Laser-Activatable CuS Nanodots to Treat Multidrug-Resistant Bacteria and Release Copper Ion to Accelerate Healing of Infected Chronic Nonhealing Wounds

Chronic nonhealing wounds have imposed serious challenges in the clinical practice, especially for the patients infected with multidrug-resistant microbes. Herein, we developed an ultrasmall copper sulfide (covellite) nanodots (CuS NDs) based dual functional nanosystem to cure multidrug-resistant bacteria-infected chronic nonhealing wound. The nanosystem could eradicate multidrug-resistant bacteria and expedite wound healing simultaneously owing to the photothermal effect and remote control of copper-ion release. The antibacterial results indicated that the combination treatment of photothermal CuS NDs with photothermal effect initiated a strong antibacterial effect for drug-resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase Escherichia coli both in vitro and in vivo. Meanwhile, the released Cu2+ could promote fibroblast cell migration and endothelial cell angiogenesis, thus accelerating wound-healing effects. In MRSA-infected diabetic mice model, the nanosystem exhibited synergistic wound healing effect of infectious wounds in vivo and demonstrated negligible toxicity and nonspecific damage to major organs. The combination of ultrasmall CuS NDs with photothermal therapy displayed enhanced therapeutic efficacy for chronic nonhealing wound in multidrug-resistant bacterial infections, which may represent a promising class of antibacterial strategy for clinical translation.Peer reviewe

Scalar-Kinetic Branes

This work tries to find out thick brane solutions in braneworld scenarios described by a real scalar field in the presence of a scalar-kinetic term $F(X,\phi)=X\phi^m$ with a single extra dimension, where $X=\frac12\nabla_M\phi\nabla^M\phi$ stands for the standard kinetic term and $m=0,1,2\cdots$. We mainly consider bent branes, namely de Sitter and Anti-de Sitter four-dimensional slices. The solutions of a flat brane are obtained when taking the four-dimensional cosmological constant $\Lambda_4\rightarrow 0$. When the parameter $m=0$, these solutions turn to those of the standard scenario. The localization and spectrum of graviton on these branes are also analyzed.Comment: 10 pages, no figures, accepted by EP

Tau deletion prevents stress-induced dendritic atrophy in prefrontal cortex: role of synaptic mitochondria

Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, awell-known inducer of neuronal/synaptic atrophy, triggers hyperphosphorylation of Tau protein and cognitive deficits. However, the cause–effect relationship between these events remains to be established. To test the involvement of Tau in stress-induced impairments of cognition,we investigated the impact of stress on cognitive behavior, neuronal structure, and the synaptic proteome in the prefrontal cortex (PFC) of Tau knock-out (Tau-KO) and wild-type (WT) mice. Whereas exposure to chronic stress resulted in atrophy of apical dendrites and spine loss in PFC neurons as well as significant impairments in working memory in WT mice, such changes were absent in Tau-KO animals. Quantitative proteomic analysis of PFC synaptosomal fractions, combined with transmission electron microscopy analysis, suggested a prominent role for mitochondria in the regulation of the effects of stress. Specifically, chronically stressed animals exhibit Tau-dependent alterations in the levels of proteins involved in mitochondrial transport and oxidative phosphorylation aswell as in the synaptic localization of mitochondria in PFC. These findings provide evidence for a causal role of Tau in mediating stress-elicited neuronal atrophy and cognitive impairment and indicate that Tau may exert its effects through synaptic mitochondria.This work was funded by the Portuguese Foundation for Science & Technology (FCT, grant number NMC-113934 to I.S.), the EU Consortium Switchbox (grant number Health-FP7-2010-259772 to O.F.X.A. and N.S.), the Deutsche Forschungsgemeinschaft (grant number FI 1895/1-1 to M.D.F.) and the Max Planck Society (M.D.F., G.M., C.W.T., and O.F.X.A.). In addition, this workwas also co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) (N.S.). S.L. and I.S. are holders of FCT Fellowships. J.V-S. is a recipient of a PhD fellowship (PD/ BD/105938/2014) of the University of Minho MD/PhD Program funded by FCT.info:eu-repo/semantics/publishedVersio

Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate

de Sitter Thick Brane Solution in Weyl Geometry

In this paper, we consider a de Sitter thick brane model in a pure geometric Weyl integrable five-dimensional space-time, which is a generalization of Riemann geometry and is invariant under a so-called Weyl rescaling. We find a solution of this model via performing a conformal transformation to map the Weylian structure into a familiar Riemannian one with a conformal metric. The metric perturbations of the model are discussed. For gravitational perturbation, we get the effective modified P$\ddot{\text{o}}$schl-Teller potential in corresponding Schr$\ddot{\text{o}}$dinger equation for Kaluza-Klein (KK) modes of the graviton. There is only one bound state, which is a normalizable massless zero mode and represents a stable 4-dimensional graviton. Furthermore, there exists a mass gap between the massless mode and continuous KK modes. We also find that the model is stable under the scalar perturbation in the metric. The correction to the Newtonian potential on the brane is proportional to $e^{-3 r \beta/2}/r^2$, where $\beta$ is the de Sitter parameter of the brane. This is very different from the correction caused by a volcano-like effective potential.Comment: 24 pages, 13 figures, published versio

Tissue-Specific Orchestration of Gilthead Sea Bream Resilience to Hypoxia and High Stocking Density

Two different O-2 levels (normoxia: 75-85% O-2 saturation; moderate hypoxia: 42-43% O-2 saturation) and stocking densities (LD: 9.5, and HD: 19 kg/m(3)) were assessed on gilthead sea bream (Sparus aurata) in a 3-week feeding trial. Reduced O-2 availability had a negative impact on feed intake and growth rates, which was exacerbated by HD despite of the improvement in feed efficiency. Blood physiological hallmarks disclosed the enhancement in O-2-carrying capacity in fish maintained under moderate hypoxia. This feature was related to a hypo-metabolic state to cope with a chronic and widespread environmental O-2 reduction, which was accompanied by a differential regulation of circulating cortisol and growth hormone levels. Customized PCR-arrays were used for the simultaneous gene expression profiling of 34-44 selected stress and metabolic markers in liver, white skeletal muscle, heart, and blood cells. The number of differentially expressed genes ranged between 22 and 19 in liver, heart, and white skeletal muscle to 5 in total blood cells. Partial Least-Squares Discriminant Analysis (PLS-DA) explained [R2Y(cum)] and predicted [Q2Y(cum)] up to 95 and 65% of total variance, respectively. The first component (R2Y = 0.2889) gathered fish on the basis of O-2 availability, and liver and cardiac genes on the category of energy sensing and oxidative metabolism (cs, hif-1 alpha, pgc1 alpha, pgc1 beta, sirts 1-2-4-5-6-7), antioxidant defense and tissue repair (prdx5, sod2, mortalin, gpx4, gr, grp-170, and prdx3) and oxidative phosphorylation (nd2, nd5, and coxi) highly contributed to this separation. The second component (R2Y = 0.2927) differentiated normoxic fish at different stocking densities, and the white muscle clearly promoted this separation by a high over-representation of genes related to GH/IGF system (ghr-i, igfbp6b, igfbp5b, insr, igfbp3, and igf-i). The third component (R2Y = 0.2542) discriminated the effect of stocking density in fish exposed to moderate hypoxia by means of hepatic fatty acid desaturases (fads2, scd1a, and scd1b) and muscle markers of fatty acid oxidation (cpt1a). All these findings disclose the different contribution of analyzed tissues (liver >= heart > muscle > blood) and specific genes to the hypoxic- and crowding stress-mediated responses. This study will contribute to better explain and understand the different stress resilience of farmed fish across individuals and species

Modeling neurocognitive and neurobiological recovery in addiction

This book focuses on "what to know" and "how to apply" information, prioritizing novel principles and delineating cutting-edge assessment, phenotyping and treatment tools

Consórcios de caupi e milho em cultivo orgânico para produção de grãos e espigas verdes.

