A systematic synthetic study was performed to explain the usual trend in selectivity towards multi-coupling, over mono-coupling, in Suzuki–Miyaura reactions. This preference was observed under ...different reaction conditions: for various halobenzenes, using substituents on the boronic acid, and changing the catalyst and temperature. Moreover, this reaction selectivity was found to increase for more reactive systems towards oxidative addition and more diluted media. The results constitute experimental evidence that the formation of the totally substituted coupling product is kinetically favoured by a reaction path location—the proximity between the regenerated catalyst and the newly formed coupling intermediate promotes the subsequent reaction.
A new species belonging to the Hoplias malabaricus complex from the Amazon basin, Brazil, is described. The new species is characterized by 15–16 predorsal scales, 37–39 lateral‐line scales, 5 scales ...from dorsal fin to lateral line, 38–39 vertebrae, iii‐iv, 7–8 anal‐fin rays, ii‐iv, 12–15 caudal‐fin rays, last vertical series of scales on the base of caudal‐fin rays forming a straight line, 6–7 dark bands in anal fin and no distinctive dark bands or blotches on flanks. The new species is also distinguished from other congeners of the H. malabaricus species‐group by means of landmark‐based morphometrics and DNA Barcoding (Cytochrome c Oxidase I gene). An identification key to species of the H. malabaricus species complex is provided.
Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this ...diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease.
Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages.
Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The C–S cross‐coupling reaction is a very efficient and powerful tool for constructing C–S bonds. Despite the well‐reported C–S cross‐coupling protocols using aryl halides, this reaction using ...sp2‐hybridized nonaromatic halides is still challenging. Herein, we report light‐assisted C–S cross‐coupling between thiols and 5‐chlorobenzofurazan under blue LED irradiation. We used a new nickel catalyst to synthesize 11 unpublished compounds. Furthermore, we assessed the mechanism and the influence of light irradiation on this reaction and proposed a plausible mechanism that is mediated by the excited state of the nickel catalyst promoted by irradiation with blue light and the C–S coupling product formed. Notably, C–S cross‐coupling under light irradiation was performed for the first time using a nickel catalyst in the absence of an external photocatalyst. We demonstrated that because nickel has a low energy barrier for oxidative addition, this protocol proceeded efficiently using chlorine as a leaving group, and the excited state of the nickel catalyst promoted reductive elimination with a lower energy barrier. It is important to mention that the procedure was tolerated by many functional groups within the thiol, affording a greater than 99% yield after reacting for 6 h.
Ion stopping in warm dense matter is a process of fundamental importance for the understanding of the properties of dense plasmas, the realization and the interpretation of experiments involving ...ion-beam-heated warm dense matter samples, and for inertial confinement fusion research. The theoretical description of the ion stopping power in warm dense matter is difficult notably due to electron coupling and degeneracy, and measurements are still largely missing. In particular, the low-velocity stopping range, that features the largest modelling uncertainties, remains virtually unexplored. Here, we report proton energy-loss measurements in warm dense plasma at unprecedented low projectile velocities. Our energy-loss data, combined with a precise target characterization based on plasma-emission measurements using two independent spectroscopy diagnostics, demonstrate a significant deviation of the stopping power from classical models in this regime. In particular, we show that our results are in closest agreement with recent first-principles simulations based on time-dependent density functional theory.
Nitroaromatic compounds-adducts of Morita⁻Baylis⁻Hillman (MBHA) reaction-have been applied in the treatment of malaria, leishmaniasis, and Chagas disease. The biological activity of these compounds ...is directly related to chemical reactivity in the environment, chemical structure of the compound, and reduction of the nitro group. Because of the last aspect, electrochemical methods are used to simulate the pharmacological activity of nitroaromatic compounds. In particular, previous studies have shown a correlation between the one-electron reduction potentials in aprotic medium (estimated by cyclic voltammetry) and antileishmanial activities (measured by the IC
) for a series of twelve MBHA. In the present work, two different computational protocols were calibrated to simulate the reduction potentials for this series of molecules with the aim of supporting the molecular modeling of new pharmacological compounds from the prediction of their reduction potentials. The results showed that it was possible to predict the experimental reduction potential for the calibration set with mean absolute errors of less than 25 mV (about 0.6 kcal·mol
).
► Neutralize redundancy between DRASTIC features using multivariate statistics. ► Automatically adjust DRASTIC feature weights to local settings. ► Validate a pioneering method of vulnerability ...mapping with pollution risk assessment.
