RESUMO
While the world awaits a widely available COVID-19 vaccine, availability of testing is limited in many regions and can be further compounded by shortages of reagents, prolonged processing time and delayed results. One approach to rapid testing is to leverage the volatile organic compound (VOC) signature of SARS-CoV-2 infection. Detection dogs, a biological sensor of VOCs, were utilized to investigate whether SARS-CoV-2 positive urine and saliva patient samples had a unique odor signature. The virus was inactivated in all training samples with either detergent or heat treatment. Using detergent-inactivated urine samples, dogs were initially trained to find samples collected from hospitalized patients confirmed with SARS-CoV-2 infection, while ignoring samples collected from controls. Dogs were then tested on their ability to spontaneously recognize heat-treated urine samples as well as heat-treated saliva from hospitalized SARS-CoV-2 positive patients. Dogs successfully discriminated between infected and uninfected urine samples, regardless of the inactivation protocol, as well as heat-treated saliva samples. Generalization to novel samples was limited, particularly after intensive training with a restricted sample set. A unique odor associated with SARS-CoV-2 infection present in human urine as well as saliva, provides impetus for the development of odor-based screening, either by electronic, chemical, or biological sensing methods. The use of dogs for screening in an operational setting will require training with a large number of novel SARS-CoV-2 positive and confirmed negative samples.
Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Cães Trabalhadores/psicologia , Animais , COVID-19/urina , Cães , Feminino , Humanos , Masculino , Programas de Rastreamento , Estudo de Prova de Conceito , SARS-CoV-2/isolamento & purificação , Saliva/química , Manejo de Espécimes/métodos , Compostos Orgânicos Voláteis/químicaRESUMO
Chemical mutagenesis followed by screening for abnormal phenotypes in the mouse holds much promise as a method for revealing gene function. This method is particularly well-suited for discovering genes involved in hearing or balance function, as these defects are relatively easy to screen for in the mouse. We report here the inner ear abnormalities and genetic localization of seven new dominant mutations created by ENU mutagenesis. All seven mutant stocks were identified because of circling and/or head-weaving behavior, which is an indication of balance dysfunction. Investigation of the inner ears of the seven mutant stocks revealed very similar lateral and posterior semicircular canal defects. Studies of the development of the canals in one mutant stock revealed that the affected canals showed reduced outgrowth and delayed canal fusion. Physiological studies performed in one mutant stock showed raised average compound-action-potential thresholds of approximately 10-20 dB sound pressure level (SPL) (depending on frequency), indicating a mild hearing impairment, although scanning electron microscopy performed in several of the mutant stocks revealed no obvious structural defects in the organ of Corti. All seven mutations mapped to the proximal portion of Chromosome (Chr) 4, near the centromere. On the basis of their similar phenotype and map location, we suggest that the seven mutant genes may be allelic and represent a highly mutable locus on Chr 4 that may be particularly susceptible to ENU-induced mutation on the BALB/c genetic background.
Assuntos
Mapeamento Cromossômico , Cóclea/embriologia , Orelha Média/embriologia , Etilnitrosoureia/farmacologia , Mutagênicos/farmacologia , Canais Semicirculares/embriologia , Alquilantes/farmacologia , Animais , Cóclea/anormalidades , Orelha Média/anormalidades , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Morfogênese/genética , Canais Semicirculares/anormalidadesRESUMO
Dominantly acting mutations that produce visible phenotypes are frequently recovered, either during routine maintenance of colonies or from mutagenesis experiments. We have studied 12 dominant mouse mutations that cause a tail dysmorphology, a coat spotting phenotype, or a combination of these. The majority of these mutations act in a semidominant manner with the homozygous state associated with embryonic lethality and a visible phenotype at or before midgestation. The homozygous phenotypes include axis truncation and neural crest cell defects, as may be expected from the heterozygous phenotypes. The majority of mutations, however, also produced other phenotypes that include neural tube closure defects and aberrant heart looping. In one coat spotting mutant the homozygous condition is lethal before neural crest cell production commences. The mutated genes often function in processes additional to those alluded to by the heterozygous phenotype.
Assuntos
Desenvolvimento Embrionário/genética , Genes Dominantes , Mutação , Alquilantes/farmacologia , Animais , Animais Congênicos , Biomarcadores , Mapeamento Cromossômico , Etilnitrosoureia/farmacologia , Feminino , Genes Letais , Marcadores Genéticos , Genoma , Cor de Cabelo/genética , Haplótipos , Homozigoto , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Mutantes , Mutagênicos/farmacologia , Polimorfismo Genético , Cauda/anormalidadesRESUMO
Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes.