scholarly journals Biallelic Mutations in LRRC56 encoding a protein associated with intraflagellar transport, cause mucociliary clearance and laterality defects

2018 ◽  
Author(s):  
Serge Bonnefoy ◽  
Christopher M. Watson ◽  
Kristin D. Kernohan ◽  
Moara Lemos ◽  
Sebastian Hutchinson ◽  
...  
Keyword(s):  
High Speed ◽  
Respiratory Infections ◽  
Fluid Flows ◽  
Intraflagellar Transport ◽  
Distal Portion ◽  
Mucus Clearance ◽  
Transmission Electron ◽  
Dynein Arms ◽  
Biallelic Mutations ◽  
Laterality Defects

ABSTRACTDefective motile cilia are responsible for a group of heterogeneous genetic conditions characterised by dysfunction of the apparatus responsible for generating fluid flows. Primary ciliary dyskinesia (PCD) is the prototype for such disorders and presents with impaired pulmonary mucus clearance, susceptibility to chronic recurrent respiratory infections, male infertility and laterality defects in about 50 % of patients. Here we report biallelic variants in LRRC56 (also known as ODA8), identified in two unrelated consanguineous families. The phenotype comprises laterality defects and chronic pulmonary infections. High speed video microscopy of cultured patient epithelial cells showed severely dyskinetic cilia, but no obvious ultra-structural abnormalities on routine transmission electron microscopy (TEM). Further investigation revealed that LRRC56 interacts with the intraflagellar transport (IFT) protein IFT88. The link to IFT was interrogated in Trypanosoma brucei. In this protist, LRRC56 is recruited to the cilium during axoneme construction, where it co-localises with IFT trains and facilitates the addition of dynein arms to the distal end of the flagellum. In T. brucei carrying LRRC56 null mutations, or a mutation (p.Leu259Pro) corresponding to the p.Leu140Pro variant seen in one of the affected families, we observed abnormal ciliary beat patterns and an absence of outer dynein arms restricted to the distal portion of the axoneme. Together, our findings confirm that deleterious variants in LRRC56 result in a human disease, and suggest this protein has a likely role in dynein transport during cilia assembly that is evolutionarily important for cilia motility.

scholarly journals Clinical and Genetic Analysis of Children with Kartagener Syndrome

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 900 ◽  
Author(s):  
Rute Pereira ◽  
Telma Barbosa ◽  
Luís Gales ◽  
Elsa Oliveira ◽  
Rosário Santos ◽  
...  
Keyword(s):  
Autosomal Recessive Disorder ◽  
Kartagener Syndrome ◽  
Mucus Clearance ◽  
Pathogenic Variants ◽  
Transmission Electron ◽  
Whole Exome ◽  
Dynein Arms ◽  
Organ Laterality ◽  
Ciliary Dyskinesia ◽  
Laterality Defects

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia causing ineffective mucus clearance and organ laterality defects. In this study, two unrelated Portuguese children with strong PCD suspicion underwent extensive clinical and genetic assessments by whole-exome sequencing (WES), as well as ultrastructural analysis of cilia by transmission electron microscopy (TEM) to identify their genetic etiology. These analyses confirmed the diagnostic of Kartagener syndrome (KS) (PCD with situs inversus). Patient-1 showed a predominance of the absence of the inner dynein arms with two disease-causing variants in the CCDC40 gene. Patient-2 showed the absence of both dynein arms and WES disclosed two novel high impact variants in the DNAH5 gene and two missense variants in the DNAH7 gene, all possibly deleterious. Moreover, in Patient-2, functional data revealed a reduction of gene expression and protein mislocalization in both genes’ products. Our work calls the researcher’s attention to the complexity of the PCD and to the possibility of gene interactions modelling the PCD phenotype. Further, it is demonstrated that even for well-known PCD genes, novel pathogenic variants could have importance for a PCD/KS diagnosis, reinforcing the difficulty of providing genetic counselling and prenatal diagnosis to families.

scholarly journals Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects

2018 ◽  
Vol 103 (5) ◽  
pp. 727-739 ◽  
Author(s):  
Serge Bonnefoy ◽  
Christopher M. Watson ◽  
Kristin D. Kernohan ◽  
Moara Lemos ◽  
Sebastian Hutchinson ◽  
...  
Keyword(s):  
Mucociliary Clearance ◽  
Intraflagellar Transport ◽  
Biallelic Mutations ◽  
Laterality Defects

