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1.
Nat Commun ; 15(1): 3868, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719793

RESUMO

This study introduces a distributed electrified heating approach that is able to innovate chemical engineering involving endothermic reactions. It enables rapid and uniform heating of gaseous reactants, facilitating efficient conversion and high product selectivity at specific equilibrium. Demonstrated in catalyst-free CH4 pyrolysis, this approach achieves stable production of H2 (530 g h-1 L reactor -1) and carbon nanotube/fibers through 100% conversion of high-throughput CH4 at 1150 °C, surpassing the results obtained from many complex metal catalysts and high-temperature technologies. Additionally, in catalytic CH4 dry reforming, the distributed electrified heating using metallic monolith with unmodified Ni/MgO catalyst washcoat showcased excellent CH4 and CO2 conversion rates, and syngas production capacity. This innovative heating approach eliminates the need for elongated reactor tubes and external furnaces, promising an energy-concentrated and ultra-compact reactor design significantly smaller than traditional industrial systems, marking a significant advance towards more sustainable and efficient chemical engineering society.

2.
Sci Rep ; 14(1): 3966, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368434

RESUMO

Producing sustainable anode materials for lithium-ion batteries (LIBs) through catalytic graphitization of renewable biomass has gained significant attention. However, the technology is in its early stages due to the bio-graphite's comparatively low electrochemical performance in LIBs. This study aims to develop a process for producing LIB anode materials using a hybrid catalyst to enhance battery performance, along with readily available market biochar as the raw material. Results indicate that a trimetallic hybrid catalyst (Ni, Fe, and Mn in a 1:1:1 ratio) is superior to single or bimetallic catalysts in converting biochar to bio-graphite. The bio-graphite produced under this catalyst exhibits an 89.28% degree of graphitization and a 73.95% conversion rate. High-resolution transmission electron microscopy (HRTEM) reveals the dissolution-precipitation mechanism involved in catalytic graphitization. Electrochemical performance evaluation showed that the trimetallic hybrid catalyst yielded bio-graphite with better electrochemical performances than those obtained through single or bimetallic hybrid catalysts, including a good reversible capacity of about 293 mAh g-1 at a current density of 20 mA/g and a stable cycle performance with a capacity retention of over 98% after 100 cycles. This study proves the synergistic efficacy of different metals in catalytic graphitization, impacting both graphite crystalline structure and electrochemical performance.

3.
Materials (Basel) ; 15(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35407861

RESUMO

Typical non-metallic inclusions in two industrial low-carbon steels for oil pipelines were investigated as three-dimensional objects on film filters after electrolytic extraction and filtration of metal samples. A method of soft chemical extraction using a 10%AA electrolyte was used to study the initial corrosion process in the steel matrix surrounding various non-metallic inclusions. To determine and compare "corrosive" inclusions and their influence on the initial stages of corrosion of the adjacent layer of the steel matrix, quantitative parameters (such as the diameter of the corrosion crater (Dcr) and pit (Dpit), and the relative dissolution coefficient of the metal matrix (KD) around various inclusions) were determined after chemical extraction. It was found that CaO-Al2O3-MgO oxides and TiN inclusions did not cause an initial corrosion of the steel matrix surrounding these inclusions. However, tensile stresses in the steel matrix occurred around CaS inclusions (or complex inclusions containing a CaS phase), which contributed to the initiation of corrosion around these inclusions.

