scholarly journals Comprehensive bioinformatics analysis ofL1CAMgene revealed Novel Pathological mutations associated with L1 syndrome

2019 ◽  
Author(s):  
Naseem S. Murshed ◽  
Mujahed I. Mustafa ◽  
Abdelrahman H. Abdelmoneim ◽  
Thwayba A. Mahmoud ◽  
Nafisa M. Elfadol ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Homo Sapiens ◽  
Muscle Stiffness ◽  
Missense Mutations ◽  
Phenotype Correlation ◽  
Left And Right ◽  
And Function ◽  
L1 Syndrome ◽  
L1 Protein ◽  
The Brain

AbstractBackgroundMutations in the human L1CAM gene cause a group of neurodevelopmental disorders known as L1 syndrome (CRASH syndrome). The L1CAM gene provides instructions for producing the L1 protein, which is found all over the nervous system on the surface of neurons. L1 syndrome involves a variety of characteristics but the most common characteristic is muscle stiffness. Patients with L1 syndrome can also suffer from difficulty speaking, seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain.MethodThe human L1CAM gene was studied from dbSNP/NCBI, 1499 SNPs were Homo sapiens; of which 450 were missense mutations. This selected for Comprehensive bioinformatics analysis by several in silico tools to investigate the effect of SNPs on L1CAM protein’s structure and function.Results34 missense mutations (26 novel mutations) out of 450 nsSNPs that are found to be the most deleterious that effect on the L1CAM structural and functional level.ConclusionBetter understanding of L1 syndrome caused by mutations in L1CAM gene was achieved using Comprehensive bioinformatics analysis. These findings describe 35 novel L1 mutations which improve our understanding on genotype-phenotype correlation. And can be used as diagnostic markers for L1 syndrome and besides in cancer diagnosis specifically in breast cancer.

The Brain as a Cultural Artefact

2008 ◽  
Vol 18 (3) ◽  
pp. 415-422 ◽  
Author(s):  
Steven Mithen ◽  
Lawrence Parsons
Keyword(s):  
Human Body ◽  
Homo Sapiens ◽  
Biological Entity ◽  
Cultural Activity ◽  
Cultural Artefact ◽  
And Function ◽  
The Brain

Where does biology end and culture begin? While the human body is now widely accepted as being both biological and cultural, the brain is still considered by archaeologists as being a biological entity that provides the capacity for culture and is subject to no further change after the evolution of Homo sapiens. This article reviews recent research that suggests that the brain has continued to evolve at an increasing rate in recent times under the influence of culturally created environments and that both the anatomy and function of individual brains can be manipulated by cultural behaviour. It describes an experiment in which one of us successfully changed his own brain in response to his cultural activity.

scholarly journals FEMALE AND MALES’ BRAIN TENDENCIES IN LEARNING ENGLISH AS A SECOND LANGUAGE

2020 ◽  
Vol 8 (7) ◽  
pp. 211-216
Author(s):  
Lamhot Naibaho
Keyword(s):  
Second Language ◽  
Left Brain ◽  
Right Brain ◽  
Library Research ◽  
Left And Right ◽  
The Right ◽  
And Function ◽  
Online Sources ◽  
The Brain ◽  
Learning English

This research is about the female and males’ brain tendencies in learning English as a second language, and it was done at Universitas Kristen Indonesia. The purposes of conducting this research is to find out female and males’ brain tendencies in learning English as a second language. This research was a library research, where researchers as "key instruments" of the research that find any information deals with the topic discussed from books, journals and proceedings sourced from “Pubmed, Google Scholar, Research Gate and other online sources” in order to answer the question. The result is that learning English as a second language achievement of students is not influenced by the competence of the right brain or left brain of students, but the left and right brain provides an understanding of the structure and function of the brain. The division of brain function based on the brain hemisphere allows students to gain a deeper understanding of how the brain works to help them improve students' mastery of subjects.

