• Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. (medscape.com)
  • SDS is predominantly caused by biallelic germline mutations in the SBDS gene 5 . (nature.com)
  • PAFAH1B1 gene mutations that occur in all of the body's cells (germline mutations) usually cause ILS. (medlineplus.gov)
  • Herein we selected a Mendelian genetics form of familial cancer such as hereditary tumor syndromic endocrine neoplasias caused by highly penetrant germline mutations leading to pheochromocytoma-paraganglioma syndromes. (intechopen.com)
  • Multiple endocrine neoplasia syndrome type 1 (MEN-1), loss-of-function germline mutations in the tumor suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumors, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumors. (intechopen.com)
  • In the case of multiple endocrine neoplasia type 2 (MEN 2), gain-of-function germline mutations clustered in specific codons of the RET proto-oncogene increase the risk of developing medullary thyroid carcinoma (MTC), phaeochromocytoma and parathyroid tumors. (intechopen.com)
  • This was demonstrated by the somatic PTEN deletion in parotid tumors in addition to the germline loss of FLCN , thereby following a model of compound heterozygosity, instead of the classic two-hit mutation. (medscape.com)
  • Furthermore, Rdd-BRCA1 protein expression was detected in recurrent carcinomas from patients who carried germline BRCA1 185delAG mutations. (jci.org)
  • Genetic factors include, but are not limited to inherited germline mutations, changing DNA methylation rate and microRNA modifications. (biomedcentral.com)
  • In 2018, the US Food and Drug Administration (FDA) expanded the indications for the first poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib (Lynparza), to become the first PARP inhibitor approved for the treatment of women with advanced breast cancer and a deleterious or suspected deleterious germline BRCA mutation, as detected by BRAC Analysis CDx test. (ahdbonline.com)
  • Pfizer), an oral PARP inhibitor, for the treatment of adults with deleterious or suspected deleterious germline BRCA mutation-positive, HER2 -negative -locally advanced or metastatic breast cancer. (ahdbonline.com)
  • 6 The -presence of a germline BRCA mutation must be iden-tified by the FDA-approved companion diagnostic BRAC Analysis CDx test. (ahdbonline.com)
  • 6 With this approval, tala-zoparib becomes the fourth PARP inhibitor available and the second that is FDA approved for the treatment of patients with germline BRCA mutation-positive advanced breast cancer and the fourth PARP inhibitor approved in the United States. (ahdbonline.com)
  • Patients should be considered for talazoparib based on the presence of a deleterious or a suspected deleterious germline BRCA mutation using the FDA-approved companion diagnostic test BRAC Analysis CDx. (ahdbonline.com)
  • 8 In this open-label study, 431 patients with germline BRCA mutation-positive, HER2 -negative locally advanced or metastatic breast cancer were randomized to talazoparib 1 mg once daily (N = 287) or to the physician's choice of single-agent chemotherapy with capecitabine, eribulin, gemcitabine, or vinorelbine (N = 144). (ahdbonline.com)
  • A spectacular example of this approach to treatment of breast cancer is application of a poly (ADP-ribose) polymerase (PARP) inhibitor, such as olaparib, to patients with germline BRCA1 mutations [4, 5]. (termedia.pl)
  • There are only a few reports on the expression of Ku70/80 in breast cancers [17-21], but the association of this protein with germline CHEK2 mutations in breast cancer patients is unknown. (termedia.pl)
  • Germline CHEK2 mutations have been associated with estrogen receptor (ER) positive breast cancer [22, 23]. (termedia.pl)
  • However, although ER positive tumors tend to have a better prognosis in unselected breast cancer patients, germline CHEK2 mutations are associated with increased risk of the development of ER positive breast cancer with an unfavorable prognosis [24-26]. (termedia.pl)
  • IDH1 We identified IDH1 mutations in 5 mutations were co-present with TP53 astrocytomas that developed in carriers mutations in 63% of low-grade diffuse of a TP53 germline mutation. (who.int)
  • Our analyses of IDH1 mutations in for R132C mutations in astrocytes or glioblastomas from a population- precursor cel s that already carry a based study (407 cases) showed that germline TP53 mutation. (who.int)
