Mechanism of the Aryl-F Bond-Forming Step from Bi(V) Fluorides.

In this article, we describe a combined experimental and theoretical mechanistic investigation of the C(sp2)-F bond formation from neutral and cationic high-valent organobismuth(V) fluorides, featuring a dianionic bis-aryl sulfoximine ligand. An exhaustive assessment of the substitution pattern in the ligand, the sulfoximine, and the reactive aryl on neutral triarylbismuth(V) difluorides revealed that formation of dimeric structures in solution promotes facile Ar-F bond formation. Noteworthy, theoretical modeling of reductive elimination from neutral bismuth(V) difluorides agrees with the experimentally determined kinetic and thermodynamic parameters. Moreover, the addition of external fluoride sources leads to inactive octahedral anionic Bi(V) trifluoride salts, which decelerate reductive elimination. On the other hand, a parallel analysis for cationic bismuthonium fluorides revealed the crucial role of tetrafluoroborate anion as fluoride source. Both experimental and theoretical analyses conclude that C-F bond formation occurs through a low-energy five-membered transition-state pathway, where the F anion is delivered to a C(sp2) center, from a BF4 anion, reminiscent of the Balz-Schiemann reaction. The knowledge gathered throughout the investigation permitted a rational assessment of the key parameters of several ligands, identifying the simple sulfone-based ligand family as an improved system for the stoichiometric and catalytic fluorination of arylboronic acid derivatives

Lipidomics Reveals Reduced Inflammatory Lipid Species and Storage Lipids after Switching from EFV/FTC/TDF to RPV/FTC/TDF: A Randomized Open-Label Trial

HIV and antiretroviral therapy affect lipid metabolism. Lipidomics quantifies several individual species that are overlooked using conventional biochemical analyses, outperforming traditional risk equations. We aimed to compare the plasma lipidomic profile of HIV patients taking efavirenz (EFV) or rilpivirine (RPV). Patients >/= 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA /=6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15). Lipidomic analyses conducted by mass spectrometry (MS) were performed at baseline and after 12 and 24 weeks. OWLiver((R)) Care and OWLiver((R)) tests were performed to estimate the presence of fatty liver disease (NAFLD). No significant differences (83% male, median age 44 years, 6 years receiving EFV/FTC/TDF, CD4(+) count 740 cells/mm(3), TC 207 [57 HDL-C/133 LDL-C] mg/dL, TG 117 mg/dL) were observed between the groups at baseline. Significant reductions in plasma lipids and lipoproteins but increased circulating bilirubin concentrations were observed in patients who switched to RPV/FTC/TDF. Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log2 [fold-change] EFV vs. 0.059 log2 [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids

Deep RNA Sequencing of the Skeletal Muscle Transcriptome in Swimming Fish

Deep RNA sequencing (RNA-seq) was performed to provide an in-depth view of the transcriptome of red and white skeletal muscle of exercised and non-exercised rainbow trout (Oncorhynchus mykiss) with the specific objective to identify expressed genes and quantify the transcriptomic effects of swimming-induced exercise. Pubertal autumn-spawning seawater-raised female rainbow trout were rested (n = 10) or swum (n = 10) for 1176 km at 0.75 body-lengths per second in a 6,000-L swimflume under reproductive conditions for 40 days. Red and white muscle RNA of exercised and non-exercised fish (4 lanes) was sequenced and resulted in 15–17 million reads per lane that, after de novo assembly, yielded 149,159 red and 118,572 white muscle contigs. Most contigs were annotated using an iterative homology search strategy against salmonid ESTs, the zebrafish Danio rerio genome and general Metazoan genes. When selecting for large contigs (.500 nucleotides), a number of novel rainbow trout gene sequences were identified in this study: 1,085 and 1,228 novel gene sequences for red and white muscle, respectively, which included a number of important molecules for skeletal muscle function. Transcriptomic analysis revealed that sustained swimming increased transcriptional activity in skeletal muscle and specifically an upregulation of genes involved in muscle growth and developmental processes in white muscle. The unique collection of transcripts will contribute to our understanding of red and white muscle physiology, specifically during the long-term reproductive migration of salmonids.Fil: Palstra, Arjan P.. Universidad de Barcelona. Facultad de Biología; España;Fil: Beltran, Sergi. Universitat de Barcelona. Centres Cientifics i Tecnològics. Unitat de Bioinformàtica; España;Fil: Burgerhout, Erik. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Brittijn, Sebastiaan A.. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Magnoni, Leonardo Julián. Universidad de Barcelona. Facultad de Biología; España; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina;Fil: Henkel, Christiaan V.. ZF-screens; Países Bajos;Fil: Jansen, Hans J.. ZF-screens; Países Bajos;Fil: Van Den Thillart, Guido E. E. J. M.. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Spaink, Herman P.. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Planas, Josep V.. Universidad de Barcelona. Facultad de Biologia; España

