MICE RESEARCHES – PLACES – CONTACTS – COUNTRIES – HISTORY @ The world needs more efficient and detailed researches to people live longer more and more urgently & The diffusion of very good ideias are fundamental to human health, of course & No, vaping did NOT cause lung cancer in mice. @ Cancer ‘vaccine’ successfully eliminates tumors in mice, clinical trials for humans underway # MOUSE ‘AVATARS’ GUIDE CANCER TREATMENTS & How to Deplete Mouse Cells from Human Tumor Xenografts – Video Protocol @ ´´Mouse models can be considered as the starting point for investigating a certain basic principle, without having an aim to translate it into humans, just like other non-human models such as yeast, fruit fly or zebrafish, depending on the nature of the question in study: for example, studying the mechanism of heat shock proteins in the antigen presentation process or understanding the survival mechanism of the gut nematode against the host immune response.´´ @ Very Important Videos, Websites, Links and Images

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  • – > Mestrado – Dissertation – Tabelas, Figuras e Gráficos – Tables, Figures and Graphics – ´´My´´ Dissertation @ #Innovation #energy #life #health #Countries #Time #Researches #Reference #Graphics #Ages #Age #Mice #People #Person #Mouse #Genetics #PersonalizedMedicine #Diagnosis #Prognosis #Treatment #Disease #UnknownDiseases #Future #VeryEfficientDrugs #VeryEfficientVaccines #VeryEfficientTherapeuticalSubstances #Tests #Laboratories #Investments #Details #HumanLongevity #DNA #Cell #Memory #Physiology #Nanomedicine #Nanotechnology #Biochemistry #NewMedicalDevices #GeneticEngineering #Internet #History #Science #World

Pathol Res Pract. 2012 Jul 15;208(7):377-81. doi: 10.1016/j.prp.2012.04.006. Epub 2012 Jun 8.

The influence of physical activity in the progression of experimental lung cancer in mice

Renato Batista Paceli 1, Rodrigo Nunes Cal, Carlos Henrique Ferreira dos Santos, José Antonio Cordeiro, Cassiano Merussi Neiva, Kazuo Kawano Nagamine, Patrícia Maluf Cury


Impact_Fator-wise_Top100Science_Journals

GRUPO_AF1 – GROUP AFA1 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO AFAN 1 – GROUP AFAN1 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO_AF2 – GROUP AFA2 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO AFAN 2 – GROUP AFAN 2 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

Slides – mestrado – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

CARCINÓGENO DMBA EM MODELOS EXPERIMENTAIS 

DMBA CARCINOGEN IN EXPERIMENTAL MODELS

Avaliação da influência da atividade física aeróbia e anaeróbia na progressão do câncer de pulmão experimental – Summary – Resumo – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

https://pubmed.ncbi.nlm.nih.gov/22683274/

Abstract

Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb – C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.

´´A dissertation is a subject you chose for yourself. The first usage of the word in the English language in 1651 also gives a useful starting definition: “an extended written treatment of a subject”. Another useful clue is found in the Latin origin of the word – dissertation comes from a Latin word ‘dissertare’ = ‘to debate’. ´´ @

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Mouse Model

Mouse models can be considered as the starting point for investigating a certain basic principle, without having an aim to translate it into humans, just like other non-human models such as yeast, fruit fly or zebrafish, depending on the nature of the question in study: for example, studying the mechanism of heat shock proteins in the antigen presentation process or understanding the survival mechanism of the gut nematode against the host immune response.

From: The Laboratory Mouse (Second Edition), 2012

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Mouse Models

Siân E. Piret, Rajesh V. Thakker, in Genetics of Bone Biology and Skeletal Disease, 2013

II Methods for Generating Mouse Models

Non-Targeted Strategies

Spontaneous mutations in mice may result in benign phenotypes such as variable coat colors, or in disorders that have similarities to diseases in humans, e.g. the hypophosphatamia (Hyp) mouse, which is representative of X-linked hypophosphatemia in humans.52 Such spontaneous mutations occur at very low frequencies, thus several techniques that increase the rate of mutation induction in the mouse genome by either non-targeted (random) or targeted strategies have been developed (see Tables 13.1 and 13.2). An early example of non-targeted mutagenesis is provided by irradiation, which generated the Gy mouse, a second model for X-linked hypophosphatemia.52 More recently, chemical mutagens have been used in large-scale mutagenesis programs. Successful agents include isopropyl methane sulfonate (iPMS) used to generate the Nuf mouse model with an activating calcium-sensing receptor (CaSR) mutation, and N-ethyl-N-nitrosourea (ENU) used to generate a mouse model for osteogenesis imperfecta with a collagen 1 alpha 1 (COL1A1) mutation. ENU, which is an alkylating agent that primarily introduces point mutations via transfer of the ENU alkyl group to the DNA base followed by mispairing and subsequent basepair substitution during the next round of DNA replication (Figure 13.1A), is the most potent mutagen in mice.14 Intraperitoneal injections of ENU to male mice generate approximately one mutation per 1–1.5 Mbp of sperm DNA,14 which allows the mutations to be inherited (Figure 13.1B). ENU mutagenesis programs utilize two complementary approaches, which are phenotype-driven and genotype-driven screens. In phenotype-driven screens, the offspring of mutagenized mice are assessed for phenotypic variances, using a panel of morphological, biochemical, or behavioral tests, in a “hypothesis-generating” strategy, which aims to elucidate new genes, pathways and mechanisms for a disease phenotype14 (Figure 13.1B). By establishing appropriate matings, phenotype-driven screens can be used to identify dominant or recessive phenotypes. Genotype-driven screens, in which mutations in a gene of interest are sought, are “hypothesis-driven” and are feasible by using available parallel archives of DNA and sperm samples from mutagenized male mice (Figure 13.1B). Archived DNA samples from the mutagenized male mice are used to search for mutations in the gene of interest, and once mutations are identified in the mouse DNA, then the corresponding sperm sample for the male mouse harboring the mutation is used to establish progeny carrying the mutation by in vitro fertilization.14 It is estimated that the probability of finding three or more mutant alleles in an archive of >5000 DNA samples is >90%.53 Thus, the gene-driven approach can be used to generate an “allelic series” of mutations within one gene, which may yield insights into genotype–phenotype correlations in the gene and disease of interest.54

