Designing a functional rice muffin formulated with prebiotic oligosaccharides and sugar reduction

Innovation of pastry products towards higher nutritional and commercial value remains a challenge to the growing field of healthy food. In this study, the prebiotic supplementation and sugar reduction were explored in a widely consumed pastry product with a low level of innovation. The prebiotic potential of commercial agave inulin and galacto-oligosaccharides (GOS) was evaluated and compared by an in vitro model using human fecal inocula. Rice muffins containing 100% of sugar or 75% of sugar supplemented with 0.8% GOS were produced and compared with commercial rice muffins regarding their physical and textural properties. GOS fermentation led to the highest production of lactate and short-chain fatty acids, besides the most significant reduction of the final pH value and of the ammonia and methane production. Inulin presented a higher selectivity towards Lactobacillaceae (51 ± 1% of all), while GOS are more efficient to stimulate Bifidobacteriaceae growth (65 ± 7% of all).This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte; COMPETE 2020 (POCI-01-0145-FEDER-006684), FoSynBio (POCI-01-0145-FEDER-029549) and NewFood (NORTE-01-0246-FEDER000043). CA and BBC acknowledge their grants (UMINHO/BPD/4/2019 and SFRH/BD/132324/2017) from FCT. RM acknowledges the financial support to the Xunta de Galicia and FEDER by the project (EDD431B 2019/01).info:eu-repo/semantics/publishedVersio

Designing new antitubercular isoniazid derivatives with improved reactivity and membrane trafficking abilities

Funding Information: We acknowledge Diogo Vila Vi?osa for valuable discussions. We acknowledge financial support from Funda??o para a Ci?ncia e a Tecnologia, Portugal through projects PTDC/MED-QUI/29036/2017, PTDC/BIA-MIC-30692/2017, UIDB/00100/2020, UIDP/00100/2020, UIDB/04046/2020, UIDP/04046/2020, and UID/Multi/04413/2020, and Grants CEECIND/02300/2017 and DL57/CEECIND/0256/2017. Contributions from JRK, CMB, and DCG supported in part by a grant from the National Science Foundation, USA (MCB 1616059). Funding Information: We acknowledge Diogo Vila Viçosa for valuable discussions. We acknowledge financial support from Fundação para a Ciência e a Tecnologia , Portugal through projects PTDC/MED-QUI/29036/2017 , PTDC/BIA-MIC-30692/2017 , UIDB/00100/2020 , UIDP/00100/2020 , UIDB/04046/2020 , UIDP/04046/2020 , and UID/Multi/04413/2020 , and Grants CEECIND/02300/2017 and DL57/CEECIND/0256/2017 . Contributions from JRK, CMB, and DCG supported in part by a grant from the National Science Foundation , USA ( MCB 1616059 ). Publisher Copyright: © 2021 The AuthorsIsoniazid (INH) is one of the two most effective first-line antitubercular drugs and is still used at the present time as a scaffold for developing new compounds to fight TB. In a previous study, we have observed that an INH derivative, an hydrazide N′-substituted with a C10acyl chain, was able to counterbalance its smaller reactivity with a higher membrane permeability. This resulted in an improved performance against the most prevalent Mycobacterium tuberculosis (Mtb) resistant strain (S315T), compared to INH. In this work, we have designed two new series of INH derivatives (alkyl hydrazides and hydrazones) with promising in silico properties, namely membrane permeabilities and spontaneous IN* radical formation. The kinetics, cytotoxicity, and biological activity evaluations confirmed the in silico predictions regarding the very high reactivity of the alkyl hydrazides. The hydrazones, on the other hand, showed very similar behavior compared to INH, particularly in biological tests that take longer to complete, indicating that these compounds are being hydrolyzed back to INH. Despite their improved membrane permeabilities, the reactivities of these two series are too high, impairing their overall performance. Nevertheless, the systematic data gathered about these compounds have showed us the need to find a balance between lipophilicity and reactivity, which is paramount to devise better INH-based derivatives aimed at circumventing Mtb resistance.publishersversionpublishe

Turning evidence into recommendations: Protocol of a study guideline development groups

