Avaliação da degradação de hidrocarbonetos policíclicos aromáticos (HPA) em solos arenosos utilizando como oxidante persulfato de sódio ativado com Ferro.

Polycyclic Aromatic Hydrocarbons (PAHs) are pollutants that can cause mutagenic and carcinogenic to humans and cause environmental harm. The present study evaluated the degradation of phenanthrene and anthracene contaminants present in sandy soils using sodium persulfate activated with Fe2+ in acid medium. It was evaluated three sandy soils named A, B and C with different organic carbon tenors of 27, 16 and 31 g kg-1 respectively. After 24 hours of reaction, it was achieved a treatment efficiency of 60, 45 and 11% for the phenanthrene and 97, 96 and 81% for anthracene. There was no change in the composition of organic carbon in soil after the use of the oxidant. However there was a change in the constitution of the soil humic fractions. The use of the persulfate oxidant may be considered promising for use in soil because it does not compete with the organic carbon in the soil

Trimethoxylated halogenated chalcones as dual inhibitors of mao-b and bace-1 for the treatment of neurodegenerative disorders

Six halogenated trimethoxy chalcone derivatives (CH1–CH6) were synthesized and spec-trally characterized. The compounds were further evaluated for their inhibitory potential against monoamine oxidases (MAOs) and β-secretase (BACE-1). Six compounds inhibited MAO-B more effectively than MAO-A, and the 2′,3′,4′-methoxy moiety in CH4–CH6 was more effective for MAO-B inhibition than the 2′,4′,6′-methoxy moiety in CH1–CH3. Compound CH5 most potently inhibited MAO-B, with an IC50 value of 0.46 µM, followed by CH4 (IC50 = 0.84 µM). In 2′,3′,4′-methoxy derivatives (CH4-CH6), the order of inhibition was –Br in CH5 >-Cl in CH4 >-F in CH6 at the para-position in ring B of chalcone. CH4 and CH5 were selective for MAO-B, with selectivity index (SI) values of 15.1 and 31.3, respectively, over MAO-A. CH4 and CH5 moderately inhibited BACE-1 with IC50 values of 13.6 and 19.8 µM, respectively. When CH4 and CH5 were assessed for their cell viability studies on the normal African Green Monkey kidney cell line (VERO) using MTT assays, it was noted that both compounds were found to be safe, and only a slightly toxic effect was observed in concentrations above 200 µg/mL. CH4 and CH5 decreased reactive oxygen species (ROS) levels of VERO cells treated with H2 O2, indicating both compounds retained protective effects on the cells by antioxidant activities. All compounds showed high blood brain barrier permeabilities analyzed by a parallel artificial membrane permeability assay (PAMPA). Molecular docking and ADME prediction of the lead compounds provided more insights into the rationale behind the binding and the CNS drug likeness. From non-test mutagenicity and cardiotoxicity studies, CH4 and CH5 were non-mutagenic and non-/weak-cardiotoxic. These results suggest that CH4 and CH5 could be considered candidates for the cure of neurological dysfunctions

Tratamento de fenantreno utilizando persulfato de sódio ativado com ferro endógeno presente em solos arenosos.

A crescente preocupação com o meio ambiente vem viabilizando estudos que possibilitam a degradação de poluentes nocivos como os hidrocarbonetos policíclicos aromáticos (HPA). O Processo Oxidativo Avançado (POA), técnica baseada na produção de radicais, espécies capazes de reagir com vários compostos orgânicos, vem sendo utilizada atualmente. O objetivo deste estudo foi avaliar a viabilidade de utilização do persulfato de sódio ativado com o ferro endógeno para degradar o fenantreno. Os resultados do teor de ferro para as amostras ES1, ES2, ES3, e ES5 foram, 1452, 1290, 846 e 821 ppm respectivamente. Os resultados mostraram que a eficiência da degradação do fenantreno foi proporcional ao teor de ferro presente no solo. Em que os teores de degradação para as amostras ES1, ES2, ES3 e ES5 foram 60%, 53%, 33% e 18%, respectivamente

An SiO Toroid and Wide-angle Outflow associated with the Massive Protostar W75N(B)-VLA2