ENU mutations most frequently result in missense mutations (>80%) that may generate hypo- and hypermorphs, although occasionally nonsense or frame-shift mutations (<10%) generating knockout models may be obtained.55 However, a more recent and reliable method for generating non-targeted knockout models on a large scale is by the use of insertional mutagenesis, utilizing gene-trap strategies.56,57 Gene-trap vectors usually consist of a reporter gene, either with or without a promoter, and a strong splice acceptor site, which causes any upstream exons to splice directly to the gene-trap15 (see Figure 13.1C). The vector is either electroporated or retrovirally infected into embryonic stem (ES) cells, after which it randomly inserts into the genome. Mutagenized ES cells are then re-introduced into developing blastocysts to generate chimeric mice, from which germline mutant mice can be bred (Figure 13.2). A recent refinement of the gene-trap strategy is targeted trapping, in which the vector also contains regions homologous to the targeted gene, thereby facilitating the deletion of a specific gene.16,56

Targeted Strategies

A specific loss of function (i.e. knockout) of a gene of interest in the germline can be generated to yield conventional targeted knockout models, as follows. A targeting construct is assembled, which contains two “arms” of sequence homologous to the gene of interest and that flank a positive selection cassette such as the E. coli neomycin phosphotransferase (NeoR) gene (Figure 13.3A). Integration of the NeoR gene (and therefore the targeting construct) into the ES cell genome allows these ES cells to survive normally toxic amounts of antibiotic treatment, thereby allowing selection of ES cells that have been successfully targeted by homologous recombination. Furthermore, replacement of an exon (or exons) by the NeoR cassette results in gene disruption, i.e. “knockout”17 (Figure 13.3A). To facilitate further the selection of ES cells that have undergone successful targeting by homologous recombination, a negative selection cassette, such as the Herpes simplex virus thymidine kinase (TK) gene, may also be used. The TK gene cassette is inserted at one end of the homologous region of the targeting construct, such that the TK cassette is lost if homologous recombination has occurred (Figure 13.3A), but retained if non-homologous recombination has occurred. In the presence of a thymidine analog in the growth medium, ES cells containing the TK cassette (i.e. following non-homologous recombination) will not undergo cell division, as the thymidine analog will undergo phosphorylation and will be incorporated into the DNA by the TK, and thereby disrupt cell division, hence selecting out these ES cells. In contrast, those ES cells that do not have the TK cassette (i.e. following homologous recombination) will not have disrupted cell division due to incorporation of the thymidine analog and, as a result, will proliferate.17 Correctly targeted ES cells are used to generate chimeric mice (see Figure 13.2), which are then bred with wild-type mice to yield mice with germline transmission of the disrupted allele, i.e. “knockout” mice, that have one copy of the disrupted allele in all of their cells. Cross-breeding of these heterozygous knockout mice can then yield homozygous knockout mice, which will have a disruption of both alleles of the gene in all of their cells. These “conventional” knockout models have proved to be very useful in studies of human diseases, although their use may be limited if the disruption of the gene in a critical organ results in early death, e.g. at any embryonic stage. To overcome such limitations, it may be useful to generate tissue-specific (i.e. conditional knockout) or time-specific (i.e. inducible knockout) models. This can be achieved by refining the gene-trap and “conventional” knockout strategies by the addition of either LoxP or flippase (FLP) recombinase target (FRT) sites in the targeting vector (Figure 13.3B). LoxP and FRT sites are short DNA sequences which are recognized and acted upon by the enzymes Cre (causes recombination) recombinase or FLP recombinase enzymes, respectively and, when inserted to flank the genomic region of interest, will result in either excision or inversion of the DNA flanked by the LoxP or FRT sequences, depending on whether the two sequences are in the same orientation (Figure 13.3B), or opposite orientations, respectively. Thus, insertion of the LoxP and FRT sequences allows several variations on the knockout mouse, including either tissue-specific (conditional) or time-specific (inducible) knockouts (see Table 13.2). Thus, if mice containing alleles in which the exon containing the start codon is flanked by LoxP sites (“floxed”) or FRT sites (“flirted”), are crossed with transgenic mice expressing Cre or FLP under the control of tissue-specific promoters (e.g. the PTH gene promoter for parathyroid-specific expression), the gene of interest can be knocked out in a specific tissue (Figure 13.3B). The inducible models utilize a fusion protein, such as a modified ligand-binding domain of the estrogen receptor fused to the Cre (CreER) or FLP gene which, on administration of an estrogen receptor antagonist (tamoxifen), translocates to the nucleus to excise the floxed allele(s), thereby allowing the gene to be permanently knocked out at the desired time, which may be either during embryonic or neonatal development, or in adult life.18 These conditional and inducible knockout mouse models have proved particularly useful to overcome embryonic or early postnatal lethality, for example in studies of Blomstrand’s chondrodysplasia due to PTHR1 loss of function (see Table 13.4), or to understand the role of a protein in one particular tissue.