  • At least 30 ACAD9 gene mutations have been found to cause ACAD9 deficiency. (medlineplus.gov)
  • Most ACAD9 gene mutations change single protein building blocks (amino acids) in the ACAD9 enzyme. (medlineplus.gov)
  • Most individuals with subcortical band heterotopia have DCX gene mutations. (medlineplus.gov)
  • PAFAH1B1 gene mutations are less common. (medlineplus.gov)
  • We are investigating the impact of specific classes of gene mutations, such as ATM, BRCA1, and MYBL2 on genome integrity. (birmingham.ac.uk)
  • About 10% of ALS cases are caused by gene mutations, and more than 40 ALS-associated genes have been identified. (jci.org)
  • This study aimed to determine the relationship between in vitro mutation severity and clinical phenotype in a large international case series of patients with homozygous GCK mutations. (ox.ac.uk)
  • Mutations may or may not produce detectable changes in the observable characteristics (phenotype) of an organism. (wikipedia.org)
  • A single synonymous mutation was sufficient to alter the substrate specificity of a multidrug resistance phenotype in mammalian cells [8].Synonymous mutations affect the stability of mRNA secondary structure in mammals [9]. (i-sis.org.uk)
  • Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
  • While important questions about the biology of this disease remain unanswered, investigations of ALS genes have delineated pathogenic roles for (a) perturbations in protein stability and degradation, (b) altered homeostasis of critical RNA- and DNA-binding proteins, (c) impaired cytoskeleton function, and (d) non-neuronal cells as modifiers of the ALS phenotype. (jci.org)
  • The BRCA1 185delAG allele is a common inherited mutation located close to the protein translation start site that is thought to produce a shortened, nonfunctional peptide. (jci.org)
  • In this study, we investigated the mechanisms that lead to PARPi and platinum resistance in the SUM1315MO2 breast cancer cell line, which harbors a hemizygous BRCA1 185delAG mutation. (jci.org)
  • rather, PARPi and platinum resistance required increased expression of a really interesting gene (RING) domain-deficient BRCA1 protein (Rdd-BRCA1). (jci.org)
  • Initiation of translation occurred downstream of the frameshift mutation, probably at the BRCA1-Met-297 codon. (jci.org)
  • In contrast to full-length BRCA1, Rdd-BRCA1 did not require BRCA1-associated RING domain 1 (BARD1) interaction for stability. (jci.org)
  • Taken together, these results indicate that RING-deficient BRCA1 proteins are hypomorphic and capable of contributing to PARPi and platinum resistance when expressed at high levels. (jci.org)
  • Two human genes, BRCA1 and BRCA2 ( BRCA1 / 2 ), produce proteins that block the growth of cancer, such as breast or ovarian cancer. (ahdbonline.com)
  • 2 Furthermore, a large study conducted in 2017 estimated that approximately 72% of women who inherit a BRCA2 mutation and approximately 69% of women who inherit a harmful BRCA1 mutation will have breast cancer by the age of 80 years. (ahdbonline.com)
  • During their study, the two scientists found that the spike protein appeared to interfere with our own DNA repair proteins: "Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. (techstartups.com)
  • To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. (nature.com)
  • To understand the molecular pathogenesis of MN in patients with SDS, we characterized the presence and dynamics of somatic mutations in serial, clinically annotated samples collected prospectively from patients enrolled in the North American SDS Registry and studied the functional consequences of recurrently mutated pathways. (nature.com)
  • 12 ] mapped non-synonymous somatic mutations of Breast Invasive Carcinoma and Colon Adenocarcinoma Tumor samples to their corresponding protein domains, in order to extract domains with significant mutation frequency. (biomedcentral.com)
  • To address the first problem, we need scientists who develop methods for estimating changes in protein stability of binding upon mutations. (cecam.org)
  • Ho, S. Y. iPTREE-STAB: interpretable decision tree based method for predicting protein stability changes upon mutations. (lu.se)
  • Rooman, M. Fast and accurate predictions of protein stability changes upon mutations using statistical potentials and neural networks: PoPMuSiC-2.0. (lu.se)
