scholarly journals Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability

2021 ◽  
Author(s):  
Gladys L. Caldeira ◽  
Angela S. Inacio ◽  
Nuno Beltrao ◽  
Carlos A.V. Barreto ◽  
Marina V. Rodrigues ◽  
...  

Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate an ID-associated mutant form of the TARP family member stargazin. Molecular dynamics analyses showed that the stargazin V143L variant weakens the overall interface of the AMPAR:stargazin complex and hinders the stability of the complex. Knock-in mice for the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation in basal dendrites, and synaptic ultrastructural alterations. These data demonstrate a causal role for mutated stargazin in the pathogenesis of ID and highlight its role in the development and function of hippocampal synapses.

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1192
Author(s):  
Massimo Mapelli ◽  
Paola Zagni ◽  
Valeria Calbi ◽  
Aliku Twalib ◽  
Roberto Ferrara ◽  
...  

Background: Williams–Beuren syndrome (WS) is a rare, complex, congenital developmental disorder including cardiovascular manifestations, intellectual disability and a peculiar cognitive and behavior profile. Supravalvular aortic stenosis (SVAS) is the most frequent cardiovascular abnormality in WS children. Data on WS patients in sub-Saharan Africa are scarce. A genetic study is usually required for a definite diagnosis, but genetic testing is often unavailable in developing countries and the combination of a typical clinical phenotype and echocardiographic profile helps to confirm the diagnosis. Case Report: We report the case of a 5-year-old Ugandan child admitted to a large no profit hospital after he was initially managed as a case of infective endocarditis. A physical examination revealed the typical features of WS. A cardiac echo showed severe SVAS (peak gradient 80 mmHg) with a normal anatomy and function of the aortic valve and mild valvular pulmonary stenosis. The child also had a moderate intellectual disability and a characteristic facies consistent with WS. Conclusion: We present the first reported case of WS in Uganda. Cardiac echo and a characteristic clinical picture could be enough to exclude more common causes of heart failure (i.e., rheumatic heart disease) and to make the diagnosis even when specific genetic tests are not available.


2020 ◽  
Vol 21 (8) ◽  
pp. 741-747
Author(s):  
Liguang Zhang ◽  
Yanan Shen ◽  
Wenjing Lu ◽  
Lengqiu Guo ◽  
Min Xiang ◽  
...  

Background: Although the stability of proteins is of significance to maintain protein function for therapeutical applications, this remains a challenge. Herein, a general method of preserving protein stability and function was developed using gelatin films. Method: Enzymes immobilized onto films composed of gelatin and Ethylene Glycol (EG) were developed to study their ability to stabilize proteins. As a model functional protein, β-glucosidase was selected. The tensile properties, microstructure, and crystallization behavior of the gelatin films were assessed. Result: Our results indicated that film configurations can preserve the activity of β-glucosidase under rigorous conditions (75% relative humidity and 37°C for 47 days). In both control films and films containing 1.8 % β-glucosidase, tensile strength increased with increased EG content, whilst the elongation at break increased initially, then decreased over time. The presence of β-glucosidase had a negligible influence on tensile strength and elongation at break. Scanning electron-microscopy (SEM) revealed that with increasing EG content or decreasing enzyme concentrations, a denser microstructure was observed. Conclusion: In conclusion, the dry film is a promising candidate to maintain protein stabilization and handling. The configuration is convenient and cheap, and thus applicable to protein storage and transportation processes in the future.


