Mutations in the exocyst component EXOC2 cause severe defects in human brain development

The exocyst, an octameric protein complex, is an essential component of the membrane transport machinery required for tethering and fusion of vesicles at the plasma membrane. We report pathogenic variants in an exocyst subunit, EXOC2 (Sec5). Affected individuals have severe developmental delay, dysmorphism, and brain abnormalities; variability associated with epilepsy; and poor motor skills. Family 1 had two offspring with a homozygous truncating variant in EXOC2 that leads to nonsense-mediated decay of EXOC2 transcript, a severe reduction in exocytosis and vesicle fusion, and undetectable levels of EXOC2 protein. The patient from Family 2 had a milder clinical phenotype and reduced exocytosis. Cells from both patients showed defective Arl13b localization to the primary cilium. The discovery of mutations that partially disable exocyst function provides valuable insight into this essential protein complex in neural development. Since EXOC2 and other exocyst complex subunits are critical to neuronal function, our findings suggest that EXOC2 variants are the cause of the patients’ neurological disorders.

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Pathogenic variants in nucleoporin TPR (translocated promoter region, nuclear basket protein) cause severe intellectual disability in humans

Human Molecular Genetics ◽

10.1093/hmg/ddab248 ◽

2021 ◽

Author(s):

Nicole J Van Bergen ◽

Katrina M Bell ◽

Kirsty Carey ◽

Russell Gear ◽

Sean Massey ◽

...

Keyword(s):

Intellectual Disability ◽

Neurological Disorders ◽

Promoter Region ◽

Nuclear Pore ◽

Valuable Insight ◽

Amino Acid Deletion ◽

Pathogenic Variants ◽

Severe Intellectual Disability ◽

Functional Analyses ◽

Insight Into

Abstract The nuclear pore complex (NPC) is a multi-protein complex that regulates the trafficking of macromolecules between the nucleus and cytoplasm. Genetic variants in components of the NPC have been shown to cause a range of neurological disorders, including intellectual disability and microcephaly. Translocated promoter region, nuclear basket protein (TPR) is a critical scaffolding element of the nuclear facing interior of the NPC. Here we present two siblings with biallelic variants in TPR who present with a phenotype of microcephaly, ataxia and severe intellectual disability. The variants result in a premature truncation variant, and a splice variant leading to a 12-amino acid deletion respectively. Functional analyses in patient fibroblasts demonstrate significantly reduced TPR levels, and decreased TPR-containing NPC density. A compensatory increase in total NPC levels was observed, and decreased global RNA intensity in the nucleus. The discovery of variants that partly disable TPR function provide valuable insight into this essential protein in human disease, and our findings suggest that TPR variants are the cause of the siblings’ neurological disorder.

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An insight into SARS-CoV-2 Membrane protein interaction with Spike, Envelope, and Nucleocapsid proteins

10.1101/2020.10.30.363002 ◽

2020 ◽

Author(s):

Amit kumar ◽

Prateek Kumar ◽

Neha Garg ◽

Rajanish Giri

Keyword(s):

Membrane Protein ◽

Protein Interactions ◽

Protein Complex ◽

Drug Targets ◽

Virus Assembly ◽

Protein Docking ◽

Structural Proteins ◽

Valuable Insight ◽

Nucleocapsid Proteins ◽

Insight Into

AbstractIntraviral protein-protein interactions are crucial for replication, pathogenicity, and viral assembly. Among these, virus assembly is a critical step as it regulates the arrangements of viral structural proteins and helps in the encapsulation of genomic material. SARS-CoV-2 structural proteins play an essential role in the self-rearrangement, RNA encapsulation, and mature virus particle formation. In SARS-CoV, the membrane protein interacts with the envelope and spike protein in Endoplasmic Reticulum Golgi Intermediate Complex (ERGIC) to form an assembly in the lipid bilayer, followed by membrane-ribonucleoprotein (nucleocapsid) interaction. In this study, using protein-protein docking, we tried to understand the interaction of membrane protein’s interaction with envelope, spike and nucleocapsid proteins. Further, simulation studies performed up to 100ns agreed that protein complexes M-E, M-S, and M-N were stable. Moreover, the calculated free binding energy and dissociation constant values support the protein complex formation. The interaction identified in the study will be of great importance, as it provides valuable insight into the protein complex, which could be the potential drug targets for future studies.