  • Mutation can result in many different types of change in sequences. (wikipedia.org)
  • Cancer is a complex genetic disease caused by abnormal alteration (mutations) in DNA sequences that leads to dyregulation of normal cellular processes thereby driving tumor growth. (intechopen.com)
  • In comparison, mRNA vaccines can be more quickly generated in the laboratory using the genetic sequences for selected pathogen proteins. (cdc.gov)
  • Until the current decade, synonymous mutations were assumed to be neutral, with no effect on the protein or any other functions of the organism. (i-sis.org.uk)
  • Sequencing a vast array of genomes has revealed surprisingly, that many synonymous mutations were causing dysfunctions and illnesses in plants and animals. (i-sis.org.uk)
  • Synonymous mutations may lead to changes in protein folding related to translation pausing, RNA splicing, and alterations in enzyme specificity [1]. (i-sis.org.uk)
  • There are many examples of synonymous mutations that are not neutral. (i-sis.org.uk)
  • Synonymous mutations may lead to ribosome stalling, thereby changing protein folding pathways affecting enzyme activity or antigenicity [5]. (i-sis.org.uk)
  • Synonymous mutations in the HIV gene Rev enhance HIV-1 replication, providing resistance to the drug enfuvirtide [6]. (i-sis.org.uk)
  • It is now clear that synonymous mutations are not neutral but instead frequently adversely affect the proteins encoded. (i-sis.org.uk)
  • The products of such transgenes carrying synonymous mutations were risk assessed using surrogates produced originally in bacteria and free from synonymous mutation. (i-sis.org.uk)
  • Thus the regulatory approval of GM crops is based on the false assumption that synonymous mutations are neutral, and hence illegitimate. (i-sis.org.uk)
  • It is reasonable to assume that the synonymous mutations may have created proteins with adverse phenotypes and contributed to the deterioration in public health, and this must now be thoroughly investigated together with mandatory labelling of GM products. (i-sis.org.uk)
  • Today, analyses completely focus on the mutations that are relatively easy to interpret, while the so-called "silent" or synonymous mutations, which do not directly alter a protein, are filtered out. (lu.se)
  • Many studies show, however, that also synonymous mutations can be functional through effects on e.g. mRNA splicing and stability or the speed of translation. (lu.se)
  • We study synonymous mutations in breast cancers from several thousand Swedish women to investigate their effects on tumour behaviour with a combination of bioinformatic analyses and functional studies. (lu.se)
  • These analyzes revealed that some mutations showed deleterious effects and change of stability and flexibility of nucleocapsid protein. (elis.sk)
  • Strikingly diverse functional abnormalities have been identified for disease-linked ATP1A2 mutations which frequently lead to changes in the enzyme's voltage-dependent properties, kinetics, or apparent cation affinities, but some mutations are truly deleterious for enzyme function and thus cause full haploinsufficiency. (frontiersin.org)
  • We evaluated FOXP1 activity by an in vitro luciferase model and assessed protein stability in vitro by western blotting. (bmj.com)
  • Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations. (mpg.de)
  • Clinical characteristics for 30 patients with diabetes due to homozygous GCK mutations (19 unique mutations, including 16 missense) were compiled and assigned a clinical severity grade (CSG) based on birth weight and age at diagnosis. (ox.ac.uk)
  • This genetic erosion eventually became a bottleneck and various techniques to induce mutations and artificially increase variation emerged in the middle of the last century [ 9 ]. (hindawi.com)
  • Also, De Vries ventured with a hipothesis: " With the knowledge of the principles of the mutations will be possible in the future to induce mutations artificially" [ 4 ]. (intechopen.com)
  • Sanger sequencing of the entire coding region and the intron-exon junctions of the HMGCL gene identified a recurrent missense mutation in exon 2. (academicjournals.org)
  • Folliculin mutation databases have been established by Wei and colleagues at the National Cancer Institute and by the European BHDS Consortium. (medscape.com)
  • The exact origin of the folliculin mutation remains under investigation. (medscape.com)
