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1.
Nat Commun ; 11(1): 5065, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033237

RESUMO

The type VI protein secretion system (T6SS) is a powerful needle-like machinery found in Gram-negative bacteria that can penetrate the cytosol of receiving cells in milliseconds by physical force. Anchored by its membrane-spanning complex (MC) and a baseplate (BP), the T6SS sheath-tube is assembled in a stepwise process primed by TssA and terminated by TagA. However, the molecular details of its assembly remain elusive. Here, we systematically examined the initiation and termination of contractile and non-contractile T6SS sheaths in MC-BP, tssA and tagA mutants by fluorescence microscopy. We observe long pole-to-pole sheath-tube structures in the non-contractile MC-BP defective mutants but not in the Hcp tube or VgrG spike mutants. Combining overexpression and genetic mutation data, we demonstrate complex effects of TssM, TssA and TagA interactions on T6SS sheath-tube dynamics. We also report promiscuous interactions of TagA with multiple T6SS components, similar to TssA. Our results demonstrate that priming of the T6SS sheath-tube assembly is not dependent on TssA, nor is the assembly termination dependent on the distal end TssA-TagA interaction, and highlight the tripartite control of TssA-TssM-TagA on sheath-tube initiation and termination.


Assuntos
Proteínas de Bactérias/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Vibrio cholerae/metabolismo , Proteínas de Bactérias/química , Membrana Celular/metabolismo , Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Membrana/metabolismo , Viabilidade Microbiana , Modelos Biológicos , Mutação/genética , Ligação Proteica , Domínios Proteicos
2.
Nat Commun ; 11(1): 5073, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033238

RESUMO

Brain cells continuously produce and release protons into the extracellular space, with the rate of acid production corresponding to the levels of neuronal activity and metabolism. Efficient buffering and removal of excess H+ is essential for brain function, not least because all the electrogenic and biochemical machinery of synaptic transmission is highly sensitive to changes in pH. Here, we describe an astroglial mechanism that contributes to the protection of the brain milieu from acidification. In vivo and in vitro experiments conducted in rodent models show that at least one third of all astrocytes release bicarbonate to buffer extracellular H+ loads associated with increases in neuronal activity. The underlying signalling mechanism involves activity-dependent release of ATP triggering bicarbonate secretion by astrocytes via activation of metabotropic P2Y1 receptors, recruitment of phospholipase C, release of Ca2+ from the internal stores, and facilitated outward HCO3- transport by the electrogenic sodium bicarbonate cotransporter 1, NBCe1. These results show that astrocytes maintain local brain extracellular pH homeostasis via a neuronal activity-dependent release of bicarbonate. The data provide evidence of another important metabolic housekeeping function of these glial cells.


Assuntos
Astrócitos/metabolismo , Bicarbonatos/metabolismo , Encéfalo/metabolismo , Espaço Extracelular/metabolismo , Acetazolamida/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Anidrases Carbônicas/metabolismo , Células Cultivadas , Estimulação Elétrica , Fluorescência , Hipocampo/metabolismo , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos C57BL , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Antagonistas Purinérgicos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores Purinérgicos/metabolismo , Transdução de Sinais , Simportadores de Sódio-Bicarbonato/metabolismo
3.
Nat Commun ; 11(1): 5061, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033262

RESUMO

The interplay between the Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and transcriptional/epigenetic co-regulators in somatic cell reprogramming is incompletely understood. Here, we demonstrate that the histone H3 lysine 27 trimethylation (H3K27me3) demethylase JMJD3 plays conflicting roles in mouse reprogramming. On one side, JMJD3 induces the pro-senescence factor Ink4a and degrades the pluripotency regulator PHF20 in a reprogramming factor-independent manner. On the other side, JMJD3 is specifically recruited by KLF4 to reduce H3K27me3 at both enhancers and promoters of epithelial and pluripotency genes. JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL and ultimately transcriptional elongation. This competition of forces can be shifted towards improved reprogramming by using early passage fibroblasts or boosting JMJD3's catalytic activity with vitamin C. Our work, thus, establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription.