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Study of the resistor material of an automotive spark plug by use of the charge-up effect along with elemental mapping in an electron microprobe

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100088026 ◽

1991 ◽

Vol 49 ◽

pp. 742-743

Author(s):

D. R. Liu ◽

S. S. Shinozaki ◽

J. S. Park ◽

B. N. Juterbock

Keyword(s):

Electron Microprobe ◽

Present Report ◽

Coated Sample ◽

Valuable Insight ◽

Elemental Mapping ◽

Spark Plug ◽

Carbon Coated ◽

Electron Image ◽

Electron Imaging ◽

Insight Into

The electric and thermal properties of the resistor material in an automotive spark plug should be stable during its service lifetime. Containing many elements and many phases, this material has a very complex microstructure. Elemental mapping with an electron microprobe can reveal the distribution of all relevant elements throughout the sample. In this work, it is demonstrated that the charge-up effect, which would distort an electron image and, therefore, is normally to be avoided in an electron imaging work, could be used to advantage to reveal conductive and resistive zones in a sample. Its combination with elemental mapping can provide valuable insight into the underlying conductivity mechanism of the resistor.This work was performed in a CAMECA SX-50 microprobe. The spark plug used in the present report was a commercial product taken from the shelf. It was sectioned to expose the cross section of the resistor. The resistor was known not to contain the precious metal Au as checked on the carbon coated sample. The sample was then stripped of carbon coating and re-coated with Au.

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Quantum Mechanical Interpretation of the Ultra-Low Energy Methyl-Rotation Dynamics in Porous Metal-Organic Frameworks Probed by Low-Frequency Vibrational Spectroscopy and ab initio Simulations

10.26434/chemrxiv.5995078.v1 ◽

2018 ◽

Author(s):

Qi Li ◽

Adam J. Zaczek ◽

Timothy M. Korter ◽

J. Axel Zeitler ◽

Michael T. Ruggiero

Keyword(s):

Ab Initio ◽

Metal Organic Frameworks ◽

Low Frequency ◽

Rotor Dynamics ◽

Quantum Mechanical ◽

Valuable Insight ◽

Void Space ◽

Ab Initio Simulations ◽

Metal Organic ◽

Insight Into

<div>Understanding the nature of the interatomic interactions present within the pores of metal-organic frameworks</div><div>is critical in order to design and utilize advanced materials</div><div>with desirable applications. In ZIF-8 and its cobalt analogue</div><div>ZIF-67, the imidazolate methyl-groups, which point directly</div><div>into the void space, have been shown to freely rotate - even</div><div>down to cryogenic temperatures. Using a combination of ex-</div><div>perimental terahertz time-domain spectroscopy, low-frequency</div><div>Raman spectroscopy, and state-of-the-art ab initio simulations,</div><div>the methyl-rotor dynamics in ZIF-8 and ZIF-67 are fully charac-</div><div>terized within the context of a quantum-mechanical hindered-</div><div>rotor model. The results lend insight into the fundamental</div><div>origins of the experimentally observed methyl-rotor dynamics,</div><div>and provide valuable insight into the nature of the weak inter-</div><div>actions present within this important class of materials.</div>

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A Review of Phytochemical and Pharmacological Studies of Inula Species

Current Bioactive Compounds ◽

10.2174/1573407215666190207093538 ◽

2020 ◽

Vol 16 (5) ◽

pp. 557-567

Author(s):

Aparoop Das ◽

Anshul Shakya ◽

Surajit Kumar Ghosh ◽

Udaya P. Singh ◽

Hans R. Bhat

Keyword(s):

Bacterial Infections ◽

Chemical Constituents ◽

Valuable Insight ◽

Important Ingredient ◽

Pharmacological Activities ◽

Medicinal Uses ◽

The Family ◽

Pharmacological Studies ◽

Perennial Herbs ◽

Insight Into

Background: Plants of the genus Inula are perennial herbs of the family Asteraceae. This genus includes more than 100 species, widely distributed throughout Europe, Africa and Asia including India. Many of them are indicated in traditional medicine, e.g., in Ayurveda. This review explores chemical constituents, medicinal uses and pharmacological actions of Inula species. Methods: Major databases and research and review articles retrieved through Scopus, Web of Science, and Medline were consulted to obtain information on the pharmacological activities of the genus Inula published from 1994 to 2017. Results: Inula species are used either alone or as an important ingredient of various formulations to cure dysfunctions of the cardiovascular system, respiratory system, urinary system, central nervous system and digestive system, and for the treatment of asthma, diabetes, cancers, skin disorders, hepatic disease, fungal and bacterial infections. A range of phytochemicals including alkaloids, essential and volatile oils, flavonoids, terpenes, and lactones has been isolated from herbs of the genus Inula, which might possibly explain traditional uses of these plants. Conclusion: The present review is focused on chemical constituents, medicinal uses and pharmacological actions of Inula species and provides valuable insight into its medicinal potential.