  • To this aim, some efforts have been made to study cancer mutations at the protein domain level. (biomedcentral.com)
  • In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. (wikipedia.org)
  • Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its original state. (wikipedia.org)
  • In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell usually causes a more severe condition called isolated lissencephaly sequence (ILS). (medlineplus.gov)
  • Identified 161 missense mutations were analyzed by using sequence and structure-based methods to predict effects of mutation on function and structure of SARS-CoV-2 N protein. (elis.sk)
  • Change in base sequence that does not alter amino acid sequence of proteins encoded nevertheless may result in alterations of the protein that make it unsafe. (i-sis.org.uk)
  • Patterns of sequence conservation are widely used in studies of proteins. (aps.org)
  • Protein families, and more recently also protein superfamilies, are characterized by a shared three-dimensional structure and patterns of conservation of amino acid sequence. (aps.org)
  • PAS domains form a diverse superfamily of signaling proteins defined by a weak but characteristic pattern of sequence conservation. (aps.org)
  • This article presents a comprehensive study to map mutations from 29 cancer types to both sequence- and structure-based domains. (biomedcentral.com)
  • Beside analyzing Pfam protein domains as sequence-based domains, CATH protein domains have also been studied as structure-based domains, which were not included in relevant studies to this date. (biomedcentral.com)
  • Developing computational methods to relate receptors by the similarity of their ligands, rather than by protein sequence or structure. (ucsf.edu)
  • Casadio, R. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. (lu.se)
  • Scientists from two major Swedish universities recently released a worrisome paper that used a series of complex scientific techniques to look for the full-length coronavirus spike protein (the one the mRNA and DNA/AAV vaccines cause your body to produce) inside the nucleus of our cells. (techstartups.com)
  • mRNA contains the chemical instructions that ribosomes, the protein-making machinery in cells, use to make proteins. (cdc.gov)
  • Using the genetic code of the SARS-CoV-2 virus, vaccine manufacturers developed mRNA that instructs ribosomes to produce the spike protein of the SARS-CoV-2 virus. (cdc.gov)
  • For vaccine mRNA to deliver the instructions for making the spike protein, it needs to be able to enter the cells so that the protein-making machinery can access it. (cdc.gov)
  • Carriers of this mutation develop a severe hereditary form of cerebral amyloid angiopathy (CAA), known as hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). This disease is associated with recurrent strokes during the fifth and sixth decades of life often causing focal neurological symptoms and signs, including focal seizures. (alzforum.org)
  • LYNPARZA is indicated for the maintenance treatment of recurrent ovarian cancer in response to platinum-based chemotherapy regardless of BRCA mutation status, and for the treatment of advanced ovarian cancer patients with a gBRCA-mutation previously treated with three or more lines of chemotherapy. (merck.com)
  • This involves a large conformational change in residues 81 to 83 and smaller shifts that extend 20 angstroms across the protein surface. (rcsb.org)
  • The observed conformational changes illustrate a general mechanism by which proteins can tolerate mutations. (rcsb.org)
  • Conformational diseases are often caused by mutations, altering protein folding and stability in vivo . (mdpi.com)
  • On the relationship between docking scores and protein conformational changes in HIV-1 protease. (mpg.de)
  • 2.There is a known phenomenon, called "induced fit", whereby a target protein undergoes conformational changes upon ligand binding. (cecam.org)
  • Induced fit phenomenon occurs also when two proteins associate, i.e. both of them undergo conformational changes, so that the structure of the complex is not equivalent to rigid composition of two proteins. (cecam.org)
  • Upon binding, proteins and small-molecule ligands can undergo significant conformational changes, as schematized by the "induced fit" and "conformational selection" paradigms [1]. (cecam.org)