Ultrastructure of developing visual cortical synapses in the cat superior colliculus

1991 ◽  
Vol 49 ◽  
pp. 156-157
Author(s):  
Caroline A. Miller ◽  
Laura L. Bruce
Keyword(s):  
Superior Colliculus ◽  
Phosphate Buffer ◽  
Receptive Fields ◽  
Visual Cortical Area ◽  
Cortical Synapses ◽  
Visual Cortical ◽  
And Function ◽  
Phosphate Buffered Saline ◽  
The Brain ◽  
Cat Superior Colliculus

The first visual cortical axons arrive in the cat superior colliculus by the time of birth. Adultlike receptive fields develop slowly over several weeks following birth. The developing cortical axons go through a sequence of changes before acquiring their adultlike morphology and function. To determine how these axons interact with neurons in the colliculus, cortico-collicular axons were labeled with biocytin (an anterograde neuronal tracer) and studied with electron microscopy.Deeply anesthetized animals received 200-500 nl injections of biocytin (Sigma; 5% in phosphate buffer) in the lateral suprasylvian visual cortical area. After a 24 hr survival time, the animals were deeply anesthetized and perfused with 0.9% phosphate buffered saline followed by fixation with a solution of 1.25% glutaraldehyde and 1.0% paraformaldehyde in 0.1M phosphate buffer. The brain was sectioned transversely on a vibratome at 50 μm. The tissue was processed immediately to visualize the biocytin.

Advantages of Complementary Stereo Images as Viewed with the Low-Temperature Field-Emission SEM

1992 ◽  
Vol 50 (2) ◽  
pp. 1314-1315
Author(s):  
William P. Wergin ◽  
Eric F. Erbe
Keyword(s):  
Fold Increase ◽  
Horizontal Displacement ◽  
Three Dimensions ◽  
Stereo Image ◽  
Stereo Pair ◽  
Sem Micrograph ◽  
Left And Right ◽  
The Common ◽  
The Brain ◽  
Pair Analysis

The eye-brain complex allows those of us with normal vision to perceive and evaluate our surroundings in three-dimensions (3-D). The principle factor that makes this possible is parallax - the horizontal displacement of objects that results from the independent views that the left and right eyes detect and simultaneously transmit to the brain for superimposition. The common SEM micrograph is a 2-D representation of a 3-D specimen. Depriving the brain of the 3-D view can lead to erroneous conclusions about the relative sizes, positions and convergence of structures within a specimen. In addition, Walter has suggested that the stereo image contains information equivalent to a two-fold increase in magnification over that found in a 2-D image. Because of these factors, stereo pair analysis should be routinely employed when studying specimens.Imaging complementary faces of a fractured specimen is a second method by which the topography of a specimen can be more accurately evaluated.

The Cooking Ape: An Interview with Richard Wrangham

2005 ◽  
Vol 5 (1) ◽  
pp. 29-37
Author(s):  
elisabeth townsend
Keyword(s):  
Social Relationships ◽  
Human Behavior ◽  
Homo Sapiens ◽  
Social Groups ◽  
Harvard University ◽  
Primate Research ◽  
Social Organizations ◽  
Cooked Food ◽  
New Research ◽  
The Brain

Humans: The Cooking Ape Perhaps the first to suggest that humans were cooking as early as 1.9 million years ago, Richard Wrangham shows through his new research and his imagination how and possibly when cooking changed humans dramatically. Wrangham, Harvard University primatologist and MacArthur Fellow, has been studying the evolution of human cooking. After 25 years of primate research at his site in Kibale, Uganda, Wrangham is best known for explaining the similarity and differences across species of primate social organizations. In Kibale, he has analyzed chimpanzees’ behavior: how it’s changed when they interact with the environment and how their social groups have evolved. In particular, he noticed how food changed their interactions with each other. Like that of chimps, human behavior has been affected by food, especially as they shifted from raw to cooked food. Moving from eating food as it was discovered to collecting edibles and cooking them altered our social relationships. Cooked food has changed Homo sapiens physically by making food more digestible thereby altering jaws, teeth, and guts, and providing more calories for more expensive organs such as the brain. Wrangham discusses when and how humans may have started using fire to cook food, what they cooked, and the transition from cooking in an outdoor fire to hearths and open ovens.