Knockout mice have been very valuable for the study of physiological functions of proteins and the elucidation of disease mechanisms. However, knockout models are not always the most appropriate, particularly when the human disease being studied is not due to a loss of function or null allele for the gene. Indeed, the majority of human diseases are unlikely to be due to null alleles, but are instead associated with point mutations, which may result in a constitutively active protein, or a toxic gain of function, as illustrated by PTHR1 mutations in Jansen’s disease (see Table 13.4), or dominant negative effects. Thus, to generate appropriate murine models for these diseases, the specific mutation needs to be introduced into the mouse genome, and this may be achieved by targeted knock-in or transgenic approaches (see Tables 13.1 and 13.2). The generation of targeted knock-in models utilizes a similar approach to that described above for targeted knockout models, except that a targeting vector which carries the desired mutation must be specifically generated (see Figure 13.3C). In addition, the positive selection cassette is normally placed in an intron and floxed so that it can be excised and cause minimal effects on gene expression.19 The generation of transgenic models utilizes a targeting construct which usually contains the cDNA carrying the mutation, together with an appropriate promoter and poly(A) sequence, which is injected into the pronucleus of fertilizd mouse eggs.20,21 The transgene undergoes random insertion into the genome, and several copies are often inserted together, which therefore generates an overexpression model. As reviewed below, these different strategies for generating mouse models of human diseases have greatly facilitated studies of inherited bone and mineral disorders that have investigated mechanisms and treatments, which would not be easily feasible in patients.View chapterPurchase book

Mouse Models of The Nuclear Envelopathies and Related Diseases

Henning F. Horn, in Current Topics in Developmental Biology, 2014

9 Conclusions

Mouse models provide a valuable tool for studying human diseases. This has certainly been true for mouse models of LINC complex proteins and their associated diseases. The various Nesprin-1 mouse models have augmented our understanding of the underlying biology of muscular dystrophy, autosomal recessive arthrogryposis, and autosomal recessive cerebellar ataxia. The mouse models for the Nesprin-4-associated hearing loss were critical in elucidating the cell biology and provided key insights into this entirely novel class of human hearing loss. And mouse models of SUN1 and KASH5 have allowed us a greater appreciation for the importance of chromosomal movement in the development of gametes. Indeed, our mouse model-generated understanding of LINC complex functions may even prove to be predictive for human diseases. For example, a novel human disorder was recently described that has features of mandibular acral dysplasia but also includes deafness and male hypogonadism as prominent associated features (Shastry et al., 2010). Several candidate genes were examined, but no mutations were found to cause this genetic condition. However, given our knowledge of the roles of SUN1, and the phenotypes of the SUN1 mouse models (hearing loss and hypogonadism), it would be interesting to check the function of SUN1 in these patients.

While a number of mouse models now exist for LINC complex proteins, the field is still relatively young. Indeed, we are still discovering novel LINC complex functions and novel variants of LINC complexes. We therefore expect that future mouse models will continue to augment our understanding of the LINC complex in normal as well as pathophysiological roles.View chapterPurchase book

Alzheimer’s Disease: Transgenic Mouse Models

K.H. Ashe, in Encyclopedia of Neuroscience, 2009

Transgenic mouse models of Alzheimer’s disease (AD) have been created to study the structural and functional consequences of the accumulation of the amyloid-β and tau proteins in the brain. They have also been used to test experimental therapeutic interventions for AD. No transgenic mouse model perfectly represents all stages and facets of AD; transgenic mouse models cannot supplant the need for studying the disease in humans and human clinical trials. However, studies in transgenic mouse models allow researchers to understand aspects of the pathophysiology of AD and coordinate efforts to diagnose and treat the illness in humans.View chapterPurchase book

In Vitro and In Vivo Animal Models

Azka Khan, … Alvina Gul, in Omics Technologies and Bio-Engineering, 2018

18.2.13 Transgenic Mouse of PD

Mouse models have been a vital tool for research in neurodegenerative diseases. They have been proved as an effective model organism for PD. Both in vitro and in vivo mouse models have been extensively used. Many transgenic mouse models have been generated to study PD; α-synuclein protein has very important role in the pathology of this disease. KO mice and some transgenic mice with the ability to overexpress α-synuclein possess familial A53T or A30P mutations. α-Synuclein KO mice are viable and fertile, and they support a significant role of α-synuclein in regulation of dopaminergic neurotransmission, synaptic plasticity, and presynaptic vesicular release and recycling (Janus and Welzl, 2010).View chapterPurchase book

Biomarkers for Assessing Risk of Cancer

Xifeng Wu, Jian Gu, in The Molecular Basis of Cancer (Fourth Edition), 2015

Mouse Models for Cancer Susceptibility Study

Mouse models that cross tumor-resistant with tumor-susceptible strains have been instrumental in mapping several candidate cancer susceptibility loci and expression quantitative trait loci (eQTLs)125-131 before the wide application of GWAS in human cancers. Although hundreds of cancer susceptibility loci have been identified through GWAS, the majority of the heritable risk of cancer cannot be explained by the main effects of common alleles. Gene-gene and gene-environment interaction clearly play important roles in cancer development, which is challenging in human studies because of the heterogeneity of human cancers. Mouse models have a defined genetic background that does not possess the genetic heterogeneity characteristic of human cancers. Crossing genetically distinct mouse strains can allow the analysis of the combinatorial effects of host genetic background and somatic events at different stages of cancer development. A recent study applied a network analysis in a mouse model of skin cancer that produces both benign tumors and malignant carcinomas and identified a genetic architecture affecting inflammation and tumor susceptibility.132 Gene–environment interactions can also be investigated using mouse models to identify how genetic modifiers of tumor initiation interact with specific environmental effects identified through epidemiological studies. Mouse models will also be a major tool for mechanistic studies of cancer susceptibility loci.View chapterPurchase book

Molecular Basis of Lung Cancer

Mitsuo Sato, … John D. Minna, in The Molecular Basis of Cancer (Third Edition), 2008

