scholarly journals Rare Human Diseases: Model Organisms in Deciphering the Molecular Basis of Primary Ciliary Dyskinesia

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1614 ◽  
Author(s):  
Martyna Poprzeczko ◽  
Marta Bicka ◽  
Hanan Farahat ◽  
Rafal Bazan ◽  
Anna Osinka ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Primary Ciliary Dyskinesia ◽  
State Of The Art ◽  
Model Organisms ◽  
Phenotypic Changes ◽  
Current State ◽  
Evolutionarily Conserved ◽  
Motile Cilia ◽  
The Impact ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a recessive heterogeneous disorder of motile cilia, affecting one per 15,000–30,000 individuals; however, the frequency of this disorder is likely underestimated. Even though more than 40 genes are currently associated with PCD, in the case of approximately 30% of patients, the genetic cause of the manifested PCD symptoms remains unknown. Because motile cilia are highly evolutionarily conserved organelles at both the proteomic and ultrastructural levels, analyses in the unicellular and multicellular model organisms can help not only to identify new proteins essential for cilia motility (and thus identify new putative PCD-causative genes), but also to elucidate the function of the proteins encoded by known PCD-causative genes. Consequently, studies involving model organisms can help us to understand the molecular mechanism(s) behind the phenotypic changes observed in the motile cilia of PCD affected patients. Here, we summarize the current state of the art in the genetics and biology of PCD and emphasize the impact of the studies conducted using model organisms on existing knowledge.

scholarly journals Primary ciliary dyskinesia: current state of the art

2007 ◽  
Vol 92 (12) ◽  
pp. 1136-1140 ◽  
Author(s):  
A. Bush ◽  
R. Chodhari ◽  
N. Collins ◽  
F. Copeland ◽  
P. Hall ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
State Of The Art ◽  
Current State ◽  
Ciliary Dyskinesia

scholarly journals Sperm defects in primary ciliary dyskinesia and related causes of male infertility

2019 ◽  
Vol 77 (11) ◽  
pp. 2029-2048 ◽  
Author(s):  
Anu Sironen ◽  
Amelia Shoemark ◽  
Mitali Patel ◽  
Michael R. Loebinger ◽  
Hannah M. Mitchison
Keyword(s):  
Male Infertility ◽  
Primary Ciliary Dyskinesia ◽  
Model Organisms ◽  
Nasal Discharge ◽  
Sperm Tail ◽  
The Core ◽  
Motile Cilia ◽  
Exact Effect ◽  
And Function ◽  
Ciliary Dyskinesia

AbstractThe core axoneme structure of both the motile cilium and sperm tail has the same ultrastructural 9 + 2 microtubular arrangement. Thus, it can be expected that genetic defects in motile cilia also have an effect on sperm tail formation. However, recent studies in human patients, animal models and model organisms have indicated that there are differences in components of specific structures within the cilia and sperm tail axonemes. Primary ciliary dyskinesia (PCD) is a genetic disease with symptoms caused by malfunction of motile cilia such as chronic nasal discharge, ear, nose and chest infections and pulmonary disease (bronchiectasis). Half of the patients also have situs inversus and in many cases male infertility has been reported. PCD genes have a role in motile cilia biogenesis, structure and function. To date mutations in over 40 genes have been identified cause PCD, but the exact effect of these mutations on spermatogenesis is poorly understood. Furthermore, mutations in several additional axonemal genes have recently been identified to cause a sperm-specific phenotype, termed multiple morphological abnormalities of the sperm flagella (MMAF). In this review, we discuss the association of PCD genes and other axonemal genes with male infertility, drawing particular attention to possible differences between their functions in motile cilia and sperm tails.

scholarly journals Smoothing additive manufactured parts using ns-pulsed laser radiation

2021 ◽  
Author(s):  
Florian Kuisat ◽  
Fernando Lasagni ◽  
Andrés Fabián Lasagni
Keyword(s):  
Surface Roughness ◽  
Mechanical Performance ◽  
State Of The Art ◽  
Pulsed Laser ◽  
Industrial Applications ◽  
Laser Source ◽  
Pulsed Laser Radiation ◽  
Current State ◽  
The Impact

AbstractIt is well known that the surface topography of a part can affect its mechanical performance, which is typical in additive manufacturing. In this context, we report about the surface modification of additive manufactured components made of Titanium 64 (Ti64) and Scalmalloy®, using a pulsed laser, with the aim of reducing their surface roughness. In our experiments, a nanosecond-pulsed infrared laser source with variable pulse durations between 8 and 200 ns was applied. The impact of varying a large number of parameters on the surface quality of the smoothed areas was investigated. The results demonstrated a reduction of surface roughness Sa by more than 80% for Titanium 64 and by 65% for Scalmalloy® samples. This allows to extend the applicability of additive manufactured components beyond the current state of the art and break new ground for the application in various industrial applications such as in aerospace.

scholarly journals Unique among ciliopathies: primary ciliary dyskinesia, a motile cilia disorder

2015 ◽  
Vol 7 ◽  
Author(s):  
Kavita Praveen ◽  
Erica E. Davis ◽  
Nicholas Katsanis
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Motile Cilia ◽  
Ciliary Dyskinesia

scholarly journals Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review

2015 ◽  
Vol 51 (2) ◽  
pp. 115-132 ◽  
Author(s):  
Adam J. Shapiro ◽  
Maimoona A. Zariwala ◽  
Thomas Ferkol ◽  
Stephanie D. Davis ◽  
Scott D. Sagel ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
State Of The Art ◽  
Consensus Recommendations ◽  
Ciliary Dyskinesia

scholarly journals Climate-dependent propagation of precipitation uncertainty into the water cycle

2020 ◽  
Author(s):  
Ali Fallah ◽  
Sungmin O ◽  
Rene Orth
Keyword(s):  
Hydrological Model ◽  
Water Cycle ◽  
State Of The Art ◽  
Rain Gauge ◽  
Multiple Sources ◽  
Current State ◽  
Wide Range ◽  
The Impact ◽  
Conceptual Hydrological Model

Abstract. Precipitation is a crucial variable for hydro-meteorological applications. Unfortunately, rain gauge measurements are sparse and unevenly distributed, which substantially hampers the use of in-situ precipitation data in many regions of the world. The increasing availability of high-resolution gridded precipitation products presents a valuable alternative, especially over gauge-sparse regions. Nevertheless, uncertainties and corresponding differences across products can limit the applicability of these data. This study examines the usefulness of current state-of-the-art precipitation datasets in hydrological modelling. For this purpose, we force a conceptual hydrological model with multiple precipitation datasets in > 200 European catchments. We consider a wide range of precipitation products, which are generated via (1) interpolation of gauge measurements (E-OBS and GPCC V.2018), (2) combination of multiple sources (MSWEP V2) and (3) data assimilation into reanalysis models (ERA-Interim, ERA5, and CFSR). For each catchment, runoff and evapotranspiration simulations are obtained by forcing the model with the various precipitation products. Evaluation is done at the monthly time scale during the period of 1984–2007. We find that simulated runoff values are highly dependent on the accuracy of precipitation inputs, and thus show significant differences between the simulations. By contrast, simulated evapotranspiration is generally much less influenced. The results are further analysed with respect to different hydro-climatic regimes. We find that the impact of precipitation uncertainty on simulated runoff increases towards wetter regions, while the opposite is observed in the case of evapotranspiration. Finally, we perform an indirect performance evaluation of the precipitation datasets by comparing the runoff simulations with streamflow observations. Thereby, E-OBS yields the best agreement, while furthermore ERA5, GPCC V.2018 and MSWEP V2 show good performance. In summary, our findings highlight a climate-dependent propagation of precipitation uncertainty through the water cycle; while runoff is strongly impacted in comparatively wet regions such as Central Europe, there are increasing implications on evapotranspiration towards drier regions.