4.
Genet Med ; 24(1): 157-169, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906508

RESUMO

PURPOSE: More than half of the familial cutaneous melanomas have unknown genetic predisposition. This study aims at characterizing a novel melanoma susceptibility gene. METHODS: We performed exome and targeted sequencing in melanoma-prone families without any known melanoma susceptibility genes. We analyzed the expression of candidate gene DENND5A in melanoma samples in relation to pigmentation and UV signature. Functional studies were carried out using microscopic approaches and zebrafish model. RESULTS: We identified a novel DENND5A truncating variant that segregated with melanoma in a Swedish family and 2 additional rare DENND5A variants, 1 of which segregated with the disease in an American family. We found that DENND5A is significantly enriched in pigmented melanoma tissue. Our functional studies show that loss of DENND5A function leads to decrease in melanin content in vitro and pigmentation defects in vivo. Mechanistically, harboring the truncating variant or being suppressed leads to DENND5A losing its interaction with SNX1 and its ability to transport the SNX1-associated vesicles from melanosomes. Consequently, untethered SNX1-premelanosome protein and redundant tyrosinase are redirected to lysosomal degradation by default, causing decrease in melanin content. CONCLUSION: Our findings provide evidence of a physiological role of DENND5A in the skin context and link its variants to melanoma susceptibility.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Melanoma , Neoplasias Cutâneas , Animais , Predisposição Genética para Doença , Humanos , Melanoma/genética , Melanossomas , Monofenol Mono-Oxigenase/metabolismo , Neoplasias Cutâneas/genética , Nexinas de Classificação , Sequenciamento do Exoma , Peixe-Zebra/genética
5.
Materials (Basel) ; 14(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500896

RESUMO

Different stainless steel slags have been successfully employed in previous experiments, for the treatment of industrial acidic wastewaters. Although, before this technology can be implemented on an industrial scale, upscaled pilot experiments need to be performed. In this study, the parameters of the upscale trials, such as the volume and mixing speeds, are firstly tested by dispersing a NaCl tracer in a water bath. Mixing time trials are used to maintain constant mixing conditions when the volumes are increased to 70, 80 and 90 L, compared to the 1 L laboratory trials. Subsequently, the parameters obtained are used in pH buffering trials, where stainless steel slags are used as reactants, replicating the methodology of previous studies. Compared to laboratory trials, the study found only a minor loss of efficiency. Specifically, in previous studies, 39 g/L of slag was needed to buffer the pH of the acidic wastewaters. To reach similar pH values within the same time span, upscaled trials found a ratio of 43 g/L and 44 g/L when 70 and 90 L are used, respectively. Therefore, when the kinetic conditions are controlled, the technology appears to be scalable to higher volumes. This is an important finding that hopefully promotes further investments in this technology.

6.
Materials (Basel) ; 14(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070215

RESUMO

In this study, CaO-containing wastes from pulp and paper industries such as fly ash (FA) and calcined lime mud (LM) were utilized to neutralize and purify acidic wastewaters from the pickling processes in steel mills. The investigations were conducted by laboratory scale trials using four different batches of wastewaters and additions of two types of CaO-containing waste materials. Primary lime (PL), which is usually used for the neutralization, was also tested in the same experimental set up in the sake of comparison. The results show that these secondary lime sources can effectively increase the pH of the acidic wastewaters as good as the commonly used primary lime. Therefore, these secondary lime sources could be potential candidates for application in neutralization processes of industrial acidic wastewater treatment. Moreover, concentrations of metals (such as Cr, Fe, Ni, Mo and Zn) can decrease dramatically after neutralization by using secondary lime. The LM has a purification effect from the given metals, similar to the PL. Application of fly ash and calcined lime mud as neutralizing agents can reduce the amount of waste from pulp and paper mills sent to landfill and decrease the need for nature lime materials in the steel industry.

7.
Materials (Basel) ; 14(8)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920392

RESUMO

Natural convection of molten steel flow in a tundish occurs due to the temperature variation of the inlet stream and heat losses through top surface and refractory walls. A computational fluid dynamics (CFD) model was applied to study the effect of thermal buoyancy on fluid flow and residence-time distribution in a single-strand tundish. The CFD model was first validated with the experimental data from a non-isothermal water model and then applied to both scale-down model and prototype. The effects of flow control devices, including weir, dam and turbulence inhibitor, were compared and analyzed. Parameter studies of different heat losses through the top surface were performed. The results show that thermal buoyancy has a significant impact on the flow pattern and temperature distributions of molten steel in the tundish. The increase of heat loss through the top surface shortens the mean residence time of molten steel in the tundish, leading to an increase in dead volume fraction and a decrease in plug flow volume fraction.

