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1.
Proc Natl Acad Sci U S A ; 120(33): e2302661120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549288

RESUMO

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.


Assuntos
Equinococose , Echinococcus , Animais , Humanos , Hotspot de Doença , Equinococose/epidemiologia , Zoonoses/epidemiologia , Fatores de Risco , El Niño Oscilação Sul
2.
Proc Natl Acad Sci U S A ; 119(35): e2200960119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35951647

RESUMO

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.


Assuntos
Encéfalo , COVID-19 , Viroses do Sistema Nervoso Central , SARS-CoV-2 , Astrócitos/patologia , Astrócitos/virologia , Encéfalo/patologia , Encéfalo/virologia , COVID-19/complicações , COVID-19/patologia , Viroses do Sistema Nervoso Central/etiologia , Viroses do Sistema Nervoso Central/patologia , Humanos , Síndrome de COVID-19 Pós-Aguda
3.
Rev Med Suisse ; 20(869): 734-738, 2024 Apr 10.
Artigo em Francês | MEDLINE | ID: mdl-38616683

RESUMO

While most episodes of community-acquired pneumonia are caused by Streptococcus pneumoniae and respiratory viruses, other atypical pathogens can also be responsible for lung infections. The Infectious Diseases Service of the Lausanne University Hospital (CHUV) organizes an annual meeting aimed at general practitioners, during which interesting clinical cases are presented. In this article, we summarize five cases of community-aquired respiratory infection due to atypical pathogens that were presented during the 2023 meeting, each with a particular teaching point. Although these infections are rare, expanding the differential diagnosis in cases of suboptimal response to therapy or particular exposures is warranted.


La plupart des épisodes de pneumonie acquise en communauté sont causés par Streptococcus pneumoniae et des virus respiratoires, mais d'autres agents pathogènes atypiques peuvent également être responsables d'infections pulmonaires. Le Service des maladies infectieuses du Centre hospitalier universitaire vaudois (CHUV) organise une réunion annuelle destinée aux médecins généralistes, au cours de laquelle des cas cliniques intéressants sont présentés. Dans cet article, nous résumons cinq cas d'infections respiratoires communautaires dus à des agents pathogènes atypiques présentés lors de la réunion de 2023, chacun avec un enseignement particulier. Bien que ces infections soient rares, élargir le diagnostic différentiel en cas de réponse thérapeutique suboptimale ou d'expositions particulières est justifié.


Assuntos
Infecções Respiratórias , Humanos , Diagnóstico Diferencial , Clínicos Gerais , Hospitais Universitários , Infecções Respiratórias/diagnóstico
4.
J Clin Monit Comput ; 37(4): 1003-1010, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37010708

RESUMO

PURPOSE: Respiratory rate (RR) is one of the most common vital signs with numerous clinical uses. It is an important indicator of acute illness and a significant change in RR is often an early indication of a potentially serious complication or clinical event such as respiratory tract infection, respiratory failure and cardiac arrest. Early identification of changes in RR allows for prompt intervention, whereas failing to detect a change may result in poor patient outcomes. Here, we report on the performance of a depth-sensing camera system for the continuous non-contact 'touchless' monitoring of Respiratory Rate. METHODS: Seven healthy subjects undertook a range of breathing rates from 4 to 40 breaths-per-minute (breaths/min). These were set rates of 4, 5, 6, 8, 10, 15, 20, 25, 30, 35 and 40 breaths/min. In total, 553 separate respiratory rate recordings were captured across a range of conditions including body posture, position within the bed, lighting levels and bed coverings. Depth information was acquired from the scene using an Intel D415 RealSenseTM camera. This data was processed in real-time to extract depth changes within the subject's torso region corresponding to respiratory activity. A respiratory rate RRdepth was calculated using our latest algorithm and output once-per-second from the device and compared to a reference. RESULTS: An overall RMSD accuracy of 0.69 breaths/min with a corresponding bias of -0.034 was achieved across the target RR range of 4-40 breaths/min. Bland-Altman analysis revealed limits of agreement of -1.42 to 1.36 breaths/min. Three separate sub-ranges of low, normal and high rates, corresponding to < 12, 12-20, > 20 breaths/min, were also examined separately and each found to demonstrate RMSD accuracies of less than one breath-per-minute. CONCLUSIONS: We have demonstrated high accuracy in performance for respiratory rate based on a depth camera system. We have shown the ability to perform well at both high and low rates which are clinically important.


