The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in ...SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. CatL is a lysosomal enzyme that participates in numerous physiological processes, including apoptosis, antigen processing, and extracellular matrix remodeling. CatL is implicated in pathological conditions like invasion and metastasis of tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, and other diseases. CatL expression is up-regulated during chronic inflammation and is involved in degrading extracellular matrix, an important process for SARS-CoV-2 to enter host cells. In addition, CatL is probably involved in processing SARS-CoV-2 spike protein. As its inhibition is detrimental to SARS-CoV-2 infection and possibly exit from cells during late stages of infection, CatL could have been considered a valuable therapeutic target. Therefore, we describe here some drugs already in the market with potential CatL inhibiting capacity that could be used to treat COVID-19 patients. In addition, we discuss the possible role of host genetics in the etiology and spreading of the disease.
c-di-GMP is a major player in the switch between biofilm and motile lifestyles. Several bacteria exhibit a large number of c-di-GMP metabolizing proteins, thus a fine-tuning of this nucleotide levels ...may occur. It is hypothesized that some c-di-GMP metabolizing proteins would provide the global c-di-GMP levels inside the cell whereas others would maintain a localized pool, with the resulting c-di-GMP acting at the vicinity of its production. Although attractive, this hypothesis has yet to be demonstrated in Pseudomonas aeruginosa. We found that the diguanylate cyclase DgcP interacts with the cytosolic region of FimV, a polar peptidoglycan-binding protein involved in type IV pilus assembly. Moreover, DgcP is located at the cell poles in wild type cells but scattered in the cytoplasm of cells lacking FimV. Overexpression of dgcP leads to the classical phenotypes of high c-di-GMP levels (increased biofilm and impaired motilities) in the wild-type strain, but not in a ΔfimV background. Therefore, our findings suggest that DgcP activity is regulated by FimV. The polar localization of DgcP might contribute to a local c-di-GMP pool that can be sensed by other proteins at the cell pole, bringing to light a specialized function for a specific diguanylate cyclase.
Superplastic deformation has a significant industrial application value due to the large elongation, which allows manufacturing parts with complex geometries but happens at elevated temperatures and ...low strain rates. Therefore, it requires alloys with fine grain size but whose grains tend to grow at processing temperatures. Second-phase particles can promote grain boundary pinning to keep a fine grain size structure during superplastic forming. In 5083 aluminum alloy, Al6Mn particles make grain boundary pinning. There are two types of 5083 aluminum alloy: conventional with manganese range from 0.4 to 1.0 wt.% and superplastic with manganese between 0.64 and 0.86. It was observed in bibliographic research that the 5083 superplastic has a higher chemical concentration of manganese than the conventional one. However, no references were found covering manganese concentration in grain size stability. This work shows grain size evolution at a constant temperature of 5083 alloys with different manganese concentrations. This work indicates that the manganese substantially impacts grain boundary pinning when the chemical composition is between 0 and 0.6 wt.%. No significant effects were observed for Mn concentrations higher than 0.6%".
The accumulation of repetitive DNA sequences on the sex-limited W or Y chromosomes is a well-known process that is likely triggered by the suppression of recombination between the sex chromosomes, ...which leads to major differences in their sizes and genetic content. Here, we report an analysis conducted on the satellitome of Megaleporinus macrocephalus that focuses specifically on the satDNAs that have been shown to have higher abundances in females and are putatively located on the W chromosome in this species. We characterized 164 satellite families in M. macrocephalus, which is, by far, the most satellite-rich species discovered to date. Subsequently, we mapped 30 satellites, 22 of which were located on the W chromosome, and 14 were shown to exist only on the W chromosome. Finally, we report two simple, quick and reliable methods that can be used for sex identification in M. macrocephalus individuals using fin clips or scales, which could be applicable to future studies conducted in the field of aquaculture.
Common ivy,
Hedera helix
L
.
, could be a potential feedstock for biochar production based on its physicochemical characterization. However, this has not been supported by plant-growth experiments ...yet. Therefore, this study aims to provide insight into possible correlations between common ivy biochar’s physicochemical characteristics and plant development, for the first time. Lab-scale 96-well plant growth experiments were performed on
Arabidopsis thaliana
seedlings, using common-ivy based biochars produced at 400 and 700 °C and with and without valuable compound extraction before pyrolysis. Potassium leaching from the biochars caused the growth medium’s pH and conductivity to increase significantly after 7 cultivation days. This leaching caused the plants to express initial growth stress responses (Pearson = 0.930), which was proven by changes in their cell cycle regulation. Further cultivation, 7–10 days, showed total recovery of the seedlings subjected to biochars produced at 400 °C. Moreover, significant increases in plant fresh weight were established at 1% biochar concentration. Besides that, biochars produced at 700 °C did not significantly affect plant development compared to the control group due to the decreased phosphate availability of the growth medium. In conclusion, low-temperature (400 °C) outperform high-temperature (700 °C) biochars, and valuable compound extraction before pyrolysis does not impact the biochar performance.
Graphical Abstract
Fabry disease is a rare X-linked inherited disorder caused by deficiency of α-Galactosidase A. Hundreds of mutations and non-coding haplotypes in the GLA gene have been described; however, many are ...variants of unknown significance, prompting doubts about the diagnosis and treatment. The α-Galactosidase A enzymatic activity in dried blood spot (DBS) samples are widely used for screening purposes; however, even when values below the normal are found, new tests are required to confirm the diagnosis. Here we describe an analysis of GLA variants and their correlation with DBS α-Galactosidase A enzymatic activity in a large Brazilian population with Fabry disease symptoms.
We analyzed GLA variants by DNA sequencing of 803 male patients with suspected Fabry disease or belonging to high-risk populations; in 179 individuals, 58 different exonic variants were detected. From these, 50 are variants described as pathogenic and eight described as variants of unknown significance. The other individuals presented complex non-coding haplotypes or had no variants. Interestingly, the enzymatic activity in DBS was different among pathogenic variants and the other genotypes, including variants of unknown significance; the first presented mean of 12% of residual activity, while the others presented levels above 70% of the activity found in healthy controls.
The activity of α-Galactosidase A in DBS was markedly reduced in males with known pathogenic variants when compared with subjects presenting variants of unknown significance, non-coding haplotypes, or without variants, indicating a possible non-pathogenic potential of these latter genotypes. These findings bring a better understanding about the biochemical results of α-Galactosidase A in DBS samples, as well as the possible non-pathogenic potential of non-coding haplotypes and variants of unknown significance in GLA gene. These results certainly will help clinicians to decide about the treatment of patients carrying variants in the gene causing this rare but life-threatening disease.
O artigo se propões a analisar o argumento de que explicações institucionais e comportamentais coexistem na Ciência Política contemporânea o que, por sua vez, aumenta o leque de desenhos de pesquisa ...disponíveis para testar os argumentos propostos. Utilizando o caso da literatura sobre o comparecimento eleitoral, identificamos duas perguntas fundamentais que remetem, cada uma, a perspectivas teóricas distintas. A primeira (por que o eleitor vota?) é explicada no nível do indivíduo e teorias comportamentais são mais apropriadas. A segunda (por que as taxas de comparecimento variam de país para país?) necessita comparar estruturas e arranjos institucionais para ser respondida. Três hipóteses são propostas sobre a coexistência dos modelos teóricos nas publicações recentes e suas respectivas relações com desenhos experimentais e qualitativos.
This work was aimed at developing an effective procedure to obtain sterile ideal host fish in mass scale with no endogenous germ cells in the germinal epithelium, owning permanent stem-cell niches ...able to be colonized by transplanted germ cells in surrogate technology experiments. Thus, triploids, diploid hybrids, and triploid hybrids were produced. To obtain hybrid offspring, oocytes from a single Astyanax altiparanae female were inseminated by sperm from five males (A. altiparanae, A. fasciatus, A. schubarti, Hyphessobrycon anisitsi, and Oligosarcus pintoi). Triploidization was conducted by inhibition of the second polar body release using heat shock treatment at 40 °C for 2 min. At 9-months of age, the offspring from each crossing was histologically evaluated to access the gonadal status of the fish. Variable morphological characteristics of the gonads were found in the different hybrids offspring: normal gametogenesis, gametogenesis without production of gametes, sterile specimens holding germ cells, and sterile specimens without germ cells, which were considered “ideal hosts”. However, only in the hybrid derived from crossing between A. altiparanae and A. fasciatus, 100% of the individuals were completely sterile. Among them 83.3% of the male did not present germ cells inside germinal epithelium, having only somatic cells in the gonad. The other 16.7% also presented spermatogonia inside the niches. Such a methodology allows the production of sterile host in mass scale, opening new insights for application of surrogate technologies.
•Triploidy does not ensure sterility in fish.•Hybridization does not ensure sterilization in fish, especially in female specimens.•Triploid hybrids arised from Astyanax altiparanae and A. fasciatus were sterile.
A challenge in molecular diagnosis and genetic counseling is the interpretation of variants of uncertain significance. Proper pathogenicity classification of new variants is important for the ...conclusion of molecular diagnosis and the medical management of patient treatments. The purpose of this study was to reclassify two RPE65 missense variants, c.247T>C (p.Phe83Leu) and c.560G>A (p.Gly187Glu), found in Brazilian families. To achieve this aim, we reviewed the sequencing data of a 224-gene retinopathy panel from 556 patients (513 families) with inherited retinal dystrophies. Five patients with p.Phe83Leu and seven with p.Gly187Glu were selected and their families investigated. To comprehend the pathogenicity of these variants, we evaluated them based on the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification guidelines. Initially, these RPE65 variants met only three pathogenic criteria: (i) absence or low frequency in the population, (ii) several missense pathogenic RPE65 variants, and (iii) 15 out of 16 lines of computational evidence supporting them as damaging, which together allowed the variants to be classified as uncertain significance. Two other pieces of evidence were accepted after further analysis of these Brazilian families: (i) p.Phe83Leu and p.Gly187Glu segregate with childhood retinal dystrophy within families, and (ii) their prevalence in Leber congenital amaurosis (LCA)/early-onset retinal dystrophy (EORD) patients can be considered higher than in other inherited retinal dystrophy patients. Therefore, these variants can now be classified as likely pathogenic according to ACMG/AMP classification guidelines.
Cartilage lesions and osteoarthritis are very prevalent and imply a significant clinical and economic burden.
To review treatments for cartilage lesions in a time life sequence and its ...particularities.
We performed a broad PUBMED database review with a sensitive systematized strategy without restriction to article date or type.
This review brings us to the aspects of chondral and osteochondral lesions throughout the different age groups of patients. Focusing mainly on surgical treatment, we present here the most widely used techniques. To facilitate discussion, patients have been divided into 3 groups: children and adolescents with open physes, adults until the fifth decade, and adult patients over the fifth decade. For open physes patients, their capacity for healing is of important consideration in both conservative and operative management. In those with closed physes, most patients are treated surgically. While marrow stimulation is the most common cartilage treatment procedure, there is a growing use of other techniques such as osteochondral autograft transplantation and osteochondral allograft transplantation. Patients over 50 years old commonly present with more severe chondral lesions, which influences the treatment decision-making process.
When attempting to optimize cartilage restoration in these 3 groups, it is important to weigh the physiologic age, the extent of the cartilage lesion, and the stage of the degenerative and osteoarthritic processes.
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