scholarly journals Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice

2019 ◽  
Vol 28 (20) ◽  
pp. 3391-3405 ◽  
Author(s):  
Alistair T Pagnamenta ◽  
Pierre Heemeryck ◽  
Hilary C Martin ◽  
Christophe Bosc ◽  
Leticia Peris ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Major Change ◽  
Speech Development ◽  
Structural Defects ◽  
Brain Abnormalities ◽  
Cognitive Deficiency ◽  
Tyrosinated Tubulin ◽  
Neuronal Physiology ◽  
Brain Tubulin ◽  
Volume Decrease

Abstract Reversible detyrosination of tubulin, the building block of microtubules, is crucial for neuronal physiology. Enzymes responsible for detyrosination were recently identified as complexes of vasohibins (VASHs) one or two with small VASH-binding protein (SVBP). Here we report three consanguineous families, each containing multiple individuals with biallelic inactivation of SVBP caused by truncating variants (p.Q28* and p.K13Nfs*18). Affected individuals show brain abnormalities with microcephaly, intellectual disability and delayed gross motor and speech development. Immunoblot testing in cells with pathogenic SVBP variants demonstrated that the encoded proteins were unstable and non-functional, resulting in a complete loss of VASH detyrosination activity. Svbp knockout mice exhibit drastic accumulation of tyrosinated tubulin and a reduction of detyrosinated tubulin in brain tissue. Similar alterations in tubulin tyrosination levels were observed in cultured neurons and associated with defects in axonal differentiation and architecture. Morphological analysis of the Svbp knockout mouse brains by anatomical magnetic resonance imaging showed a broad impact of SVBP loss, with a 7% brain volume decrease, numerous structural defects and a 30% reduction of some white matter tracts. Svbp knockout mice display behavioural defects, including mild hyperactivity, lower anxiety and impaired social behaviour. They do not, however, show prominent memory defects. Thus, SVBP-deficient mice recapitulate several features observed in human patients. Altogether, our data demonstrate that deleterious variants in SVBP cause this neurodevelopmental pathology, by leading to a major change in brain tubulin tyrosination and alteration of microtubule dynamics and neuron physiology.

Research on articulation problems of Turkish children who have Down syndrome at age 3 to 12

2017 ◽  
Vol 16 (2) ◽  
Author(s):  
Mehmet Ongun ◽  
Nebi Mustafa Gumus ◽  
Selim Ünsal ◽  
Ali Yildirim ◽  
Sevda Yüksel ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Speech Development ◽  
Structural Defects ◽  
Critical Periods ◽  
Patient Identification ◽  
Motor Assessment ◽  
Turkish Children ◽  
Highly Educated ◽  
Oral Motor ◽  
Assessment Survey

AbstractBackground:Articulation is a process that allows air to pass through vocal cords and then form words and syllables using the tongue, teeth, mentum and palatine tonsils. A person who has pronunciation problems produces, syllables or words inaccurately so; the auditoria have got difficulty to understand what did say, such that the listener has difficulty in understanding what is being said. Due to being genetically different the Down syndrome individual has difficulty with speech due to structural defects in the mouth and problems with the mouth-tongue muscles.Aim:Here the determination of the articulation (pronunciation) problems and the probable causes of the determined problems have been studied.Methods:This study involved children without hearing loss problems; 17 females and 23 males who have Down syndrome and were ages between 3 and 12 years. The Ankara articulation test (AAT) was applied to the individuals. The articulation (pronunciation) ages have been determined according to the ATT. By the detailed assessment of the ATT, it was determined which voices were uttered correctly or not. Through a family interview survey, the information that affected the development of the Down syndrome child’s speech and academic development was obtained. Through a patient identification survey, the education and health information that may effect the speech development were obtained. Through an oral motor assessment survey, the information regarding the competence of oral motor skills that may effect articulation problems were collected. The data were analyzed. Using a family survey, child identification survey and an oral motor assessment survey the correlation between articulation age and articulation defects were viewed.Results:It has been detected that the articulation age of Down syndrome children between 3 and 12 years of age are quite a bit lower when compared to the chronological age according to the ATT. Moreover, in terms of results from the ATT, children with Down syndrome whose cronological age is 8 years 7 months have a 3 year 5 months’ articulation age according to the ATT. They have some difficulties with Turkish vowels such as (/a/, /e/, /ı/, /i/). Also they have some difficulties with consonants such as (/r/, /j/, /z/, /ş/, /z/, /l/, /s/, /n/). Articulation defects at various levels have been detected for all Down syndrome children. Articulation (pronunciation) problems were encountered less in children from highly educated and more concerned families. It has been shown that articulation (pronunciation) problems are less children who receive early treatment, therapy and education services.Conclusion:Significant correlation between the level of articulation usage by individuals and frequency of the articulation problem were detected. For this reason, attaching importance to oral motor studies are considered. Raising parental awareness is required on prenatal diagnosis of Down syndrome. By treating the problems of the speech organs at an early age and including the children who have Down syndrome into the early education programs around 0–3 years and accurate intervention during critical periods, the articulation problems can be reduced. Using a wider age range and having more participants, it is considered that more efficient results may be obtained.