New Transgenic Mouse Models of Lung Cancer

Mouse models that recapitulate the carcinogenic process of human lung cancer are powerful tools to improve our understanding of lung cancer pathogenesis, develop targeted therapeutics, and evaluate their in vivo efficacies. Several different types of transgenic mouse models for studying lung cancer have been developed with innovative strategies. Bitransgenic models using Cre/LoxP recombination or tetracycline-inducible gene expression system have enabled regulating the expression of a gene in mice in a timely and spatially controlled manner. Two groups engineered mouse strains harboring conditional mutant K-ras alleles that are expressed only after Cre/LoxP-mediated recombination occurs. Both groups showed that oncogenic K-ras activation induces lung adenocarcinoma, demonstrating the contributions of oncogenic K-ras to lung cancer pathogenesis (46). Moreover, Meuwissen et al. developed a mouse model of SCLC by inactivating both Rb and p53 using Cre/LoxP recombination system (46). Using a tetracycline-inducible gene expression system, mice harboring EGFR tyrosine kinase domain mutations were engineered. These mice developed adenocarcinomas very similar to human adenocarcinomas with EGFR mutations. Although there can be significant differences in lung tumor development between humans and mice, mouse models have a complete physiologic environment and allow analyzing host tumor interaction and angiogenesis, which cannot be studied in tissue culture. Finally, no mouse model of squamous cell carcinoma of the lung has been developed.View chapterPurchase book

Huntington Disease

Laura A. Wagner, … Blair R. Leavitt, in Animal and Translational Models for CNS Drug Discovery, 2008

Validity of Animal Models of HD

Mouse models of HD are important to the discovery and validation of drug targets for HD as well as central to proving drug efficacy preceding human therapeutic trials. The development and validation of an effective mouse model of disease is no trivial matter and requires extensive characterization and rigorous validation (see Table 6.2). The ideal mouse model for HD agrees in etiology, pathophysiology, symptomatology, and response to therapeutics when compared to the human condition. Originally, chemical models of HD were investigated based on their similar striatal neurodegenerative pattern as seen in human HD patients. These chemical models met the very basic symptomatology criterion alone. Since the discovery of the HD gene, however, more accurate gene models of HD have been developed as transgenic mice representing HD etiology, pathophysiology, and symptomatology. Although species differences complicate the exact phenotype comparisons that can be made, genetic HD mice overall recapitulate cognitive failure, motor dysfunction, and striatal neurodegeneration as seen in human HD patients.

Table 6.2. Validation of animal models of diseasea

Face validity- a superficial resemblance between the mouse model and human disease. A similarity seen in symptoms is a common justification in this case (e.g., chemical models of HD).
Predictive validity- the ability of a model to predict the performance of the condition being modeled. One example is a model’s capacity to predict compound efficacy in therapeutic human trials.
Construct validity- a theoretical clarification of what a model is supposed to represent. This validation accounts for the inherent difference that may occur in a process when looking across species.
Etiological validity- in this case the model and the human condition must undergo identical etiologies. The simplest disease to model in this situation is that of a simple inheritance disease.

aVan Dam and De Deyn. (2006). Drug discovery in dementia: The role of rodent models. Nat Rev: Drug Discov 5:956–970.

Three basic design strategies have been applied in developing HD gene mouse models giving rise to three broad model categories including: (i) fragment models containing N-terminal fragments of the human mutant Htt protein in addition to both alleles of murine Hdh, (ii) full-length models containing the full-length human HD gene with an expanded polyglutamine tract in addition to both alleles of murine Hdh, and (iii) knock-in models of HD with pathogenic CAG expansions in murine Hdh. Individually these gene models are believed to represent certain aspects of HD based on their design and phenotype. These characteristics help define the strength of the model and its subsequent use in the field of HD research. Together these different gene models provide confirmatory proof of the dysfunction and disease caused by a Htt CAG expansion in mice. As a result, HD gene mouse models provide a powerful analysis for target validation and drug discovery preceding clinical trials. To date, the fourth criterion of an ideal HD mouse model, its predictive power in identifying effective drugs for HD awaits verification by emerging and ongoing human clinical trials.View chapterPurchase book

Application of Mouse Genetics to Human Disease

Teresa M. Gunn, Brenda Canine, in Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition), 2015

Summary

Mouse models have led – and are certain to continue to lead – to significant breakthroughs in identifying genes, mechanisms, and pathways that underlie human neurologic diseases. Mice are also ideal for testing therapeutic approaches, something we are likely to see more of in the coming years. New methodologies have increased the speed and accuracy with which new mouse models can be generated, and technological advances have led to improved tools to analyze them. Models of multigenic disorders remain scarce. This is primarily because it is difficult to identify the variants that cause these traits, and most mouse models are presently generated using gene targeting, which requires the causative loci be known. Random mutagenesis and thorough phenotypic analysis (including behavioral studies) of existing mutants may reveal subtle and/or unexpected traits, and will complement other, ongoing projects aimed at discovering disease-associated variants in human populations. There is much excitement over the ability to reprogram fibroblasts or other patient-derived cells into induced pluripotent stem cells (iPSC), and the ability to differentiate those iPSC into neuronal stem cells allows for the analysis of those cells in culture. Injecting these cells into the mouse brain will create a new class of mouse models that will provide insight into the in vivo behavior of patient-derived cells in the mammalian nervous system. Combining these models with existing genetic models and reporter mice will create a powerful system for analyzing the pathogenesis of neurological disorders.View chapterPurchase book

Gsα, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune–Albright Syndrome

Lee S. Weinstein, Michael T. Collins, in Genetics of Bone Biology and Skeletal Disease (Second Edition), 2018

3.4 Animal Models

Mouse models leading to constitutively activation of cAMP formation have been created by transgenic overexpression of Gsα, by expression of R201H or Q227L mutant forms of Gsα, or by expression of the cholera toxin A1 subunit, which covalently modifies R201 (Fig. 35.1). Transgenic expression of the cholera toxin A1 subunit in somatotrophs leads to pituitary hyperplasia and gigantism, whereas expression in thyroid cells leads to thyroid hyperplasia and hyperthyroidism.109 Gsα overexpression in the heart leads to cardiomyopathy,110 and expression of constitutively-activated forms of Gsα in the forebrain disrupts associative and spatial learning.111 A model of FD was created by transplanting Gsα-mutated skeletal progenitor cells into immunocompromised mice.112 A mouse model with germline expression of the R201C mutation survived, and with aging developed a skeletal dysplasia radiographically and histologically similar to FD.113View chapterPurchase book