We have carried out ALMA observations of the massive star-forming region W75N(B), which contains the massive protostars VLA1, VLA2, and VLA3. Particularly, VLA2 is an enigmatic protostar associated with a wind-driven H$_2$O maser shell, which has evolved from an almost isotropic outflow to a collimated one in just 20 years. The shell expansion seemed to be halted by an obstacle located to the northeast of VLA2. Here we present our findings from observing the 1.3 mm continuum and H$_2$CO and SiO emission lines. Within a region of $\sim 30"$ ($\sim 39,000$ au) diameter, we have detected 40 compact mm-continuum sources, three of them coinciding with VLA1, VLA2, and VLA3. While the H$_2$CO emission is mainly distributed in a fragmented structure around the three massive protostars, but without any of the main H$_2$CO clumps spatially coinciding with them, the SiO is highly concentrated on VLA2, indicating the presence of very strong shocks generated near this protostar. The SiO emission is clearly resolved into an elongated structure ($\sim 0.6"\times0.3"$; $\sim 780$ au$\times$390 au) perpendicular to the major axis of the wind-driven maser shell. The structure and kinematics of the SiO emission are consistent with a toroid and a wide-angle outflow surrounding a central mass of $\sim 10$ M$_{\odot}$, thus supporting previous theoretical predictions regarding the evolution of the outflow. Additionally, we have identified the expected location and estimated the gas density of the obstacle that is hindering the expansion of the maser shell.Comment: To be published in The Astrophysical Journal Letters. Sixteen pages, seven figures. Updated metadat

The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.

The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer.CRUK

Intraepithelial and Interstitial Deposition of Pathological Prion Protein in Kidneys of Scrapie-Affected Sheep

Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE). The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrPSc. We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrPSc from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla) and occasional interstitial (papilla) deposition of PrPSc in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrPSc. PrPSc was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrPSc in kidney varied from approximately 27% (subclinical) to 73.6% (clinical) in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrPSc. Here we demonstrate unexpectedly frequent deposition of high levels of PrPSc in ovine kidneys of various flocks. Renal deposition of PrPSc is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep

Circadian Clocks in Mouse and Human CD4+ T Cells

Though it has been shown that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression by qPCR in unstimulated CD4+ T cells and immune responses of PMA/ionomycin stimulated CD4+ T cells by FACS analysis purified from blood of healthy subjects at different time points throughout the day. Molecular clock as well as immune function was further analyzed in unstimulated T cells which were cultured in serum-free medium with circadian clock reporter systems. We found robust rhythms of clock gene expression as well as, after stimulation, IL-2, IL-4, IFN-γ production and CD40L expression in freshly isolated CD4+ T cells. Further analysis of IFN-γ and CD40L in cultivated T cells revealed that these parameters remain rhythmic in vitro. Moreover, circadian luciferase reporter activity in CD4+ T cells and in thymic sections from PER2::LUCIFERASE reporter mice suggest that endogenous T cell clock rhythms are self-sustained under constant culture conditions. Microarray analysis of stimulated CD4+ T cell cultures revealed regulation of the NF-κB pathway as a candidate mechanism mediating circadian immune responses. Collectively, these data demonstrate for the first time that CD4+ T cell responses are regulated by an intrinsic cellular circadian oscillator capable of driving rhythmic CD4+ T cell immune responses

Mesenchymal Stromal Cells Improve Salivary Function and Reduce Lymphocytic Infiltrates in Mice with Sjögren's-Like Disease

Non-obese diabetic (NOD) mice develop Sjögren's-like disease (SS-like) with loss of saliva flow and increased lymphocytic infiltrates in salivary glands (SGs). There are recent reports using multipotent mesenchymal stromal cells (MSCs) as a therapeutic strategy for autoimmune diseases due to their anti-inflammatory and immunomodulatory capabilities. This paper proposed a combined immuno- and cell-based therapy consisting of: A) an injection of complete Freund's adjuvant (CFA) to eradicate autoreactive T lymphocytes, and B) transplantations of MSCs to reselect lymphocytes. The objective of this was to test the effectiveness of CD45(-)/TER119(-) cells (MSCs) in re-establishing salivary function and in reducing the number of lymphocytic infiltrates (foci) in SGs. The second objective was to study if the mechanisms underlying a decrease in inflammation (focus score) was due to CFA, MSCs, or CFA+MSCs combined.Donor MSCs were isolated from bones of male transgenic eGFP mice. Eight week-old female NOD mice received one of the following treatments: insulin, CFA, MSC, or CFA+MSC (combined therapy). Mice were followed for 14 weeks post-therapy. CD45(-)/TER119(-) cells demonstrated characteristics of MSCs as they were positive for Sca-1, CD106, CD105, CD73, CD29, CD44, negative for CD45, TER119, CD11b, had high number of CFU-F, and differentiated into osteocytes, chondrocytes and adipocytes. Both MSC and MSC+CFA groups prevented loss of saliva flow and reduced lymphocytic infiltrations in SGs. Moreover, the influx of T and B cells decreased in all foci in MSC and MSC+CFA groups, while the frequency of Foxp3(+) (T(reg)) cell was increased. MSC-therapy alone reduced inflammation (TNF-α, TGF-β), but the combination of MSC+CFA reduced inflammation and increased the regenerative potential of SGs (FGF-2, EGF).The combined use of MSC+CFA was effective in both preventing saliva secretion loss and reducing lymphocytic influx in salivary glands