Assuntos
Taxa Respiratória , Sinais Vitais , Humanos , Postura , Algoritmos , Monitorização Fisiológica
5.
Arch Microbiol ; 204(5): 277, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35460374

RESUMO

An actinobacterium, designated strain EGI L100131T, was isolated from saline lake sediment in Xinjiang Province, China. The taxonomic position of the isolate was determined using analysis based on the polyphasic taxonomy and phylogenomics. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that strain EGI L100131T formed a distinct clade with Ornithinimicrobium murale DSM 22056T and Ornithinimicrobium cavernae CFH 30183T, and shared sequence identities of 97.8% and 97.0%, respectively. The novel isolate could be distinguished from other species of the genus Ornithinimicrobium by its distinct phenotypic, physiological, and genotypic characteristics. Cells of strain EGI L100131T were aerobic, Gram-staining positive, and coccoid to rod-shaped. Optimal growing conditions of strain EGI L100131T occurred at pH 8.0 and 28 ºC. Ornithine was the diagnostic diamino acid in the cell-wall peptidoglycan. The respiratory quinone was MK-8 (H4), while the major fatty acids (> 10%) were C17:1 ω8c, C17:0, iso-C16:0, and iso-C15:0. The detected polar lipids included diphosphatidylglycerol, phosphatidylinositol, phosphatidylglycerol, and a glycophospholipid. The G + C content based on genomic DNA was 71.5%. According to the phenotypic, physiological, genotypic, and phylogenetic data, strain EGI L100131T represents a new species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium sediminis sp. nov. is proposed. The type strain is EGI L100131T (= KCTC 49716 T = CGMCC 1.19241T).


Assuntos
Actinomycetales , Lagos , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
6.
Artigo em Inglês | MEDLINE | ID: mdl-35544312

RESUMO

An actinobacterium, designated strain EGI L10124T, was isolated from saline lake sediment collected in Xinjiang province, PR China. The taxonomic position of the isolate was determined based on polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that strain EGI L10124T formed a distinct clade with Rhabdothermincola sediminis SYSU G02662T, with a shared sequence identity of 95.2 %. The novel isolate could be distinguished from species in the genus Rhabdothermincola by its distinct phenotypic, physiological and genotypic characteristics. The cells of strain EGI L10124T were aerobic, Gram-stain-positive and short rod-shaped. Optimal growth conditions of strain EGI L10124T on marine agar 2216 were registered at pH 8.0 at 37 °C. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major respiratory quinone was MK-9 (H8), while the major fatty acids were iso-C16 : 0, C17 : 0 and C16 : 0. The polar lipids included diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. Based on the genome sequence of strain EGI L10124T, it appears that the G+C content of the novel isolate was 71.8 mol%. According to our data, strain EGI L10124T represents a new species of the genus Rhabdothermincola, for which the name Rhabdothermincola salaria sp. nov. is proposed. The type strain of the proposed novel isolate is EGI L10124T (=CGMCC 1.19113T=KCTC 49679T).


Assuntos
Actinobacteria , Perciformes , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Lagos , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
7.
Adv Exp Med Biol ; 1382: 85-94, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36029405

RESUMO

Parkinson's disease (PD) is a complex neurodegenerative disorder characterised by progressive degeneration of the dopaminergic neurons in the substantia nigra leading to severe motor complications. The etiology of the disease is unknown with its sporadic form accounting for 90% of cases. To date, over 20 genes have been identified as the cause of the inherited form of PD, many of them linked to the protein alpha-synuclein and mitochondrial function. Post-translational modifications of proteins allow cells to dynamically control signalling networks and diversify protein functions. This chapter will discuss briefly the main types of post-translational modifications, how to study them and how they affect proteins involved in PD.


