A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14

A C-terminally modified ubiquitin (Ub) derivative, ubiquitin vinyl sulfone (UbVS), was synthesized as an active site-directed probe that irreversibly modifies a subset of Ub C-terminal hydrolases (UCHs) and Ub-specific processing proteases (UBPs). Specificity of UbVS for deubiquitylating enzymes (DUBs) is demonstrated not only by inhibition of [(125)I]UbVS labeling with N-ethylmaleimide and Ub aldehyde, but also by genetic analysis. [(125)I]UbVS modifies six of the 17 known and putative yeast deubiquitylating enzymes (Yuh1p, Ubp1p, Ubp2p, Ubp6p, Ubp12p and Ubp15p), as revealed by analysis of corresponding mutant strains. In mammalian cells, greater numbers of polypeptides are labeled, most of which are likely to be DUBs. Using [(125)I]UbVS as a probe, we report the association of an additional DUB with the mammalian 26S proteasome. In addition to the 37 kDa enzyme reported to be part of the 19S cap, we identified USP14, a mammalian homolog of yeast Ubp6p, as being bound to the proteasome. Remarkably, labeling of 26S-associated USP14 with [(125)I]UbVS is increased when proteasome function is impaired, suggesting functional coupling between the activities of USP14 and the proteasome.     

Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals

Cellulosic nanomaterials provide a novel and sustainable platform for the production of high performance materials enabled by nanotechnology. Bacterial cellulose (BC) is a highly crystalline material and contains pure cellulose without lignin and hemicellulose. BC offers an opportunity to provide control of the products’ properties in-situ, via specific BC production methods and culture conditions. The BC potential in advanced material applications are hindered by a limited knowledge of optimal BC production conditions, efficient process scale-up, separation methods, and purification methods. There is a growing body of work on the production of bacterial cellulose nanocrystals (BCNs) from BC fibers. However, there is limited information regarding the effect of BC fibers’ characteristics on the production of nanocrystals. This review describes developments in BC and BCNs production methods and factors affecting their yield and physical characteristics.     

The pulmonary pharmacology of [4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide] (2NTX-99), an anti-atherotrombotic compound with therapeutic potential in pathological conditions that target lung vasculature

The pharmacological activity of 2NTX-99 ([4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide]) was investigated in vitro in the intact, rat pulmonary vasculature and in guinea pig airways. Rat lungs were perfused at constant flow and changes in vascular tone recorded. Challenge with the TXA? analogue 9,11-dideoxy-9α11α-methanoepoxy ProstaglandinF? (U46619, 0.5 μM) increased vessel tone (32.48±1.5 vs 13.13±0.56 mmHg; n=12). 2NTX-99 (0.1-100 μM; n=5), caused a concentration-dependent relaxation, prevented by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 μM, n=4), an inhibitor of soluble guanylate cyclase. Acetylcholine (0.1-10 μM; n=3) and a reference NO-donor, isosorbide-5-mononitrate (5-100 μM; n=4), were ineffective. Intraluminal perfusion of washed human platelets (2 × 10? cells/ml) increased intravascular pressure after challenge with arachidonic acid (AA, 2 μM; n=5), an increase abolished by acetylsalicylic acid and significantly reduced by 2NTX-99 (40 μM; n=5). TXB? in the lung perfusate was detected after platelet activation, 2NTX-99 inhibited TXA? synthesis (6.45±0.6 and 1.10±0.2 ng/ml, respectively). 2NTX-99 did not alter central or peripheral airway responsiveness to Histamine (0.001-300 μM; n=6), U46619 (0.001-3 μM, n=3) or LTD? (1 pM-1 μM; n=6). 2NTX-99 vasodilates the pulmonary vasculature via the release of nitric oxide (NO) and reduces intraluminal, AA-induced, TXA? formation. The combined activity of 2NTX-99 as an NO-donor and a TXA?-synthesis inhibitor provides strong support for its potential therapeutic use in pathologies of the pulmonary vascular bed (e.g. pulmonary hypertension).     

Effects of maternal leptin treatment during lactation on the body weight and leptin resistance of adult offspring

We investigate whether leptin treatment to lactating rats affects food intake, body weight and leptin serum concentration and its anorectic effect on their adult offspring. Lactating rats were divided into 2 groups: Lep-single injected with recombinant rat leptin (8 microg/100 g of body weight, daily for the last 3 consecutive days of lactation) and control group (C) that received the same volume of saline. After weaning all pups had free access to the control diet, their body weight and food intake were monitored at each 4 days until 180 days of age, when they were tested for its food intake and response to either leptin (0.5 mg/kg body wt, ip) or saline vehicle. The offspring of the leptin-treated dams gained more weight and had higher food intake from day 37 onward (p<0.05), higher amount of retroperitoneal white adipose tissue (RPWAT) (37%, p<0.05) and higher leptin serum concentration (40%, p<0.05) at 180 days of age compared to control group. The food intake at 2, 4, 6 and 24 h was unaffected after acute injection of leptin in these animals, suggesting resistance to the anorectic effect of leptin. The maternal leptin treatment during lactation makes their adult offspring more susceptible to overweight with resistance to the anorectic effect of leptin.     