8.
Materials (Basel) ; 14(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33573038

RESUMO

The flow behavior of gas in compressible and incompressible systems was investigated at an ambient temperature in an air-water system and at an operating process temperature in the IronArc system, using computational fluid dynamics. The simulation results were verified by experiments in the air-water system and established empirical equations to enable reliable predictions of the penetration length. The simulations in the air-water system were found to replicate the experimental behavior using both the incompressible and compressible models, with only small deviations of 7-8%. A lower requirement for the modified Froude number of the gas blowing to produce a jetting behavior was also found. For gas blowing below the required modified Froude number, the results illustrate that the gas will form large pulsating bubbles instead of a steady jet, which causes the empirical equation calculations to severely underpredict the penetration length. The lower modified Froude number limit was also found to be system dependent and to have an approximate value of 300 for the studied IronArc system. For submerged blowing applications, it was found that it is important to ensure sufficiently high modified Froude numbers of the gas blowing. Then, the gas penetration length will remain stable as a jet and it will be possible to predict the values using empirical equations.

9.
Microorganisms ; 9(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466313

RESUMO

Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFNλs; IL-28A, IL-28B, IL29, and IFNλ4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-ß (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine.

10.
ACS Omega ; 5(45): 28992-29001, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33225130

RESUMO

Catalyst regeneration is economically attractive, and it saves resources. Thus, it is important to determine the influence of catalyst regeneration on the chemical composition of upgraded oil. The catalyst was regenerated several times, and the regenerated catalyst was reloaded in the reactor to proceed with the next run. The composition of the derived upgraded pyrolysis oils in relation to catalyst regeneration was determined. The results revealed that the catalyst cracking abilities decreased with an increased number of reaction cycles. The opposite trends of the organic fraction and water yields indicated that the deoxygenation process occurred via H2O production. A decrease in the CO and CO2 yields revealed that the deoxygenation in catalytic pyrolysis with a catalyst mixture occurred via decarbonylation, decarboxylation, and dehydration mechanisms. The chemical formula of bio-oil changed from CH0.17O0.91 for a noncatalytic experiment to CH0.14O0.66 for a catalytic pyrolysis experiment after five reaction cycles, which indicated that the oxygen in the bio-oil decreased at the expense of hydrogen. The high heating value (HHV) of bio-oils decreased as the number of reaction cycles increased, albeit the minimum value of 22.41 wt % in the 6th reaction cycle was still higher than the value for the noncatalytic experiment. Compared to the HHVs of diesel fuel and gasoline petrol, the values of the produced bio-oil with catalyst mixtures were still low. The catalyst regained 94% of the surface area for the fresh catalyst, which indicated that the regeneration procedure was effective.

11.
Sci Total Environ ; 708: 135069, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31791785

RESUMO

Lignin and ferrous salt were mechanically mixed, melted, carbonized and steam activated to produce magnetic bio-activated carbons (MBACs). Phosphate adsorption capacity measurement was conducted on representative MBAC, which has a high surface iron oxide proportion and mesoporous volume. The results indicate that iron species are embedded into the carbon matrix by lignin melting. Steam is not only an activation agent for pore generation and widening but is also effective for the oxidization of Hagg iron carbide produced via ferrous salt decomposition and subsequent reduction during the carbonization process to form magnetite. The porous and magnetic properties and surface iron oxide content of the produced MBACs can be modified by controlling the steam/magnetic biochar (MBC) ratio. The MBAC production process is streamlined and novel, compared with conventional coprecipitation or impregnation methods. The maximum phosphate adsorption onto the representative MBAC product using the best fitting model, i.e., the Langmuir-Freundlich model, is estimated to be 21.18 mg/g, suggesting that the representative MBAC product has a comparable phosphate adsorption capacity to most of the reported MBCs and MBACs.


