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Naturally occurring collective motion is a fascinating phenomenon in which swarming individuals aggregate and coordinate their motion. Many theoretical models of swarming assume idealized, perfect perceptual capabilities, and ignore the underlying perception processes, particularly for agents relying on visual perception. Specifically, biological vision in many swarming animals, such as locusts, utilizes monocular non-stereoscopic vision, which prevents perfect acquisition of distances and velocities. Moreover, swarming peers can visually occlude each other, further introducing estimation errors. In this study, we explore necessary conditions for the emergence of ordered collective motion under restricted conditions, using non-stereoscopic, monocular vision. We present a model of vision-based collective motion for locust-like agents: elongated shape, omni-directional visual sensor parallel to the horizontal plane, and lacking stereoscopic depth perception. The model addresses (i) the non-stereoscopic estimation of distance and velocity, (ii) the presence of occlusions in the visual field. We consider and compare three strategies that an agent may use to interpret partially-occluded visual information at the cost of the computational complexity required for the visual perception processes. Computer-simulated experiments conducted in various geometrical environments (toroidal, corridor, and ring-shaped arenas) demonstrate that the models can result in an ordered or near-ordered state. At the same time, they differ in the rate at which order is achieved. Moreover, the results are sensitive to the elongation of the agents. Experiments in geometrically constrained environments reveal differences between the models and elucidate possible tradeoffs in using them to control swarming agents. These suggest avenues for further study in biology and robotics.
Assuntos
Gafanhotos , Percepção de Movimento , Humanos , Animais , Visão Ocular , Modelos Teóricos , Simulação por Computador , Movimento (Física) , Percepção de ProfundidadeRESUMO
BACKGROUND: Dupilumab, a monoclonal antibody targeting IL-4 and IL-13, has demonstrated its efficacy in several clinical trials. However, to date, real-life data remains limited. OBJECTIVE: The aim of our study was to assess the real-life impact of dupilumab on patients with severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) quality of life. MATERIALS AND METHODS: This was a retrospective, monocentric, observational, real-life study, conducted in accordance with the STROBE guidelines. The following parameters were collected before treatment and at 1, 4, and 12 months: Sino-Nasal Outcome Test-22 (SNOT-22), nasal polyp score (NPS), Sniffin' Sticks-16 (SST-16), visual analog scale (VAS) for loss of smell, nasal congestion score (NCS), gustatory VAS, asthma control, oral corticosteroid usage, surgery rates, and occurrence of side effects. RESULTS: The study included 47 patients. SNOT-22 scores decreased from 52.4 ± 24.3 to 12.7 ± 10.5 at 12 months (p < 0.001). NPS decreased from 6.15 ± 1.71 to 1.57 ± 1.40 at 12 months (p < 0.001). SST-16 scores increased from 1.6 ± 2.83 to 9.1 ± 5.4 at 12 months (p < 0.001). NCS decreased from 2.45 ± 0.72 to 0.38 ± 0.63 at 12 months (p < 0.001). Prior to treatment, 72.3% were using oral corticosteroids, compared to 17.0% at 12 months (p < 0.01). Two patients required additional surgery, and 17% reported completely uncontrolled asthma, compared to 0% at 12 months (p < 0.01). CONCLUSION: Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP.
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Collection of accurate and representative data from agricultural fields is required for efficient crop management. Since growers have limited available resources, there is a need for advanced methods to select representative points within a field in order to best satisfy sampling or sensing objectives. The main purpose of this work was to develop a data-driven method for selecting locations across an agricultural field given observations of some covariates at every point in the field. These chosen locations should be representative of the distribution of the covariates in the entire population and represent the spatial variability in the field. They can then be used to sample an unknown target feature whose sampling is expensive and cannot be realistically done at the population scale. An algorithm for determining these optimal sampling locations, namely the multifunctional matching (MFM) criterion, was based on matching of moments (functionals) between sample and population. The selected functionals in this study were standard deviation, mean, and Kendall's tau. An additional algorithm defined the minimal number of observations that could represent the population according to a desired level of accuracy. The MFM was applied to datasets from two agricultural plots: a vineyard and a peach orchard. The data from the plots included measured values of slope, topographic wetness index, normalized difference vegetation index, and apparent soil electrical conductivity. The MFM algorithm selected the number of sampling points according to a representation accuracy of 90% and determined the optimal location of these points. The algorithm was validated against values of vine or tree water status measured as crop water stress index (CWSI). Algorithm performance was then compared to two other sampling methods: the conditioned Latin hypercube sampling (cLHS) model and a uniform random sample with spatial constraints. Comparison among sampling methods was based on measures of similarity between the target variable population distribution and the distribution of the selected sample. MFM represented CWSI distribution better than the cLHS and the uniform random sampling, and the selected locations showed smaller deviations from the mean and standard deviation of the entire population. The MFM functioned better in the vineyard, where spatial variability was larger than in the orchard. In both plots, the spatial pattern of the selected samples captured the spatial variability of CWSI. MFM can be adjusted and applied using other moments/functionals and may be adopted by other disciplines, particularly in cases where small sample sizes are desired.
