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TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifiers and scaffold proteins. Mutant p53 protein can also transcriptionally regulate the expression of microRNAs, small non-coding RNAs that regulate gene expression at the posttranscriptional level. Each microRNA can putatively target the expression of hundred mRNAs and consequently impact on many cellular functions. Thus, gain of function mutant p53 proteins can exert their oncogenic activities through the modulation of both non-coding and coding regions of human genome. Over the past 3 decades, the regulation of p53 has been extensively studied. However, the regulation of mutant p53 remained largely unexplored. This snapshot focuses on recent discovery of mutant p53 GOF and regulation.
mouse models --- mutant p53 --- dominant netagive --- therapies --- Oncogenic addiction --- gain of function --- mouse models --- mutant p53 --- dominant netagive --- therapies --- Oncogenic addiction --- gain of function
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Bacteria --- Bacillus --- Génétique --- genetics --- Biotechnologie --- Biotechnology --- Bacillus subtilis --- Enzymes --- Mutant --- Mutants --- Bacillus (Bacteria) --- Genetics --- Congresses
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Mice, Mutant Strains --- B-Lymphocytes --- T-Lymphocytes --- Genetics --- Congresses --- Immunology --- immunology --- Congresses.
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Teenage Mutant Ninja Turtles (Fictitious characters) --- Turtles --- Ninja --- Superheroes --- New York (N.Y.)
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The two most prominent mycobacterial diseases in animals include bovine tuberculosis, caused by Mycobacterium bovis and Johne’s disease, caused by Mycobacterium avium subspecies paratuberculosis. Erradication of both diseases has been hampered by a variety of factors. In many countries, the persistence of tuberculosis in cattle has been attributed to reservoirs of M. bovis in wildlife species. Brushtail possums, deer and badgers are notable examples of wildlife reservoirs for M. bovis. The difficulties in eliminating the wildlife reservoir for M. bovis further suggest the need for vaccination of farmed livestock. Vaccination of wildlife species has also been attempted with mixed results. Delivery of the vaccine to wildlife species appears to be a chief obstacle. Vaccination itself leads to complications for diagnostics. For example, when cattle are vaccinated with both BCG and a commercial Johne’s vaccine there is a biased toward the avian tuberculin skin test reaction. Despite these issues, BCG seems to be the clear standard for vaccination against M. bovis, yet many laboratories are investigating ways to improve on BCG. For Johne’s disease, the available commercial vaccines consist of whole-cell preparations in one form or another. But with the ability to generate directed knockouts of specific genes, a number of defined mutants have been constructed in a few laboratories. These should be tested and directly compared with each other and alongside commercial vaccine formulations to determine not only which vaccine is most protective, but which animal model is best for predicting protection in the target host. To this end, there has been a nation-wide, multi-institutional effort to test the best live, attenuated vaccine against Johne's disease in cattle, sheep and goats. This vaccine trial has spanned six years and was conducted in three phases. The first phase examined attenuation in bovine macrophages, the second phase was colonization of spleen and liver in mice and the third phase was protection from bacterial challenge in goats. Many new ideas and retrospective approaches have emerged from this unprecedented effort. These aspects will be captured in this Research Topic. In this Research Topic, we will seek articles on these above topics, but other issues surrounding vaccination of animals against mycobacteria will also be explored. These include immune parameters, correlates of protection, adjuvants and other vaccine formulations, etc.
Veterinary vaccines. --- Bacterial vaccines. --- Tuberculosis in cattle --- Bacterial Vaccines --- goat trial --- correlates of protection --- Paratuberculosis --- Johne's disease --- Attenuated mutant --- Vaccine --- Prevention. --- immunology. --- goat trial --- correlates of protection --- Paratuberculosis --- Johne's disease --- Attenuated mutant --- Vaccine
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Génétique --- genetics --- Plante --- plants --- Photosynthèse --- Photosynthesis --- Mutant --- Mutants --- Fixation de l'azote --- Nitrogen fixation --- Biochimie --- biochemistry --- Plant biochemical genetics. --- Plant biochemical genetics
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La chaîne photosynthétique de transport des électrons est un élément essentiel au bon développement des organismes photosynthétiques. Cette chaîne dépend notamment de protéines à centres Fer-Soufre (Fe-S) qui, en plus de leur rôle dans la chaîne, exercent des fonctions variées dans différents métabolismes importants de la cellule. Ces protéines Fe-S vont nécessiter un assemblage complexe, appelé « maturation des protéines Fe-S » au sein de systèmes spécifiques présents dans différents compartiments de la cellule : le système d’assemblage mitochondrial ISC (iron-sulfur cluster), le système d’assemblage cytosolique et nucléaire CIA (cytosolic iron-sulfur cluster assembly) et le système chloroplastique SUF (sulfur mobilization). Lors de l’étape de maturation, des facteurs spécifiques de maturation vont jouer le rôle de transporteurs pour transférer les centres Fe-S synthétisés à des apoprotéines cibles ; c’est notamment le cas des facteurs chloroplastiques NFU1 et NFU3, récemment caractérisés chez Arabidopsis thaliana. Contrairement à ceux-ci, le rôle des facteurs NFU1 et NFU3 de Chlamydomonas n’est pas encore élucidé. Il a été proposé que CrNFU3 soit l’orthologue de AtNFU1, cependant les 2 protéines sont différentes, notamment par la présence d’une extension N-terminale chez CrNFU3. A l’aide de trois mutants provenant d’une banque, le facteur NFU3 a été caractérisé moléculairement et physiologiquement. Les résultats ont montré un retard de croissance, une diminution de l’activité du photosystème II et une dérégulation des mécanismes de dissipation d’énergie non-photochimique. De plus, suivant la position de la cassette d’inactivation, l’effet phénotypique est plus ou moins important, l’insertion de la cassette dans la 5’UTR du transcrit ayant un impact moins important, ce qui suggère que le transcrit NFU3 soit produit dans ce cas, bien que probablement moins stable. Enfin, les résultats suggèrent des différences par rapport à l’orthologue de NFU3 chez Arabidopsis thaliana, AtNFU1.
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Culture de cellule --- Cell culture --- Culture de tissu --- Tissue culture --- Culture d'organe --- Organ culture --- Plante --- plants --- Développement embryonnaire --- Embryonic development --- Mutant --- Mutants --- Protoplaste --- protoplasts --- #ABIB:atte --- Basic Sciences. Biotechnology --- Micropropagation --- TEC Biotechnology --- biotechnology --- Micropropagation.
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The Special Issue “Juvenile Onset Huntington’s Disease” highlights the growing interest in understanding the unique aspects of this ultra-rare disorder. After decades of research, gene therapy trials are underway for Adult Onset Huntington’s Disease (AOHD). However, patients with Juvenile Onset Huntington’s Disease (JOHD) are often excluded from these efforts, leaving many questions regarding its phenomenology. The current issue includes seven articles spanning work on the difficult emotional experiences of parents of children with JOHD; a review of the clinical manifestations of JOHD; behavioral issues in JOHD; CAG repeat and age of motor onset; autonomic nervous system dysfunction; and abnormality in MRI metabolic markers. Finally, a review of the therapeutic advances is included, highlighting future possibilities of clinical trials in JOHD subjects. The HD community—patients, family members at-risk for HD, caregivers, health-care professionals and scientists—is keen on expanding our understanding of JOHD. In the flurry of research on AOHD, those with JOHD were seemingly ‘left behind.’ The study of patients who are afflicted early in life with HD has become imperative, with this Special Issue representing just the beginning of the required effort to address this urgent need.
Medicine --- Huntington's disease --- CAG repeat --- mutant huntingtin (mHTT) --- therapeutics --- neurodegeneration --- juvenile Huntington's disease --- pediatric Huntington's disease --- early-onset Huntington's disease --- personal experiences --- caregivers --- case series --- juvenile-onset Huntington's disease --- T1-Rho --- neuroimaging --- behavioral regulation --- executive function --- trinucleotide repeat disorder --- CAG --- motor onset --- juvenile-onset Huntington's Disease --- autonomic --- Huntington's disease --- CAG repeat --- mutant huntingtin (mHTT) --- therapeutics --- neurodegeneration --- juvenile Huntington's disease --- pediatric Huntington's disease --- early-onset Huntington's disease --- personal experiences --- caregivers --- case series --- juvenile-onset Huntington's disease --- T1-Rho --- neuroimaging --- behavioral regulation --- executive function --- trinucleotide repeat disorder --- CAG --- motor onset --- juvenile-onset Huntington's Disease --- autonomic
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The book by M. Imran Kozgar aims to cover the problems of mutation breeding in pulse crops in the light of issues related to food insecurity and malnutrition, which according to FAO are the major threats at the present time. So far the research on induction of mutation in pulse crops is negligible compared to cereal crops, though the pulse crops and especially the chickpea are the largest grown crops in India. The main objective of the book is to reveal and explore the possibility of inducing genetic variability in early generations of mutated chickpea, describe the positive aspects of mutagenic treatments, evaluate the content of mineral elements (iron, manganese, zinc and copper) and physiological parameters of isolated high yielding mutant lines. The author hopes that his book will help to advance studies on pulse crops, and that in the long term it will help to reduce the food insecurity and malnutrition problems presently persisting in various developing countries, including India.
Chickpea --- Agriculture --- Earth & Environmental Sciences --- Plant Sciences --- Bengal gram --- Chestnut bean --- Chich --- Chich-pea --- Chick-pea --- Cicer arietinum --- Dwarf pea --- Garavance --- Garbanzo --- Gram (Legume) --- Gram pea --- Pea, Chick --- Cicer --- Mutation breeding --- Mutation breeding. --- pulse crops, chickpea, mutation breeding, effectiveness of mutagenic treatments, bioavailability of minerals, physiological parameters of mutant lines.
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