Assuntos
Carvão Vegetal , Adsorção , Lignina , Fenômenos Magnéticos , Fosfatos , Poluentes Químicos da Água
12.
Materials (Basel) ; 12(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500134

RESUMO

A number of carbon-rich (containing up to 47 wt% C) and lime-rich (containing up to 96 wt% of CaO-compounds) waste products from the pulp and paper industries can be used in iron and steel industry as fuels and slag formers for various metallurgical processes such as blast furnaces (BF), cupola furnaces (CF), argon oxygen decarburization (AOD) converters and electric arc furnaces (EAF). In most cases, these wastes consist of different size powders. In order to facilitate loading, transportation and charging of these powder wastes, briquetting is required. In this study, a pulverized AOD slag was tested as a binder component for briquetting of CaO-containing wastes (such as mesa, lime mud and fly ash) from pulp and paper industries. Moreover, mechanical testing of the possibilities for loading, transportation and unloading operations were done, specifically drop test trials were done for briquettes with different chemical compositions and treatments such as heating and storage. The results showed that an addition of 10-20% of AOD slag as a binder component followed by heat-treatment at 850 °C significantly improved the mechanical properties of the CaO-containing briquettes. An application of these briquettes will significantly reduce the consumption of natural resources (such as nature lime) in the metallurgical processes. Moreover, it can reduce the landfill area of wastes from pulp and paper industries, which is important from an environmental point-of-view.

13.
Exp Cell Res ; 381(1): 129-138, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31077711

RESUMO

Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role for Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at gene regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interacts with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but could rather regulate other processes in the nucleoplasm.


Assuntos
Células-Tronco Embrionárias Murinas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Animais , Linhagem Celular , Cromatina/metabolismo , Técnicas de Silenciamento de Genes , Camundongos , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição SOXB1/genética
14.
J Virol Methods ; 255: 29-37, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29425680

RESUMO

Enteroviruses (EVs), such as the Coxsackie B-viruses (CVBs), are common human pathogens, which can cause severe diseases including meningitis, myocarditis and neonatal sepsis. EVs encode two proteases (2Apro and 3Cpro), which perform the proteolytic cleavage of the CVB polyprotein and also cleave host cell proteins to facilitate viral replication. The 2Apro cause direct damage to the infected heart and tools to investigate 2Apro and 3Cpro expression may contribute new knowledge on virus-induced pathologies. Here, we developed new antibodies to CVB-encoded 2Apro and 3Cpro; Two monoclonal 2Apro antibodies and one 3Cpro antibody were produced. Using cells infected with selected viruses belonging to the EV A, B and C species and immunocytochemistry, we demonstrate that the 3Cpro antibody detects all of the EV species B (EV-B) viruses tested and that the 2Apro antibody detects all EV-B viruses apart from Echovirus 9. We furthermore show that the new antibodies work in Western blotting, immunocyto- and immunohistochemistry, and flow cytometry to detect CVBs. Confocal microscopy demonstrated the expression kinetics of 2Apro and 3Cpro, and revealed a preferential cytosolic localization of the proteases in CVB3 infected cells. In summary, the new antibodies detect proteases that belong to EV species B in cells and tissue using multiple applications.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Cisteína Endopeptidases/imunologia , Enterovirus Humano B/imunologia , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/imunologia , Proteínas Virais/imunologia , Proteases Virais 3C , Animais , Antígenos Virais/genética , Células Cultivadas , Clonagem Molecular , Cisteína Endopeptidases/genética , Enterovirus Humano B/enzimologia , Enterovirus Humano B/genética , Infecções por Enterovirus/virologia , Expressão Gênica , Células HeLa , Humanos , Imuno-Histoquímica , Camundongos , Sorogrupo , Proteínas Virais/genética
15.
J Infect Dis ; 216(10): 1308-1317, 2017 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-28968805

