Hair cells are mechanosensors for the perception of sound, acceleration, and fluid motion. Mechanotransduction channels in hair cells are gated by tip links, which connect the stereocilia of a hair ...cell in the direction of their mechanical sensitivity. The molecular constituents of the mechanotransduction channels of hair cells are not known. Here, we show that mechanotransduction is impaired in mice lacking the tetraspan TMHS. TMHS binds to the tip-link component PCDH15 and regulates tip-link assembly, a process that is disrupted by deafness-causing Tmhs mutations. TMHS also regulates transducer channel conductance and is required for fast channel adaptation. TMHS therefore resembles other ion channel regulatory subunits such as the transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor regulatory proteins (TARPs) of AMPA receptors that facilitate channel transport and regulate the properties of pore-forming channel subunits. We conclude that TMHS is an integral component of the hair cell’s mechanotransduction machinery that functionally couples PCDH15 to the transduction channel.
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► TMHS is a component of the hair cell’s mechanotransduction machinery ► TMHS binds to the tip-link component PCDH15 and regulates tip-link assembly ► TMHS regulates transducer channel conductance and is required for adaptation ► TMHS is structurally similar to other ion channel regulatory subunits such as TARPs
The tetraspan TMHS is identified as an accessory subunit of the hair cell mechanotransducer channel. TMHS regulates transducer channel conductance and functionally couples the tip-link component protocadherin 15 to the transduction channel.
•Few studies published about removal of micropollutants from WWTP effluent by CWs.•Organic enhanced adsorption substrates in CWs increase micropollutant removal.•Long-term efficiency of enhanced ...adsorption substrate is unknown.•Horizontal subsurface flow CWs show limited removal of micropollutants from WWTP effluent.•No studies about the effect of active aeration on micropollutant removal from WWTP effluent.
The removal of micropollutants from wastewater by constructed wetlands (CWs) has been extensively studied and reviewed over the past years. However, most studies do not specifically focus on the removal of micropollutants from the effluent of conventional wastewater treatment plants (WWTP) that still contains micropollutants, but on the removal of micropollutants from raw wastewater. Raw wastewater has a significantly different composition compared to WWTP effluent, which positively or negatively affects micropollutant removal mechanisms. To determine the optimal CW design for post-treatment of WWTP effluent to achieve additional micropollutant removal, this review analyzes the removal of 16 Dutch indicator micropollutants for post-treatment technology evaluation from WWTP effluent by different types of CWs. It was concluded that CW systems with organic enhanced adsorption substrates reach the highest micropollutant removal efficiency as a result of adsorption, but that the longevity of the enhanced adsorption effect is not known in the systems studied until now. Aerobic biodegradation and photodegradation are other relevant removal mechanisms for the studied micropollutants. However, a current knowledge gap is whether active aeration to stimulate the aerobic micropollutant biodegradation results in an increased micropollutant removal from WWTP effluent. Further knowledge gaps that impede the wider application of CW systems for micropollutant removal from WWTP effluent and allow a fair comparison with other post-treatment technologies for enhanced micropollutant removal, such as ozonation and activated carbon adsorption, relate to i) saturation of enhanced adsorption substrate; ii) the analysis of transformation products and biological effects; iii) insights in the relationship between microbial community composition and micropollutant biodegradation; iv) plant uptake and in-plant degradation of micropollutants; v) establishing design rules for appropriate hydraulic loading rates and/or hydraulic retention times for CWs dedicated to micropollutant removal from WWTP effluent; and vi) the energy- and carbon footprint of different CW systems. This review finishes with detailed suggestions for future research directions that provide answers to these knowledge gaps.
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Cyber Threat Intelligence (CTI) sharing has become a novel weapon in the arsenal of cyber defenders to proactively mitigate increasing cyber attacks. Automating the process of CTI sharing, and even ...the basic consumption, has raised new challenges for researchers and practitioners. This extensive literature survey explores the current state-of-the-art and approaches different problem areas of interest pertaining to the larger field of sharing cyber threat intelligence. The motivation for this research stems from the recent emergence of sharing cyber threat intelligence and the involved challenges of automating its processes. This work comprises a considerable amount of articles from academic and gray literature, and focuses on technical and non-technical challenges. Moreover, the findings reveal which topics were widely discussed, and hence considered relevant by the authors and cyber threat intelligence sharing communities.
Quantifying the potential of a braided riverscape to be colonized by a plant species is essential for assessing the ecological state of the river and provides an important basis for nature ...conservation planning and the implementation of restoration measures. Common connectivity indices are largely unsuitable for describing the situation for the mostly wind-dispersed plant species. Our approach provides a set of comparable metrics that allows the quantification of the colonization potential of riverscapes at the patch and riverscape level. We propose a set of cell-based, spatially explicit measures that can easily be implemented. We demonstrate their application using two typical plant species and three riverscapes with different habitat configurations as examples. Our metrics consider shape, size and the spatial configuration of habitat patches, along with the dispersal characteristics of the respective species. The metrics provide a linear, balanced, and realistic representation of the colonization potential at the cell, patch, and riverscape levels. The results are comparable between different riverscapes and species, can be easily extended and used for further modeling. The metrics provide a valuable tool for the planning and evaluation of conservation, restoration, and reintroduction measures and close the gap between habitat availability analyses and large-scale terrestrial connectivity indices.