An assessment of aquifer intrinsic vulnerability was conducted in the Sordo river basin, a small watershed located in the Northeast of Portugal that drains to a lake used as public resource of drinking water. The method adopted to calculate intrinsic vulnerability was the DRASTIC model, which hinges on a weighted addition of seven hydrogeologic features, but was combined with a pioneering approach for feature reduction and adjustment of feature weights to local settings, based on a multivariate statistical method. Basically, with the adopted statistical technique-Correspondence Analysis-one identified and minimized redundancy between DRASTIC features, allowing for the calculation of a composite index based on just three of them: topography, recharge and aquifer material. The combined algorithm was coined vector-DRASTIC and proved to describe more realistically intrinsic vulnerability than DRASTC. The proof resulted from a validation of DRASTIC and vector-DRASTIC by the results of a groundwater pollution risk assessment standing on the spatial distribution of land uses and nitrate concentrations in groundwater, referred to as NO3--DRASTIC method. Vector-DRASTIC and NO3--DRASTIC portray the Sordo river basin as an environment with a self-capability to neutralize contaminants, preventing its propagation downstream. This observation was confirmed by long-standing low nitrate concentrations in the lake water and constitutes additional validation of vector-DRASTIC results. Nevertheless, some general recommendations are proposed in regard to agriculture management practices for water quality protection, as part of an overall watershed approach.
This study investigated the secondary stress responses of Paralichthys orbignyanus exposed to ammonia and nitrite and after recovery. Fish were exposed to 0.12, 0.28, and 0.57 mg NH3‐N/L, or 5.72, ...10.43, and 15.27 mg NO2‐N/L for 10 d followed by the same time length for recovery. Ammonia‐ and nitrite‐free water was used as a control treatment. Blood samples were collected after 1, 5, and 10 d of exposure and after recovery. Fish exposed to ammonia presented lower and higher glucose levels after 10 d of exposure and recovery, respectively. Ammonia induced initial and transient ionic disturbances and metabolic alkalosis. Nitrite exposure caused hyperglycemia, increased plasma K+ levels, and respiratory alkalosis, whereas metabolic acidosis was observed after recovery. Increased proportion of monocytes and/or granulocytes and reduced number of lymphocytes were demonstrated in fish exposed to 0.28 mg NH3‐N/L (Day 1) and 10.43 mg NO2‐N/L (Day 5) and after recovery in the 0.28 and 0.57 mg NH3‐N/L treatments. Exposure to ammonia decreased the proportion of granulocytes on Day 5. In conclusion, exposure to concentrations at 0.12 mg NH3‐N/L and 5.72 mg NO2‐N/L provoked physiological disorders in Brazilian flounder. Nonetheless, fish exposed to 5.72 mg NO2‐N/L following a 10‐d recovery period showed complete resumption of homeostasis.
A complete homologous series of fluorescent phosphatidylethanolamines (diCnPE), labelled at the head group with a 7-nitrobenz-2-oxa-1,3-diazo-4-yl(NBD) fluorophore and inserted in 1-palmitoyl, ...2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers, was studied using atomistic molecular dynamics simulations. The longer-chained derivatives of NBD-diCnPE, with n = 14, 16, and 18, are commercially available, and widely used as fluorescent membrane probes. Properties such as location of atomic groups and acyl chain order parameters of both POPC and NBD-diCnPE, fluorophore orientation and hydrogen bonding, membrane electrostatic potential and lateral diffusion were calculated for all derivatives in the series. Most of these probes induce local disordering of POPC acyl chains, which is on the whole counterbalanced by ordering resulting from binding of sodium ions to lipid carbonyl/glycerol oxygen atoms. An exception is found for NBD-diC16PE, which displays optimal matching with POPC acyl chain length and induces a slight local ordering of phospholipid acyl chains. Compared to previously studied fatty amines, acyl chain-labelled phosphatidylcholines, and sterols bearing the same fluorescent tag, the chromophore in NBD-diCnPE locates in a similar region of the membrane (near the glycerol backbone/carbonyl region) but adopts a different orientation (with the NO2 group facing the interior of the bilayer). This modification leads to an inverted orientation of the P-N axis in the labelled lipid, which affects the interface properties, such as the membrane electrostatic potential and hydrogen bonding to lipid head group atoms. The implications of this study for the interpretation of the photophysical properties of NBD-diCnPE (complex fluorescence emission kinetics, differences with other NBD lipid probes) are discussed.
Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long‐term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore ...assessed the HCC incidence beyond year 5 of entecavir/tenofovir (ETV/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10‐center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/TDF for ≥1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5‐10 (median, 6.8) years. HCCs have been diagnosed in 101/1,951 (5.2%) patients within the first 5 years and 17/1,205 (1.4%) patients within 5‐10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness ≥12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender‐Hepatitis B score at baseline or year 5 developed HCC. Conclusion: The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially ≥50 years), lower platelets, and liver stiffness ≥12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444–1453).
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