Gsα, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune–Albright Syndrome

Lee S. Weinstein, … Allen M. Spiegel, in Genetics of Bone Biology and Skeletal Disease, 2013

Animal Models

Mouse models leading to constitutively activation of cAMP formation have been created by transgenic overexpression of Gsα, by expression of R201H or Q227L mutant forms of Gsα, or by expression of the cholera toxin A1 subunit which covalently modifies R201 (see Figure 27.1). Transgenic expression of the cholera toxin A1 subunit in somatotrophs leads to pituitary hyperplasia and gigantism, whereas expression in thyroid cells leads to thyroid hyperplasia and hyperthyroidism.73 Gsα overexpression in the heart leads to cardiomyopathy,74 and expression of constitutively-activated forms of Gsα in the forebrain disrupts associative and spatial learning.75 A model of FD was created by transplanting Gsα-mutated skeletal progenitor cells into immunocompromised mice.76 A mouse model replicating the full MAS phenotype has not been reported, perhaps because of the adverse effects of more generalized cAMP activation on normal development.View chapterPurchase book

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´´A thorough, logical and reflective analysis of a sentence thought and/or described by a particular person can significantly influence the way they see and reflect the world around them´´. Rodrigo Nunes Cal ´´A análise minuciosa, lógica e reflexiva de uma frase pensada e/ou descrita por uma determinada pessoa pode influenciar significativamente no modo de ver e refletir o mundo ao seu redor´´. Rodrigo Nunes Cal “Para uma ideia que não parece insana à primeira vista, não há esperança.” Albert Einstein -- “For an idea that does not first seem insane, there is no hope.” ― Albert Einstein - - “A verdadeira lógica deste mundo está no cálculo de probabilidades.” James Clerk Maxwell “The true logic of this world is in the calculus of probabilities.” —James Clerk Maxwell - Virtual Induction Into The Human Mind = Indução Virtual Na Mente Humana #Probability #probabilidade(s) #Internet - Virtual Induction Of The Human Mind = Indução Virtual Da Mente Humana @ #probability #probabilities #RealFacts #RealFact #vision #thinking #Thoughts #NegativeFacts #PositiveFacts #analysis #research #researches #reference #people #communication #person #law #countries #country #Internet #work #team #pionner #pionners #blog #videos #video #photo #photos #information #knowledge #money #price #intelligence #TrueFacts #FalseFacts #HumanEvolution I N T E R N E T #Intenções #Imaginations #Thoughts #Pensamento(s) #Imaginações #Influences #Influência(s) -- Nem sempre o que fazemos na Internet com seus vários tipos de influências, faremos no ´´Mundo Real´´, obviamente. - Not always what we do on the Internet with its various types of influences, we will do in the ´´Real World´´, obviously. - “The true logic of this world is in the calculus of probabilities.” —James Clerk Maxwell * Nothing is better than reading and gaining more and more knowledge.” — Stephen Hawking #time #data #messages #information #knowledge #intentions #reading #probability #people #mind #photo #name #image #video #influences #actions #health #person #life #speak #write #researches #reference #type #listen #InternetHistory #objectives #improvement #longevity #imaginations #thinking #reality #Internet #ScientificDiscoveries #books #journals #importance #websites #analysis #SocialNetworks #links #blogs #countries #innovations #graphics #feedbacks #facts #science #technologies #ScienceEvents #poster #abstract #methodology #article #publications #team #DirectInvitations #speaker #Delegate #cities #feelings #energy #pionner #lives #work #contribuitions #pionners #minds #WorldHistory #ranking #economy ´´The world people need to have very efficient researches and projects resulting in very innovative drugs, vaccines, therapeutical substances, medical devices and other technologies according to the age, the genetics and medical records of the person. So, the treatment, diagnosis and prognosis will be very efficient and better, of course´´. Rodrigo Nunes Cal ´´O mundo precisa ter pesquisas e projetos muito eficientes que resultem em medicamentos, vacinas, substâncias terapêuticas, dispositivos médicos e outras tecnologias muito inovadoras de acordo com a idade, a genética e o prontuário da pessoa. Assim, o tratamento, o diagnóstico e o prognóstico serão bem mais eficientes e melhores, é claro´´. Rodrigo Nunes Cal ´´As you know, the world needs to have very efficient researches resulting new therapeutical substances, medical devices, prevention, diagnostic and prognostic methods, drugs and vaccines, for example. Very detailed researches are fundamental in this process. So, high impact innovations are essential to the world people!!´´ Rodrigo Nunes Cal  ´´Como você sabe, o mundo precisa de pesquisas muito eficientes que resultem em novas substâncias terapêuticas, aparelhos médicos, métodos de prevenção, de diagnósticos e de prognósticos, medicamentos e vacinas, por exemplo. Pesquisas muito detalhadas são fundamentais neste processo, obviamente. Portanto, inovações de grande impacto são essenciais para as pessoas do mundo todo!!