Many efforts have been made to understand the pathogenesis of bovine mastitis to reduce losses and promote animal welfare. Staphylococcus aureus may cause bovine clinical mastitis, but it is mainly ...associated with subclinical infection, which is usually persistent and can easily reoccur. Here, we conducted a comparative genomic analysis between strains of S. aureus causing subclinical infection (Sau170, 302, 1269, 1364), previously sequenced by our group, and two well-characterized strains causing clinical mastitis (N305 and RF122) to find differences that could be linked to mastitis outcome. A total of 146 virulence-associated genes were compared and no appreciable differences were found between the bacteria. However, several nonsynonymous single nucleotide polymorphisms (SNPs) were identified in genes present in the subclinical strains when compared to RF122 and N305, especially in genes encoding host immune evasion and surface proteins. The secreted and surface proteins predicted by in silico tools were compared through multidimensional scaling analysis (MDS), revealing a high degree of similarity among the strains. The comparison of orthologous genes by OrthoMCL identified a membrane transporter and a lipoprotein as exclusive of bacteria belonging to the subclinical and clinical groups, respectively. No hit was found in RF122 and N305 for the membrane transporter using BLAST algorithm. For the lipoprotein, sequences of Sau170, 302, 1269, and 1364 with identities between 68-73% were found in the MDS dataset. A conserved region found only in the lipoprotein genes of RF122 and N305 was used for primer design. Although the polymerase chain reaction (PCR) on field isolates of S. aureus did not validate the findings for the transporter, the lipoprotein was able to separate the clinical from the subclinical isolates. These results show that sequence variation among bovine S. aureus, and not only the presence/absence of virulence factors, is an important aspect to consider when comparing isolates causing different mastitis outcomes.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Tyrosol derivatives and 1,2,3-triazoles are potential acetylcholinesterase inhibitors•Derived from 4-methylumbelliferone (30) showed an IC50 value of 14.66 ± 2.29 μmol L−1•Kinetic ...study and computational simulation suggested competitive inhibition mechanism•High potential prototypes for the development of new acetylcholinesterase inhibitors•Development of new drugs and pesticides, including for managing Alzheimer's disease
The present work proposed the preparation of triazolic analogues of tyrosol, a biophenol found in olive oil and whose wide range of bioactivities has been the target of many studies. We obtained fifteen novel tyrosol derivatives and the compounds of the series were later evaluated as acetylcholinesterase (AChE) inhibitors. The study of AChE inhibition is important for the development of new drugs and pesticides, and especially the research for managing Alzheimer's disease. The most active compound, namely 7-({1-2-(4-hydroxyphenyl)ethyl-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (30), showed IC50 value of 14.66 ± 2.29 μmol L−1. Docking experiments corroborated by kinetic assay are suggestive of a competitive inhibition mechanism. Derivatives interacted with amino acids from the AChE active site associated to the development of Alzheimer's disease. The results indicate that the compounds synthesized have a high potential as prototypes for the development of new acetylcholinesterase inhibitors.
The benzophenones are synthetic and natural compounds presenting a variety of activities, including photoprotective, cytotoxic and antiviral. It is herein described the preparation of a series of ...twenty-seven benzophenone derivatives bearing 1,2,3-triazole functionalities and the evaluation of their photoprotective, cytotoxic and antiviral on Zika Virus (ZIKV) activities. The compounds were prepared in three steps, namely reduction of benzophenone, alkylation of diphenylmethanol and CuAAC reactions. The in vitro evaluation of the photoprotective activity revealed that the most active derivative 4-((benzhydryloxy)methyl)-1-(4-nitrobenzyl)-1H-1,2,3-triazole (4k) displayed UVB sun protection factor equal to 6,9±0,53, which make this compound a possible candidate to be used in formulations for photoprotective applications. In terms of cytotoxicity, the compounds were evaluated against MDA-MB-231 and B16F10 cell lines. It was observed that the compounds were more active against MDA-MB-231 cells and three of them were capable of reducing cell viability by approximately 55% at 100 µmol L-1. In the antiviral screening against ZIKV, compound 4-(3-benzhydryloxy)propyl)-1-(3-methylbenzyl)-1H-1,2,3-triazole (5j) was the most effective in mantaining Vero cell viability.
Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira spp. This zoonotic disease is distributed globally and affects domestic animals, including cattle. Leptospira interrogans ...serogroup Sejroe serovar Hardjo and Leptospira borgpetersenii serogroup Sejroe serovar Hardjo remain important species associated with this reproductive disease in livestock production. Previous studies on Brazilian livestock have reported that L. interrogans serovar Hardjo is the most prevalent leptospiral agent in this country and is related to clinical signs of leptospirosis, which lead to economic losses in production. Here, we described the isolation of three clinical strains (Norma, Lagoa and Bolivia) obtained from leptospirosis outbreaks that occurred in Minas Gerais state in 1994 and 2008.
Serological and molecular typing using housekeeping (secY and 16SrRNA) and rfb locus (ORF22 and ORF36) genes were applied for the identification and comparative analysis of Leptospira spp. Our results identified the three isolates as L. interrogans serogroup Sejroe serovar Hardjo and confirmed the occurrence of this bacterial strain in Brazilian livestock. Genetic analysis using ORF22 and ORF36 grouped the Leptospira into serogroup Sejroe and subtype Hardjoprajitno. Genetic approaches were also applied to compare distinct serovars of L. interrogans strains by verifying the copy numbers of the IS1500 and IS1533 insertion sequences (ISs). The IS1500 copy number varied among the analyzed L. interrogans strains.
This study provides evidence that L. interrogans serogroup Sejroe serovar Hardjo subtype Hardjoprajitno causes bovine leptospirosis in Brazilian production. The molecular results suggested that rfb locus (ORF22 and ORF36) could improve epidemiological studies by allowing the identification of Leptospira spp. at the serogroup level. Additionally, the IS1500 and IS1533 IS copy number analysis suggested distinct genomic features among closely related leptospiral strains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Integrated microfluidic devices fabricated with FDM 3D printing technology.•FDM is used as an alternative technique for cost-effective device prototyping.•Different materials integrated within the ...microchannel during the printing process.•Fabrication of a 3D printed microfluidic e-tongue sensor.•Good distinction of basic tastes with concentrations below the human threshold.
Microfluidic devices based on polydimethylsiloxane shown a plethora of experimental possibilities due to good transparency, flexibility and ability to adhere reversibly and irreversibly to distinct materials. Though PDMS is a milestone in microfluidic developments, its cost and handling directed the field to search for new options. 3D printing technology nowadays starts a revolution offering materials and possibilities that can contribute positively to current methodologies. Here we explored the fused deposition modeling 3D printing technique to obtain integrated, transparent and sealed microchannels made with polylactic acid, a cheap alternative material to set up microfluidic systems. Using a home-made 3D printer, devices could be assembled in a simplified process, enabling the integration of different materials such as paper, glass, wire and polymers within the microchannel. To demonstrate the efficacy of this approach, a 3D-printed electronic tongue sensor was built, enabling the distinction of basic tastes below the human threshold.
Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be ...mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.
The T. rangeli haploid genome is ∼ 24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heat-shock proteins.
Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Magellanic Clouds are the most massive and closest satellite galaxies of the Milky Way, with stars covering ages from a few Myr up to 13 Gyr. This makes them important for validating integrated ...light methods to study stellar populations and star-formation processes, which can be applied to more distant galaxies. We characterized a set of stellar clusters in the Small Magellanic Cloud (SMC), using the \(\textit{Southern Photometric Local Universe Survey}\). This is the first age (metallicity) determination for 11 (65) clusters of this sample. Through its 7 narrow bands, centered on important spectral features, and 5 broad bands, we can retrieve detailed information about stellar populations. We obtained ages and metallicities for all stellar clusters using the Bayesian spectral energy distribution fitting code \(\texttt{BAGPIPES}\). With a sample of clusters in the color range \(-0.20 < r-z < +0.35\), for which our determined parameters are most reliable, we modeled the age-metallicity relation of SMC. At any given age, the metallicities of SMC clusters are lower than those of both the Gaia Sausage-Enceladus disrupted dwarf galaxy and the Milky Way. In comparison with literature values, differences are \(\Delta\)log(age)\(\approx0.31\) and \(\Delta\)Fe/H\(\approx0.41\), which is comparable to low-resolution spectroscopy of individual stars. Finally, we confirm a previously known gradient, with younger clusters in the center and older ones preferentially located in the outermost regions. On the other hand, we found no evidence of a significant metallicity gradient.
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