scholarly journals Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Adrian Israel Lehvy ◽  
Guy Horev ◽  
Yarden Golan ◽  
Fabian Glaser ◽  
Yael Shammai ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Zinc Homeostasis ◽  
Healthy Population ◽  
Missense Mutations ◽  
Protein Alignment ◽  
Loss Of Function ◽  
Intracellular Zinc ◽  
Dismal Prognosis ◽  
Zinc Levels ◽  
And Function

Abstract Zinc is vital for the structure and function of ~3000 human proteins and hence plays key physiological roles. Consequently, impaired zinc homeostasis is associated with various human diseases including cancer. Intracellular zinc levels are tightly regulated by two families of zinc transporters: ZIPs and ZnTs; ZIPs import zinc into the cytosol from the extracellular milieu, or from the lumen of organelles into the cytoplasm. In contrast, the vast majority of ZnTs compartmentalize zinc within organelles, whereas the ubiquitously expressed ZnT1 is the sole zinc exporter. Herein, we explored the hypothesis that qualitative and quantitative alterations in ZnT1 activity impair cellular zinc homeostasis in cancer. Towards this end, we first used bioinformatics to analyze inactivating mutations in ZIPs and ZNTs, catalogued in the COSMIC and gnomAD databases, representing tumor specimens and healthy population controls, respectively. ZnT1, ZnT10, ZIP8, and ZIP10 showed extremely high rates of loss of function mutations in cancer as compared to healthy controls. Analysis of the putative functional impact of missense mutations in ZnT1-ZnT10 and ZIP1-ZIP14, using homologous protein alignment and structural predictions, revealed that ZnT1 displays a markedly increased frequency of predicted functionally deleterious mutations in malignant tumors, as compared to a healthy population. Furthermore, examination of ZnT1 expression in 30 cancer types in the TCGA database revealed five tumor types with significant ZnT1 overexpression, which predicted dismal prognosis for cancer patient survival. Novel functional zinc transport assays, which allowed for the indirect measurement of cytosolic zinc levels, established that wild type ZnT1 overexpression results in low intracellular zinc levels. In contrast, overexpression of predicted deleterious ZnT1 missense mutations did not reduce intracellular zinc levels, validating eight missense mutations as loss of function (LoF) mutations. Thus, alterations in ZnT1 expression and LoF mutations in ZnT1 provide a molecular mechanism for impaired zinc homeostasis in cancer formation and/or progression.

scholarly journals Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
M. Asada-Utsugi ◽  
K. Uemura ◽  
M. Kubota ◽  
Y. Noda ◽  
Y. Tashiro ◽  
...  
Keyword(s):  
Memory Function ◽  
Three Dimensional ◽  
Excitatory Synapses ◽  
Missense Mutations ◽  
Glutamatergic Synapses ◽  
Learning Tasks ◽  
Transmission Electron ◽  
Nmdar Activation ◽  
And Function

AbstractN-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.

scholarly journals Pan-cancer analysis of CD274 (PD-L1) mutations in 314,631 patient samples and subset correlation with PD-L1 protein expression

2021 ◽  
Vol 9 (6) ◽  
pp. e002558
Author(s):  
Richard S.P. Huang ◽  
Brennan Decker ◽  
Karthikeyan Murugesan ◽  
Matthew Hiemenz ◽  
Douglas A. Mata ◽  
...  
Keyword(s):  
Protein Expression ◽  
Checkpoint Inhibitors ◽  
Endometrial Adenocarcinoma ◽  
Primary Melanoma ◽  
B Cell Lymphoma ◽  
Unknown Primary ◽  
Future Research ◽  
Tumor Type ◽  
Missense Mutations ◽  
L1 Protein