Assuntos
Doença de Parkinson , Neurônios Dopaminérgicos , Humanos , Mitocôndrias , Processamento de Proteína Pós-Traducional , Substância Negra , alfa-Sinucleína
8.
Adv Exp Med Biol ; 1400: 65-73, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35930226

RESUMO

Treating schizophrenia is a challenge currently handled with the use of antipsychotic drugs. Despite being the most applied treatment strategy, current antipsychotics present severe limitations and side effects which impact patients' health and quality of life. For instance, although these drugs target mainly the dopamine system, they present target promiscuity and work by distinct mechanisms of action. As a consequence, complete comprehension of their pharmacological properties remains elusive. This chapter highlights research from the past 5 years that contributed to our current understanding of the mechanism of action and molecular features triggered by antipsychotic drugs in brain cells. In addition, we briefly discuss potential new therapeutic targets and strategies to treat schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Encéfalo , Dopamina/química , Humanos , Qualidade de Vida , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico
9.
Adv Exp Med Biol ; 1286: 251-264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33725358

RESUMO

Psychiatric and neurodegenerative disorders such as schizophrenia (SCZ), Parkinson's disease (PD), and Alzheimer's disease (AD) continue to grow around the world with a high impact on health, social, and economic outcomes for the patient and society. Despite efforts, the etiology and pathophysiology of these disorders remain unclear. Omics technologies have contributed to the understanding of the molecular mechanisms that underlie these complex disorders and have suggested novel potential targets for treatment and diagnostics. Here, we have highlighted the unique and common pathways shared between SCZ, PD, and AD and highlight the main proteomic findings over the last 5 years using in vitro models, postmortem brain samples, and cerebrospinal fluid (CSF) or blood of patients. These studies have identified possible therapeutic targets and disease biomarkers. Further studies including target validation, the use of large sample sizes, and the integration of omics findings with bioinformatics tools are required to provide a better comprehension of pharmacological targets.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Biomarcadores , Humanos , Doenças Neurodegenerativas/genética , Proteômica
10.
Curr Issues Mol Biol ; 38: 123-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31967579

RESUMO

Several icy moons of the outer solar system have been receiving considerable attention and are currently seen as major targets for astrobiological research and the search for life beyond our planet. Despite the limited amount of data on the oceans of these moon, we expect them to be composed of brines with variable chemistry, some degree of hydrothermal input, and be under high pressure conditions. The combination of these different conditions significantly limits the number of extreme locations, which can be used as terrestrial analogues. Here we propose the use of deep-sea brines as potential terrestrial analogues to the oceans in the outer solar system. We provide an overview of what is currently known about the conditions on the icy moons of the outer solar system and their oceans as well as on deep-sea brines of the Red Sea and the Mediterranean and their microbiology. We also identify several threads of future research, which would be particularly useful in the context of future exploration of these extra-terrestrial oceans.


Assuntos
Archaea/isolamento & purificação , Bactérias/isolamento & purificação , Meio Ambiente Extraterreno/química , Sais/química , Concentração de Íons de Hidrogênio , Gelo , Oceano Índico , Júpiter , Mar Mediterrâneo , Metagenômica , Oceanos e Mares , RNA Ribossômico 16S/genética , Salinidade , Temperatura
11.
Curr Issues Mol Biol ; 38: 197-244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31967581

RESUMO

The Earth's atmosphere is an extremely large and sparse environment which is quite challenging for the survival of microorganisms. We have long wondered about the limits to life in the atmosphere, starting with Leeuwenhoek's observation of "animalcules" collected from the air. In the past century, significant progress has been made to capture and identify biological material from varying elevations, from a few meters above ground level, to the clouds near mountaintops, and the jet streams, the ozone layer, and even higher up in the stratosphere. Collection and detection techniques have been developed and advanced in order to assess the potential diversity of life from very high altitudes. Studies of microbial life in the stratosphere with its multiple stressors (cold, dry, irradiated, with low pressure and limited nutrients), have recently garnered considerable attention. Here, we review studies of Earth's atmosphere, with emphasis on the stratosphere, addressing implications for astrobiology, the dispersal of microbes around our planet, planetary protection, and climate change.