<p>Abstract</p> <p>Background</p> <p>Health care practice based on research evidence requires that evidence is synthesised, and that recommendations based on this evidence are implemented. It also requires an intermediate step: translating synthesised evidence into practice recommendations. There is considerable literature on evidence synthesis and implementation, but little on how guideline development groups (GDGs) produce recommendations. This is a complex process, with many influences on communication and decision-making, <it>e.g</it>., the quality of evidence, methods of presentation, practical/resource constraints, individual values, professional and scientific interests, social and psychological processes. To make this process more transparent and potentially effective, we need to understand these influences. Psychological theories of decision-making and social influence provide a framework for this understanding.</p> <p>Objectives</p> <p>This study aims to investigate the processes by which GDGs formulate recommendations, drawing on psychological theories of decision-making and social influence. The findings will potentially inform the further evolution of GDG methods, such as choice of members and procedures for presenting evidence, conducting discussion and formulating recommendations.</p> <p>Methods</p> <p>Longitudinal observation of the meetings of three National Institute of Health and Clinical Excellence (NICE) GDGs, one from each of acute, mental health and public health, will be tape recorded and transcribed. Interviews with a sample of GDG members at the beginning, middle, and end of the GDG's work will be recorded and transcribed. Site documents including relevant e-mail interchanges, GDG meeting minutes, and stakeholders' responses to the drafts of the recommendations will be collected. Data will be selected for analysis if they refer to either evidence or recommendations; the focus is on "hot spots", <it>e.g</it>., dilemmas, conflicts, and uncertainty. Data will be analysed thematically and by content analysis, drawing on psychological theories of decision-making and social influence.</p

Transcriptome dynamics of CD4⁺ T cells during malaria maps gradual transit from effector to memory

The dynamics of CD4⁺ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4⁺ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T_H1) and follicular helper T (T_(FH)) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T_H1 and T_(FH) trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T_(FH) and central memory were revealed, with antimalarials modulating these responses and boosting T_H1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4⁺ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene–gene correlations (http://haquelab.mdhs.unimelb.edu.au/cd4_memory/)

Uncoupling Protein-4 (UCP4) Increases ATP Supply by Interacting with Mitochondrial Complex II in Neuroblastoma Cells

Mitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP+), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis

Structure, Function, and Evolution of the Thiomonas spp. Genome

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

Transcriptome dynamics of CD4⁺ T cells during malaria maps gradual transit from effector to memory

The dynamics of CD4⁺ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4⁺ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T_H1) and follicular helper T (T_(FH)) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T_H1 and T_(FH) trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T_(FH) and central memory were revealed, with antimalarials modulating these responses and boosting T_H1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4⁺ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene–gene correlations (http://haquelab.mdhs.unimelb.edu.au/cd4_memory/)

CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey - The Hubble Space Telescope Observations, Imaging Data Products and Mosaics

This paper describes the Hubble Space Telescope imaging data products and data reduction procedures for the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS). This survey is designed to document the evolution of galaxies and black holes at $z\sim1.5-8$, and to study Type Ia SNe beyond $z>1.5$. Five premier multi-wavelength sky regions are selected, each with extensive multiwavelength observations. The primary CANDELS data consist of imaging obtained in the Wide Field Camera 3 / infrared channel (WFC3/IR) and UVIS channel, along with the Advanced Camera for Surveys (ACS). The CANDELS/Deep survey covers \sim125 square arcminutes within GOODS-N and GOODS-S, while the remainder consists of the CANDELS/Wide survey, achieving a total of \sim800 square arcminutes across GOODS and three additional fields (EGS, COSMOS, and UDS). We summarize the observational aspects of the survey as motivated by the scientific goals and present a detailed description of the data reduction procedures and products from the survey. Our data reduction methods utilize the most up to date calibration files and image combination procedures. We have paid special attention to correcting a range of instrumental effects, including CTE degradation for ACS, removal of electronic bias-striping present in ACS data after SM4, and persistence effects and other artifacts in WFC3/IR. For each field, we release mosaics for individual epochs and eventual mosaics containing data from all epochs combined, to facilitate photometric variability studies and the deepest possible photometry. A more detailed overview of the science goals and observational design of the survey are presented in a companion paper.Comment: 39 pages, 25 figure