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What is the fastest way to heat a system which is coupled to a temperature controlled oven? The intuitive answer is to use only the hottest temperature available. However, we show that often it is possible to achieve an exponentially faster heating protocol. Surprisingly, this protocol can have a precooling stage-cooling the system before heating it shortens the heating time significantly. To demonstrate such improvements in many-body systems, we developed a projection-based method with which such protocols can be found in large systems, as we demonstrate on the 2D antiferromagnet Ising model.
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We address the Λ hypernuclear "overbinding problem" in light hypernuclei which stands for a 1-3 MeV excessive Λ separation energy calculated in _{Λ}^{5}He. This problem arises in most few-body calculations that reproduce ground-state Λ separation energies in the lighter Λ hypernuclei within various hyperon-nucleon interaction models. Recent pionless effective field theory (πEFT) nuclear few-body calculations are extended in this work to Λ hypernuclei. At leading order, the ΛN low-energy constants are associated with ΛN scattering lengths, and the ΛNN low-energy constants are fitted to Λ separation energies (B_{Λ}^{exp}) for A≤4. The resulting πEFT interaction reproduces in few-body stochastic variational method calculations the reported value B_{Λ}^{exp}(_{Λ}^{5}He)=3.12±0.02 MeV within a fraction of MeV over a broad range of πEFT cutoff parameters. Possible consequences and extensions to heavier hypernuclei and to neutron-star matter are discussed.
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BACKGROUND: Canine joint sarcomas, designated synovial sarcomas, are uncommon malignant mesenchymal neoplasms that occur in the large joints of the extremities of middle-aged, large-breed dogs. We report the diagnosis of an intrathoracic sarcoma with ultrastructural characteristics reminiscent of human synovial sarcoma in a dog. CASE PRESENTATION: A 7-year-old female spayed Tibetan terrier crossbred dog was presented for acute severe labored breathing and diagnosed with an intrathoracic neoplastic mass. The neoplasm resulted in the accumulation of substantial amounts of viscous pleural fluid that led to dyspnea. The neoplastic mass consisted of interweaving bundles of large pleomorphic mesenchymal cells, supported by an alcian blue positive myxomatous matrix. The neoplastic cells were immunohistochemically negative for cytokeratin and CD18. Transmission electron microscopy indicated that the neoplastic cells had desmosome junctions, short microvilli-like structures and ample amounts of rough endoplasmic reticulum resembling type B-like synoviocytes and synovial sarcoma as reported in people. Despite complete surgical excision of the neoplastic mass, clinical signs recurred after a month and led to the euthanasia of the dog. CONCLUSION: Currently, there are no immunohistochemical markers specific for synovial sarcoma. Canine neoplasms with transmission electron microscopy characteristics resembling type B-like synoviocytes should be considered similar to the human sarcomas that carry the specific translocations between chromosomes X and 18.
Assuntos
Doenças do Cão/patologia , Sarcoma Sinovial/veterinária , Neoplasias Torácicas/veterinária , Animais , Cães , Feminino , Microscopia Eletrônica de Transmissão , Sarcoma Sinovial/patologia , Sarcoma Sinovial/ultraestrutura , Neoplasias Torácicas/patologia , Neoplasias Torácicas/ultraestruturaRESUMO
The D(03) dibaryon is generated dynamically as a resonance pole in a πNΔ' three body model, where Δ' is a stable Δ baryon. Using separable interactions dominated by the Δ(1232) isobar for πN and by the D(12)(2150) isobar for NΔ', with D(12)(2150) the NΔ dibaryon deduced in and constrained by (1)D(2) pp scattering, the model reduces to an effective two body problem for ΔΔ' which is solved. The mass and width of D(03) are found close to those of the I(J(P))=0(3(+)) resonance peak observed by WASA-at-COSY in pion-production pn collisions at 2.37 GeV.