Dynamics of thin precursor film in wetting of nanopatterned surfaces

2021 ◽  
Vol 118 (38) ◽  
pp. e2108074118
Author(s):  
Utkarsh Anand ◽  
Tanmay Ghosh ◽  
Zainul Aabdin ◽  
Siddardha Koneti ◽  
XiuMei Xu ◽  
...  
Keyword(s):  
High Speed ◽  
Liquid Droplet ◽  
Water Film ◽  
Precursor Film ◽  
Intermediate Step ◽  
Dense Array ◽  
Flat Surfaces ◽  
Transmission Electron ◽  
Phase Transmission ◽  
Two Stages

The spreading of a liquid droplet on flat surfaces is a well-understood phenomenon, but little is known about how liquids spread on a rough surface. When the surface roughness is of the nanoscopic length scale, the capillary forces dominate and the liquid droplet spreads by wetting the nanoscale textures that act as capillaries. Here, using a combination of advanced nanofabrication and liquid-phase transmission electron microscopy, we image the wetting of a surface patterned with a dense array of nanopillars of varying heights. Our real-time, high-speed observations reveal that water wets the surface in two stages: 1) an ultrathin precursor water film forms on the surface, and then 2) the capillary action by nanopillars pulls the water, increasing the overall thickness of water film. These direct nanoscale observations capture the previously elusive precursor film, which is a critical intermediate step in wetting of rough surfaces.

Venom flow in rattlesnakes: mechanics and metering

2001 ◽  
Vol 204 (24) ◽  
pp. 4345-4351
Author(s):  
Bruce A. Young ◽  
Krista Zahn
Keyword(s):  
Functional Morphology ◽  
Delivery System ◽  
Flow Rate ◽  
High Speed ◽  
Distal Portion ◽  
Retrograde Flow ◽  
Crotalus Atrox ◽  
Direct Recording ◽  
Significant Difference ◽  
Digital Videography

SUMMARY The functional morphology of venom injection in Crotalus atrox was explored using high-speed digital videography combined with direct recording of venom flow using perivascular flow probes. Although venom flow was variable, in most strikes the onset of venom flow was coincidental with fang penetration, and retrograde flow (venom suction) was observed prior to fang withdrawal. The duration of venom flow was consistently less than the duration of fang penetration. The occurrence of retrograde flow, ‘dry bites’ (which accounted for 35 % of the strikes) and unilateral strikes all support a hypothesis for venom pooling in the distal portion of the venom-delivery system. No significant difference in temporal or volumetric aspects of venom flow were found between defensive strikes directed at small and large rodents. With the species and size of target held constant, the duration of venom flow, maximum venom flow rate and total venom volume were all significantly lower in predatory than in defensive strikes.

scholarly journals Free boundary problems in shock reflection/diffraction and related transonic flow problems

2015 ◽  
Vol 373 (2050) ◽  
pp. 20140276 ◽  
Author(s):  
Gui-Qiang Chen ◽  
Mikhail Feldman
Keyword(s):  
Free Boundary ◽  
High Speed ◽  
Free Boundary Problems ◽  
Fluid Flows ◽  
Shock Reflection ◽  
Two Dimensional ◽  
Open Problems ◽  
Boundary Problems ◽  
Flow Problems ◽  
Concave Corner

Shock waves are steep wavefronts that are fundamental in nature, especially in high-speed fluid flows. When a shock hits an obstacle, or a flying body meets a shock, shock reflection/diffraction phenomena occur. In this paper, we show how several long-standing shock reflection/diffraction problems can be formulated as free boundary problems, discuss some recent progress in developing mathematical ideas, approaches and techniques for solving these problems, and present some further open problems in this direction. In particular, these shock problems include von Neumann's problem for shock reflection–diffraction by two-dimensional wedges with concave corner, Lighthill's problem for shock diffraction by two-dimensional wedges with convex corner, and Prandtl-Meyer's problem for supersonic flow impinging onto solid wedges, which are also fundamental in the mathematical theory of multidimensional conservation laws.

Simulation of Hypersonic Viscous Flow Past a 2D Circular Cylinder Using Lattice Boltzmann Method

2010 ◽  
Author(s):  
R. Kamali ◽  
A. H. Tabatabaee Frad
Keyword(s):  
Circular Cylinder ◽  
Lattice Boltzmann Method ◽  
Lattice Boltzmann ◽  
High Speed ◽  
Fluid Flows ◽  
Boltzmann Distribution ◽  
Equilibrium Distribution Function ◽  
Complex Flows ◽  
Compressible Viscous Flows ◽  
Boltzmann Method