´´ Rodrigo Nunes Cal ´´Ter grandes metas, muitas das quais ditas como impossíveis é muito importante porque pode induzir de várias maneiras em diferentes intensidades na sociedade científica mundial o surgimento de grandes descobertas científicas para toda a humanidade, beneficiando significativamente a vida das pessoas e fazendo com que a expectativa de vida humana aumente significativamente. Dessa forma, doenças conhecidas hoje como sendo fatais e incuráveis, podem se tornar doenças curáveis, com a obtenção de novas tecnologias altamente eficazes de prevenção, diagnóstico, prognóstico e de tratamento´´. Rodrigo Nunes Cal ´´Having big goals, many of which are said to be impossible, is very important because it can induce, in different ways, in different intensities in the world scientific society, the emergence of great scientific discoveries for all of humanity, significantly benefiting people's lives and causing the increase of human life expectancy significantly. Thus, diseases known today as being fatal and incurable, can become curable diseases, with the achievement of highly effective prevention, diagnosis, prognosis and treatment technologies´´. Rodrigo Nunes Cal * ´´The very unknown path may be the best path to take in life´´. Rodrigo Nunes Cal ´´O caminho muito desconhecido pode ser o melhor caminho a seguir na vida´´. Rodrigo Nunes Cal ´´A Ciência abre um leque de possibilidades dos mais variados assuntos e dos mais variados níveis de dificuldades. Sendo assim, a compreensão total dos mecanismos fisiológicos envolvidos na patogênese das doenças, destacando-se as doenças fatais que ocorrem em humanos, é de suma importância para a humanidade, com toda certeza. Quem sabe num futuro próximo essa compreensão seja muito bem entendida e quem sabe, como muitas pessoas sonham na imortalidade física, dentre elas cientistas, essa grande conquista pode ser adquirida. Como você sabe, a humanidade necessita urgentemente de novas descobertas científicas, destacando-se a aquisição de medicamentos e vacinas altamente eficazes contra um grande número de doenças, dentre elas as doenças desconhecidas e silenciosas, a obtenção de aparelhos médicos muito eficientes de diagnóstico, prognóstico e tratamento de doenças, entre outros. Com certeza, precisamos ter esperança e motivação para a realização de ótimos trabalhos e para uma qualidade de vida bem melhor e uma expectativa de vida cada vez maior´´. Rodrigo Nunes Cal ´´Science opens up a range of possibilities for the most varied subjects and the most varied levels of difficulties. Therefore, the full understanding of the physiological mechanisms involved in the pathogenesis of diseases, highlighting the fatal diseases that occur in humans, is of paramount importance for humanity, for sure. Maybe in the near future this understanding will be very well understood and who knows, as many people dream of physical immortality, among them scientists, this great achievement can be acquired. As you know, humanity urgently needs new scientific discoveries, highlighting the acquisition of highly effective medicines and vaccines against a large number of diseases, including unknown and silent diseases, obtaining very efficient medical devices for diagnosis, prognosis and treatment of diseases, among others. Certainly, we need to have hope and motivation to do great work and for a much better quality of life and an ever-increasing life expectancy´´. Rodrigo Nunes Cal - Very important note: The statistics on the number of people who visited this blog in 2018 were not entirely based on real visitors. - Observação muito importante: As estatísticas sobre número de pessoas que acessaram este blog no ano de 2018 não foram totalmente baseadas em visitantes reais. ´´Great difficulties may have come, but it is of great importance to have in mind the possibility of great victories in the future, bringing happiness and health for a long time´´. Rodrigo Nunes Cal ´´O caminho muito desconhecido pode ser o melhor caminho a seguir na vida´´. Rodrigo Nunes Cal ´´Understanding the great difficulties of a given subject can be a very long process, however, of great value for the progress of Science in all aspects´´. Rodrigo Nunes Cal ´´Entender as grandes dificuldades de um determinado assunto pode ser um processo muito longo, mas de grande valor para o progresso da Ciência em todos os seus aspectos´´. Rodrigo Nunes Cal My Curriculum Lattes: http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4240145A2 My Facebook Page: www.facebook.com/scientificblog IT´S A VERY EASY, FAST AND PRACTICAL WAY TO KNOW EXCELLENT INFORMATION ABOUT SCIENCE, TECHNOLOGY AND INNOVATION, AS AN EXAMPLE, APPLYING THE SEARCH MECHANISM Ctrl + F IN THIS BLOG FOR A WORD OR WORDS. SO, THIS BLOG SHARING IS VERY IMPORTANT TO THE WORLD SOCIETY! I hope in some way with this blog to help significantly in the socio-economic and technical-scientific development of the countries. My E-mail Accounts: rodrigoncal1984@gmail.com rodrigonunescal@yahoo.com rodrigoncal1984@yahoo.com ´´NÃO VÁ PARA ONDE O CAMINHO PODE TE LEVAR. VÁ ONDE NÃO HÁ CAMINHO E DEIXE UMA TRILHA. ´´ ´´DON'T GO WHERE THE PATH CAN TAKE YOU. GO WHERE THERE IS NO PATH AND LEAVE A TRAIL. ´´ @ KNOWING THE UNKNOWN.. CONHECENDO O DESCONHECIDO.. The world needs very innovative ideas to people live better and longer more and more. I have been invited as a Speaker/Delegate in numerous International Conferences and Congresses. * DISCOVERING HOW THE INITIAL STAGES OF A CERTAIN DISEASES WORK, SUCH AS A FATAL DISEASES, IS OF HUGE IMPORTANCE FOR SCIENCE, FOR SURE. THERE ARE SEVERAL BIOLOGICAL FACTORS CONNECTED IN THE HUMAN BODY THAT ACTING IN A VERY COMPLEX FORM. THEREFORE, IT IS OF GREAT NECESSITY TO CARRY OUT NEW SCIENTIFIC RESEARCHES MUCH MORE DETAILED AND MODERN, WITH A HIGH DEGREE OF PRECISION, EVEN IF THERE IS NO SIGNIFICANT STATISTICAL DIFFERENCE BETWEEN CERTAIN FACTORS. * DESCOBRIR COMO FUNCIONA OS ESTÁGIOS INICIAIS DE DETERMINADAS DOENÇAS, TAIS COMO AS DOENÇAS FATAIS, É DE ENORME IMPORTÂNCIA PARA A CIÊNCIA , COM CERTEZA. HÁ VÁRIOS FATORES BIOLÓGICOS INTERLIGADOS NO CORPO HUMANO QUE ATUAM DE FORMA MUITO COMPLEXA. PORTANTO, É DE GRANDE NECESSIDADE A REALIZAÇÃO DE NOVAS PESQUISAS CIENTÍFICAS MUITO MAIS MINUCIOSAS E MODERNAS, COM ALTO GRAU DE PRECISÃO, MESMO QUE NÃO HAJA DIFERENÇA ESTATÍSTICA SIGNIFICATIVA ENTRE DETERMINADOS FATORES. * The discussion of certain facts in science envolving stastistics is fundamental to the scientific community, for example, the analysis and interpretation of very important, innovative and interesting graphics with no statistical difference between them can have a big value to the researches and to the future researches. So, the quality and efficiency of researches can increase so much in a little time, increasing the possiblities of excellent references and new scientific