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The locus for autosomal dominant congenital stationary night blindness (adCSNB) has recently been assigned to distal chromosome 4p by linkage analysis in a large Danish family. Within the candidate gene encoding the beta-subunit of rod photoreceptor cGMP-specific phosphodiesterase (beta PDE), we have identified a heterozygous C to A transversion in exon 4, predicting a His258Asp change in the polypeptide. We found a perfect cosegregation (Zmax = 22.6 at theta = 0.00) of this mutation with the disease phenotype suggesting that this missense mutation is responsible for the disease in this pedigree. Homozygous nonsense mutations in the beta PDE gene have been found recently in patients with autosomal recessive retinitis pigmentosa, a common hereditary photoreceptor dystrophy.
Assuntos
3',5'-GMP Cíclico Fosfodiesterases/genética , Genes Dominantes , Cegueira Noturna/genética , Mutação Puntual , Segmento Externo da Célula Bastonete/enzimologia , 3',5'-GMP Cíclico Fosfodiesterases/deficiência , Adulto , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 4 , Dinamarca , Feminino , Heterozigoto , Humanos , Modelos Genéticos , Dados de Sequência Molecular , Cegueira Noturna/classificação , Cegueira Noturna/enzimologia , Linhagem , Polimorfismo Genético , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness with all other visual functions, including visual acuity, visual field, and colour vision being usually normal. A typical clinical feature of the disorder is a golden or gray-white discolouration of the fundus which disappears in the dark-adapted state and reappears shortly after the onset of light ('Mizuo phenomenon'; Fig. 1). The course of dark adaptation of rod photoreceptors is extremely retarded in Oguchi disease while that of cones appears to proceed normally. The locus for Oguchi disease was recently mapped between D2S172 and D2S345 on distal chromosome 2q by linkage analysis. Interestingly, the gene for arrestin, an intrinsic rod photoreceptor protein implicated in the recovery phase of light transduction, also maps to this region of chromosome 2q (refs 6, 7). Here we report that in five out of six unrelated Japanese patients with Oguchi disease, we have identified a homozygous deletion of nucleotide 1147 (1147delA) in codon 309 of the arrestin gene, predicting a shift in the reading frame and a premature termination of translation which may result in 'functional null alleles.'
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Antígenos/genética , Proteínas do Olho/genética , Cegueira Noturna/genética , Deleção de Sequência , Adolescente , Adulto , Sequência de Aminoácidos , Arrestina , Sequência de Bases , Criança , Códon/genética , DNA/genética , Primers do DNA/genética , Mutação da Fase de Leitura , Genes Recessivos , Homozigoto , Humanos , Japão , Dados de Sequência Molecular , Cegueira Noturna/congênito , Cegueira Noturna/metabolismo , Reação em Cadeia da Polimerase , Potássio/metabolismo , Retina/metabolismoRESUMO
A candidate gene for Norrie disease, an X-linked disorder characterized by blindness, deafness and mental disturbances, was recently isolated and found to contain microdeletions in numerous patients. No strong homologies were identified. By studying the number and spacing of cysteine residues, we now detect homologies between the Norrie gene product and a C-terminal domain which is common to a group of proteins including mucins. Three newly-characterized missense mutations, replacing evolutionarily conserved cysteines or creating new cysteine codons, emphasize the functional importance of these sites. These findings and the clinical features of this disorder suggest a possible role for the Norrie gene in neuroectodermal cell-cell interaction.
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Cegueira/genética , Surdez/genética , Mucinas/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Cegueira/congênito , Criança , Pré-Escolar , Mapeamento Cromossômico , Cisteína/genética , DNA/genética , Análise Mutacional de DNA , Éxons , Ligação Genética , Humanos , Lactente , Deficiência Intelectual/genética , Íntrons , Masculino , Dados de Sequência Molecular , Mutação Puntual , Homologia de Sequência de Aminoácidos , Cromossomo XRESUMO
Mutation of a receptor tyrosine kinase gene, Mertk, in the Royal College of Surgeons (RCS) rat results in defective phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) and retinal degeneration. We screened the human orthologue, MERTK, located at 2q14.1 (ref. 10), in 328 DNA samples from individuals with various retinal dystrophies and found three mutations in three individuals with retinitis pigmentosa (RP). Our findings are the first conclusive evidence implicating the RPE phagocytosis pathway in human retinal disease.