It is known that the Lattice Boltzmann Method is not very effective when it is being used for the high speed compressible viscous flows; especially complex fluid flows around bodies. Different reasons have been reported for this unsuccessfulness; Lacking in required isotropy in the employed lattices and the restriction of having low Mach number in Taylor expansion of the Maxwell Boltzmann distribution as the equilibrium distribution function, might be mentioned as the most important ones. In present study, a new numerical method based on Li et al. scheme is introduced which enables the Lattice BoltzmannMethod to stably simulate the complex flows around a 2D circular cylinder. Furthermore, more stable implementation of boundary conditions in Lattice Boltzmann method is discussed.

scholarly journals Fabrication and evaluation of slow-release lignin-based avermectin nano-delivery system with UV-shielding property

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dongmei Mo ◽  
Xiangying Li ◽  
Yong Chen ◽  
Yang Jiang ◽  
Chunfang Gan ◽  
...  
Keyword(s):  
Electron Microscope ◽  
Controlled Release ◽  
Delivery System ◽  
High Speed ◽  
Large Scale ◽  
Diazonium Salt ◽  
Sodium Lignosulfonate ◽  
Ultrasonic Dispersion ◽  
Transmission Electron ◽  
The Stability

AbstractNanopesticide is one of the best pesticide formulation technologies to overcome the disadvantages of traditional pesticides, which has received great attention from the international community. Using high-speed emulsification and ultrasonic dispersion technology, an avermectin nano-delivery system (Av-NDs) with a particle size of 80–150 nm was prepared through embedding the pesticide molecule utilizing the cross-linking reaction between sodium lignosulfonate and p-phenylenediamine diazonium salt. The formulation and composition of Av-NDs were optimized, the morphology of Av-NDs was analyzed by scanning electron microscope, transmission electron microscope and dynamic light scattering, and the structure of Av-NDs was characterized by UV, IR and 1H NMR. Anti-photolysis and controlled-release tests show that the stability of Av-NDs is 3–4 times of the original avermectin (Av) and possesses the pH-responsive controlled release property. Furthermore, the insecticidal activity of Av-NDs is better than that of avermectin suspension concentrate (Av-SC). The Av-NDs with anti-photolysis and controlled-release characteristics is suitable for large-scale industrial production and is capable to be utilized as effective insecticide in the field.

Attritious Wear of Silicon Carbide

1976 ◽  
Vol 98 (4) ◽  
pp. 1125-1134 ◽  
Author(s):  
R. Komanduri ◽  
M. C. Shaw
Keyword(s):  
Silicon Carbide ◽  
Electron Microscope ◽  
High Temperature ◽  
High Speed ◽  
Layer By Layer ◽  
Wear Area ◽  
Work Material ◽  
Transmission Electron ◽  
Metal Silicides ◽  
Boundary Fracture

Attritious wear of silicon carbide in simulated grinding tests against a cobalt base superalloy at high speed and extremely small feed rate was studied using a scanning electron microscope (SEM) and an auger electron spectroscope (AES). In many cases the wear area of silicon carbide was found to be concave rather than planar in shape. Several microcracks and grain boundary fracture were also observed. No evidence of metal build-up was observed on silicon carbide which was not the case with aluminum oxide. AES study of the rubbed surface on the work material and transmission electron microscope (TEM) investigation of the wear debris suggest that attritious wear of silicon carbide is due to one or more of the following mechanisms: 1 – Preferential removal of surface atoms on the abrasive, layer by layer, by oxidation under high temperature and a favorably directed shear stress; 2 – disassociation of silicon carbide at high temperature and (a) diffusion of silicon into the work material and formation of metal silicides and (b) diffusion of carbon into the work material and formation of unstable metal carbides (in the present case Ni3C and Co3C) which decompose during cooling to metal and carbon atoms; 3 – pinocoidal cleavage fracture of silicon carbide on basal planes c(0001) resulting in the removal of many micron-sized crystallites.

Biallelic Mutations in Tetratricopeptide Repeat Domain 26 ( Intraflagellar Transport 56 ) Cause Severe Biliary Ciliopathy in Humans

Hepatology ◽  
2020 ◽  
Vol 71 (6) ◽  
pp. 2067-2079 ◽  
Author(s):  
Ranad Shaheen ◽  
Saud Alsahli ◽  
Nour Ewida ◽  
Fatema Alzahrani ◽  
Hanan E. Shamseldin ◽  
...  
Keyword(s):  
Intraflagellar Transport ◽  
Tetratricopeptide Repeat ◽  
Repeat Domain ◽  
Tetratricopeptide Repeat Domain ◽  
Biallelic Mutations

scholarly journals Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia

2019 ◽  
Vol 57 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Sylvain Blanchon ◽  
Marie Legendre ◽  
Mathieu Bottier ◽  
Aline Tamalet ◽  
Guy Montantin ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Central Complex ◽  
Ciliary Beating ◽  
Recovery Stroke ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.

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