P.3.b.010 Structural brain abnormalities and altered sensitivity to psychotomimetic drugs in neuregulin-1 knockout mice

2009 ◽  
Vol 19 ◽  
pp. S508-S509
Author(s):  
C. O'Tuathaigh ◽  
G. O'Sullivan ◽  
C. O'Leary ◽  
O. Tighe ◽  
L. Desbonnet ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Brain Abnormalities ◽  
Neuregulin 1 ◽  
Psychotomimetic Drugs ◽  
Altered Sensitivity ◽  
Structural Brain

Maytansine-Induced Mitotic Arrest in Human Lymphoblasts

1977 ◽  
Vol 35 ◽  
pp. 460-461
Author(s):  
Tai-Te Chao ◽  
John Sullivan ◽  
Awtar Krishan
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Transmission Electron Microscopy ◽  
Tubulin Polymerization ◽  
Vinca Alkaloids ◽  
Antimitotic Activity ◽  
Transmission Electron ◽  
Flow Microfluorometry ◽  
Brain Tubulin

Maytansine, a novel ansa macrolide (1), has potent anti-tumor and antimitotic activity (2, 3). It blocks cell cycle traverse in mitosis with resultant accumulation of metaphase cells (4). Inhibition of brain tubulin polymerization in vitro by maytansine has also been reported (3). The C-mitotic effect of this drug is similar to that of the well known Vinca- alkaloids, vinblastine and vincristine. This study was carried out to examine the effects of maytansine on the cell cycle traverse and the fine struc- I ture of human lymphoblasts.Log-phase cultures of CCRF-CEM human lymphoblasts were exposed to maytansine concentrations from 10-6 M to 10-10 M for 18 hrs. Aliquots of cells were removed for cell cycle analysis by flow microfluorometry (FMF) (5) and also processed for transmission electron microscopy (TEM). FMF analysis of cells treated with 10-8 M maytansine showed a reduction in the number of G1 cells and a corresponding build-up of cells with G2/M DNA content.

Transmission electron microscopy of composite materials

1988 ◽  
Vol 46 ◽  
pp. 1012-1015
Author(s):  
K.P.D. Lagerlof
Keyword(s):  
Composite Materials ◽  
Physical Properties ◽  
Structural Defects ◽  
Structural Composites ◽  
Multiphase Materials ◽  
Structural Reinforcement ◽  
Transmission Electron ◽  
Reinforced Fiber ◽  
Particulate Reinforced Composites ◽  
Definition Of

Although most materials contain more than one phase, and thus are multiphase materials, the definition of composite materials is commonly used to describe those materials containing more than one phase deliberately added to obtain certain desired physical properties. Composite materials are often classified according to their application, i.e. structural composites and electronic composites, but may also be classified according to the type of compounds making up the composite, i.e. metal/ceramic, ceramic/ceramie and metal/semiconductor composites. For structural composites it is also common to refer to the type of structural reinforcement; whisker-reinforced, fiber-reinforced, or particulate reinforced composites [1-4].For all types of composite materials, it is of fundamental importance to understand the relationship between the microstructure and the observed physical properties, and it is therefore vital to properly characterize the microstructure. The interfaces separating the different phases comprising the composite are of particular interest to understand. In structural composites the interface is often the weakest part, where fracture will nucleate, and in electronic composites structural defects at or near the interface will affect the critical electronic properties.

High-angle electron scattering from amorphous silicon

1995 ◽  
Vol 53 ◽  
pp. 162-163
Author(s):  
M. Libera ◽  
J.A. Ott ◽  
K. Siangchaew ◽  
L. Tsung
Keyword(s):  
Electron Scattering ◽  
Amorphous Material ◽  
Structural Defects ◽  
Constant Thickness ◽  
High Angle ◽  
Fast Electrons ◽  
Angle Scattering ◽  
Stem Image ◽  
Amorphous Si ◽  
Thermal Vibrations

Channeling occurs when fast electrons follow atomic strings in a crystal where there is a minimum in the potential energy (1). Channeling has a strong effect on high-angle scattering. Deviations in atomic position along a channel due to structural defects or thermal vibrations increase the probability of scattering (2-5). Since there are no extended channels in an amorphous material the question arises: for a given material with constant thickness, will the high-angle scattering be higher from a crystal or a glass?Figure la shows a HAADF STEM image collected using a Philips CM20 FEG TEM/STEM with inner and outer collection angles of 35mrad and lOOmrad. The specimen (6) was a cross section of singlecrystal Si containing: amorphous Si (region A), defective Si containing many stacking faults (B), two coherent Ge layers (CI; C2), and a contamination layer (D). CBED patterns (fig. lb), PEELS spectra, and HAADF signals (fig. lc) were collected at 106K and 300K along the indicated line.