2018 ◽  
Vol 4 (2) ◽  
pp. 150
Author(s):  
Rahmadini Darwas

<p><strong><em>Abstract<br /></em></strong><em>Laboratory is one of the supporting facilities in im[roving the learning process. Problems found by students regarding the information system laboratory facilities at STMIK Indonesia Padang are</em><em> the computers that suddenly die when operated, the less cold room, display data is blurred, making the inconvenience in the learning process that causes the students less satisfied with the services provided. Students will feel satisfied if the service is expected to match the received. Therefore, a decision support system is needed to analyze the quality of services provided to the students so that it can support the role and function of the laboratory optimally and what attributes need to be improved the quality of service. The method used is Fuzzy Service Quality (Servqual) method. The results showed that the service quality received was not in accordance with the expected because there is a gap of -1.55 for tangibles dimension. Attributes that need to be improved the quality of services are laboratory space is cool and comfortable, the use of laboratories relevant to the field of science, the responsibility of laboratory assistant, the availability of professional teachers and attitudes and behavior of labor officers.<br /></em></p><p><strong><em>Abstrak<br /></em></strong>Laboratorium merupakan salah satu fasilitas pendukung dalam meningkatkan proses pembelajaran. Permasalahan yang ditemukan mahasiswa mengenai fasilitas laboratorium sistem informasi pada STMIK Indonesia Padang adalah komputer yang tiba-tiba mati saat dioperasikan, ruangan yang kurang dingin, data <em>display</em> yang buram sehingga membuat ketidaknyamanan dalam proses pembelajaran yang menyebabkan mahasiswa kurang puas terhadap layanan yang diberikan. Mahasiswa akan merasa puas apabila layanan yang diharapkan sesuai dengan yang diterima. Oleh sebab itu, diperlukan suatu sistem pendukung keputusan untuk menganalisis kualitas layanan yang diberikan kepada mahasiswa sehingga dapat mendukung peran dan fungsi laboratorium secara optimal serta atribut apa saja yang perlu ditingkatkan kualitas layanannya. Metode yang digunakan adalah metode <em>Fuzzy Service Quality </em>(<em>Servqua</em>l). Hasil penelitian menunjukkan bahwa kualitas layanan yang diterima belum sesuai dengan yang diharapkan karena terdapat <em>gap</em> sebesar -1.55 untuk dimensi <em>tangibles</em>. Atribut yang perlu ditingkatkan kualitas layanannya yaitu ruangan laboratorium yang sejuk dan nyaman, penggunaan laboratorium yang relevan dengan bidang ilmu, tanggungjawab asisten labor, tersedianya tenaga pengajar yang professional dan sikap serta perilaku petugas labor</p><p><strong><em>Kata kunci</em></strong><strong> : sistem pendukung keputusan, laboratorium, <em>fuzzy</em>, <em>servqual</em></strong></p><p><strong><em><br /></em></strong></p>


2020 ◽  
Vol 56 (2) ◽  
pp. 119-122
Author(s):  
Doris Adams Hill ◽  
Theoni Mantzoros ◽  
Jonté C. Taylor

Special educators are often considered the experts in their school when it comes to developing functional behavior assessments (FBA) and behavior intervention plans (BIP), yet rarely are they trained much beyond basic antecedents, behaviors, and consequences (ABC). This column discusses concepts that will expand special education professionals’ knowledge to make better decisions regarding interventions for the students they serve. Specifically, the focus is on motivating operations (MO) and function-based interventions and the implications of these on behavior. Knowledge of the concept of MOs can enhance a teacher’s ability to provide evidence-based interventions and more fully developed behavioral interventions for students in their purview.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hai Huang ◽  
Bin-Fei Zhang ◽  
Ping Liu ◽  
Hong-Li Deng ◽  
Peng-Fei Wang ◽  
...  

Abstract Background It is difficult to judge the stability of lateral compression type-1 (LC-1) pelvic fracture, as it is often based on static images of the pelvis. Compared with the traditional experience strategy, ultrasonography examination may be able to distinguish operative and conservative patients before definitive treatment. However, in previous studies, we have not compared the outcomes between traditional experience strategy (TES group) and combined ultrasonography examination (CUE group). Thus, the aim of the study is comparing the differences between TES and CUE strategy, to identify the value of ultrasonography examination. Methods Medical records system for patients with LC-1 pelvic fractures who were treated with TES and CUE strategy were included. Patients’ baseline characteristics, treatment strategy, and function were recorded at follow-up. Functional outcomes were evaluated using the Majeed grading system. Results In total, 77 patients with LC-1 pelvic fractures were included in the study. There were 42 and 35 patients in TES and CUE group, respectively. Compared to TES group (69 %), there were less proportion patients chosen the operative treatment in CUE group (43 %, P = 0.021). The volume of intraoperative blood loss in CUE operative group was more than TES operative group (P = 0.037). There were more patients with complete sacral fracture in CUE operative group than TES operative group (P = 0.002). The Majeed scores in CUE conservative group was higher than TES conservative group (P = 0.008). The overall Majeed scores in CUE group was higher than that in TES group (P = 0.039). Conclusions The ultrasonography examination could relatively accurately identify the unstable LC-1 pelvis than the traditional experience strategy, the operative rate could be reduced and the overall function of LC-1 patients could be improved under the ultrasonography examination. Level of evidence Level III.