Assuntos
Atmosfera , Bactérias/isolamento & purificação , Planeta Terra , Ambientes Extremos , Pressão Atmosférica , Bactérias/crescimento & desenvolvimento , Bactérias/efeitos da radiação , Resposta ao Choque Frio , Radiação Cósmica , Dessecação , Poeira , Exobiologia , Nutrientes , Raios Ultravioleta
12.
Mol Biol Rep ; 47(5): 3919-3928, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32399808

RESUMO

A functional screening of 1152 clones from a plasmid library constructed with DNA extracted from Brazilian mangrove sediments revealed 3 positive clones for ester-hydrolyzing enzymes, or about one lipolytic gene per 1.2 Mb DNA, which corroborates the idea that oil-contaminated mangroves are a good source of novel microbial lipases/esterases. The partial sequence of the clone LipG7 (1179 bp) showed 30.2% of predicted structure identity with a known esterase, confirming LipG7 as a new member of family VIII esterases. LigG7 shared 80% sequence identity with 1,4-butanediol diacrylate esterase from the Gammaprotebacteria Porticoccus hydrocarbonoclasticus, suggesting it belongs to the Porticoccaceae family. LipG7 was heterologously expressed in Escherichia coli Rosetta-Gami DE3; the purified recombinant enzyme exhibited a predicted molecular weight of 45.2 kDa and exceptional activity towards 4-nitrophenyl butyrate, compared with other recombinant esterases, highlighting its enormous potential for biological applications.


Assuntos
Carboxilesterase/genética , Carboxilesterase/isolamento & purificação , Gammaproteobacteria/genética , Sequência de Aminoácidos/genética , Bactérias/genética , Bactérias/metabolismo , Sequência de Bases/genética , Brasil , Butiratos/metabolismo , Carboxilesterase/metabolismo , Esterases/metabolismo , Gammaproteobacteria/metabolismo , Expressão Gênica/genética , Biblioteca Gênica , Metagenoma/genética , Filogenia , Plasmídeos/genética , Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Especificidade por Substrato/genética , Áreas Alagadas
13.
Brain ; 142(8): 2402-2416, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243443

RESUMO

Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.


Assuntos
Antiparkinsonianos/administração & dosagem , GTP Cicloidrolase/administração & dosagem , Vetores Genéticos/uso terapêutico , Levodopa/biossíntese , Transtornos Parkinsonianos/terapia , Putamen/metabolismo , Tirosina 3-Mono-Oxigenase/administração & dosagem , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/análogos & derivados , Animais , Antiparkinsonianos/uso terapêutico , Dependovirus/genética , Avaliação Pré-Clínica de Medicamentos , Feminino , GTP Cicloidrolase/análise , GTP Cicloidrolase/genética , GTP Cicloidrolase/metabolismo , Genes Reporter , Genes Sintéticos , Vetores Genéticos/administração & dosagem , Humanos , Macaca mulatta , Masculino , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Parte Compacta da Substância Negra/química , Parte Compacta da Substância Negra/patologia , Estudo de Prova de Conceito , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/análise , Proteínas Recombinantes/uso terapêutico , Tirosina 3-Mono-Oxigenase/análise , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
14.
Anesth Analg ; 131(5): 1520-1528, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079875