BackgroundThe effects of non-amplification short variant (SV) mutations in CD274 (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of CD274 mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1.MethodsCGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements. PD-L1 IHC was performed on a subset of cases (n=58,341) using the DAKO 22C3 PD-L1 IHC assay and scored with the tumor proportion score (TPS).ResultsOverall, the prevalence of CD274 SV mutations was low (0.3%, 1081/314,631) with 577 unique variants. The most common CD274 SV mutations were R260H (n=51), R260C (n=18), R125Q (n=12), C272fs*13 (n=11), R86W (n=10), and R113H (n=10). The prevalence of CD274 mutations varied depending on tumor type with diffuse large B-cell lymphoma (1.9%, 19/997), cutaneous squamous cell carcinoma (1.6%, 14/868), endometrial adenocarcinoma (1.0%, 36/3740), unknown primary melanoma (0.9%, 33/3679), and cutaneous melanoma (0.8%, 32/3874) having the highest frequency of mutations. Of the R260H cases concurrently tested with PD-L1 IHC, most (81.8%, 9/11) had no PD-L1 expression, which contrasts to the five E237K cases where most (80%, 4/5) had PD-L1 expression. In addition, we saw a significantly lower level of PD-L1 expression in samples with a clonal truncating variant (nonsense or frameshift indel) when compared with samples with a subclonal truncating variants (mean: TPS=1 vs TPS=38; p<0.001), and also in clonal versus subclonal missense mutations (mean: TPS=11 vs TPS=22, respectively; p=0.049)ConclusionsWe defined the landscape of CD274 mutations in a large cohort of tumor types that can be used as a reference for examining CD274 mutations as potential resistance biomarkers for ICPI. Furthermore, we presented novel data on the correlation of CD274 mutations and PD-L1 protein expression, providing important new information on the potential functionality of these mutations and can serve as a basis for future research.

Revision Targeted Muscle Reinnervation Improves Secondary Pain Insult in an Upper Extremity Amputee: A Case Report

Hand ◽  
2021 ◽  
pp. 155894472199246
Author(s):  
David D. Rivedal ◽  
Meng Guo ◽  
James Sanger ◽  
Aaron Morgan
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerves ◽  
Nerve Biopsy ◽  
Sensory Cortex ◽  
Denervated Muscle ◽  
Unique Case ◽  
Targeted Muscle Reinnervation ◽  
Muscle Reinnervation ◽  
And Function ◽  
The Brain

Targeted muscle reinnervation (TMR) has been shown to improve phantom and neuropathic pain in both the acute and chronic amputee population. Through rerouting of major peripheral nerves into a newly denervated muscle, TMR harnesses the plasticity of the brain, helping to revert the sensory cortex back toward the preinsult state, effectively reducing pain. We highlight a unique case of an above-elbow amputee for sarcoma who was initially treated with successful transhumeral TMR. Following inadvertent nerve biopsy of a TMR coaptation site, his pain returned, and he was unable to don his prosthetic. Revision of his TMR to a more proximal level was performed, providing improved pain and function of the amputated arm. This is the first report to highlight the concept of secondary neuroplasticity and successful proximal TMR revision in the setting of multiple insults to the same extremity.

scholarly journals The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

2020 ◽  
Author(s):  
Enrico Castroflorio ◽  
Joery den Hoed ◽  
Daria Svistunova ◽  
Mattéa J. Finelli ◽  
Alberto Cebrian-Serrano ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Regulatory Protein ◽  
Molecular Function ◽  
Neuronal Connectivity ◽  
Nuclear Receptor Coactivator ◽  
Lysm Domain ◽  
Behavioural Assessment ◽  
And Function ◽  
The Brain

Abstract Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment. Graphic abstract

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