New aryldithiolethione derivatives as potent histone deacetylase inhibitors

A series of dithiolethione derivatives was synthesized and the in vitro HDAC inhibitory activity was tested. The most active compounds, 1 and 2, exhibited an IC₅₀ in nM range with a strong hyperacetylation of histone H4 in A549 cells. The HDAC inhibitory activity comparable to that of SAHA and the inhibition of A549 cell proliferation suggest that these compounds are worthy of further studies as potential anticancer agents.     

Synthesis,antimalarial activity,and cellular toxicity of new arylpyrrolylaminoquinolines

A set of nine new arylpyrrolyl derivatives of 7-chloro-4-aminoquinoline, characterized by different substituents on the phenyl ring or different distance between the pyrrolic nitrogen and the 4-aminoquinoline, has been synthesized and tested for their activity against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited activity against the CQ-S strain in the low nM range, comparable to that of chloroquine. Some of them were also highly active against the CQ-R strain and not toxic against normal cells. The antimalarial activity of this new class of compounds seems to be related to the inhibition of heme detoxification process of parasites, as in the case of chloroquine.     

Do pollination syndromes cause modularity and predict interactions in a pollination network in tropical high‐altitude grasslands?

The concept of pollination syndromes has been widely questioned, since plant–pollinator interactions have proved to be more generalist than was previously thought. We examined whether the network of a tropical high‐altitude grassland contained groups of plants and pollinators that interact preferentially with each other. A general binary matrix was created. To assess the robustness of myophily, in all analyses we considered: 1) the whole network, 2) the network after the wasps were removed, and 3) the network after the flies were removed. For each network we evaluated whether: 1) the observed interactions were more related to syndromes than expected by chance, compared to an expected matrix; 2) there was a modular structure; 3) the modules found were more related to syndromes than expected by chance, compared to another expected matrix; 4) the syndromes were equally robust. For this analysis, the general matrix was subdivided into smaller matrices that included each pollination syndrome separately. To test the influence of the functional groups of pollinators and the phylogeny of plants, in addition to the general matrix, we also considered the first expected matrix, a quantitative functional group and a plant phylogeny matrix. The pollination syndromes determined the pattern of interactions in the network: 69% of the total interactions resulted from the functional group of pollinators predicted by the plant syndrome. The network showed greater modularity (13 modules) than expected by chance, mostly consisting of the expected functional groups of pollinators and plant syndromes. The modules were associated with pollination syndromes more than was predicted by chance. Most of the variation in interactions was explained by functional groups of pollinators or by plant syndromes. Plant phylogeny did not account for a significant amount of variation in the interactions. Our findings support the concept of pollination syndromes. However, the interactions were not equally predicted by different pollination syndromes, and the accuracy of the prediction was strongest for ornithophily and melittophily.     

The Lepidoptera Associated with Forestry Crop Species in Brazil: a Historical Approach

Despite the long history of forestry activity in Brazil and its importance to the national economy, there is still much disorder in the information regarding pests of forestry species. Considering the importance of the entomological knowledge for the viability of silvicultural management, this work aimed to gather information on the species of Lepidoptera associated with forestry crops within Brazil using a historical approach. Through a literature review, all registered species of Lepidoptera related to forestry crops in Brazil from 1896 to 2010 were identified. The historical evaluation was based on the comparison of the number of published articles, species richness, and community similarities of the Lepidoptera and their associated forest crops, grouped in 10-year samples. A total of 417 occurrences of Lepidoptera associated with forestry species were recorded, from which 84 species are related with 40 different forestry crops. The nocturnal Lepidoptera were dominant on the records, with Eacles imperialis magnifica Walker as the most frequent pest species cited. Myrtaceae was the most frequent plant family, with Cedrela fissilis as the most cited forestry crop species. A successional change in both Lepidoptera species and their host plants was observed over the decades. The richness of lepidopteran pest species increased over the years, unlike the richness of forestry crop species. This increase could be related to the inefficient enforcement of sanitary barriers, to the increase of monoculture areas, and to the adaptability of native pests to exotic forestry species used in monoculture stands.