Deep RNA sequencing of the skeletal muscle transcriptome in swimming fish

Deep RNA sequencing (RNA-seq) was performed to provide an in-depth view of the transcriptome of red and white skeletal muscle of exercised and non-exercised rainbow trout (Oncorhynchus mykiss) with the specific objective to identify expressed genes and quantify the transcriptomic effects of swimming-induced exercise. Pubertal autumn-spawning seawater-raised female rainbow trout were rested (n = 10) or swum (n = 10) for 1176 km at 0.75 body-lengths per second in a 6,000-L swim-flume under reproductive conditions for 40 days. Red and white muscle RNA of exercised and non-exercised fish (4 lanes) was sequenced and resulted in 15-17 million reads per lane that, after de novo assembly, yielded 149,159 red and 118,572 white muscle contigs. Most contigs were annotated using an iterative homology search strategy against salmonid ESTs, the zebrafish Danio rerio genome and general Metazoan genes. When selecting for large contigs (>500 nucleotides), a number of novel rainbow trout gene sequences were identified in this study: 1,085 and 1,228 novel gene sequences for red and white muscle, respectively, which included a number of important molecules for skeletal muscle function. Transcriptomic analysis revealed that sustained swimming increased transcriptional activity in skeletal muscle and specifically an up-regulation of genes involved in muscle growth and developmental processes in white muscle. The unique collection of transcripts will contribute to our understanding of red and white muscle physiology, specifically during the long-term reproductive migration of salmonids

Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

A standardized terminology for describing reproductive development in fishes

19 páginas, 12 figuras, 3 tablas.-- Open access journalAs the number of fish reproduction studies has proliferated, so has the number of gonadal classification schemes and terms. This has made it difficult for both scientists and resource managers to communicate and for comparisons to be made among studies.We propose the adoption of a simple, universal terminology for the phases in the reproductive cycle, which can be applied to all male and female elasmobranch and teleost fishes. These phases were chosen because they define key milestones in the reproductive cycle; the phases include immature, developing, spawning capable, regressing, and regenerating. Although the temporal sequence of events during gamete development in each phase may vary among species, each phase has specific histological and physiological markers and is conceptually universal. The immature phase can occur only once. The developing phase signals entry into the gonadotropin-dependent stage of oogenesis and spermatogenesis and ultimately results in gonadal growth. The spawning capable phase includes (1) those fish with gamete development that is sufficiently advanced to allow for spawning within the current reproductive cycle and (2) batch-spawning females that show signs of previous spawns (i.e., postovulatory follicle complex) and that are also capable of additional spawns during the current cycle. Within the spawning capable phase, an actively spawning subphase is defined that corresponds to hydration and ovulation in females and spermiation in males. The regressing phase indicates completion of the reproductive cycle and, for many fish, completion of the spawning season. Fish in the regenerating phase are sexually mature but reproductively inactive. Species-specific histological criteria or classes can be incorporated within each of the universal phases, allowing for more specific divisions (subphases) while preserving the overall reproductive terminology for comparative purposes. This terminology can easily be modified for fishes with alternate reproductive strategies, such as hermaphrodites (addition of a transition phase) and livebearers (addition of a gestation phase)Fish Reproduction and Fisheries (FRESH; European Cooperation in Science and Technology Action FA0601) and theWest Palm Beach Fishing Club (Florida) provided funding for the gonadal histology workshops where this terminology was developed and refined. Additionally, we thank FRESH for travel and publication fundsPeer reviewe

From vineyards to feedlots: a fund-flow scanning of sociometabolic transition in the Vallès County (Catalonia) 1860-1956-1999

