The effect of kefir addition on microstructure parameters and physical properties of porous white bread

The effect of kefir concentration on the quality of porous white bread has been investigated. Quality evaluation was done using flatbed scanning (FBS) for measuring crumb porosity, instrumental texture profile analysis (TPA), crust and crumb color (L ^* a ^* b ^*), moisture, specific volume, and density determination techniques. The correlations between porosity, brightness, and firmness were also investigated. Long fermentation time of the sourdough changed significantly (p<0.05) the cell mean area (mm²), cell mean perimeter (mm), firmness (N), chewiness (N), light reflectance, and specific volume (ml/g). A strong correlation was found between microstructure of porous white bread, brightness (L), and firmness from TPA test. Kefir prolonged the shelf life of bread.     

In vitro steroidogenic effects of mixtures of persistent organic pollutants (POPs) extracted from burbot (Lota lota) caught in two Norwegian lakes

This study investigated the effects of two mixtures of persistent organic pollutants (POPs) on steroidogenesis in the H295R cell line. The two mixtures were obtained from the livers of burbot (Lota lota) caught in two Norwegian lakes (Mjøsa and Losna) with different contaminant profiles. Steroid hormone levels in the cell culture medium and mRNA levels of 16 genes involved in steroidogenesis were investigated. The crude Lake Mjøsa extract had to be diluted ten times more than the Lake Losna extract in order to prevent cytotoxicity. The ten times diluted Lake Mjøsa mixture had higher levels of DDT and derivates (∑ DDTs, 1.7 times) and brominated flame retardants (∑ BDEs and HBCD, 15-25 times) than the Lake Losna mixture, which, on the other hand, had higher concentrations of ∑ PCBs (1.5 times higher) and also of HCB, ∑ HCH isomers and ∑ chlordane isomers (5-20 times higher).In the cell culture media, only cortisol levels were increased at the highest exposure concentration to the Lake Mjøsa mixture, while both cortisol and estradiol levels were increased following exposure to the two highest Lake Losna mixture exposure concentrations. Testosterone levels decreased only at the highest exposure concentration of the Lake Losna mixture. Multivariate models suggested that ∑ PCBs, and to a lesser extent ∑ DDTs, were responsible for the cortisol responses, while estradiol and testosterone alterations were best explained by HCB and ∑ PCBs, respectively. Exposure to the mixtures generally increased mRNA levels, with smaller effects exerted by the Lake Mjøsa mixture than the Lake Losna mixture. It was concluded that both mixtures affected steroidogenesis in the H295R cells. Small differences in mixture composition, rather than the high content of brominated flame retardants in the Lake Mjøsa mixture, were suggested to be the most probable reason for the apparent differences in potencies of the two mixtures.     

Probing the Conformational States of Thimet Oligopeptidase in Solution

Thimet oligopeptidase (TOP) is a metallopeptidase involved in the metabolism of oligopeptides inside and outside cells of various tissues. It has been proposed that substrate or inhibitor binding in the TOP active site induces a large hinge-bending movement leading to a closed structure, in which the bound ligand is enclosed. The main goal of the present work was to study this conformational change, and fluorescence techniques were used. Four active TOP mutants were created, each equipped with a single-Trp residue (fluorescence donor) and a p-nitro-phenylalanine (pNF) residue as fluorescence acceptor at opposite sides of the active site. pNF was biosynthetically incorporated with high efficiency using the amber codon suppression technology. Inhibitor binding induced shorter Donor-Acceptor (D-A) distances in all mutants, supporting the view that a hinge-like movement is operative in TOP. The activity of TOP is known to be dependent on the ionic strength of the assay buffer and D-A distances were measured at different ionic strengths. Interestingly, a correlation between the D-A distance and the catalytic activity of TOP was observed: the highest activities corresponded to the shortest D-A distances. In this study for the first time the hinge-bending motion of a metallopeptidase in solution could be studied, yielding insight about the position of the equilibrium between the open and closed conformation. This information will contribute to a more detailed understanding of the mode of action of these enzymes, including therapeutic targets like neurolysin and angiotensin-converting enzyme 2 (ACE2).     

miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA–miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA–miRNA regulation during disease progression.     

Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels

Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining the role of extracellular cysteines (Cys) in the gating and function of Cx46 hemichannels. We studied Cx46 and mutated all of its extracellular Cys to alanine (Ala) (one at a time) and studied the effects of the Cys mutations on Cx46 expression, localization, and hemichannel activity. Wild-type Cx46 and Cys mutants were expressed at comparable levels, with similar cellular localization. However, functional experiments showed that hemichannels formed by the Cys mutants did not open either in response to membrane depolarization or removal of extracellular divalent cations. Molecular-dynamics simulations showed that Cys mutants may show a possible alteration in the electrostatic potential of the hemichannel pore and an altered disposition of important residues that could contribute to the selectivity and voltage dependency in the hemichannels. Replacement of extracellular Cys resulted in “permanently closed hemichannels”, which is congruent with the inhibition of the Cx46 hemichannel by lipid peroxides, through the oxidation of extracellular Cys. These results point to the modification of extracellular Cys as potential targets for the treatment of Cx46-hemichannel associated pathologies, such as cataracts and cancer, and may shed light into the gating mechanisms of other Cx hemichannels.     

Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function

Microcirculation homeostasis depends on several channels permeable to ions and/or small molecules that facilitate the regulation of the vasomotor tone, hyperpermeability, the blood–brain barrier, and the neurovascular coupling function. Connexin (Cxs) and Pannexin (Panxs) large-pore channel proteins are implicated in several aspects of vascular physiology. The permeation of ions (i.e., Ca²⁺) and key metabolites (ATP, prostaglandins, D-serine, etc.) through Cxs (i.e., gap junction channels or hemichannels) and Panxs proteins plays a vital role in intercellular communication and maintaining vascular homeostasis. Therefore, dysregulation or genetic pathologies associated with these channels promote deleterious tissue consequences. This review provides an overview of current knowledge concerning the physiological role of these large-pore molecule channels in microcirculation (arterioles, capillaries, venules) and in the neurovascular coupling function.     

Distributed text search using suffix arrays

Text search is a classical problem in Computer Science, with many data-intensive applications. For this problem, suffix arrays are among the most widely known and used data structures, enabling fast searches for phrases, terms, substrings and regular expressions in large texts. Potential application domains for these operations include large-scale search services, such as Web search engines, where it is necessary to efficiently process intensive-traffic streams of on-line queries. This paper proposes strategies to enable such services by means of suffix arrays. We introduce techniques for deploying suffix arrays on clusters of distributed-memory processors and then study the processing of multiple queries on the distributed data structure. Even though the cost of individual search operations in sequential (non-distributed) suffix arrays is low in practice, the problem of processing multiple queries on distributed-memory systems, so that hardware resources are used efficiently, is relevant to services aimed at achieving high query throughput at low operational costs. Our theoretical and experimental performance studies show that our proposals are suitable solutions for building efficient and scalable on-line search services based on suffix arrays.     

P2P OLAP: Data model,implementation and case study

It is a common situation nowadays that business groups own different companies that operate in an autonomous way. Nevertheless, these companies must be requested to provide the headquarters with summarized information for decision-making. An architecture for cooperative interchange of decision-making information seems to be a natural solution for this problem. We propose the use of a peer-to-peer (P2P) architecture for addressing the problem of processing OLAP data in a distributed environment, in a way that all companies involved can maintain full autonomy over the use of its own data resources. In a scenario like this, data exchange between peers occurs when one of them, in the role of a local peer, receives a query and, for answering it, requests data available in other nodes, denoted acquaintances. No global schema is assumed to exist for any data under this computing paradigm. Henceforth, data provided by an acquaintance of a local peer must be adapted, in a manner that answers to queries posed by local peer users conform the view those users have of their data. Because multidimensional data normally consist of a collection of views of aggregated data, a careful translation process is needed in this case, in order to transform any summary concept that appears in a peer acquaintance into a summary concept meaningful to the requesting peer. We first present a model for multidimensional data distributed in a P2P network, and a query rewriting technique, that allows a local peer to propagate OLAP queries among its acquaintances, obtaining a meaningful and correct answer. Mappings are performed using a novel technique called revise and map, based on belief revision concepts. Revising a dimension instance allows to produce consistent aggregations when an OLAP query is answered at more than one node. We then describe an implementation of a P2P system for answering OLAP queries over a network of data warehouses. We apply our proposal to a real-world case study of an insurance group. Finally, we report the results of an experimental evaluation of our implementation, and discuss the issues that must be accounted for in this setting.     

Spatial Control of Substitutional Dopants in Hexagonal Monolayer WS2: The Effect of Edge Termination

The ability to control the density and spatial distribution of substitutional dopants in semiconductors is crucial for achieving desired physicochemical properties. Substitutional doping with adjustable doping levels has been previously demonstrated in 2D transition metal dichalcogenides (TMDs); however, the spatial control of dopant distribution remains an open field. In this work, edge termination is demonstrated as an important characteristic of 2D TMD monocrystals that affects the distribution of substitutional dopants. Particularly, in chemical vapor deposition (CVD)-grown monolayer WS₂, it is found that a higher density of transition metal dopants is always incorporated in sulfur-terminated domains when compared to tungsten-terminated domains. Two representative examples demonstrate this spatial distribution control, including hexagonal iron- and vanadium-doped WS₂ monolayers. Density functional theory (DFT) calculations are further performed, indicating that the edge-dependent dopant distribution is due to a strong binding of tungsten atoms at tungsten-zigzag edges, resulting in the formation of open sites at sulfur-zigzag edges that enable preferential dopant incorporation. Based on these results, it is envisioned that edge termination in crystalline TMD monolayers can be utilized as a novel and effective knob for engineering the spatial distribution of substitutional dopants, leading to in-plane hetero-/multi-junctions that display fascinating electronic, optoelectronic, and magnetic properties.