at phylum level), morphometry, enzymatic activities, and abundance. Instead, bacterial diversity in the river sediments appeared to be influenced by the micro-niche conditions, with differences in the relative abundance of selected taxa. In particular, our results highlighted the occurrence of bacterial taxa directly involved in the C, Fe, and N cycles, as well as in the degradation of organic pollutants and toxic compounds.Benthic Microbial Communities in a Seasonally Ice-Covered Sub-Arctic River (Pasvik River, Norway) Are Shaped by Site-Specific Environmental ConditionspublishedVersio

Restituire un museo alla cittadinanza. Il caso del MusAB

Nato nel 2015 come museo dell’Istituto Nazionale di Astrofisica e riconosciuto dalla Regione Lombardia come collezione museale, il Museo Astronomico di Brera (MusAB) è una straordinaria collezione di strumenti utilizzati dal personale dell’Osservatorio astronomico di Brera nel corso di 250 anni di storia. Oggi, grazie a un finanziamento della Regione Lombardia, nell’ambito di un’iniziativa volta al miglioramento dei luoghi della cultura, il MusAB ha l’ambizione di rispondere alla domanda: cosa fa l’astronomo/a? Osservare, scoprire, misurare, rappresentare, sono le operazioni che caratterizzano il loro lavoro e che la nuova esposizione cerca di illustrare con l’aiuto degli antichi strumenti della Specola di Brera. La realizzazione di questo nuovo allestimento ha coinvolto diverse figure professionali che hanno trovato soluzioni per raccontare difficili argomenti scientifici al grande pubblico, attraverso i testi discorsivi, una nuova distribuzione nello spazio degli strumenti e immagini evocative. La comunicazione del progetto ha sfruttato i canali dell’Osservatorio, valorizzando la nuova identità visiva del museo e il portale web. In attesa della riapertura sono stati realizzati materiali divulgativi e multimediali con studenti delle scuole superiori e stagisti in master in divulgazione della scienza. Il museo ha inaugurato il nuovo allestimento il 5 marzo 2021, in occasione di Milano MuseoCity in diretta sul canale YouTube dell’INAF-Osservatorio Astronomico di Brera, ma ha riaperto ufficialmente, a causa dell’emergenza pandemica, solamente il 7 dicembre 2021. Nella parte finale di questo documento analizziamo l’impatto sul pubblico di questo progetto attraverso i dati raccolti in questa prima giornata di apertura

Trophic and Microbial Patterns in the Ross Sea Area (Antarctica): Spatial Variability during the Summer Season

In open regions of the Ross Sea, the role of the microbial community in the turnover of organic matter has scarcely been investigated; indeed, very little is known on how microbial distribution and functional diversity respond to environmental conditions and hydrographic structures. During the austral summer of 2017, two pelagic areas of the Ross Sea [the Drygalski Ice Tongue and the nearby Terra Nova Bay polynya (A area), and the continental Shelf Break area near Cape Adare (C area)] were studied at selected depths [surface, Deep Chlorophyll Maximum (DCM), Circumpolar Deep Water (CDW), deep waters]. Trophic properties [nutrient concentrations, particulate (POC), dissolved organic carbon (DOC) and its optically significant fraction (CDOM) were measured, together with the main hydrological variables. Microbial community abundance [total prokaryotes, living, dead, and actively respiring fraction, high- and low nucleic acid cells (HNA and LNA), picoand nano-eukaryotes, culturable heterotrophic bacteria], composition, and metabolism (as whole community and as isolated bacteria) were also assessed. Through a multidisciplinary dataset, this study highlighted the variable response of microbial abundance, diversity, and metabolism of the microbial community to the changing local environmental conditions of the Ross Sea. Different forces, such as organic matter inputs (mostly of detrital nature) released from the Drygalski glacier in the A area, and a coastal-to-offshore gradient in the C area, coexisted within this extreme ecosystem. This resulted in a significant spatial segregation of the edaphic parameters, and of the microbial community distribution and metabolic activity patterns

What eddy-covariance measurements tell us about prior land flux errors in CO2-flux inversion schemes

0.2 after 200 km). Separating out the plant functional types did not increase the spatial correlations, except for the deciduous broad-leaved forests. Using the statistics of the flux measurements as a proxy for the statistics of the prior flux errors was shown not to be a viable approach. A statistical model allowed us to upscale the site-level flux error statistics to the coarser spatial and temporal resolutions used in regional or global models. This approach allowed us to quantify how aggregation reduces error variances, while increasing correlations. As an example, for a typical inversion of grid point (300 km × 300 km) monthly fluxes, we found that the prior flux error follows an approximate e-folding correlation length of 500 km only, with correlations from one month to the next as large as 0.6

Direct observations of CO2 emission reductions due to COVID-19 lockdown across European urban districts

The measures taken to contain the spread of COVID-19 in 2020 included restrictions of people's mobility and reductions in economic activities. These drastic changes in daily life, enforced through national lockdowns, led to abrupt reductions of anthropogenic CO(2 )emissions in urbanized areas all over the world. To examine the effect of social restrictions on local emissions of CO2, we analysed district level CO(2 )fluxes measured by the eddy-covariance technique from 13 stations in 11 European cities. The data span several years before the pandemic until October 2020 (six months after the pandemic began in Europe). All sites showed a reduction in CO2 emissions during the national lockdowns. The magnitude of these reductions varies in time and space, from city to city as well as between different areas of the same city. We found that, during the first lockdowns, urban CO2 emissions were cut with respect to the same period in previous years by 5% to 87% across the analysed districts, mainly as a result of limitations on mobility. However, as the restrictions were lifted in the following months, emissions quickly rebounded to their pre-COVID levels in the majority of sites.Peer reviewe

Substantial hysteresis in emergent temperature sensitivity of global wetland CH4 emissions

Wetland methane (CH4) emissions (FCH4) are important in global carbon budgets and climate change assessments. Currently, FCH4 projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent FCH4 temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that FCH4 are often controlled by factors beyond temperature. Here, we evaluate the relationship between FCH4 and temperature using observations from the FLUXNET-CH4 database. Measurements collected across the globe show substantial seasonal hysteresis between FCH4 and temperature, suggesting larger FCH4 sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH4 production are thus needed to improve global CH4 budget assessments. Wetland methane emissions contribute to global warming, and are oversimplified in climate models. Here the authors use eddy covariance measurements from 48 global sites to demonstrate seasonal hysteresis in methane-temperature relationships and suggest the importance of microbial processes.Peer reviewe

Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2

Cell signaling is central to neuronal activity and its dysregulation may lead to neurodegeneration and cognitive decline. Here, we show that selective genetic potentiation of neuronal ERK signaling prevents cell death in vitro and in vivo in the mouse brain, while attenuation of ERK signaling does the opposite. This neuroprotective effect mediated by an enhanced nuclear ERK activity can also be induced by the novel cell penetrating peptide RB5. In vitro administration of RB5 disrupts the preferential interaction of ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates ERK1/2 nuclear translocation, and enhances global ERK activity. Importantly, RB5 treatment in vivo promotes neuroprotection in mouse models of Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) disease, and enhances ERK signaling in a human cellular model of HD. Additionally, RB5‐mediated potentiation of ERK nuclear signaling facilitates synaptic plasticity, enhances cognition in healthy rodents, and rescues cognitive impairments in AD and HD models. The reported molecular mechanism shared across multiple neurodegenerative disorders reveals a potential new therapeutic target approach based on the modulation of KPNA2‐ERK1/2 interactions