RESUMO

Acute respiratory virus infections predispose the cystic fibrosis (CF) lung to chronic bacterial colonization, which contributes to high mortality. For reasons unknown, respiratory virus infections have a prolonged duration in CF. Here, we demonstrate that mice carrying the most frequent cystic fibrosis transmembrane conductance regulator (CFTR) mutation in humans, ΔF508, show increased morbidity and mortality following infection with a common human enterovirus. ΔF508 mice demonstrated impaired viral clearance, a slower type I interferon response and delayed production of virus-neutralizing antibodies. While the ΔF508 mice had a normal immune cell repertoire, unchanged serum immunoglobulin concentrations and an intact immune response to a T-cell-independent antigen, their response to a T-cell-dependent antigen was significantly delayed. Our studies reveal a novel function for CFTR in antiviral immunity and demonstrate that the ΔF508 mutation in cftr is coupled to an impaired adaptive immune response. This important insight could open up new approaches for patient care and treatment.


Assuntos
Imunidade Adaptativa/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Fibrose Cística/imunologia , Imunidade Inata/genética , Mutação , Viroses/etiologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Códon , Fibrose Cística/complicações , Modelos Animais de Doenças , Resistência à Doença/genética , Resistência à Doença/imunologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Interferon-alfa/biossíntese , Camundongos , Poli I-C/imunologia , Taxa de Sobrevida , Carga Viral
16.
Vaccine ; 35(30): 3718-3725, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28579231

RESUMO

Coxsackie B viruses are among the most common enteroviruses, causing a wide range of diseases. Recent studies have also suggested that they may contribute to the development of type 1 diabetes. Vaccination would provide an effective way to prevent CVB infections, and the objective of this study was to develop an efficient vaccine production protocol for the generation of novel CVB vaccines. Various steps in the production of a formalin-inactivated Coxsackievirus B1 (CVB1) vaccine were optimized including the Multiplicity Of Infection (MOI) used for virus amplification, virus cultivation time, type of cell growth medium, virus purification method and formulation of the purified virus. Safety and immunogenicity of the formalin inactivated CVB1 vaccine was characterized in a mouse model. Two of the developed methods were found to be optimal for virus purification: the first employed PEG-precipitation followed by gelatin-chromatography and sucrose cushion pelleting (three-step protocol), yielding 19-fold increase in virus concentration (0.06µg/cm2) as compared to gold standard method. The second method utilized tandem sucrose pelleting without a PEG precipitation step, yielding 83-fold increase in virus concentration (0.24µg/cm2), but it was more labor-intensive and cannot be efficiently scaled up. Both protocols provide radically higher virus yields compared with traditional virus purification protocols involving PEG-precipitation and sucrose gradient ultracentrifugation. Formalin inactivation of CVB1 produced a vaccine that induced a strong, virus-neutralizing antibody response in vaccinated mice, which protected against challenge with CVB1 virus. Altogether, these results provide valuable information for the development of new enterovirus vaccines.


Assuntos
Infecções por Coxsackievirus/prevenção & controle , Enterovirus Humano A/imunologia , Imunogenicidade da Vacina , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Chlorocebus aethiops , Infecções por Coxsackievirus/imunologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Enterovirus Humano A/crescimento & desenvolvimento , Enterovirus Humano A/isolamento & purificação , Feminino , Formaldeído/farmacologia , Camundongos , Polissorbatos/farmacologia , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/isolamento & purificação , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/isolamento & purificação , Cultura de Vírus
17.
Nucleic Acids Res ; 45(5): 2629-2643, 2017 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-28100699

RESUMO

Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.


