The mitochondrial outer membrane protein porin 1 (Por1), the yeast orthologue of mammalian voltage-dependent anion channel (VDAC), is the major permeability pathway for the flux of metabolites and ...ions between cytosol and mitochondria. In yeast, several Por1 phosphorylation sites have been identified. Protein phosphorylation is a major modification regulating a variety of biological activities, but the potential biological roles of Por1 phosphorylation remains unaddressed.
In this work, we analysed 10 experimentally observed phosphorylation sites in yeast Por1 using bioinformatics tools. Two of the residues, T100 and S133, predicted to reduce and increase pore permeability, respectively, were validated using biological assays. In accordance, Por1T100D reduced mitochondrial respiration, while Por1S133E phosphomimetic mutant increased it. Por1T100A expression also improved respiratory growth, while Por1S133A caused defects in all growth conditions tested, notably in fermenting media.
In conclusion, we found phosphorylation has the potential to modulate Por1, causing a marked effect on mitochondrial function. It can also impact on cell morphology and growth both in respiratory and, unpredictably, also in fermenting conditions, expanding our knowledge on the role of Por1 in cell physiology.
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•The voltage-dependent anion channel (VDAC) is vital for metabolite flux across mitochondria.•Yeast VDAC1 (Por1) was reported phosphorylated, but its physiological significance is unknown.•Bioinformatic analysis predicts an impact of phosphorylation on Por1 structure.•Biological assays indicate phosphorylation at T100 and S133 impact mitochondrial respiration.•Phosphomimetics point for Por1 to affect yeast growth also in fermenting conditions.
Functional neuroimaging studies have consistently shown abnormal limbic activation patterns in socially anxious individuals, but structural data on the amygdala and hippocampus of these patients are ...scarce. This study explored the existence of structural differences in the whole brain, amygdala, and hippocampus of subjects with clinical and subthreshold social anxiety compared to healthy controls. We hypothesized that there would be volumetric differences across groups, without predicting their direction (i.e. enlargement or reduction).
Subjects classified as having social anxiety disorder (n = 12), subthreshold social anxiety (n = 12) and healthy controls (n = 14) underwent structural magnetic resonance imaging scans. The amygdala and hippocampus were defined a priori as regions of interest and volumes were calculated by manual tracing. Whole brain volume was calculated using voxel-based morphometry.
The bilateral amygdala and left hippocampus were enlarged in socially anxious individuals relative to controls. The volume of the right hippocampus was enlarged in subthreshold social anxiety participants relative to controls. No differences were found across groups in respect to total brain volume.
Our results show amygdalar and hippocampal volume alterations in social anxiety, possibly associated with symptom severity. The time course of such alterations and the cellular and molecular bases of limbic plasticity in social anxiety should be further investigated.
Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate ...their performance according to different PJI definitions.
A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin.
Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values.
All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.
Wild-type (wt) polyglutamine (polyQ) regions are implicated in stabilization of protein-protein interactions (PPI). Pathological polyQ expansion, such as that in human Ataxin-1 (ATXN1), that causes ...spinocerebellar ataxia type 1 (SCA1), results in abnormal PPI. For ATXN1 a larger number of interactors has been reported for the expanded (82Q) than the wt (29Q) protein.
To understand how the expanded polyQ affects PPI, protein structures were predicted for wt and expanded ATXN1, as well as, for 71 ATXN1 interactors. Then, the binding surfaces of wt and expanded ATXN1 with the reported interactors were inferred.
Our data supports that the polyQ expansion alters the ATXN1 conformation and that it enhances the strength of interaction with ATXN1 partners. For both ATXN1 variants, the number of residues at the predicted binding interface are greater after the polyQ, mainly due to the AXH domain. Moreover, the difference in the interaction strength of the ATXN1 variants was due to an increase in the number of interactions at the N-terminal region, before the polyQ, for the expanded form.
There are three regions at the AXH domain that are essential for ATXN1 PPI. The N-terminal region is responsible for the strength of the PPI with the ATXN1 variants. How the predicted motifs in this region affect PPI is discussed, in the context of ATXN1 post-transcriptional modifications.
Genome-wide expression analysis using microarrays has been used as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the ...prediction of acute coronary syndrome (ACS) with a differentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS.