discoveries. The facts veracity and the disclosure of them are essential for the scientific community, of course. Reconhecer o(s) erro(s) cometido(s) e não praticá-lo(s) novamente é um ato de grande sabedoria e importância para si mesmo e para a(s) outra(s) pessoa(s). Acknowledging mistakes and not doing them again is an act of great wisdom and importance for yourself and to the other person or people. ´´O IMPOSSÍVEL PODE SER POSSÍVEL´´. ´´THE IMPOSSIBLE CAN BE POSSIBLE´´. I have received positive feedbacks about this blog by LinkedIn, Twitter, Facebook, E-mails and Instagram. ´´EVERYONE DIES. THE GOAL IS NOT TO LIVE FOREVER. THE GOAL S TO CREATE SOMETHING THAT WILL´´ # time #time #internet #technologies #HighTechnologies #Cell Phones #Computer #Notebook  # Television #radio #communication #tempo  #InternetSociety # Society #person # people # age #ages #genetics #longevity #investigations #researches #efficiency #projects #ideas #reference #references #article #articles #journal # journals #magazines #websites #blogs #sites #links #SocialNetworks #energy #graphics #dissertation #monograph #citations #ImpactFactor #pesquisa #pesquisas #tecnologias #DiferentesPercepções #DifferentPerceptions #mind #mente #minds #MentesHumanas #emails #email e-mails reading #MenteHumana leitura mensagem mensagens probabilidade(s) probabilities messages message importance importância relevância assunto(s) subject subjects issue tema reflexão reflections vision visão pioneirismo pionners prêmio(s) prizes awards innovations inovações Grupos de Estudo Grupos Controle saúde doença(s) nome(s) tempo(s) Início da doença - Momento inicial da doença - Momento(s) inicial(ais) da(s) doença(s) humana(s) - Semelhança genética com camundongos - Mice researches - vaccines - drugs - eficiência - medicamento(s) - vacina(s) - High efficiency - Fatal diseases - Doenças fatais - Investments - investimentos - laboratórios - industries - indústrias - laboratories - Centros de Pesquisa - Países - cidades - cities - longevidade - desafio(s) - challenges - gráficos detalhados - interações biológicas - fatores biológicas - análise minuciosa - Very detailed analysis @ Initial moment of disease - Initial moments of human diseases - No Name @ discussion - discussão científica - science facts - detailed graphics - fatos científicos - publicação de trabalhos científicos - publications - hard work - better results - better science - diagnóstico - prognósticos - Diferença Estatística Significativa 100 Diferença Estatística Significativa @ Significant Statistical Difference - V X I Interpretations interpretações intenções intenions countries EU 100 gene Sem genes Cem genes 1 0 0 gene(s) time(s) times 100 limites limite(s) limits 1 0 0 limit NO LIMIT 10 0 @ 100 genes @ 100 gene & NO GENE NO TEMPO NOS TEMPOS NO(S) TEMPO(S) NOS TIMES NO TIME 100 GENE No Time # no time @ nos genes no(s) gene(s) * no(s) limite(s) - words- palavra(s) - listen - write - type - fala - escuta - ler - virtualidade - virtuality - reality - realidade - mundo real - mundo virtual - vida real - virtual life - real life - vida virtual - imaginations - thoughts - pensamento(s) - imaginações - melhoria - improvement - respect - respeito - speak - nome(s) - trabalho(s) - dinheiro - money - team - equipe - objetivo(s) - Best Universities of the World - Scientific Discoveries - Brazil - World - RNA - Cell - DNA - Idade biológica - biological age - pessoas - idade - idade(s) - pessoa - História da Computação Mundial - Harvard - Names - Places - City - researches - scientists - professors - pesquisador(es) - cientistas - professores - professor(es) - Produção científica - Fatores de Impacto - feelings - logic - sentimento(s) - lógica - história - world history - difficulties - dificuldades - Scientific community - comunidade científica mundial - vidas humanas - vida(s) humana(s) - trabalho(s) - human lives - life - human life - única - one life - person people @ momentos - moments memories memory memória longevidade energias energia(s) Many people liked my Twitter and Facebook comments that I informed this blog like great professors, scientists and researchers around the world who work in human health area! Many data about it aren´t in this blog. #database #system #time #data #search #information #InternetHistory #contribuitions #improvement #analysis #intentions Intenções @ #person #people #age #longevity #work #reading #probabilities #energy #money #price #clicks #jobs #country #city #countries #cities #knowledge #HumanInterdependence #WorldHistory #communication #HumanRelations #websites #e-mails #SocialNetworks #ranking #links #images #photos #texts #messages #videos #writing #typing #speak #listen #think #feelings #ideas #ScientificDiscoveries #investigations #researches #articles #ImpactFactors #journals #citations #influence #dissertations #monographs #ScientificWorks #Inventions #graphics #subjects #books #references #blogs ´´Compreender as grandes dificuldades de um determinado assunto pode ser um processo muito demorado, porém, de grande valia para o progresso da Ciência em todos os aspectos´´ Rodrigo Nunes Cal Observação/Note: I won a scholarship by FAPEMIG during the period of ´´my´´ monograph in Uberaba. Ganhei bolsa de estudo pela FAPEMIG durante o período da ´´minha´´ monografia em Uberaba. During the period that I participated of ´´my´´ dissertation at FAMERP, I didn't win a scholarship. Já durante o mestrado que fiz na FAMERP, não ganhei bolsa de estudo. ´´Os gráficos baseados em dados da ´´minha´´ dissertação que fiz podem ser uma excelente referência para muitos tipos de pesquisas e projetos, é claro !! Por exemplo, para pesquisas e projetos que tenham como objetivo analisar os tipos de influências das idades em camundongos e humanos (estudos genéticos, por exemplo) em relação a diferentes estágios de determinadas doenças, como aquelas em que a comunidade científica desconhece (doenças desconhecidas) e que poderão surgir no mundo. Outros tipos de pesquisas e projetos que podem ser feitos são aqueles que analisam a eficácia