Assuntos
Reprogramação Celular , Histona Desmetilases com o Domínio Jumonji/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Animais , Catálise , Proliferação de Células , Senescência Celular , Desmetilação , Elementos Facilitadores Genéticos/genética , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genoma , Histonas/metabolismo , Lisina/metabolismo , Camundongos , Modelos Biológicos , Regiões Promotoras Genéticas , Ativação Transcricional/genética
4.
Nat Commun ; 11(1): 4945, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009378

RESUMO

Spring warming substantially advances leaf unfolding and flowering time for perennials. Winter warming, however, decreases chilling accumulation (CA), which increases the heat requirement (HR) and acts to delay spring phenology. Whether or not this negative CA-HR relationship is correctly interpreted in ecosystem models remains unknown. Using leaf unfolding and flowering data for 30 perennials in Europe, here we show that more than half (7 of 12) of current chilling models are invalid since they show a positive CA-HR relationship. The possible reason is that they overlook the effect of freezing temperature on dormancy release. Overestimation of the advance in spring phenology by the end of this century by these invalid chilling models could be as large as 7.6 and 20.0 days under RCPs 4.5 and 8.5, respectively. Our results highlight the need for a better representation of chilling for the correct understanding of spring phenological responses to future climate change.


Assuntos
Mudança Climática , Temperatura Baixa , Folhas de Planta/fisiologia , Estações do Ano , Betula/fisiologia , Temperatura Alta , Modelos Lineares , Modelos Biológicos
5.
Nat Commun ; 11(1): 4956, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009383

RESUMO

Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs reveals hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), show decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we find Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further reveals mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation is found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment.


Assuntos
5-Metilcitosina/análogos & derivados , Diferenciação Celular , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA/metabolismo , 5-Metilcitosina/metabolismo , Animais , Especificidade de Anticorpos/imunologia , Sequência de Bases , Corpos Embrioides/metabolismo , Camundongos , Modelos Biológicos , Células-Tronco Pluripotentes/metabolismo , Ligação Proteica , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma/genética
6.
Nat Commun ; 11(1): 4939, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009390

RESUMO

Acoustic communication is enabled by the evolution of specialised hearing and sound producing organs. In this study, we performed a large-scale macroevolutionary study to understand how both hearing and sound production evolved and affected diversification in the insect order Orthoptera, which includes many familiar singing insects, such as crickets, katydids, and grasshoppers. Using phylogenomic data, we firmly establish phylogenetic relationships among the major lineages and divergence time estimates within Orthoptera, as well as the lineage-specific and dynamic patterns of evolution for hearing and sound producing organs. In the suborder Ensifera, we infer that forewing-based stridulation and tibial tympanal ears co-evolved, but in the suborder Caelifera, abdominal tympanal ears first evolved in a non-sexual context, and later co-opted for sexual signalling when sound producing organs evolved. However, we find little evidence that the evolution of hearing and sound producing organs increased diversification rates in those lineages with known acoustic communication.


Assuntos
Acústica , Evolução Biológica , Gafanhotos/classificação , Gafanhotos/genética , Filogenia , Vocalização Animal , Animais , Teorema de Bayes , Genoma Mitocondrial , Gafanhotos/anatomia & histologia , Audição/fisiologia , Modelos Biológicos , Som , Fatores de Tempo , Transcriptoma/genética
7.
Nat Commun ; 11(1): 4958, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009395

RESUMO

Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release is under tonic inhibition by striatal GABA. Ambient striatal GABA tone on striatal projection neurons can be determined by plasma membrane GABA uptake transporters (GATs) located on astrocytes and neurons. However, whether striatal GATs and astrocytes determine DA output are unknown. We reveal that DA release in mouse dorsolateral striatum, but not nucleus accumbens core, is governed by GAT-1 and GAT-3. These GATs are partly localized to astrocytes, and are enriched in dorsolateral striatum compared to accumbens core. In a mouse model of early parkinsonism, GATs are downregulated, tonic GABAergic inhibition of DA release augmented, and nigrostriatal GABA co-release attenuated. These data define previously unappreciated and important roles for GATs and astrocytes in supporting DA release in striatum, and reveal a maladaptive plasticity in early parkinsonism that impairs DA output in vulnerable striatal regions.


Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Regulação para Baixo , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Transtornos Parkinsonianos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Astrócitos/metabolismo , Membrana Celular/metabolismo , Modelos Animais de Doenças , Glutamato Descarboxilase/metabolismo , Camundongos Endogâmicos C57BL , Modelos Biológicos , Núcleo Accumbens/metabolismo
8.
Crit Care ; 24(1): 594, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023604

RESUMO

BACKGROUND: Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19. METHODS: We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19. RESULT: Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy. CONCLUSIONS: Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.


Assuntos
Infecções por Coronavirus , Modelos Animais de Doenças , Modelos Biológicos , Pandemias , Pneumonia Viral , Animais , Humanos
9.
Phys Rev Lett ; 125(12): 128103, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33016731

RESUMO

While many cellular mechanisms leading to chemotherapeutic resistance have been identified, there is an increasing realization that tumor-stroma interactions also play an important role. In particular, mechanical alterations are inherent to solid cancer progression and profoundly impact cell physiology. Here, we explore the influence of compressive stress on the efficacy of chemotherapeutics in pancreatic cancer spheroids. We find that increased compressive stress leads to decreased drug efficacy. Theoretical modeling and experiments suggest that mechanical stress decreases cell proliferation which in turn reduces the efficacy of chemotherapeutics that target proliferating cells. Our work highlights a mechanical form of drug resistance and suggests new strategies for therapy.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Modelos Biológicos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Estresse Mecânico
10.
Crit Care ; 24(1): 594, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: covidwho-818126

RESUMO

BACKGROUND: Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19. METHODS: We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19. RESULT: Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy. CONCLUSIONS: Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.


Assuntos
Infecções por Coronavirus , Modelos Animais de Doenças , Modelos Biológicos , Pandemias , Pneumonia Viral , Animais , Humanos
11.
Mediators Inflamm ; 2020: 3764515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061826

RESUMO

This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Cistatina C/sangue , Pandemias , Pneumonia Viral/sangue , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Estado Terminal , Feminino , Humanos , Mediadores da Inflamação/sangue , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Dinâmica não Linear , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
12.
Cells ; 9(9)2020 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-32932592

RESUMO

Feline coronaviruses (FCoVs) infect both wild and domestic cat populations world-wide. FCoVs present as two main biotypes: the mild feline enteric coronavirus (FECV) and the fatal feline infectious peritonitis virus (FIPV). FIPV develops through mutations from FECV during a persistence infection. So far, the molecular mechanism of FECV-persistence and contributing factors for FIPV development may not be studied, since field FECV isolates do not grow in available cell culture models. In this work, we aimed at establishing feline ileum and colon organoids that allow the propagation of field FECVs. We have determined the best methods to isolate, culture and passage feline ileum and colon organoids. Importantly, we have demonstrated using GFP-expressing recombinant field FECV that colon organoids are able to support infection of FECV, which were unable to infect traditional feline cell culture models. These organoids in combination with recombinant FECVs can now open the door to unravel the molecular mechanisms by which FECV can persist in the gut for a longer period of time and how transition to FIPV is achieved.


Assuntos
Coronavirus Felino/crescimento & desenvolvimento , Peritonite Infecciosa Felina/patologia , Técnicas de Cultura de Órgãos/veterinária , Organoides/crescimento & desenvolvimento , Animais , Gatos , Linhagem Celular , Colo/citologia , Colo/virologia , Coronavirus Felino/genética , Feminino , Células HEK293 , Humanos , Íleo/citologia , Íleo/virologia , Modelos Biológicos , Técnicas de Cultura de Órgãos/métodos , Organoides/citologia
13.
Phys Rev E ; 102(2-1): 022310, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32942454

RESUMO

The frequent emergence of diseases with the potential to become threats at local and global scales, such as influenza A(H1N1), SARS, MERS, and recently COVID-19 disease, makes it crucial to keep designing models of disease propagation and strategies to prevent or mitigate their effects in populations. Since isolated systems are exceptionally rare to find in any context, especially in human contact networks, here we examine the susceptible-infected-recovered model of disease spreading in a multiplex network formed by two distinct networks or layers, interconnected through a fraction q of shared individuals (overlap). We model the interactions through weighted networks, because person-to-person interactions are diverse (or disordered); weights represent the contact times of the interactions. Using branching theory supported by simulations, we analyze a social distancing strategy that reduces the average contact time in both layers, where the intensity of the distancing is related to the topology of the layers. We find that the critical values of the distancing intensities, above which an epidemic can be prevented, increase with the overlap q. Also we study the effect of the social distancing on the mutual giant component of susceptible individuals, which is crucial to keep the functionality of the system. In addition, we find that for relatively small values of the overlap q, social distancing policies might not be needed at all to maintain the functionality of the system.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Modelos Biológicos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças , Humanos , Modelos Estatísticos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Distância Social , Rede Social , Análise de Sistemas , Teoria de Sistemas
14.
Chaos ; 30(8): 081104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32872802