RESUMO

BACKGROUND: Cerebral blood flow (CBF) is maintained over a range of blood pressures through cerebral autoregulation (CA). Blood pressure outside the range of CA, or impaired autoregulation, is associated with adverse patient outcomes. Regional oxygen saturation (rSO2) derived from near-infrared spectroscopy (NIRS) can be used as a surrogate CBF for determining CA, but existing methods require a long period of time to calculate CA metrics. We have developed a novel method to determine CA using cotrending of mean arterial pressure (MAP) with rSO2that aims to provide an indication of CA state within 1 minute. We sought to determine the performance of the cotrending method by comparing its CA metrics to data derived from transcranial Doppler (TCD) methods. METHODS: Retrospective data collected from 69 patients undergoing cardiac surgery with cardiopulmonary bypass were used to develop a reference lower limit of CA. TCD-MAP data were plotted to determine the reference lower limit of CA. The investigated method to evaluate CA state is based on the assessment of the instantaneous cotrending relationship between MAP and rSO2 signals. The lower limit of autoregulation (LLA) from the cotrending method was compared to the manual reference derived from TCD. Reliability of the cotrending method was assessed as uptime (defined as the percentage of time that the state of autoregulation could be measured) and time to first post. RESULTS: The proposed method demonstrated minimal mean bias (0.22 mmHg) when compared to the TCD reference. The corresponding limits of agreement were found to be 10.79 mmHg (95% confidence interval [CI], 10.09-11.49) and -10.35 mmHg (95% CI, -9.65 to -11.05). Mean uptime was 99.40% (95% CI, 99.34-99.46) and the mean time to first post was 63 seconds (95% CI, 58-71). CONCLUSIONS: The reported cotrending method rapidly provides metrics associated with CA state for patients undergoing cardiac surgery. A major strength of the proposed method is its near real-time feedback on patient CA state, thus allowing for prompt corrective action to be taken by the clinician.


Assuntos
Circulação Cerebrovascular , Homeostase , Monitorização Neurofisiológica Intraoperatória/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Pressão Arterial , Pressão Sanguínea , Ponte Cardiopulmonar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Retrospectivos , Ultrassonografia Doppler Transcraniana
15.
Artigo em Inglês | MEDLINE | ID: mdl-33739249

RESUMO

A novel slightly halophilic Gram-stain-negative bacterial strain (MKS20T) was isolated from a brine sample collected from one of the Anderton brine springs in the Cheshire salt district, located in Northern England. Phylogenetic analysis of the 16S rRNA gene sequence revealed a close proximity to Motilimonas eburnea (98.30 %), followed by Motilimonas pumila (96.62 %), the two currently described species within the genus Motilimonas. Strain MKS20T forms white-beige-pigmented colonies and grows optimally at 28-30 °C, in 1-3 % (w/v) NaCl and at pH 7-7.5. The strain was facultatively anaerobic and showed a broader range of carbohydrate use than other species in the genus Motilimonas. Q-8 was the sole respiratory quinone and the major fatty acids (>10 %) were summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) and C16 : 0. The polar lipid profile included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidyglycerol and several unidentified lipids. The G+C content of the genomic DNA was 44.2 mol%. Average nucleotide identity and DNA-DNA hybridization data were consistent with assignment to a separate species. Based on the phylogenetic and genomic-based analyses, as well as physiological and biochemical characteristics, we propose that strain MKS20T (=DSM 109936T, MCCC 1K04071T) represents a new species of the genus Motilimonas, with the name Motilimonas cestriensis sp. nov.

16.
Brain ; 141(7): 2014-2031, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788236

RESUMO

Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.


Assuntos
Capsídeo/fisiologia , Terapia Genética/métodos , Engenharia de Proteínas/métodos , Animais , Dependovirus/genética , Feminino , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucopolissacaridose III/genética , Mucopolissacaridose III/terapia , Células Fotorreceptoras/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retina/fisiologia , Distribuição Tecidual , Transdução Genética
17.
BMC Genomics ; 19(1): 382, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29788916

RESUMO

BACKGROUND: The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions. RESULTS: We report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans-acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species. CONCLUSIONS: B. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems.


Assuntos
Bacillus/genética , Bacillus/metabolismo , Produtos Biológicos/metabolismo , Simulação por Computador , Genômica , Família Multigênica/genética , Bacillus/enzimologia , Bacteriocinas/metabolismo , Genoma Bacteriano/genética , Peptídeo Sintases/genética , Policetídeo Sintases/genética , Ribossomos/metabolismo
18.
Cereb Cortex ; 27(11): 5083-5094, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27664963

RESUMO

Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our study is one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for 2 hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.


