A new species of Hyphoderma (Meruliaceae, Polyporales) and its discrimination from closely related taxa

Thirty-five corticioid collections from the Canary Islands and Azores Archipelago were examined morphologically and subjected to molecular phylogenetic analysis. These specimens, almost all collected on endemic and/or xerophilic vegetation, were similar in morphological and ecological characteristics to Hypochnicium prosopidis from the Sonoran Desert (Arizona, USA) and Hyphoderma amoenum. Thirty-seven new ITS nrDNA sequences from these specimens, including the nomenclatural type of the above-mentioned species, were obtained and aligned with homologous sequences from GenBank. These collections were distributed in two strongly supported monophyletic clades. However, similar patterns of morphological variability shared by specimens included in both clades and their differences with related species suggest that they should be described as a single new species. Therefore Hyphoderma macaronesicum is proposed. Studies will be required to test, in a more robust multilocus genealogical framework, whether these populations constitute two cryptic species or whether they are the same taxon. The position of Hypochnicium prosopidis in the resolved tree and its morphological characters suggest that it should be included in Hyphoderma and the new combination Hyphoderma prosopidis is proposed.     

Cancer Progression Mediated by Horizontal Gene Transfer in an In Vivo Model

It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy.     

CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

ABSTRACT: BACKGROUND: The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2) to bind to N-type voltage-activated calcium channels (CaV2.2) [Brittain et al..., Nature Medicine 17:822[EN DASH]829 (2011)]. RESULTS AND DISCUSSION: Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K) that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion) observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP) release by compared to vehicle control. CONCLUSIONS: Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against particular subset of voltage-gated calcium channels resulting in a multipharmacology of action on the target.     

Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein

The hepatitis B virus L protein forms a dual topology in the endoplasmic reticulum (ER) via a process involving cotranslational membrane integration and subsequent posttranslational translocation of its preS subdomain. Here, we show that preS posttranslocation depends on the action of the ER chaperone BiP. To modulate the in vivo BiP activity, we designed an approach based on overexpressing its positive and negative regulators, ER-localized DnaJ-domain containing protein 4 (ERdj4) and BiP-associated protein (BAP), respectively. The feasibility of this approach was confirmed by demonstrating that BAP, but not ERdj4, destabilizes the L/BiP complex. Overexpressing BAP or ERdj4 inhibits preS posttranslocation as does the reduction of ATP levels. These results hint to a new role of BiP in guiding posttranslational polypeptide import into the mammalian ER.     

Development of alcoholic and malolactic fermentations in highly acidic and phenolic apple musts

This work reports the influence of the high acidity and high phenolic content in apple musts on the development of alcoholic and malolactic fermentations and on the final chemical and microbiological composition of the ciders. Four different musts were obtained by pressing several varieties and proportions of cider apples from the Basque Country (Northern Spain). Specially acidic and phenolic varieties were selected. Three musts were obtained in experimental stations and the fourth one, in a cider factory following usual procedures. The evolution of these musts was monitored during five months by measuring 18 parameters throughout eight samplings. In the most acidic of the three experimental musts, yeasts were added to complete the alcoholic fermentation. In the rest of the musts, alcoholic and malolactic fermentations took place spontaneously due to natural microflora and no chemical was added to control these processes. Malolactic fermentation (MLF) finished before alcoholic fermentation in the three tanks obtained in experimental stations, even in the most acidic and phenolic one (pH 3.18, 1.78 g tannic acid/l). After four months, these ciders maintained low levels of lactic acid bacteria (10(4)CFU/ml) and low content of acetic acid (<0.60 g/l). Both fermentations began simultaneously in the must obtained in the cider factory, but MLF finished 10 days after alcoholic fermentation. Subsequently, this must maintained a high population of lactic acid bacteria (>10(6)CFU/ml), causing a higher production of acetic acid (>1.00 g/l) than in the other ciders. These results show the possible advantages of MLF finishing before alcoholic fermentation.     

The effects of cutting and herbicide treatment on Pteridium aquilinum encroachment

Abstract. Pteridium aquilinum (bracken) encroachment is an important factor in the loss of certain habitats in the United Kingdom. However, no information exists as to whether prevention of encroachment is a cost‐effective strategy for Pteridium management. Conventional methods for the control of Pteridium (cutting, asulam application) were tested at one site (Levisham) to quantify their ability to prevent or delay encroachment and to affect the vigour of the Pteridium at the edge of the stand. The effects of encroachment and asulam application on the vegetation present were monitored at a second site (Ramsley), where techniques commonly used for moorland restoration were employed in combination with asulam application. Cutting once per year or a single application of asulam delayed the advance of the Pteridium front. At Levisham, the untreated front advanced 2.7 m in 5 yr, while in the same period the cut front advanced 0.88 m and the sprayed front was 1.5 m behind its initial position. At Ramsley, the untreated front invaded 1.8 m in 5 yr, and the sprayed front was again 1.5 m behind its starting position. Both spraying and cutting reduced frond biomass, frond cover and rhizome biomass. Herbicide spraying prevented the loss of Calluna vulgaris, though the restoration treatments had little effect. The merits of a balanced targeting of control on encroaching fronts or Pteridium at the stand level are discussed for different situations.     

Immunological evaluation of Escherichia coli-derived hepatitis C virus second envelope protein (E2) variants.

Two variants of the hepatitis C virus (HCV) E2 envelope protein, lacking the C-terminal domain and comprising amino acids 458-650 (E2A) and 382-605 (E2C), respectively, were efficiently produced in BL21 (DE3) Escherichia coli cells. E2A and E2C were used to immunize mice. The E2C variant induced the maximal mean antibody titer. Anti-E2C mouse sera reacted mainly with E2 synthetic peptides covering the 70 amino acid N-terminal region of the E2 protein. Moreover, a panel of anti-HCV positive human sera recognized only the E2C protein (28.2%) and the synthetic peptide covering the HVR-1 of the E2 protein (23.1%). These data indicate the existence of an immunologically relevant region in the HVR-1 of the HCV E2 protein.     

Effect of angiotensin converting enzyme inhibitors on 1.25-(OH)2 D levels of hypertensive patients. Relationship with ACE polymorphisms.

BACKGROUND: The effect of angiotensin converting enzyme inhibitors (ACEIs) on 1.25-dihydroxyvitamin D [1.25-(OH)2D] levels has not been studied. The purpose of this study is to assess the relationship between 1.25-dihydroxyvitamin D levels and I/D angiotensin-converting enzyme polymorphism (ACE) in hypertensive patients. MATERIALS AND METHODS: The study included 60 individuals (31 females and 29 males) with systolic and/or diastolic hypertension. The 25-hydroxyvitamin D levels were measured by HPLC and the 1.25-(OH)2 D was determined by RIA. ACE polymorphism was analyzed by Polymerase Chain Reaction (PCR) using a modification of the original method described by Rigat. RESULTS: Treatment with ACEIs produced an increase in total calcium (p=0.003) and a decrease in the 1.25-(OH)2 D (p=0.0001). No relationship between final calcium and 1.25-(OH)2 D (r=-0.171, p=0.198) was observed. When the effects of enalapril and quinapril were analyzed separately, the results were similar. When the patients were divided according to genotype, the decrease in 1.25-(OH)2 D was observed only in patients with D allele, genotype Ins/Del (69+/-23 vs. 48+/-19, p=0.021 ) and in those of genotype Del/Del (64+/-19 vs. 17, p=0.004). CONCLUSION: The ACE inhibitors in combination with the presence of the DD genotype decrease the level of 1.25-(OH)2 D. There was no difference between enalapril and quinapril treated groups.