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Proteínas do Olho/genética , Fagocitose , Proteínas Proto-Oncogênicas , Ratos Endogâmicos/genética , Receptores Proteína Tirosina Quinases/genética , Degeneração Retiniana/veterinária , Retinose Pigmentar/genética , Doenças dos Roedores/genética , Adulto , Substituição de Aminoácidos , Animais , Cromossomos Humanos Par 2/genética , Clonagem Molecular , Códon/genética , Consanguinidade , Análise Mutacional de DNA , Modelos Animais de Doenças , Éxons/genética , Feminino , Mutação da Fase de Leitura , Genes Recessivos , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Mutação Puntual , Polimorfismo Conformacional de Fita Simples , Sítios de Splice de RNA/genética , Ratos , Receptores Proteína Tirosina Quinases/deficiência , Degeneração Retiniana/enzimologia , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Retinose Pigmentar/enzimologia , Segmento Externo da Célula Bastonete/patologia , Doenças dos Roedores/enzimologia , Deleção de Sequência , Especificidade da Espécie , Regiões Terminadoras Genéticas/genética , c-Mer Tirosina QuinaseRESUMO
The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.
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Aciltransferases/genética , Mutação , Degeneração Retiniana/genética , Aciltransferases/metabolismo , Idade de Início , Animais , Células COS , Membrana Celular/metabolismo , Feminino , Genes Recessivos , Humanos , Masculino , Repetições de Microssatélites , Mutação Puntual , Polimorfismo Conformacional de Fita SimplesRESUMO
X-linked forms of mental retardation (XLMR) include a variety of different disorders and may account for up to 25% of all inherited cases of mental retardation. So far, seven X-chromosomal genes mutated in nonspecific mental retardation (MRX) have been identified: FMR2, GDI1, RPS6KA3, IL1RAPL, TM4SF2, OPHN1 and PAK3 (refs 2-9). The products of the latter two have been implicated in regulation of neural plasticity by controlling the activity of small GTPases of the Rho family. Here we report the identification of a new MRX gene, ARHGEF6 (also known as alphaPIX or Cool-2), encoding a protein with homology to guanine nucleotide exchange factors for Rho GTPases (Rho GEF). Molecular analysis of a reciprocal X/21 translocation in a male with mental retardation showed that this gene in Xq26 was disrupted by the rearrangement. Mutation screening of 119 patients with nonspecific mental retardation revealed a mutation in the first intron of ARHGEF6 (IVS1-11T-->C) in all affected males in a large Dutch family. The mutation resulted in preferential skipping of exon 2, predicting a protein lacking 28 amino acids. ARHGEF6 is the eighth MRX gene identified so far and the third such gene to encode a protein that interacts with Rho GTPases.
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Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 21 , Fatores de Troca do Nucleotídeo Guanina/genética , Deficiência Intelectual/genética , Mutação , Translocação Genética , Cromossomo X , Proteínas rho de Ligação ao GTP/genética , Sequência de Bases , Mapeamento Cromossômico , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Deficiência Intelectual/enzimologia , Íntrons , Masculino , Dados de Sequência Molecular , Linhagem , Fatores de Troca de Nucleotídeo Guanina RhoRESUMO
Usher syndrome type 1 (USH1) is an autosomal recessive sensory defect involving congenital profound sensorineural deafness, vestibular dysfunction and blindness (due to progressive retinitis pigmentosa)1. Six different USH1 loci have been reported. So far, only MYO7A (USH1B), encoding myosin VIIA, has been identified as a gene whose mutation causes the disease. Here, we report a gene underlying USH1C (MIM 276904), a USH1 subtype described in a population of Acadian descendants from Louisiana and in a Lebanese family. We identified this gene (USH1C), encoding a PDZ-domain-containing protein, harmonin, in a subtracted mouse cDNA library derived from inner ear sensory areas. In patients we found a splice-site mutation, a frameshift mutation and the expansion of an intronic variable number of tandem repeat (VNTR). We showed that, in the mouse inner ear, only the sensory hair cells express harmonin. The inner ear Ush1c transcripts predicted several harmonin isoforms, some containing an additional coiled-coil domain and a proline- and serine-rich region. As several of these transcripts were absent from the eye, we propose that USH1C also underlies the DFNB18 form of isolated deafness.