RESUMO

The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Modelos Biológicos , Pneumonia Viral/fisiopatologia , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma , Biomarcadores/metabolismo , Infecções por Coronavirus/metabolismo , Difusão , Humanos , Pandemias , Pneumonia Viral/metabolismo , Fatores de Tempo
15.
J Biol Dyn ; 14(1): 730-747, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32875961

RESUMO

In this study, we estimate the severity of the COVID-19 outbreak in Pakistan prior to and after lockdown restrictions were eased. We also project the epidemic curve considering realistic quarantine, social distancing and possible medication scenarios. The pre-lock down value of R 0 is estimated to be 1.07 and the post lock down value is estimated to be 1.86. Using this analysis, we project the epidemic curve. We note that if no substantial efforts are made to contain the epidemic, it will peak in mid-September, 2020, with the maximum projected active cases being close to 700, 000. In a realistic, best case scenario, we project that the epidemic peaks in early to mid-July, 2020, with the maximum active cases being around 120, 000. We note that social distancing measures and medication will help flatten the curve; however, without the reintroduction of further lock down, it would be very difficult to make R 0 < 1 .


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Pneumonia Viral/epidemiologia , Número Básico de Reprodução/estatística & dados numéricos , Bioestatística , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Epidemias , Previsões/métodos , Humanos , Conceitos Matemáticos , Modelos Biológicos , Paquistão/epidemiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Quarentena/estatística & dados numéricos
16.
J Zhejiang Univ Sci B ; 21(9): 749-751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32893532

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found initially in Wuhan, China in early December 2019. The pandemic has spread to 216 countries and regions, infecting more than 23310 000 people and causing over 800 000 deaths globally by Aug. 24, 2020, according to World Health Organization (https://www.who.int/emergencies/diseases/ novel-coronavirus-2019). Fever, cough, and dyspnea are the three common symptoms of the condition, whereas the conventional transmission route for SARS-CoV-2 is through droplets entering the respiratory tract. To date, infection control measures for COVID-19 have been focusing on the involvement of the respiratory system. However, ignoring potential faecal transmission and the gastrointestinal involvement of SARS-CoV-2 may result in mistakes in attempts to control the pandemic.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Fezes/virologia , Gastroenteropatias/virologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Betacoronavirus/genética , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Microbiologia Ambiental , Humanos , Modelos Biológicos , Pandemias , Pneumonia Viral/epidemiologia , RNA Viral/análise , RNA Viral/genética , Eliminação de Partículas Virais
17.
Eur J Epidemiol ; 35(8): 749-761, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32888169

RESUMO

The global pandemic of the 2019-nCov requires the evaluation of policy interventions to mitigate future social and economic costs of quarantine measures worldwide. We propose an epidemiological model for forecasting and policy evaluation which incorporates new data in real-time through variational data assimilation. We analyze and discuss infection rates in the UK, US and Italy. We furthermore develop a custom compartmental SIR model fit to variables related to the available data of the pandemic, named SITR model, which allows for more granular inference on infection numbers. We compare and discuss model results which conducts updates as new observations become available. A hybrid data assimilation approach is applied to make results robust to initial conditions and measurement errors in the data. We use the model to conduct inference on infection numbers as well as parameters such as the disease transmissibility rate or the rate of recovery. The parameterisation of the model is parsimonious and extendable, allowing for the incorporation of additional data and parameters of interest. This allows for scalability and the extension of the model to other locations or the adaption of novel data sources.