  • Such buried ionizable groups destabilize the protein and may trigger conformational changes in response to pH variations. (lu.se)
  • In the spring of 2020, they managed to solve and started to analyse one of these proteins, Nsp10, by using the BioMAX beamline at MAX IV Laboratory. (lu.se)
  • TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. (nature.com)
  • Tumor suppressor genes code for proteins that inhibit cell division and growth, acting as a control mechanism to prevent excessive cell proliferation. (pharmiweb.com)
  • Some tumor suppressor proteins are involved in maintaining cell adhesion, preventing cells from breaking away and spreading to other parts of the body (metastasis). (pharmiweb.com)
  • They also demonstrated a Birt-Hogg-Dubé syndrome tumor-suppressor protein, folliculin. (medscape.com)
  • [ 42 ] Another study by Nahorski et al demonstrated tumor suppression by the interaction of p0071 (plakophilin-4, a potential novel folliculin-interacting protein) and the regulation of RhoA. (medscape.com)
  • To investigate the relation between protein stability and the predicted stabilities of individual secondary structural elements, residue Pro86 in an alpha-helix in phage T4 lysozyme was replaced by ten different amino acids. (rcsb.org)
  • All or other nearby charged groups, the pKa shift of a buried pH-dependent properties of proteins are ultimately governed residue is dominated by the large electrostatic self-energy by the electrostatic interactions of ionizable side chains. (lu.se)
  • These complexes interact with 5'-AMP-activated protein kinase (AMPK) that is part of the mechanistic target of rapamycin (mTOR) pathway, which is involved in cellular energy, cytokinesis, cell motility, cellular adhesion, and nutrient sensing. (medscape.com)
  • Ku70/80 forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK [7]. (termedia.pl)
  • Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
  • Guerois R, Nielsen JE, Serrano L. Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. (lu.se)
  • Mutations in four genes have been identified in familial hemiplegic migraine (FHM), from which CACNA1A (FHM type 1) and SCN1A (FHM type 3) code for neuronal voltage-gated calcium or sodium channels, respectively, while ATP1A2 (FHM type 2) encodes the α 2 isoform of the Na + ,K + -ATPase's catalytic subunit, thus classifying FHM primarily as an ion channel/ion transporter pathology. (frontiersin.org)
  • Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability. (ox.ac.uk)
  • Conversely, homozygous loss-of-function mutations cause permanent neonatal diabetes requiring lifelong insulin treatment. (ox.ac.uk)
  • These are the first two cases of a homozygous GCK mutation diagnosed outside infancy. (ox.ac.uk)
  • We report the largest case series of homozygous GCK mutations to date and demonstrate that they can cause childhood-onset diabetes, with protein instability being the major determinant of mutation severity. (ox.ac.uk)
  • HMGCL gene, 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMG-CoA lyase) deficiency, homozygous mutation, protein stability. (academicjournals.org)
  • A systematic review of the Variant with Spike Protein untreated mortality of murine typhus. (cdc.gov)
  • As you probably know, the spike protein is the mechanism that the SARS-CoV-2 (coronavirus) uses to attach itself to the cell. (techstartups.com)
  • The vaccine produces its own spike protein infects the also enters into the cell but does not replicate in the same way. (techstartups.com)
  • The vaccine-generated spike protein stimulates the body's immune system to produce antibodies to fight the virus. (techstartups.com)
  • As part of their research, they also examine how the spike protein might impact the repair of damaged DNA in the nucleus. (techstartups.com)
  • To be clear, the scientists did NOT prove the spike protein was causing these problems in people, or even animals. (techstartups.com)
  • Nor did they show they had found the spike protein in human nuclei following the administration of Covid vaccines. (techstartups.com)
  • And surprisingly, the scientists said they, " found an abundance of the spike protein in the nucleus . (techstartups.com)
  • Together, these data demonstrate that the spike protein directly affects DNA repair in the nucleus . (techstartups.com)