Silicon layers grown over SiO2 by liquid phase epitaxy: Electron Microscopical study

1990 ◽  
Vol 48 (4) ◽  
pp. 566-567
Author(s):  
F. Banhart ◽  
F.O. Phillipp ◽  
R. Bergmann ◽  
E. Czech ◽  
M. Konuma ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Liquid Phase ◽  
Plasma Etching ◽  
Liquid Phase Epitaxy ◽  
Three Dimensional ◽  
Microscopical Study ◽  
Sample Temperature ◽  
Structural Defects ◽  
Si Substrates ◽  
Etched Surface

Defect-free silicon layers grown on insulators (SOI) are an essential component for future three-dimensional integration of semiconductor devices. Liquid phase epitaxy (LPE) has proved to be a powerful technique to grow high quality SOI structures for devices and for basic physical research. Electron microscopy is indispensable for the development of the growth technique and reveals many interesting structural properties of these materials. Transmission and scanning electron microscopy can be applied to study growth mechanisms, structural defects, and the morphology of Si and SOI layers grown from metallic solutions of various compositions.The treatment of the Si substrates prior to the epitaxial growth described here is wet chemical etching and plasma etching with NF3 ions. At a sample temperature of 20°C the ion etched surface appeared rough (Fig. 1). Plasma etching at a sample temperature of −125°C, however, yields smooth and clean Si surfaces, and, in addition, high anisotropy (small side etching) and selectivity (low etch rate of SiO2) as shown in Fig. 2.

Passy-Muir Speaking Valve Use in a Children's Hospital: An Interdisciplinary Approach

2008 ◽  
Vol 18 (2) ◽  
pp. 76-86 ◽  
Author(s):  
Lauren Hofmann ◽  
Joseph Bolton ◽  
Susan Ferry
Keyword(s):  
Tracheostomy Tube ◽  
Pediatric Population ◽  
Interdisciplinary Approach ◽  
Extended Period ◽  
Speech Development ◽  
Tube Placement ◽  
Background Information ◽  
Speaking Valve ◽  
Children's Hospital ◽  
Children’S Hospital

Abstract At The Children's Hospital of Philadelphia (CHOP) we treat many children requiring tracheostomy tube placement. With potential for a tracheostomy tube to be in place for an extended period of time, these children may be at risk for long-term disruption to normal speech development. As such, speaking valves that restore more normal phonation are often key tools in the effort to restore speech and promote more typical language development in this population. However, successful use of speaking valves is frequently more challenging with infant and pediatric patients than with adult patients. The purpose of this article is to review background information related to speaking valves, the indications for one-way valve use, criteria for candidacy, and the benefits of using speaking valves in the pediatric population. This review will emphasize the importance of interdisciplinary collaboration from the perspectives of speech-language pathology and respiratory therapy. Along with the background information, we will present current practices and a case study to illustrate a safe and systematic approach to speaking valve implementation based upon our experiences.

Physiologic Studies Provide New Perspectives on Early Speech Development

2010 ◽  
Vol 20 (2) ◽  
pp. 29-36
Author(s):  
Erin M. Wilson ◽  
Ignatius S. B. Nip
Keyword(s):  
Motor Control ◽  
Motor Development ◽  
Motion Tracking ◽  
Speech Development ◽  
Speech Motor Control ◽  
Therapeutic Approaches ◽  
Facial Motion ◽  
Disordered Speech ◽  
Speech Motor ◽  
Physiologic Data

Abstract Although certain speech development milestones are readily observable, the developmental course of speech motor control is largely unknown. However, recent advances in facial motion tracking systems have been used to investigate articulator movements in children and the findings from these studies are being used to further our understanding of the physiologic basis of typical and disordered speech development. Physiologic work has revealed that the emergence of speech is highly dependent on the lack of flexibility in the early oromotor system. It also has been determined that the progression of speech motor development is non-linear, a finding that has motivated researchers to investigate how variables such as oromotor control, cognition, and linguistic factors affect speech development in the form of catalysts and constraints. Physiologic data are also being used to determine if non-speech oromotor behaviors play a role in the development of speech. This improved understanding of the physiology underlying speech, as well as the factors influencing its progression, helps inform our understanding of speech motor control in children with disordered speech and provide a framework for theory-driven therapeutic approaches to treatment.

Sign in / Sign up

Export Citation Format

Share Document