The SLC9A-C Mammalian Na+/H+Exchanger Family: Molecules, Mechanisms, and Physiology

2019 ◽  
Vol 99 (4) ◽  
pp. 2015-2113 ◽  
Author(s):  
S. F. Pedersen ◽  
L. Counillon
Keyword(s):  
State Of The Art ◽  
Expression Profiles ◽  
Tissue Expression ◽  
Gene Organization ◽  
Core Knowledge ◽  
Current State ◽  
Organ Systems ◽  
Evolutionarily Conserved ◽  
Solute Carrier ◽  
Art Research

Na+/H+exchangers play pivotal roles in the control of cell and tissue pH by mediating the electroneutral exchange of Na+and H+across cellular membranes. They belong to an ancient family of highly evolutionarily conserved proteins, and they play essential physiological roles in all phyla. In this review, we focus on the mammalian Na+/H+exchangers (NHEs), the solute carrier (SLC) 9 family. This family of electroneutral transporters constitutes three branches: SLC9A, -B, and -C. Within these, each isoform exhibits distinct tissue expression profiles, regulation, and physiological roles. Some of these transporters are highly studied, with hundreds of original articles, and some are still only rudimentarily understood. In this review, we present and discuss the pioneering original work as well as the current state-of-the-art research on mammalian NHEs. We aim to provide the reader with a comprehensive view of core knowledge and recent insights into each family member, from gene organization over protein structure and regulation to physiological and pathophysiological roles. Particular attention is given to the integrated physiology of NHEs in the main organ systems. We provide several novel analyses and useful overviews, and we pinpoint main remaining enigmas, which we hope will inspire novel research on these highly versatile proteins.

scholarly journals Gene discovery for motile cilia disorders: mutation spectrum in primary ciliary dyskinesia and discovery of mutations in CCDC151

Cilia ◽  
2015 ◽  
Vol 4 (Suppl 1) ◽  
pp. P30
Author(s):  
A Onoufriadis ◽  
R Hjeij ◽  
CM Watson ◽  
CE Slagle ◽  
NT Klena ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Gene Discovery ◽  
Mutation Spectrum ◽  
Motile Cilia ◽  
Ciliary Dyskinesia

scholarly journals The patient’s experience of primary ciliary dyskinesia: a systematic review

2017 ◽  
Vol 26 (9) ◽  
pp. 2265-2285 ◽  
Author(s):  
Laura Behan ◽  
Bruna Rubbo ◽  
Jane S. Lucas ◽  
Audrey Dunn Galvin
Keyword(s):  
Quality Of Life ◽  
Primary Ciliary Dyskinesia ◽  
Age Groups ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
The Uk ◽  
The Impact ◽  
Ciliary Dyskinesia

Abstract Background Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by progressive sinopulmonary disease, with symptoms starting soon after birth. The aim of this study is to critically review, analyse, and synthesise the literature in order to understand the experiences of patients with primary ciliary dyskinesia (PCD) and the impact on health-related quality of life. Method MEDLINE, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE were searched according to the inclusion criteria. A qualitative analysis of 14 studies was conducted. Results Fourteen studies were included in the review, five with qualitative methodologies. Studies originated from the UK, USA, Italy, Denmark and Belgium, one study included a survey distributed internationally. Significant relationships were found between age and worsening of respiratory symptoms, physical, and mental domains of health-related quality of life, with a greater decline compared with reference populations. Variations between the UK and Italy were found for health-related quality of life and its correlation with time since diagnosis. PCD was found to have a physical impact in all age groups: patients found it difficult to keep up with others, and found energy levels were easily depleted compared to family or peers. In terms of social impact, symptoms lead to embarrassment and a sense of isolation, with patients concealing symptoms and/or their diagnosis. In turn, isolation was also linked with the lack of public and medical knowledge. In relation to emotional impact, anxiety was reported in a number of qualitative studies; patients were anxious about getting sick or when thinking about their future health. The burden of treatment and factors influencing adherence were also discussed in depth. Conclusion Health-related quality of life decreases with age in patients with PCD. For all age groups, PCD was found to greatly impact physical, emotional, social functioning, and treatment burden. More research is needed on the psychosocial impact of the illness, disease burden and its effect on quality of life.

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