  • In comparison to the Delta variant, both the entire spike protein and the RBD in Omicron include a high proportion of hydrophobic amino acids such as leucine and phenylalanine. (cdc.gov)
  • The spike protein acts as the antigen that the immune system recognizes as a foreign "invader," prompting a safe and protective immune response. (cdc.gov)
  • The spike protein of SARS-CoV--a target for vaccine and therapeutic development. (who.int)
  • The ChAdOx1-S [recombinant] vaccine uses a DNA adenovirus vector to elicit antibodies to the SARS-CoV-2 spike protein. (who.int)
  • Missense mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus may cause changes in the structure of proteins. (elis.sk)
  • The resulting duplication of the lnp1(+) gene, which encodes an endoplasmic reticulum membrane protein, suppressed lem2∆ phenotypes, whereas the lem2∆ lnp1∆ double mutant showed a severe growth defect. (nih.gov)
  • We found that mice with RTT-associated missense mutations, such as R106W, T158M and T158A, develop RTT-like phenotypes and show deficits in neural circuitry. (upenn.edu)
  • The ACAD9 enzyme is critical in helping assemble a group of proteins known as complex I. Complex I is one of several complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy. (medlineplus.gov)
  • Cell adhesion molecules are a diverse group of proteins that play a crucial role in mediating cell-to-cell interactions and cell-to-extracellular matrix interactions. (pharmiweb.com)
  • It has long been known that a particular group of proteins - known as PIWI proteins - are essential for this ability to regenerate. (bionity.com)
  • Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53 . (nature.com)
  • Somatic TP53 mutations have been observed in patients with SDS who develop MDS 13 , raising the possibility that next-generation sequencing could be integrated into surveillance for somatic clones with enhanced leukemia potential. (nature.com)
  • However, TP53 mutations have also been identified in SDS patients without MN 14 , suggesting that additional factors must be uncovered before implementing molecular surveillance as a predictive tool in SDS. (nature.com)
  • from April 2008) after acquisition of a TP53 mutation or loss of 1p/19q, suggesting that IDH1 We assessed IDH1 mutations in brain mutations are very early events in tumors diagnosed in patients from 3 gliomagenesis and may affect a common families with Li-Fraumeni syndrome. (who.int)
  • Computational modeling of protein mutant stability: analysis and optimization of statistical potentials and structural features reveal insights into prediction model development. (brenda-enzymes.org)
  • an analysis of 115 FLCN mutation carriers from 35 BHD families. (medscape.com)
  • Birt-Hogg-Dubé syndrome is caused by a mutation in the folliculin ( FLCN ) gene that has been mapped to the short arm of chromosome 17, specifically 17p11.2. (medscape.com)
  • In recent studies, renal and pulmonary tumors in Birt-Hogg-Dubé syndrome appear to follow the two-hit tumorigenesis theory relating to the interaction of folliculin with the FLCN-interacting protein 1 (FNIP1) and FLCN-interacting protein 2 (FNIP2). (medscape.com)
  • Then, a survey is given about ATP1A2 mutations implicated in migraine cases as documented in the literature with focus on mutations that were described to completely destroy enzyme function, or lead to misfolded or mistargeted protein in particular model cell lines. (frontiersin.org)
  • As plant genetic engineering has "advanced" the crucial active domains of toxins, and enzyme are "improved" to such an extent that the gene for the original source protein is hardly recognizable. (i-sis.org.uk)
  • ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1 , resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins. (medscape.com)
  • Recent evidence indicates that altered degradation rate of mutant proteins represents a pathogenic mechanism underlying genetic diseases. (frontiersin.org)
  • Further analysis revealed conserved residues that affect protein stability and in vivo protein production, indicating that both effects drive evolutionary conservation in PYP, but through two largely distinct sets of residues. (aps.org)
  • While the standard redox potentials of those systems are known, the in vivo "steady state" redox potential imposed onto protein thiol disulfide pairs in the periplasm remains unknown. (bvsalud.org)
  • Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements. (wikipedia.org)
  • Mismatch repair proteins correct King Khalid University Hospital, King mal nuclear staining in lymphocytes the insertion and deletion mutations Saud University, Riyadh, Saudi Arabia and normal epithelial or stromal cells that occur when DNA is copied be- between 2007 and 2009 were retrieved was required serving as internal con- fore cell division. (who.int)
  • Discriminating driver mutations from the ones that play no role in cancer is a severe bottleneck in elucidating molecular mechanisms underlying cancer development. (biomedcentral.com)
  • A litmus test for classifying recognition mechanisms of transiently binding proteins. (mpg.de)
  • Heterozygous loss-of-function mutations cause mild fasting hyperglycemia irrespective of mutation severity due to compensation from the unaffected allele. (ox.ac.uk)
  • Structural Analysis and Prediction of Protein Mutant Stability using Distance and Torsion Potentials: Role of Secondary Structure and Solvent Accessibility. (brenda-enzymes.org)
  • Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication (translesion synthesis). (wikipedia.org)
  • These molecules, also known as "messenger RNAs", contain information for the synthesis of proteins. (bionity.com)
  • A crucial problem that advanced computational approaches could solve is that of specificity: how are biologically unique connections made between proteins taken from a wealth of thousands of possible partners? (cecam.org)
  • Potapov V, Cohen M, Schreiber G. Assessing computational methods for predicting protein stability upon mutation: good on average but not in the details. (lu.se)
  • We used computational studies to examine the Delta and Omicron variants in this work and found that the Omicron variant had a higher affinity for human ACE2 than the Delta variant due to a significant number of mutations in the SARS-CoV-2 receptor binding domain, indicating a higher potential for transmission. (cdc.gov)
  • We examine the impact that processes such as transcription and replication have on genome stability. (birmingham.ac.uk)
  • To understand the molecular pathogenesis of RTT, we have developed mouse models recapitulating RTT-associated mutations. (upenn.edu)
  • Dystrophin protein is integral to the structural stability of the myofiber. (medscape.com)
  • These results, together with structural analysis, confirm that the chaperone activity of RidA is concomitant with the loss of positive charges on the protein surface, leading to an increased overall protein hydrophobicity. (bvsalud.org)
  • These amino acids are located within the protein's core and are required for structural stability. (cdc.gov)
  • Together, the gain-of-expression variant showed a higher stability and a doubled half-life compared to WT-TRPM4. (frontiersin.org)
  • D3L, S194L, S235F, and P13L (Omicron variant) mutations were further analyzed in our study due to their importance in the literature and in our results. (elis.sk)
  • PON-tstab: Protein Variant Stability Predictor. (lu.se)
  • Therefore, distinguishing mutations with drastic impacts on protein functionality may help discriminate driver mutations from less significant ones. (biomedcentral.com)
  • Impacts of genotoxic agents on rates of ribosomal mutations in the 30S ribosomal rspE gene. (brown.edu)
  • LNP include lipids, phospholipids, cholesterol and polyethylene glycol (PEG), which increases LNP stability. (cdc.gov)
  • Since protein domains are representatives of functional regions within proteins, mutations on them may disturb the protein functionality. (biomedcentral.com)
  • Therefore, studying mutations at domain level may point researchers to more accurate assessment of the functional impact of the mutations. (biomedcentral.com)
  • Besides, performing interactome analysis on specific proteins of each cancer type showed high levels of interconnectivity among them, which implies their functional relationship. (biomedcentral.com)
  • Loss of expression of the respec- rectal cancers [4,5] and is known to tive mismatch repair genes protein arise due to mutations in DNA mis- Tissue blocks of 32 different patients was defined as absence of nuclear match repair genes [6]. (who.int)
  • However, the toxicity of the transgenic proteins in animals and humans was not studied. (i-sis.org.uk)
