Antigenicity of chimeric synthetic peptides based on HTLV-1 antigens and the impact of epitope orientation

The present study evaluated four chimeric synthetic peptides incorporating immunodominant sequences from HTLV-1 virus. Monomeric peptides M1, M2, and M3 represent sequences from core (p19) and envelope (gp46) of the virus. The peptide M1 is a p19 (105-124) sequence, the peptide M2 is a gp46 (190-207) sequence, and the peptide M3 is a gp 46 sequence with substitution of proline at position 192 by serine. Those peptides were arranged in such a way that permits one to obtain different combinations of chimeric peptides (M1-M2, M2-M1, M1-M3, and M3-M1). Two glycine residues were used as arm spacers for separating the two sequences. The antigenicity of these peptides was evaluated in an ultramicroenzyme-linked immunosorbent assay (UMELISA) using sera of human T cell leukemia virus type I (HTLV-I)-infected individuals (n = 24), while specificity was evaluated with anti-HTLV-II-positive samples (n = 11) and healthy blood donors (n = 25). The results were compared to plates coated with monomeric peptides M1, M2, and M3. The chimeric peptide orientation (M1-M2) and the proline at position 192 of the gp46 peptide showed higher sensitivity.     

Metformin directly targets the H3K27me3 demethylase KDM6A/UTX

Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure‐ and ligand‐based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3‐specific demethylase subfamily, KDM6A/UTX. AlphaScreen and AlphaLISA assays confirmed the ability of metformin to inhibit the demethylation activity of purified KDM6A/UTX enzyme. Structural studies revealed that metformin might occupy the same set of residues involved in H3K27me3 binding and demethylation within the catalytic pocket of KDM6A/UTX. Millimolar metformin augmented global levels of H3K27me3 in cultured cells, including reversion of global loss of H3K27me3 occurring in premature aging syndromes, irrespective of mitochondrial complex I or AMPK. Pharmacological doses of metformin in drinking water or intraperitoneal injection significantly elevated the global levels of H3K27me3 in the hepatic tissue of low‐density lipoprotein receptor‐deficient mice and in the tumor tissues of highly aggressive breast cancer xenograft‐bearing mice. Moreover, nondiabetic breast cancer patients receiving oral metformin in addition to standard therapy presented an elevated level of circulating H3K27me3. Our biocomputational approach coupled to experimental validation reveals that metformin might directly regulate the biological machinery of aging by targeting core chromatin modifiers of the epigenome.     

Autocuidado: nueva evidencia sobre su medida en adultos mayores

Introduction

A major challenge in today's society is getting older people, not only live longer, but to have a better life, and achieve successful aging. Self-care has been identified as relevant construct in its relation to physical, psychological, and social health. Therefore, this paper aims to provide first evidence of the psychometric properties of a scale to assess self-care in older people.

Relationship between shoot-rooting and root-sprouting abilities and the carbohydrate and nitrogen reserves of Mediterranean dwarf shrubs

BACKGROUND AND AIMS: This study analysed the differences in nitrogen (N), non-structural carbohydrates (NSC) and biomass allocation to the roots and shoots of 18 species of Mediterranean dwarf shrubs with different shoot-rooting and resprouting abilities. Root N and NSC concentrations of strict root-sprouters and species resprouting from the base of the stems were also compared. METHODS: Soluble sugars (SS), starch and N concentrations were assessed in roots and shoots. The root : shoot ratio of each species was obtained by thorough root excavations. Cross-species analyses were complemented by phylogenetically independent contrasts (PICs). KEY RESULTS: Shoot-rooting species showed a preferential allocation of starch to shoots rather than roots as compared with non-shoot-rooting species. Resprouters displayed greater starch concentrations than non-sprouters in both shoots and roots. Trends were maintained after PICs analyses, but differences became weak when root-sprouters versus non-root-sprouters were compared. Within resprouters, strict root-sprouters showed greater root concentrations and a preferential allocation of starch to the roots than stem-sprouters. No differences were found in the root : shoot ratio of species with different rooting and resprouting abilities. CONCLUSIONS: The shoot-rooting ability of Mediterranean dwarf shrubs seems to depend on the preferential allocation of starch and SS to shoots, though alternative C-sources such as current photosynthates may also be involved. In contrast to plants from other mediterranean areas of the world, the resprouting ability of Mediterranean dwarf shrubs is not related to a preferential allocation of N, NSC and biomass to roots.     