This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1, n=9 and CG-Ph1, n=6) was used in order to select potential mRNA biomarkers candidates. A subsequent phase 2 study was performed using selected phase 1 markers analyzed by RT-qPCR using a larger and independent casuistic (ACS-Ph2, n=74 and CG-Ph2, n=41). A total of 549 genes were found to be differentially expressed in the first 48h after the ACS-Ph1. Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are differentially expressed in both phases of this study.
Transcriptomic analysis by microarray technology demonstrated differential expression during a 48h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery.
•The whole genomic expression from patients with very early stage of ACS•Thirteen genes were differently expressed during a 48h time course of ACS.•Two independent casuistic were evaluated at cardiac emergency unit.•Potential biomarkers of ACS to be future investigated in peripheral blood cell
Folk medicine suggests that pomegranate (peels, seeds and leaves) has anti-inflammatory properties; however, the precise mechanisms by which this plant affects the inflammatory process remain ...unclear. Herein, we analyzed the anti-inflammatory properties of a hydroalcoholic extract prepared from pomegranate leaves using a rat model of lipopolysaccharide-induced acute peritonitis. Male Wistar rats were treated with either the hydroalcoholic extract, sodium diclofenac, or saline, and 1 h later received an intraperitoneal injection of lipopolysaccharides. Saline-injected animals (i. p.) were used as controls. Animals were culled 4 h after peritonitis induction, and peritoneal lavage and peripheral blood samples were collected. Serum and peritoneal lavage levels of TNF-
as well as TNF-
mRNA expression in peritoneal lavage leukocytes were quantified. Total and differential leukocyte populations were analyzed in peritoneal lavage samples. Lipopolysaccharide-induced increases of both TNF-
mRNA and protein levels were diminished by treatment with either pomegranate leaf hydroalcoholic extract (57 % and 48 % mean reduction, respectively) or sodium diclofenac (41 % and 33 % reduction, respectively). Additionally, the numbers of peritoneal leukocytes, especially neutrophils, were markedly reduced in hydroalcoholic extract-treated rats with acute peritonitis. These results demonstrate that pomegranate leaf extract may be used as an anti-inflammatory drug which suppresses the levels of TNF-
in acute inflammation.
Reconstructive surgery with endoprostheses is the chosen method for treating bone malignancies. Postoperative infections are frequent complications, and their treatment involves prolonged hospital ...stays and antibiotic therapy. Among the advancements aimed at reducing the rate of postoperative infection, the use of incisional negative pressure therapy (iNPT) has shown promising results, with no reports in the literature regarding its use in patients with such conditions.
To evaluate the effectiveness of iNPT in reducing postoperative complications in surgeries for resection of bone tumors associated with modular endoprosthesis reconstruction.
Retrospective case series of 16 patients diagnosed with osteosarcoma, who underwent resection and reconstruction with endoprosthesis associated with iNPT during the postoperative period. Follow-up was performed for a period of six months, and the evaluated outcomes were the incidence of postoperative infection and complications of the surgical wound.
The use of iNPT for a postoperative period of seven days resulted in only three (18.7%) cases of postoperative infection. No cases of wound dehiscence, seroma formation, or hematoma at the surgical site were observed.
The rate of surgical wound complications in our case series is lower than that reported in most of the literature, and iNPT appears to be an efficient way to reduce the rate of local complications in reconstructive surgeries with endoprosthesis after resection of bone malignancies.
The first electrochemical investigation of composites materials based in polyoxometalates (POMs) encapsulated in the porous Metal-Organic Framework (MOF) MIL-101 is reported. The electrochemical ...behaviour of the porous MIL-101 and composite materials based in two monovacant Keggin-type POMs {K7PW11O39·10H2O (PW11) and K8SiW11O39·13H2O (SiW11)} encapsulated in MIL-101 (respectively, PW11@MIL-101 and SiW11@MIL-101) were studied by cyclic voltammetry. Initially, to investigate the influence of the support MIL-101 in the electrochemical behaviour of the two monovacant POMs, the compounds were individually immobilized on the surface of a pyrolytic graphite (PG) electrode. A reversible surface-controlled redox signal attributed to the chromium metal centres (Cr3+/Cr2+) was identified in MIL-101, and this represents the first electrochemical study of this MOF material. The monovacant compounds PW11 and SiW11 also revealed surface-controlled processes corresponding to WVI↔WV reductions. PW11 showed two reversible signals (involving one or two electrons), whereas SiW11 showed a quasi-reversible one-electron and a reversible two-electron process for the first and second W reductions, respectively. For the latter, an extra process was detected and attributed to the formation of β-isomer (β-SiW11). When the composites materials PW11@MIL-101 and SiW11@MIL-101 were immobilized on the surface of the electrode, the support MIL-101 maintained its characteristic electrochemistry and the redox potentials of the POMs were not significantly changed. However, when encapsulated inside the cages of the support material the POMs revealed a distinct electrochemical behaviour, given that their redox processes became diffusion-controlled, indicating that the POMs have some degree of mobility inside the support framework.