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Proteínas de Transporte/genética , Mutação da Fase de Leitura , Células Ciliadas Auditivas Internas/patologia , Perda Auditiva Neurossensorial/genética , Mutação , Degeneração Retiniana/genética , Proteínas Adaptadoras de Transdução de Sinal , Alelos , Animais , Sequência de Bases , Northern Blotting , Proteínas de Transporte/biossíntese , Proteínas de Transporte/química , Proteínas de Ciclo Celular , Proteínas do Citoesqueleto , Análise Mutacional de DNA , DNA Complementar/metabolismo , Éxons , Saúde da Família , Deleção de Genes , Biblioteca Gênica , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Vestibulares/metabolismo , Heterozigoto , Humanos , Imuno-Histoquímica , Íntrons , Camundongos , Repetições Minissatélites/genética , Modelos Genéticos , Dados de Sequência Molecular , Linhagem , Isoformas de Proteínas , Estrutura Terciária de Proteína , Splicing de RNA/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Distribuição Tecidual , Transcrição GênicaRESUMO
Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss, vestibular dysfunction and visual impairment due to early onset retinitis pigmentosa (RP). So far, six loci (USH1A-USH1F) have been mapped, but only two USH1 genes have been identified: MYO7A for USH1B and the gene encoding harmonin for USH1C. We identified a Cuban pedigree linked to the locus for Usher syndrome type 1D (MIM 601067) within the q2 region of chromosome 10). Affected individuals present with congenital deafness and a highly variable degree of retinal degeneration. Using a positional candidate approach, we identified a new member of the cadherin gene superfamily, CDH23. It encodes a protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. In the Cuban family, we detected two different mutations: a severe course of the retinal disease was observed in individuals homozygous for what is probably a truncating splice-site mutation (c.4488G-->C), whereas mild RP is present in individuals carrying the homozygous missense mutation R1746Q. A variable expression of the retinal phenotype was seen in patients with a combination of both mutations. In addition, we identified two mutations, Delta M1281 and IVS51+5G-->A, in a German USH1 patient. Our data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype. In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.
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Caderinas/genética , Perda Auditiva Neurossensorial/genética , Família Multigênica/genética , Mutação/genética , Processamento Alternativo/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas Relacionadas a Caderinas , Caderinas/química , Caderinas/metabolismo , Clonagem Molecular , Sequência Consenso/genética , Cuba , Análise Mutacional de DNA , Éxons/genética , Feminino , Genótipo , Alemanha , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Sítios de Splice de RNA/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SíndromeRESUMO
Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa. Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA. Disease genes implicated in other forms of arCSRD are expected to encode proteins present in the neuroretina or in the retinal pigment epithelium (RPE). The RPE, a monolayer of cells separating the vascular-rich choroid and the neuroretina, is in intimate contact with the outer segments of rods and cones via the microvilli surrounding the photoreceptors. The RPE expresses a tissue-specific and evolutionarily highly conserved 61 kD protein (RPE65) present at high levels in vivo. Although the function of RPE65 is not yet known, an important role in the RPE/photoreceptor vitamin-A cycle is suggested by the fact that RPE65 associates both with serum retinol-binding protein and with the RPE-specific 11-cis retinol dehydrogenase, an enzyme active in the synthesis of the visual pigment chromophore 11-cis retinal. Here we report that the analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation (Pro363Thr), two point mutations affecting splicing (912 + 1G-->T and 65 + 5G-->A) and two small re-arrangements (ins144T and 831del8) on a total of nine alleles of five patients with arCSRD. In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina.
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Proteínas do Olho/genética , Mutação , Proteínas , Degeneração Retiniana/genética , Idade de Início , Sequência de Bases , Proteínas de Transporte , Criança , Pré-Escolar , Consanguinidade , Primers do DNA/genética , Éxons , Feminino , Genes Recessivos , Ligação Genética , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , cis-trans-IsomerasesRESUMO
Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of 1 in 3,500 individuals worldwide. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina-specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.
