Search results for "Dominant"
showing 10 items of 231 documents
Human molecular chaperones share with SARS-CoV-2 antigenic epitopes potentially capable of eliciting autoimmunity against endothelial cells: possible…
2020
Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the cause of COVID-19 disease, has the potential to elicit autoimmunity because mimicry of human molecular chaperones by viral proteins. We compared viral proteins with human molecular chaperones, many of which are heat shock proteins, to determine if they share amino acid-sequence segments with immunogenic-antigenic potential, which can elicit cross-reactive antibodies and effector immune cells with the capacity to damage-destroy human cells by a mechanism of autoimmunity. We identified the chaperones that can putatively participate in molecular mimicry phenomena after SARS-CoV-2 infection, focusing on those for which endotheli…
Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.
2016
Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGI…
One NF1 Mutation may Conceal Another
2019
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the NF1 and SPRED1 genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent NF1 variants. All NF1 variants were classified as pathogenic, according to t…
Human R1441C LRRK2 regulates the synaptic vesicle proteome and phosphoproteome in a Drosophila model of Parkinson's disease
2016
International audience; Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinsons disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model. To explore the function of LRRK2 variants in vivo, we …
Personalized vaccines for cancer immunotherapy
2018
Cancer is characterized by an accumulation of genetic alterations. Somatic mutations can generate cancer-specific neoepitopes that are recognized by autologous T cells as foreign and constitute ideal cancer vaccine targets. Every tumor has its own unique composition of mutations, with only a small fraction shared between patients. Technological advances in genomics, data science, and cancer immunotherapy now enable the rapid mapping of the mutations within a genome, rational selection of vaccine targets, and on-demand production of a therapy customized to a patient’s individual tumor. First-in-human clinical trials of personalized cancer vaccines have shown the feasibility, safety, and immu…
European ADPKD Forum multidisciplinary position statement on autosomal dominant polycystic kidney disease care
2018
Autosomal dominant polycystic kidney disease (ADPKD) is a chronic, progressive condition characterized by the development and growth of cysts in the kidneys and other organs and by additional systemic manifestations. Individuals with ADPKD should have access to lifelong, multidisciplinary, specialist and patient-centred care involving: (i) a holistic and comprehensive assessment of the manifestations, complications, prognosis and impact of the disease (in physical, psychological and social terms) on the patient and their family; (ii) access to treatment to relieve symptoms, manage complications, preserve kidney function, lower the risk of cardiovascular disease and maintain quality of life;…
Skaņu rīku izmantošana valodas attīstības veicināšanai rotaļnodarbībās ar literatūras dominanti 5-6 gadus veciem bērniem
2017
Diplomdarbā ir veikts pētījums, lai noskaidrotu kā skaņu rīku izmantošana rotaļnodarbībās ar literatūras dominanti palīdz vecināt 5 – 6 gadu vecu bērnu valodas attīstību. Darbā ir analizēta teorētiskā literatūra par bērna valodas attīstību, rotaļām ar skaņām un skaņu rīkiem, rotaļnodarbības būtību un literatūras nozīmi pirmsskolas izglītības mācību saturā. Izpētīta X pirmsskolas izglītības iestādes grupu materiālā bāze – pieejamie skaņu rīki, kā arī veikta aptauja par skaņu rīku izmantošanas pieredzi pirmsskolas pedagoģiskajā procesā. Tāpat diplomdarba ietvaros tika veikta bērnu valodas attīstības izpēte pirms pedagoģiskā izmēģinājuma darbības un izstrādāta rotaļnodarbību kopa, kurā tiek iz…
HETEROGENITY OF AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIA IN SICILY
2004
Plēsonīgo cenu jēdziens Latvijas konkurences tiesībās
2015
Plēsonīgo cenu stratēģijas realizēšana Latvijas doktrīnā līdz šim nav apskatīta. Lielākā problēma, kas saistīta ar plēsonīgajām cenām, ir plēsonīgo cenu piemērošanas nošķiršana no ikdienišķas biznesa prakses. Eiropas Savienības doktrīnā un Eiropas Savienības Tiesas praksē ir nostiprināti dažādi kritēriji, meklējot risinājumu iepriekš minētajai problēmai. Autors pētījuma gaitā analizē plēsonīgo cenu jēdzienu, kā arī Eiropas Savienības Tiesas praksi un tās piedāvātos kritērijus plēsonīgo cenu piemērošanas identificēšanai. Tāpat darba gaitā autors salīdzina Konkurences padomes nolēmumos nostiprinātos kritērijus ar Eiropas Savienības Tiesas praksi. Darbā, cita starpā, autors analizē arī Amerika…
La Corte di giustizia rinviene una fattispecie che si assumeva perduta: l'abuso di struttura
2023
The article provides an analysis on the relationship between Article 102 TEUF (and its scope) and EU Regulation No 139/04 on mergers