de diversos tipos de substâncias terapêuticas em camundongos e humanos nos diversos tipos de doenças com o objetivo de saber qual a melhor substância terapêutica para cada doença, levando em consideração a idade e genética, com certeza. Contudo, realizar pesquisas com o objetivo de avaliar qual é a influência da idade e da genética na eficiência terapêutica em animais de experimentação e em humanos, consequentemente, possui um grande valor, já que muitas pessoas adoecem e acabam falecendo mesmo sendo submetidas à ótimos sistemas de diagnóstico, tratamento e prognóstico, dependendo da doença que possui e do estágio da mesma´´. ´´A partir daí, ao comprovar que há influência significativa da idade e da genética, consequentemente, no processo de patogênese de doenças nos animais de experimentação e nos humanos, seria muito mais conveniente e lógico um grupo de indivíduos de certa faixa etária e histórico familiar e individual de doenças adquiridas e possíveis de serem adquiridas no decorrer do tempo serem tratados com outros tipos de medicamentos, substâncias terapêuticas, vacinas, dentre outros. Com certeza, para a realização destes tipos de pesquisa deve haver grande investimento financeiro nos laboratórios a fim de aquisição de aparelhos científicos altamente eficientes. Com certeza, pesquisas à nível genético e com relação à influência da idade do ser vivo na patogênese de doenças, até das doenças desconhecidas pelo mundo científico. O fato é que este tipo de pesquisa é muito importante porque como todos sabem, há muitas doenças que voltam a se manifestar nas pessoas mesmo depois de excelentes tratamentos, dos mais variados tipos. E outro ponto a ser refletido é a permanência de doenças fatais´´. ´´Assim, este tipo de influência da idade e consequentemente da genética na fisiopatologia das doenças hereditárias ou não hereditárias, um indivíduo de uma determinada idade será submetido a um tratamento terapêutico diferente de outro com a mesma doença mas com idade diferente da de até a pesquisa mostrou uma influência significativa na patogênese da doença, portanto, utilizará outro tipo de substância terapêutica, medicamentos, entre outros. Isso certamente acontecerá se a comunidade científica mundial comprovar cientificamente essas hipóteses por meio de várias pesquisas e projetos científicos. As pessoas precisam ter excelentes inovações para a expectativa de vida humana aumentar muito rapidamente cada vez mais. Portanto, quanto mais a medicina personalizada for, melhor será para cada um de nós´´. Rodrigo Nunes Cal ´´The graphics based on data from ´´my´´ dissertation I did can be an excellent reference for many types of researches and projects, of course!! For example, for researches and projects that the goals are analyse the type of influences of ages in mice and human (genetic studies, for example) in relation to different stages of determined diseases, like those that the scientific community do not know about them (unknown diseases). Other types of researches and projects that can be done is those that analyse the efficiency of many types of therapeutical substances in mice and human in many types of diseases with the objective of knowing which is the best therapeutic substance for each disease, taking into account age and genetics, for sure. For example, to carry out research with the objective of evaluating the influence of age and genetics on therapeutic efficiency in experimental animals and in humans´´. ´´Thus, by proving that there is a significant influence of age and genetics, consequently, in the process of pathogenesis of diseases in experimental animals and in humans, it would be much more convenient and logical to have a group of individuals of a certain age group and family and individual history of acquired diseases and possible to be acquired over time being treated with other types of drugs, therapeutic substances, vaccines, among others. Certainly, to carry out these types of research there must be a large financial investment in laboratories in order to acquire highly efficient scientific devices. Certainly, research at the genetic level and regarding the influence of the age of the living being on the pathogenesis of diseases, even diseases unknown to the scientific world. The fact is that this type of research is very important because as everyone knows, there are many diseases that come back to manifest in people even after excellent treatments, of the most varied types. And another point to be reflected on is the permanence of fatal diseases´´. ´´Taking into account this type of influence of age and consequently genetics on the pathophysiology of inherited or not inherited diseases, an individual of a certain age will be submitted to a different therapeutic treatment from another with the same disease but who has a different age than through the research has shown a significant influence on the pathogenesis of the disease, therefore, will use another type of therapeutic substance, medicine, among others. This will certainly happen if the world scientific community scientifically proves these hypotheses through various research and scientific projects. So, the people need to have excellent innovation to the human expectancy  of life increase so much faster more and more´´. Rodrigo Nunes Cal Note/Obs: I thought each person could do their own friend request permission setting since Facebook's technology is so big. Eu achava que cada pessoa poderia fazer sua própria configuração de permissão de solicitação de amizade já que a tecnologia do Facebook é muito grande. Very important note: I can earn money with this blog if the person do a donation to increase the dissemination of this blog and to recognize the hard work to do it. - Observação muito importante: Posso ganhar dinheiro com este blog se alguém fizer uma doação pra mim para aumentar a divulgação deste blog e pelo reconhecimento de fazer este blog. Foi um trabalho árduo pra fazer este blog.

22 Comments

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