ABSTRACT Brackish waters represent great potential for profitable agricultural production; however, productive usage depends on the adoption of proper cultural practices as well as a culture tolerant ...of salinity, which can require some restrictions related to soil and crop production. Given the lack of information pertaining to hydroponic melon culture, the objective of this study was to investigate physiological changes promoted by the use of brackish water in the preparation of the nutrient solution for melon (Cucumis melo L., cv. AF 015) growth in coconut fiber substrate under greenhouse conditions in Mossoró-RN, a semiarid region of Brazil. The experimental design was completely randomized, with 12 treatments arranged in a 4 x 3 factorial scheme, with 4 salt concentration levels (1.1 - control, 2.5, 4.0 and 5.5 dS m-1) and 3 exposition times (vegetative growth: 10-30 days after transplanting, DAT; flowering: 31 to 50 DAT; and fruiting and ripening: 51-70 DAT, which are the assessment phases of physiological maturation). Increasing salt concentrations in the nutrient solution reduced photosynthetic efficiency, stomatal conductance and transpiration, but increased the intercellular CO2 concentration in melon plants. A salt concentration in the low to intermediate range (2.5 dS m-1) resulted in the best water use efficiency by melon crops.
RESUMO A água salobra pode representar um grande potencial para a produção agrícola rentável, com base na adoção de práticas culturais adequadas e tolerância das culturas à salinidade, contrapondo aos problemas produtivos e de solo que normalmente ocasionam. Devido à escassez de informações sobre o cultivo hidropônico de melão, o presente estudo teve o objetivo de investigar as alterações fisiológicas provocadas pelo uso de água salobra no preparo da solução nutritiva para o cultivo de melão (Cucumis melo L., cv. AF 015) em ambiente protegido e em substrato de fibra de coco, em Mossoró-RN, região semiárido do Brasil. O delineamento experimental utilizado foi o inteiramente casualizado, com 12 tratamentos arranjados em esquema fatorial 4 x 3, sendo 4 níveis de concentração de sais (1,1 dS m-1 - controle, 2,5, 4,0 e 5,5 dS m-1) e 3 fases de desenvolvimento (vegetativo: 10-30 dias após o transplantio, DAT; floração: 31-50 DAT e frutificação: 51-70 DAT, que representam as fases de avaliação da maturação fisiológica) com três repetições. O aumento da concentração de sal da solução nutritiva reduziu a eficiência da fotossíntese, da condutância estomática e da transpiração e aumentou a concentração intracelular de CO2 em plantas de melão. A melhor eficiência do uso da água pela cultura do melão cultivada em fibra de coco foi alcançada na solução nutritiva com concentração de 2.5 dS m-1.
•The petroleum industry is currently a very complex, dynamic and competitive business.•Operational Research was taught in the industrial environment.•Refinery planners/schedulers acquired practical ...skills on large-scale optimization.•Learners became technically enabled and motivated to rethink work processes.
Introducing a good educational program in the industrial environment may importantly differ from implementing a well-taught course in academic settings in a number of aspects. Potential troublesome aspects should be identified in advance such that the learning environment can properly tackle those issues through specialized or innovative ways. In this paper, we highlight the key role of Operations Research (OR) for the modern, high-performing oil industry and describe the in-house implementation of a pioneer, corporate-wide strategic learning program on OR techniques at PETROBRAS, a semi-public Brazilian multinational energy company. The learners were chemical engineers working at the planning/scheduling department of oil refineries, which has a high profile in the organization. Under tutoring, they acquired theoretical knowledge and practical skills concerning the development of optimization models, solution techniques and finished OR-based tools in a community of OR experts, thereby enabling them to rehearse their reflective and computational skills related to day-to-day activities. Most importantly, since aimed to foster the development of self-regulated, reflective learners, this course technically enabled and motivated planners and schedulers to develop further specialization, to rethink inefficient work processes, to change the attitudes and culture in the refinery, to question previous assumptions and operational paradigms.
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