Assuntos
Proteínas Fúngicas/genética , Genoma Fúngico , Malassezia/genética , Anotação de Sequência Molecular/métodos , Proteogenômica/métodos , Genes Fúngicos , Genoma Mitocondrial , Peptídeos/genética , Domínios Proteicos , Análise de Sequência de RNA
18.
Int J Cardiol ; 228: 742-748, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27886618

RESUMO

BACKGROUND: Germline genetic variants are an important cause of dilated cardiomyopathy (DCM). However, recent sequencing studies have revealed rare variants in DCM-associated genes also in individuals without known heart disease. In this study, we investigate variant prevalence and genotype-phenotype correlations in Swedish DCM patients, and compare their genetic variants to those detected in reference cohorts. METHODS AND RESULTS: We sequenced the coding regions of 41 DCM-associated genes in 176 unrelated patients with idiopathic DCM and found 102 protein-altering variants with an allele frequency of <0.04% in reference cohorts; the majority were missense variants not previously described in DCM. Fifty-five (31%) patients had one variant, and 24 (14%) patients had two or more variants in the analysed genes. Detection of genetic variants in any gene, and in LMNA, MYH7 or TTN alone, was associated with early onset disease and reduced transplant-free survival. As expected, nonsense and frameshift variants were more common in DCM patients than in healthy individuals of the reference cohort 1000 Genomes Europeans. Surprisingly however, the prevalence, conservation and pathogenicity scores, and localization of missense variants were similar in DCM patients and healthy reference individuals. CONCLUSION: To our knowledge, this is the first study to identify correlations between genotype and prognosis when sequencing a large number of genes in unselected DCM patients. The similar distribution of missense variants in DCM patients and healthy reference individuals questions the pathogenic role of many variants, and suggests that results from genetic testing of DCM patients should be interpreted with caution.


Assuntos
Cardiomiopatia Dilatada/genética , Adolescente , Adulto , Idoso , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/terapia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Análise de Sobrevida , Suécia , Adulto Jovem
19.
Genes Chromosomes Cancer ; 55(7): 601-11, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27074266

RESUMO

We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology. © 2016 Wiley Periodicals, Inc.


Assuntos
Proteína BRCA2/genética , Dano ao DNA/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Melanoma/genética , RNA Helicases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi , Feminino , Seguimentos , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Linhagem , Prognóstico
20.
J Clin Virol ; 69: 165-71, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26209400

RESUMO

BACKGROUND: Enteroviral infections are common, affecting humans across all age groups. RT-PCR is widely used to detect these viruses in clinical samples. However, there is a need for sensitive and specific in situ detection methods for formalin-fixed tissues, allowing for the anatomical localization of the virus and identification of its serotype. OBJECTIVES: The aim was to design novel enterovirus probes, assess the impact of probe design for the detection and optimize the new single molecule in situ hybridization technology for the detection of enteroviruses in formalin-fixed paraffin-embedded samples. STUDY DESIGN: Four enterovirus RNA-targeted oligonucleotide RNA probes - two probes for wide range enterovirus detection and two for serotype-targeted detection of Coxsackievirus B1 (CVB1) - were designed and validated for the commercially available QuantiGene ViewRNA in situ hybridization method. The probe specificities were tested using a panel of cell lines infected with different enterovirus serotypes and CVB infected mouse pancreata. RESULTS: The two widely reactive probe sets recognized 19 and 20 of the 20 enterovirus serotypes tested, as well as 27 and 31 of the 31 CVB1 strains tested. The two CVB1 specific probe sets detected 30 and 14 of the 31 CVB1 strains, with only minor cross-reactivity to other serotypes. Similar results were observed in stained tissues from CVB -infected mice. CONCLUSIONS: These novel in-house designed probe sets enable the detection of enteroviruses from formalin-fixed tissue samples. Optimization of probe sequences makes it possible to tailor the assay for the detection of enteroviruses on the serotype or species level.


Assuntos
Infecções por Enterovirus/diagnóstico , Enterovirus/classificação , Enterovirus/genética , Hibridização In Situ/métodos , Sondas RNA/análise , Animais , Linhagem Celular , Chlorocebus aethiops , Biologia Computacional/métodos , Enterovirus/isolamento & purificação , Infecções por Enterovirus/virologia , Células HeLa , Humanos , Camundongos , Técnicas de Diagnóstico Molecular/métodos , Pâncreas/virologia , RNA Viral/genética , Sensibilidade e Especificidade , Células Vero
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