We analyse the changes to agricultural metabolism in four municipalities of Vallès County (Catalonia, Iberia) by accounting for their agroecosystemfunds and flows during the socioecological transition from organic to industrial farming between the late nineteenth and twentieth centuries. The choice of three different stages in this transition allows us to observe the transformation of its funds and flows over time, the links established between them and the effect on their energy profiles.We emphasize the relevance of the integration and consistency of agroecosystem funds for energy efficiency in agriculture and their role as underlying historical drivers of this socioecological transition. While readjustment to market conditions and availability and affordability of external inputs are considered the main drivers of the transition, we also highlight the role of societal energy and nutritional transitions. An analysis of advanced organic agriculture c. 1860 reveals the great effort required to reproduce soil fertility and livestock from the internal recirculation of biomass. Meanwhile, a balance between land produce and livestock densities enabled the integration of funds, with a positive impact on energy performance. The adoption of fossil fuels and synthetic fertilizers c. 1956 reduced somewhat the pressure exerted on the land by overcoming the former dependence on local biomass flows to reproduce the agroecosystem. Yet external inputs diminished sustainability. Partial dependence on external markets existed congruently with internal crop diversity and the predominance of organic over industrial farm management. A shift towards animal production and consumption led to a new specialization process c. 1999 that resulted in crop homogenization and agroecological landscape disintegration. The energy returns of this linear feed-food livestock bioconversion declined compared to earlier mixed farming. Huge energy flows driven by a globalized economy ran through this agroecosystem, provoking deep impacts at both a local and external scale

Aerobic swimming in intensive finfish aquaculture: applications for production, mitigation and selection

We review knowledge on applications of sustained aerobic swimming as a tool to promote productivity and welfare of farmed fish species. There has been extensive interest in whether providing active species with a current to swim against can promote growth. The results are not conclusive but the studies have varied in species, life stage, swimming speed applied, feeding regime, stocking density and other factors. Therefore, much remains to be understood about mechanisms underlying findings of ‘swimming‐enhanced growth’, in particular to demonstrate that swimming can improve feed conversion ratio and dietary protein retention under true aquaculture conditions. There has also been research into whether swimming can alleviate chronic stress, once again on a range of species and life stages. The evidence is mixed but swimming does improve recovery from acute stresses such as handling or confinement. Research into issues such as whether swimming can improve immune function and promote cognitive function is still at an early stage and should be encouraged. There is promising evidence that swimming can inhibit precocious sexual maturation in some species, so studies should be broadened to other species where precocious maturation is a problem. Swimming performance is a heritable trait and may prove a useful selection tool, especially if it is related to overall robustness. More research is required to better understand the advantages that swimming may provide to the fish farmer, in terms of production, mitigation and selection

A multidisciplinary approach to identify priority areas for the monitoring of a vulnerable family of fishes in Spanish Marine National Parks

Background Syngnathid fishes (Actinopterygii, Syngnathidae) are flagship species strongly associated with seaweed and seagrass habitats. Seahorses and pipefishes are highly vulnerable to anthropogenic and environmental disturbances, but most species are currently Data Deficient according to the IUCN (2019), requiring more biological and ecological research. This study provides the first insights into syngnathid populations in the two marine Spanish National Parks (PNIA—Atlantic- and PNAC—Mediterranean). Fishes were collected periodically, marked, morphologically identified, analysed for size, weight, sex and sexual maturity, and sampled for stable isotope and genetic identification. Due the scarcity of previous information, habitat characteristics were also assessed in PNIA. Results Syngnathid diversity and abundance were low, with two species identified in PNIA (Hippocampus guttulatus and Syngnathus acus) and four in PNAC (S. abaster, S. acus, S. typhle and Nerophis maculatus). Syngnathids from both National Parks (NP) differed isotopically, with much lower δ15N in PNAC than in PNIA. The dominant species were S. abaster in PNAC and S. acus in PNIA. Syngnathids preferred less exposed sites in macroalgal assemblages in PNIA and Cymodocea meadows in PNAC. The occurrence of very large specimens, the absence of small-medium sizes and the isotopic comparison with a nearby population suggest that the population of Syngnathus acus (the dominant syngnathid in PNIA) mainly comprised breeders that migrate seasonally. Mitochondrial cytochrome b sequence variants were detected for H. guttulatus, S. acus, and S. abaster, and a novel 16S rDNA haplotype was obtained in N. maculatus. Our data suggest the presence of a cryptic divergent mitochondrial lineage of Syngnathus abaster species in PNAC. Conclusions This is the first multidisciplinary approach to the study of syngnathids in Spanish marine NPs. Habitat preferences and population characteristics in both NPs differed. Further studies are needed to assess the occurrence of a species complex for S. abaster, discarding potential misidentifications of genus Syngnathus in PNAC, and evaluate migratory events in PNIA. We propose several preferential sites in both NPs for future monitoring of syngnathid populations and some recommendations for their conservation.Postprin