Assuntos
Infecções por Coronavirus/epidemiologia , Previsões , Pandemias , Pneumonia Viral/epidemiologia , Informática em Saúde Pública/métodos , Teorema de Bayes , Betacoronavirus , Simulação por Computador , Surtos de Doenças , Humanos , Itália/epidemiologia , Modelos Biológicos , Modelos Estatísticos , Quarentena , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
18.
BMC Res Notes ; 13(1): 421, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894167

RESUMO

OBJECTIVE: The advent of new technologies has made it possible to explore alternative ventilator manufacturing to meet the worldwide shortfall for mechanical ventilators especially in pandemics. We describe a method using rapid prototyping technologies to create an electro-mechanical ventilator in a cost effective, timely manner and provide results of testing using an in vitro-in vivo testing model. RESULTS: Rapid prototyping technologies (3D printing and 2D cutting) were used to create a modular ventilator. The artificial manual breathing unit (AMBU) bag connected to wall oxygen source using a flow meter was used as air reservoir. Controlled variables include respiratory rate, tidal volume and inspiratory: expiratory (I:E) ratio. In vitro testing and In vivo testing in the pig model demonstrated comparable mechanical efficiency of the test ventilator to that of standard ventilator but showed the material limits of 3D printed gears. Improved gear design resulted in better ventilator durability whilst reducing manufacturing time (< 2-h). The entire cost of manufacture of ventilator was estimated at 300 Australian dollars. A cost-effective novel rapid prototyped ventilator for use in patients with respiratory failure was developed in < 2-h and was effective in anesthetized, healthy pig model.


Assuntos
Desenho de Equipamento/métodos , Respiração Artificial/instrumentação , Ventiladores Mecânicos/provisão & distribução , Anestesia Geral/métodos , Animais , Infecções por Coronavirus/terapia , Volume de Reserva Expiratória/fisiologia , Feminino , Humanos , Volume de Reserva Inspiratória/fisiologia , Modelos Biológicos , Pandemias , Pneumonia Viral/terapia , Impressão Tridimensional/instrumentação , Respiração Artificial/economia , Respiração Artificial/métodos , Taxa Respiratória/fisiologia , Suínos , Volume de Ventilação Pulmonar/fisiologia , Ventiladores Mecânicos/economia
19.
Phys Rev Lett ; 125(8): 088102, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32909763

RESUMO

We perform a bidimensional Stokes experiment in an active cellular material: an autonomously migrating monolayer of Madin-Darby canine kidney epithelial cells flows around a circular obstacle within a long and narrow channel, involving an interplay between cell shape changes and neighbor rearrangements. Based on image analysis of tissue flow and coarse-grained cell anisotropy, we determine the tissue strain rate, cell deformation, and rearrangement rate fields, which are spatially heterogeneous. We find that the cell deformation and rearrangement rate fields correlate strongly, which is compatible with a Maxwell viscoelastic liquid behavior (and not with a Kelvin-Voigt viscoelastic solid behavior). The value of the associated relaxation time is measured as τ=70±15 min, is observed to be independent of obstacle size and division rate, and is increased by inhibiting myosin activity. In this experiment, the monolayer behaves as a flowing material with a Weissenberg number close to one which shows that both elastic and viscous effects can have comparable contributions in the process of collective cell migration.


Assuntos
Movimento Celular/fisiologia , Células Epiteliais/química , Células Epiteliais/citologia , Modelos Biológicos , Substâncias Viscoelásticas/química , Animais , Cães , Células Madin Darby de Rim Canino
20.
Phys Rev Lett ; 125(8): 088101, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32909810

RESUMO

Characterization of the differences between biological and random networks can reveal the design principles that enable the robust realization of crucial biological functions including the establishment of different cell types. Previous studies, focusing on identifying topological features that are present in biological networks but not in random networks, have, however, provided few functional insights. We use a Boolean modeling framework and ideas from the spin glass literature to identify functional differences between five real biological networks and random networks with similar topological features. We show that minimal frustration is a fundamental property that allows biological networks to robustly establish cell types and regulate cell fate choice, and that this property can emerge in complex networks via Darwinian evolution. The study also provides clues regarding how the regulation of cell fate choice can go awry in a disease like cancer and lead to the emergence of aberrant cell types.


Assuntos
Fenômenos Fisiológicos Celulares , Modelos Biológicos , Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/fisiologia , Humanos
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