No período de outono-inverno-primavera de 2007, foi conduzido um estudo em Seropédica, Região Metropolitana do estado do Rio de Janeiro (Baixada Fluminense), com o objetivo de avaliar diferentes tipos de consórcio entre caupi (cv. Mauá) e milho (cv. AG-1051), em sistema orgânico de produção. O experimento foi instalado em área de Argissolo Vermelho-Amarelo no delineamento de blocos ao acaso, com quatro repetições. Os tratamentos constaram de diferentes épocas ou intervalos de tempo de semeadura do caupi em relação à do milho, a saber: (E1) 21 dias antes do milho; (E2) 14 dias antes do milho; (E3) 7 dias antes do milho; e (E4) no mesmo dia do milho. Tratamentos correspondentes aos cultivos solteiros do caupi e do milho foram incluídos, ambos semeados na data do tratamento E4. O cultivo consorciado com o caupi não interferiu na produtividade do milho em espigas verdes e também em termos de comprimento e diâmetro basal dessas espigas, independentemente do intervalo entre semeaduras. Com referência ao caupi, a produtividade em grãos verdes no cultivo solteiro foi superior à dos consórcios com o milho. Os valores obtidos para os Índices de Equivalência de Área (IEA), foram todos acima de 1,0, indicando que os consórcios foram eficientes quanto ao desempenho agronômico/biológico. Considerando, ainda a produtividade de cada cultura participante do consórcio, a semeadura do caupi antecipada de 21 dias em relação à do milho afigura-se mais adequada ao manejo orgânico adotado e às condições edafoclimáticas da região

Modulating process parameters to change physical properties of bigels for food applications

The effect of the process parameters involved in the production of bigels was investigated through the study of structural, mechanical and rheological properties. Four level (24) Central Composite Rotational Design (CCRD) configuration was applied in order to study the organogelator concentration, hydrocolloid concentration, organogel:hydrogel ratio and shear of mixing. Gellan gum and high oleic sunflower oil with glycerol monostearate were used to produce hydrogels and organogels, respectively. All formulations were water-in-oil systems with gel-like behavior. FTIR and XRD results showed that bigels were formed only by physical arrangement with no chemical interactions, but gellan gum decreased the crystallinity of the systems due to its amorphous character. However, hydrogel particles acted as an active filler, reinforcing the structure in comparison to pure gels. Also, the glycerol monostearate present in the organogel could self-assemble at the interface in order to interact with the aqueous phase, improving the interaction and affinity between the phases. Moreover, depending on the composition, systems could be softer or harder and present some frequency dependence. CCRD showed that all parameters evaluated changed with organogel:hydrogel ratio and organogel concentration. Shear of mixing was also significant for some parameters; however, hydrocolloid concentration did not exert a significant effect on the range studied. From PCA analysis it was possible to distinguish different groups, which means that some conditions produced bigels with similar characteristics. Thus, it is expected that these results will allow customizing and fine-tuning properties of structured two-phase systems for diverse applications, ranging from food to pharmaceutical and cosmetic industries.This study was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145- FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. and of the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER027462)info:eu-repo/semantics/publishedVersio

Evolution of Highly Polymorphic T Cell Populations in Siblings with the Wiskott-Aldrich Syndrome

Population level evolutionary processes can occur within a single organism when the germ line contains a mutation that confers a cost at the level of the cell. Here we describe how multiple compensatory mutations arose through a within-individual evolutionary process in two brothers with the immune deficiency Wiskott-Aldrich Syndrome (WAS). As a result, both brothers have T lymphocyte populations that are highly polymorphic at the locus of the germ line defect, and no single allele achieves fixation. WASP, the gene product affected in this disease, is specific to white blood cells where it is responsible for regulating actin cytoskeleton dynamics in a wide range of cellular responses. The brothers inherited a rare allele predicted to result in truncated WASP lacking the carboxy-terminal VCA domains, the region that directly catalyzes actin filament generation. Although the brothers' T cell populations are highly polymorphic, all share a corrective effect relative to the inherited allele in that they restore the VCA domain. This indicates massive selection against the truncated germ line allele. No single somatic allele becomes fixed in the circulating T cell population of either brother, indicating that a regulated step in maturation of the affected cell lineage is severely compromised by the germ line allele. Based on the finding of multiple somatic mutations, the known maturation pathway for T-lineage cells and the known defects of T cells and precursor thymocytes in mice with truncated WASP, we hypothesize that the presence of truncated WASP (WASPΔVCA) confers an extreme disadvantage in early developing thymocytes, above and beyond the known cost of absence of full-length WASP, and that the disadvantage likely occurs through dominant negative competition of WASPΔVCA with N-WASP, a protein that otherwise partially compensates for WASP absence in developing thymocytes