ECFS best practice guidelines: the 2018 revision Castellani, Carlo; Duff, Alistair J.A.; Bell, Scott C. ...
Journal of cystic fibrosis,
March 2018, 2018-03-00, 20180301, Letnik:
17, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have ...minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the potential to enjoy good quality of life in adulthood with ever-increasing life expectancy. The landmark Standards of Care published in 2005 set out what high quality CF care is and how it can be delivered throughout Europe. This underwent a fundamental re-write in 2014, resulting in three documents; center framework, quality management and best practice guidelines. This document is a revision of the latter, updating standards for best practice in key aspects of CF care, in the context of a fast-moving and dynamic field.
In continuing to give a broad overview of the standards expected for newborn screening, diagnosis, preventative treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support, this consensus on best practice is expected to prove useful to clinical teams both in countries where CF care is developing and those with established CF centres. The document is an ECFS product and endorsed by the CF Network in ERN LUNG and CF Europe.
Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is ...unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing beta cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.
The reuse of cooling tower blowdown (CTBD) in the cooling tower itself requires CTBD deionization and a pre-treatment before deionization to remove organic compounds (OCs) that induce membrane ...fouling. This study assesses the potential of electrochemical oxidation (EO) with a boron-doped diamond (BDD) and a Ti/RuO2 mixed-metal oxide (MMO) anode for CTBD pre-treatment. Also, the influence of the applied current density (j), initial pH, hydrodynamic conditions, and supporting electrolyte on the process performance was evaluated. Results show that COD and TOC removal were 85 and 51%, respectively, with the BDD-anode; however, they were 50 and 12% with MMO-anode at a j-value of 8.7 mA cm−2 and neutral pH. An increased j-value increased the COD and TOC removal; however, different pHs, hydrodynamic conditions, and the addition of supporting electrolytes had a minor impact on the removal with both anodes. Liquid chromatography-organic carbon detection analysis showed that the OC in CTBD mainly consisted of humic substances (HS). EO with the BDD-anode resulted in 35% HS mineralization, while the rest of the HS were partially oxidized into low molecular weight compounds and building blocks. However, HS mineralization was limited with the MMO-anode. The mineralization and oxidation were accompanied by the formation of organic and inorganic chlorinated species. These species increased the toxicity to Vibrio fischeri 20-fold compared to the initially low-toxic CTBD. Thus, EO with a BDD-anode is a promising pre-treatment technology for the removal of OCs before CTBD deionization, but measures to minimize the chlorinated species formation are required before its application.
•Electrochemical oxidation to remove organic compounds from cooling tower blowdown.•Boron-doped diamond anode has higher removal efficiency than mixed-metal oxide anode.•The applied current density influences the organic compound removal efficiency.•Electrochemical oxidation results in the partial transformation of organic compounds.•The formation of toxic chlorinated by-products needs to be prevented.
About 30 million people in the EU and USA, respectively, suffer from a rare disease. Driven by European legislative requirements, national strategies for the improvement of care in rare diseases are ...being developed. To improve timely and correct diagnosis for patients with rare diseases, the development of a registry for undiagnosed patients was recommended by the German National Action Plan. In this paper we focus on the question on how such a registry for undiagnosed patients can be built and which information it should contain.
To develop a registry for undiagnosed patients, a software for data acquisition and storage, an appropriate data set and an applicable terminology/classification system for the data collected are needed. We have used the open-source software Open-Source Registry System for Rare Diseases (OSSE) to build the registry for undiagnosed patients. Our data set is based on the minimal data set for rare disease patient registries recommended by the European Rare Disease Registries Platform. We extended this Common Data Set to also include symptoms, clinical findings and other diagnoses. In order to ensure findability, comparability and statistical analysis, symptoms, clinical findings and diagnoses have to be encoded. We evaluated three medical ontologies (SNOMED CT, HPO and LOINC) for their usefulness. With exact matches of 98% of tested medical terms, a mean number of five deposited synonyms, SNOMED CT seemed to fit our needs best. HPO and LOINC provided 73% and 31% of exacts matches of clinical terms respectively. Allowing more generic codes for a defined symptom, with SNOMED CT 99%, with HPO 89% and with LOINC 39% of terms could be encoded.
With the use of the OSSE software and a data set, which, in addition to the Common Data Set, focuses on symptoms and clinical findings, a functioning and meaningful registry for undiagnosed patients can be implemented. The next step is the implementation of the registry in centres for rare diseases. With the help of medical informatics and big data analysis, case similarity analyses could be realized and aid as a decision-support tool enabling diagnosis of some undiagnosed patients.
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