Avian diversity and behavior in an Eocene coastal plain,Svalbard: the ichnological evidence

Abstract

This study presents an ichnotaxonomical assessment of bird footprints from a coastal plain setting in the Eocene lower to middle Aspelintoppen Formation in Brongniartfjellet and Storvola, Svalbard. These footprints are unique evidence for Paleogene birds from Svalbard and the second evidence of Paleogene avifauna of the Arctic (along with scarce fossil remains from Ellesmere Island). The analyzed footprints are assigned to six ichnotaxa belonging to three ichnofamilies: Aquatilavipes isp., avian footprint morphotype A and B (ichnofamily Avipedidae); Gruipeda cf. G. abeli, Gruipeda cf. G. dominguensis (ichnofamily Gruipedidae); and Gyeongsangornipes isp. (ichnofamily unknown). Associated invertebrate ichnofossils include Helminthoidichnites tenuis, Cochlichnus anguineus, and Helminthopsis isp. The avian footprints reflect small, medium-sized and rare large birds that can be morphologically compared to those of modern relatives including crane, heron, plover, moorhen, gallinule, oystercatcher and curlew. It is also proposed that in situ sets of shorebird footprints showing a preferred orientation, not composing trackways and showing overprinting, can be used as an indicator of the position and orientation of the shoreline.     

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

The modulation of acetylcholine (ACh) release by botulinum toxin injection into epicardial fat diminishes atrial fibrillation (AF) recurrence. These results suggest an interaction between autonomic imbalance and epicardial fat as risk factors of AF. Our aim was to study the inflammatory, lipidic and fibroblastic profile of epicardial stroma from patients who underwent open‐heart surgery, their regulation by cholinergic activity and its association with AF. We performed in vitro and ex vivo assays from paired subcutaneous and epicardial stromal cells or explants from 33 patients. Acute ACh effects in inflammation and lipid‐related genes were analysed by qPCR, in intracellular calcium mobilization were performed by Fluo‐4 AM staining and in neutrophil migration by trans‐well assays. Chronic ACh effects on lipid accumulation were visualized by AdipoRed. Plasma protein regulation by parasympathetic denervation was studied in vagotomized rats. Our results showed a higher pro‐inflammatory profile in epicardial regarding subcutaneous stromal cells. Acute ACh treatment up‐regulated monocyte chemoattractant protein 1 levels. Chronic ACh treatment improved lipid accumulation within epicardial stromal cells (60.50% [22.82‐85.13] vs 13.85% [6.17‐23.16], P < .001). Additionally, patients with AF had higher levels of fatty acid‐binding protein 4 (1.54 ± 0.01 vs 1.47 ± 0.01, P = .005). Its plasma levels were pronouncedly declined in vagotomized rats (2.02 ± 0.21 ng/mL vs 0.65 ± 0.23 ng/mL, P < .001). Our findings support the characterization of acute or chronic cholinergic activity on epicardial stroma and its association with AF.     

Fast replenishment of initial carbon stores after defoliation by the pine processionary moth and its relationship to the re-growth ability of trees

Defoliation by herbivores may alter the source:sink balance of trees leading to transient decreases in carbon (C) stores. When C stores are replenished concurrently with re-growth both processes may compete, store formation proceeding at the expenses of growth. However, the interactions between both processes are not fully understood. We investigated the effects of defoliation by the pine processionary moth (PPM, Thaumetopoea pityocampa Dennis and Schiff.) on the non-structural carbohydrate (NSC) and nitrogen (N) stores and the growth of Pinus nigra Arnold trees. Short-term effects were evaluated immediately after a PPM outbreak and at the end of the first growing season in trees suffering a range of defoliation damage. Long-term effects were explored by a 17-year-long PPM defoliation experiment, with 11?years of repeated defoliation treatments followed by 6?years of recovery. Defoliation by PPM was followed by transient NSC decreases, but trees were able to exceed initial NSC pools and compensate growth in just one growing season. Such recovery was linked to increased foliage N. Repeated severe defoliations decreased growth and survival of trees in the long-term, but trees increased starch allocation to stems. Defoliation led to an accumulation of C storage compounds in P. nigra trees irrespective of their ability to re-grow. In trees included in the short-term experiment, the accumulation of stores proceeded concurrently with re-growth. However, the repeated severe defoliations included in our long-term experiment impaired the growth of trees, surplus C being accumulated as stores. These results indicate that, growth declines in pines defoliated by PPM are not due to C (source) limitation but may respond to the reduced sink strength of growing meristems due to defoliation, and thus, a decrease in C allocation to growth.     

13C NMR spectra of olean-18-ene derivatives

The ¹³C NMR signals of sixteen derivatives of olean-18-ene-triterpenes have been assigned.     

New diterpenes from Sideritis candicans

The three new diterpenes candol-A (ent-16-kauren-7α-ol, I), candol-B (ent-16-kauren-18-ol, III) and epicandicandiol 7β-monoacetate (ent-7α-acetoxy-16-kauren-18-ol, V) as well as epicandicandiol (VII) have been isolated from Sideritis candicans.     

Linkiol,a new sesquiterpene from Ferula linkii

A new sesquiterpene ester, linkiol with a daucane skeleton was isolated from Ferula linkii.