  • The synonymous codons were assumed to be neutral and to have no effect on the transgenic proteins, and presumed to be safe [2] ( Bt Toxins in Genetically Modified Crops: Regulation by Deceit , SiS 22). (i-sis.org.uk)
  • The scientists were not looking for the vaccine material but instead for the presence of the coronavirus proteins, including the spike, in the nucleus. (techstartups.com)
  • Mutations can also occur in non-genic regions. (wikipedia.org)
  • Statistical analysis was performed to identify candidate domains in which mutations occur with high statistical significance. (biomedcentral.com)
  • A clear understanding of protein-protein interactions, both for stable complexes and for transient ones, would therefore mark a major step forward, and it would have enormous consequences for designing new strategies of therapeutic intervention in diseases like cancer. (cecam.org)
  • Most males with subcortical band heterotopia have a DCX gene mutation that is not inherited and is present in only some of the body's cells, a situation known as mosaicism. (medlineplus.gov)
  • When subcortical band heterotopia is caused by a PAFAH1B1 gene mutation, it is generally not inherited but arises from a mutation in the body's cells that occurs after conception, which leads to mosaicism. (medlineplus.gov)
  • The main purpose of this study is to detect missense mutations in the SARS-CoV-2 N protein and to reveal the effects of these mutations on protein structure by using in silico approaches. (elis.sk)
  • Multiple in silico software predicted this mutation as disease-causing. (academicjournals.org)
  • Six of 16 missense mutations exhibited severe kinetic defects (RAI ≤ 0.01). (ox.ac.uk)
  • When the immune system recognizes the spike proteins, which aren't normally there, they start generating antibodies and building an immune response against them. (techstartups.com)
  • Mutations in HMG-CoA lyase cause HMG-CoA lyase deficiency (HMGCLD), which is an autosomal recessive congenital disorder of metabolism. (academicjournals.org)
  • This study was designed to detect mutation in the 3-hydroxy-3-methylglutaryl-CoA lyase ( HMGCL ) gene in a Saudi family segregating HMG-CoA lyase deficiency (HMGCLD). (academicjournals.org)
  • The concept of mutation was coined by Hugo De Vries in 1901, whom worked with plants species of the genus Oenothera where he discovered some phenotypic hereditary characteristics that he coined as "mutations" and "mutants" to those individuals that have these phenotypic alterations. (intechopen.com)
  • Ponnuswamy, M. N. Average assignment method for predicting the stability of protein mutants. (lu.se)
  • Here, we report that Lem2 maintains genome stability in the fission yeast Schizosaccharomyces pombe. (nih.gov)
  • These genetic interactions imply that Lem2 cooperates with the nuclear membrane protein network to regulate genome stability. (nih.gov)
  • Inner nuclear membrane proteins interact with chromosomes in the nucleus and are important for chromosome activity. (nih.gov)
  • Lem2 and Man1 are conserved members of the LEM-domain nuclear membrane protein family. (nih.gov)
  • A combination of mutations in Lem2 and Bqt4, which encodes a nuclear membrane protein that anchors telomeres to the nuclear membrane, caused synthetic lethality. (nih.gov)
  • The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. (nih.gov)
  • Binding and segregation of proteins in membrane adhesion: theory, modeling, and simulations. (mpg.de)
  • Membrane-mediated cooperativity of proteins. (mpg.de)
  • In addition to uncovering new pathways - the chains of chemical reactions that trigger changes in a cell - the researchers report newly discovered mutations, which will provide fodder for follow-up investigations in the field of multiple myeloma research. (broadinstitute.org)
  • Other mutations affect the ACAD9 enzyme's structure or stability and likely disrupt both complex I assembly and long-chain fatty acid oxidation. (medlineplus.gov)
  • Recombinant mutant GCK proteins were analyzed for kinetic and thermostability characteristics and assigned a relative activity index (RAI) or relative stability index (RSI) value. (ox.ac.uk)
  • Eighty percent of the remaining mutations showed reduced thermostability, the exceptions being the two later-onset mutations which exhibited increased thermostability. (ox.ac.uk)
  • Unexpectedly, all ten amino acid substitutions marginally reduce protein thermostability. (rcsb.org)