2021 ◽  
Vol 22 (11) ◽  
pp. 6167
Author(s):  
Carla Liaci ◽  
Mattia Camera ◽  
Giovanni Caslini ◽  
Simona Rando ◽  
Salvatore Contino ◽  
...  

Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular level and moving toward higher levels of organization, i.e., cell compartment and functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations that have an impact on cell processes such as neuronal migration, neuritogenesis, and synaptic plasticity rebound on the overall establishment of an effective network and consequently on the cognitive phenotype. Systems biology (SB) approaches are more focused on the overall interconnected network rather than on individual genes, thus encouraging the design of therapies that aim to correct common dysregulated biological processes. This review summarizes current knowledge about cytoskeleton control in neurons and its relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of those findings into biomedical research.


2021 ◽  
Vol 22 (5) ◽  
pp. 2732
Author(s):  
Nadine Reichhart ◽  
Vladimir M. Milenkovic ◽  
Christian H. Wetzel ◽  
Olaf Strauß

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.


1992 ◽  
Vol 6 ◽  
pp. 16-16 ◽  
Author(s):  
Richard K. Bambach ◽  
J. John Sepkoski

The first two ranks above the species level in the traditional Linnean hierarchy — the genus and family — are species based: genera have been erected to unify groups of morphologically similar, closely related species and families have been erected to group genera recognized as closely related because of the shared morphologic characteristics of their species. Diversity patterns of traditional genera and families thus appear congruent with those of species in (a) the Recent (e. g., latitudinal gradients in many groups), (b) compilations of all marine taxa for the entire Phanerozoic (including the stage level), (c) comparisons through time within individual taxa (e. g., Foraminifera, Rugosa, Conodonta), and (d) simulation studies. Genera and families often have a more robust fossil record of diversity than species, especially for poorly sampled groups (e. g., echinoids), because of the range-through record of these polytypic taxa. Simulation studies indicate that paraphyly among traditionally defined taxa is not a fatal problem for diversity studies; in fact, when degradation of the quality of the fossil record is modelled, both diversity and rates of origination and extinction are better represented by including paraphyletic taxa than by restricting data to monophyletic clades. This result underscores the utility of traditional rank-based analyses of the history of diversity.In contrast, the three higher ranks of the Linnean hierarchy — orders, classes and phyla — are defined and recognized by key character complexes assumed to be rooted deep in the developmental program and, therefore, considered to be of special significance. These taxa are unified on the basis of body plan and function, not species morphology. Even if paraphyletic, recognition of such taxa is useful because they represent different functional complexes that reflect biological organization and major evolutionary innovations, often with different ecological capacities. Phanerozoic diversity patterns of orders, classes and phyla are not congruent with those of lower taxa; the higher groups each increased rapidly in the early Paleozoic, during the explosive diversification of body plans in the Cambrian, and then remained stable or declined slightly after the Ordovician. The diversity history of orders superficially resembles that of lower taxa, but this is a result only of ordinal turnover among the Echinodermata coupled with ordinal radiation in the Chordata; it is not a highly damped signal derived from the diversity of species, genera, or families. Despite the stability of numbers among post-Ordovician Linnean higher taxa, the diversity of lower taxa within many of these Bauplan groups fluctuated widely, and these diversity patterns signal embedded ecologic information, such as differences in flexibility in filling or utilizing ecospace.Phylogenetic analysis is vital for understanding the origins and genealogical structure of higher taxa. Only in such fashion can convergence and its implications for ecological constraints and/or opportunities be understood. But blind insistence on the use of monophyletic classifications in all studies would obscure some of the important information contained in traditional taxonomic groupings. The developmental modifications that characterize Linnean higher taxa (and traditionally separate them from their paraphyletic ancestral taxa) provide keys to understanding the role of shifting ecology in macroevolutionary success.


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