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Comparison of plasma and cerebrospinal fluid proteomes identifies gene products guiding adult neurogenesis and neural differentiation in birds

Scientific Reports ◽

10.1038/s41598-021-84274-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eleni Voukali ◽

Nithya Kuttiyarthu Veetil ◽

Pavel Němec ◽

Pavel Stopka ◽

Michal Vinkler

Keyword(s):

Cerebrospinal Fluid ◽

Adult Neurogenesis ◽

Neural Development ◽

Neural Differentiation ◽

Csf Proteins ◽

Nymphicus Hollandicus ◽

Liquid Chromatography Tandem Mass ◽

Genome Information ◽

Insight Into ◽

Brain Homeostasis

AbstractCerebrospinal fluid (CSF) proteins regulate neurogenesis, brain homeostasis and participate in signalling during neuroinflammation. Even though birds represent valuable models for constitutive adult neurogenesis, current proteomic studies of the avian CSF are limited to chicken embryos. Here we use liquid chromatography–tandem mass spectrometry (nLC-MS/MS) to explore the proteomic composition of CSF and plasma in adult chickens (Gallus gallus) and evolutionarily derived parrots: budgerigar (Melopsittacus undulatus) and cockatiel (Nymphicus hollandicus). Because cockatiel lacks a complete genome information, we compared the cross-species protein identifications using the reference proteomes of three model avian species: chicken, budgerigar and zebra finch (Taeniopygia guttata) and found the highest identification rates when mapping against the phylogenetically closest species, the budgerigar. In total, we identified 483, 641 and 458 unique proteins consistently represented in the CSF and plasma of all chicken, budgerigar and cockatiel conspecifics, respectively. Comparative pathways analyses of CSF and blood plasma then indicated clusters of proteins involved in neurogenesis, neural development and neural differentiation overrepresented in CSF in each species. This study provides the first insight into the proteomics of adult avian CSF and plasma and brings novel evidence supporting the adult neurogenesis in birds.

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Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

BMC Medical Genomics ◽

10.1186/s12920-021-00911-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Carla De Angelis ◽

Alicia B. Byrne ◽

Rebecca Morrow ◽

Jinghua Feng ◽

Thuong Ha ◽

...

Keyword(s):

Cortical Development ◽

Occipital Cortex ◽

Compound Heterozygous ◽

Valuable Insight ◽

Periventricular Nodular Heterotopia ◽

Case Presentation ◽

Malformation Of Cortical Development ◽

Nodular Heterotopia ◽

Compound Heterozygous Variants ◽

Insight Into

Abstract Background Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. Case presentation We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. Conclusion We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

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Detecting Convergence Trends among EU Universities

Economies ◽

10.3390/economies9020042 ◽

2021 ◽

Vol 9 (2) ◽

pp. 42

Author(s):

Maria Adamakou ◽

Dimitris Kallioras ◽

George Petrakos

Keyword(s):

Methodological Approach ◽

Basic Research ◽

Valuable Insight ◽

Traditional Role ◽

University Ranking ◽

Convergence Clubs ◽

Development Processes ◽

The Impact ◽

The Empirical Analysis ◽

Insight Into

Universities are emerging growth determinants. This is so as, in addition to the fulfillment of their traditional role in teaching and (basic) research, universities, as aptly described within the helix framework, are expected to engage in regional development processes. The paper aims to detect trends of convergence among EU universities in terms of performance. To the best of our knowledge, this topic has not hitherto been examined. The empirical analysis of the paper covers the period 2014–2021, utilizes data obtained from URAP (University Ranking by Academic Performance), and employs the methodological approach of convergence clubs. The findings of the paper provide valuable insight into both theory and policy-making. We conclude that despite the unification of EU educational space, trends of divergence among EU universities are still present, and notable divisions still remain. Consequently, this indicates that the impact of EU universities on the formation of spatial disparities across EU space is not neutral.

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Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells

Genes ◽

10.3390/genes12050737 ◽

2021 ◽

Vol 12 (5) ◽

pp. 737

Author(s):

Ji-Eun Jeong ◽

Binna Seol ◽

Han-Seop Kim ◽

Jae-Yun Kim ◽

Yee-Sook Cho

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Alternative Splicing ◽

Functional Enrichment ◽

Actin Binding ◽

Pcr Analysis ◽

Valuable Insight ◽

Sequencing Analysis ◽

Induced Pluripotent ◽

Insight Into

Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 3′ (15.2%) and 5′ (12.8%) splice sites, and mutually exclusive exons (9.1%). Functional enrichment analysis showed that the differentially spliced genes (|FC| > 2 and BF > 20) were mainly enriched in functions associated with focal adhesion, extracellular exosomes, extracellular matrix organization, cell adhesion, and actin binding. Splice isoforms of selected genes including TRPT1, CNN2, and AP1G2, identified in sashimi plots, were further validated by RT-PCR analysis. This study provides valuable insight into the biology of iMSCs and the translation of mechanistic understanding of iMSCs into therapeutic applications.

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Craniopharyngioma: 10 Selected Works That Provide Comprehensive and Valuable Insight into These Complex Tumors

World Neurosurgery ◽

10.1016/j.wneu.2018.09.220 ◽

2019 ◽

Vol 122 ◽

pp. 710-712 ◽

Cited By ~ 2

Author(s):

José María Pascual ◽

Ruth Prieto ◽

Rodrigo Carrasco

Keyword(s):

Valuable Insight ◽

Insight Into

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