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Mutação , Retina/metabolismo , Retinose Pigmentar/genética , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Criança , Cromossomos Humanos Par 8/genética , Proteínas do Olho/genética , Feminino , Genes Dominantes , Heterozigoto , Homozigoto , Humanos , Masculino , Proteínas Associadas aos Microtúbulos , Dados de Sequência Molecular , Linhagem , Polimorfismo Genético , Homologia de Sequência de AminoácidosRESUMO
During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination. Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits. Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated. The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology. Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX. NYX, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.
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Proteínas do Olho/genética , Genes , Interneurônios/patologia , Cegueira Noturna/genética , Proteoglicanas/genética , Cromossomo X/genética , Adulto , Motivos de Aminoácidos , Sequência de Aminoácidos , Análise Mutacional de DNA , DNA Complementar/genética , Etiquetas de Sequências Expressas , Proteínas do Olho/química , Proteínas do Olho/fisiologia , Perfilação da Expressão Gênica , Glicosilfosfatidilinositóis/metabolismo , Humanos , Interneurônios/metabolismo , Rim/metabolismo , Leucina/análise , Masculino , Dados de Sequência Molecular , Cegueira Noturna/classificação , Especificidade de Órgãos , Linhagem , Proteoglicanas/química , Proteoglicanas/deficiência , Proteoglicanas/fisiologia , Sequências Repetitivas de Aminoácidos , Retina/patologia , Células Ganglionares da Retina/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transmissão Sináptica/fisiologia , Visão Ocular/fisiologiaRESUMO
Approximately 50% of childhood deafness is caused by mutations in specific genes. Autosomal recessive loci account for approximately 80% of nonsyndromic genetic deafness. Here we report the identification of a new transmembrane serine protease (TMPRSS3; also known as ECHOS1) expressed in many tissues, including fetal cochlea, which is mutated in the families used to describe both the DFNB10 and DFNB8 loci. An 8-bp deletion and insertion of 18 monomeric (approximately 68-bp) beta-satellite repeat units, normally present in tandem arrays of up to several hundred kilobases on the short arms of acrocentric chromosomes, causes congenital deafness (DFNB10). A mutation in a splice-acceptor site, resulting in a 4-bp insertion in the mRNA and a frameshift, was detected in childhood onset deafness (DFNB8). This is the first description of beta-satellite insertion into an active gene resulting in a pathogenic state, and the first description of a protease involved in hearing loss.
Assuntos
DNA Satélite/genética , Surdez/congênito , Surdez/enzimologia , Genes Recessivos/genética , Proteínas de Membrana , Mutagênese Insercional/genética , Proteínas de Neoplasias , Serina Endopeptidases/genética , Adulto , Idade de Início , Sequência de Bases , Criança , Consanguinidade , Mapeamento de Sequências Contíguas , Análise Mutacional de DNA , Surdez/epidemiologia , Surdez/genética , Éxons/genética , Feminino , Mutação da Fase de Leitura/genética , Humanos , Hibridização in Situ Fluorescente , Israel , Masculino , Dados de Sequência Molecular , Paquistão , Linhagem , Sítios de Splice de RNA/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Alinhamento de Sequência , Serina Endopeptidases/metabolismoRESUMO
Swarming or collective motion is ubiquitous in natural systems, and instrumental in many technological applications. Accordingly, research interest in this phenomenon is crossing discipline boundaries. A common major question is that of the intricate interactions between the individual, the group, and the environment. There are, however, major gaps in our understanding of swarming systems, very often due to the theoretical difficulty of relating embodied properties to the physical agents-individual animals or robots. Recently, there has been much progress in exploiting the complementary nature of the two disciplines: biology and robotics. This, unfortunately, is still uncommon in swarm research. Specifically, there are very few examples of joint research programs that investigate multiple biological and synthetic agents concomitantly. Here we present a novel research tool, enabling a unique, tightly integrated, bio-inspired, and robot-assisted study of major questions in swarm collective motion. Utilizing a quintessential model of collective behavior-locust nymphs and our recently developed Nymbots (locust-inspired robots)-we focus on fundamental questions and gaps in the scientific understanding of swarms, providing novel interdisciplinary insights and sharing ideas disciplines. The Nymbot-Locust bio-hybrid swarm enables the investigation of biology hypotheses that would be otherwise difficult, or even impossible to test, and to discover technological insights that might otherwise remain hidden from view.