The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

Airborne pollen: a potential warning alert for tickborne encephalitis risk

The circulation of tick-borne encephalitis virus (TBEv) depends on population dynamics of host tick and rodents, which in turn depend on nutrient resources. Tree seeds are the main food for rodents, and their fluctuating production is strongly correlated to pollen abundance. Our study aims to fill the gap and investigate whether airborne pollen is directly associated to recorded TBEv human cases in the Alpine biogeographical region. Materials and Methods We focused our study within the province of Trento (northern Italy, 6,000km2, 500,000 inhabitants). The territory is included in the Alpine biogeographical region (EEA Report No 1/2002) and the main forest tree species growing within a 5-km radius from the pollen sampler are represented by hop-hornbeam (Ostrya carpinifolia Scop.), beech (Fagus sylvatica L.), spruce (Picea abies L.), pine (Pinus sylvestris L. and P. nigra J. F. Arnold), downy oak (Quercus pubescens Willd.), manna ash (Fraxinus ornus L.), and hazel (Corylus avellana L.). Airborne pollen concentration has been monitored since 1989 at Fondazione Edmund Mach, in San Michele all’Adige (Latitude 46.19 N, Longitude 11.13 E, 220 m a.s.l.), while TBEv human cases have been recorded since 1992 by the local Public Health Agency. Airborne pollen was sampled by a Hirst-type trap, processed, and analyzed following conventional techniques and standardized protocols (UNI EN 16868:2019). First, we statistically investigated the association between the annual total pollen concentration of the dominant arboreal plant taxa and the annual number of TBEv human cases (1989-2020) with different time lags by univariate linear models. Consequently, we built a full model by considering all significant covariates, we computed all possible sub-models and finally we selected the best (the one with the lowest Akaike’s Information Criterion score). Results and Discussion We found a significant positive association between pollen abundances for beech (p=0.04), oak p=0.012), hop hornbeam (p=0.013) and TBEv human cases with a two-year lag (Figure 1). All other lags and taxa resulted in non-significant relationships. Subsequently, we identified the best model, which considered only hop-hornbeam and oak pollen quantities, both with positive coefficients, consistently with the univariate analysis. Conclusions To the best of our knowledge, this is the first attempt at quantifying the potential relationship between airborne pollen abundances of tree species and TBEv infections, based on a three-decade time series of data. If validated at a larger spatial scale, pollen data might therefore be used to realize an early warning system for the risk of TBEv transmission, two years in advance. Moreover, as pollen monitoring is routinely performed worldwide at multiple sites and provides quantitative measures, the association between pollen abundances and TBEv infections could be replicated in different biogeographical regions

Serum sclerostin levels in Paget's disease and prostate cancer with bone metastases with a wide range of bone turnover

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Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration

Aging is a prominent risk factor for neurodegenerative disorders (NDDs); however, the molecular mechanisms rendering the aged brain particularly susceptible to neurodegeneration remain unclear. Here, we aim to determine the link between physiological aging and NDDs by exploring protein turnover using metabolic labeling and quantitative pulse-SILAC proteomics. By comparing protein lifetimes between physiologically aged and young adult mice, we found that in aged brains protein lifetimes are increased by ~20% and that aging affects distinct pathways linked to NDDs. Specifically, a set of neuroprotective proteins are longer-lived in aged brains, while some mitochondrial proteins linked to neurodegeneration are shorter-lived. Strikingly, we observed a previously unknown alteration in proteostasis that correlates to parsimonious turnover of proteins with high biosynthetic costs, revealing an overall metabolic adaptation that preludes neurodegeneration. Our findings suggest that future therapeutic paradigms, aimed at addressing these metabolic adaptations, might be able to delay NDD onset

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition.

Melatonin, a metabolic product of the amino acid tryptophan, induces a dose-dependent energy drop correlated with a decrease in the oxidative phosphorylation process in isolated rat liver mitochondria. This effect involves a gradual decrease in the respiratory control index and significant alterations in the state 4/state 3 transition of membrane potential (ΔΨ). Melatonin, alone, does not affect the insulating properties of the inner membrane but, in the presence of supraphysiological Ca2+, induces a ΔΨ drop and colloid-osmotic mitochondrial swelling. These events are sensitive to cyclosporin A and the inhibitors of Ca2+ transport, indicative of the induction or amplification of the mitochondrial permeability transition. This phenomenon is triggered by oxidative stress induced by melatonin and Ca2+, with the generation of hydrogen peroxide and the consequent oxidation of sulfydryl groups, glutathione and pyridine nucleotides. In addition, melatonin, again in the presence of Ca2+, can also induce substantial release of cytochrome C and AIF (apoptosis-inducing factor), thus revealing its potential as a pro-apoptotic agent

SCOPE: a scorecard for osteoporosis in Europe

Summary The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. Introduction The scorecard for osteoporosis in Europe (SCOPE) is an independent project that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis. Methods The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap). Results There was a marked difference in fracture risk among the EU27. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27, only a minority of patients at high risk receive treatment for osteoporosis even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. Conclusions The scorecard will enable healthcare professionals and policy makers to assess their country’s general approach to the disease and provide indicators to inform future provision of healthcare

Smart Metering, Water Pricing and Social Media to Stimulate Residential Water Efficiency: Opportunities for the SmartH2O Project

Abstract The SmartH2O project aims to provide water utilities, municipalities and citizens with an ICT enabled platform to design, develop and implement better water management policies using innovative metering, social media and pricing mechanisms. This project has as a working hypothesis that high data quality obtained from smart meters and communicable through social media and other forms of interaction could be used to design and implement innovative and effective water pricing policies. Planned case studies in the UK and Switzerland are introduced. We anticipate that SmartH20 research outcomes will be of use to those interested in linking smart metering, social media and smart pricing approaches to achieve more sustainable water management outcomes