Assuntos
Modelos Teóricos , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana , Adulto , Campos Eletromagnéticos , Eletromiografia , Potencial Evocado Motor , Feminino , Análise de Elementos Finitos , Mãos/fisiologia , Cabeça/diagnóstico por imagem , Cabeça/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/diagnóstico por imagem , Músculo Esquelético/fisiologia , Estimulação Magnética Transcraniana/instrumentação , Estimulação Magnética Transcraniana/métodos , Adulto Jovem
19.
Nucleic Acids Res ; 44(D1): D624-33, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26546514

RESUMO

Microorganisms produce an enormous variety of chemical compounds. It is of general interest for microbiology and biotechnology researchers to have means to explore information about molecular and genetic basis of functioning of different microorganisms and their ability for bioproduction. To enable such exploration, we compiled 45 topic-specific knowledgebases (KBs) accessible through DESM portal (www.cbrc.kaust.edu.sa/desm). The KBs contain information derived through text-mining of PubMed information and complemented by information data-mined from various other resources (e.g. ChEBI, Entrez Gene, GO, KOBAS, KEGG, UniPathways, BioGrid). All PubMed records were indexed using 4,538,278 concepts from 29 dictionaries, with 1 638 986 records utilized in KBs. Concepts used are normalized whenever possible. Most of the KBs focus on a particular type of microbial activity, such as production of biocatalysts or nutraceuticals. Others are focused on specific categories of microorganisms, e.g. streptomyces or cyanobacteria. KBs are all structured in a uniform manner and have a standardized user interface. Information exploration is enabled through various searches. Users can explore statistically most significant concepts or pairs of concepts, generate hypotheses, create interactive networks of associated concepts and export results. We believe DESM will be a useful complement to the existing resources to benefit microbiology and biotechnology research.


Assuntos
Bases de Dados Factuais , Microbiologia Industrial , Antituberculosos/farmacologia , Archaea/genética , Archaea/metabolismo , Bactérias/genética , Bactérias/metabolismo , Mineração de Dados , Dicionários como Assunto , Reposicionamento de Medicamentos , Fungos/genética , Fungos/metabolismo , Humanos , Internet , Bases de Conhecimento , Vírus/genética , Vírus/metabolismo , Vocabulário Controlado
20.
Rev Med Suisse ; 14(622): 1806-1809, 2018 Oct 10.
Artigo em Francês | MEDLINE | ID: mdl-30307141

RESUMO

Extraspinal tuberculous arthritis is a rare entity in developed countries, mostly found in populations of migrants. We describe a case of foot osteoarthritis in a young migrant, with an arduous diagnostic process. The sequence of the diagnostic studies (imaging, articular tap, bone biopsy together with cultures and molecular biology) must follow a logic based on clinical suspicion and on the knowledge of the diagnostic values of different tests. The diagnosis of tuberculous arthritis, a slowly progressing infection with a low bacteriologic burden, is difficult. The reported case emphases the need for perseverance. It shows the value of diagnostic procedures, their limits and the need for their integration to the clinical judgement.


L'arthrite tuberculeuse non rachidienne est rare dans les pays occidentaux où elle touche avant tout les populations de migrants. Nous décrivons un cas d'ostéoarthrite du pied, dont le processus diagnostique s'est révélé ardu. La succession des examens pratiqués (radiologie, ponction puis biopsie avec les cultures et la biologie moléculaire) doit s'inscrire dans une logique dictée par la suspicion clinique et la connaissance des performances diagnostiques des différents tests. Le diagnostic d'arthrite tuberculeuse, une infection d'évolution lente, pauvre en charge bactérienne, est difficile. Le cas présenté révèle le besoin de persévérer et permet de discuter la valeur des procédures diagnostiques, leurs limites et leur intégration dans le raisonnement clinique.


Assuntos
Artrite , Tuberculose Osteoarticular , Artrite/diagnóstico , Artrite/microbiologia , Humanos , Tuberculose Osteoarticular/diagnóstico
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