Guatemalan plants extracts as virucides against HIV-1 infection

Prevention methods to avoid transmission of pathogens, including HIV, are crucial in the control of infectious diseases, not only to block epidemic spread but to avoid long-term treatments leading to emergence of resistances and drug associated side effects. Together with vaccine development, the discovery of new virucidal agents represents a research priority in this setting. In the screening of new compounds with antiviral activity, three Guatemalan plant extracts from Justicia reptans, Neurolaena lobata and Pouteria viridis were evaluated with a classic antiviral assay and were found to inhibit HIV replication. This activity was corroborated by an original recombinant virus assay, leading us to perform a deeper study of the virucidal activity. Active fractions were non-toxic in vitro and also inhibited other enveloped viruses. Moreover, these fractions were able to inhibit the transfer of HIV from dendritic cells (DCs) to lymphocytes, that represents the main way of HIV spread in vivo.     

Synthesis, structure and biological activity of a new and efficient Cd(II)–uracil derivative complex system for cleavage of DNA

The new complex formed by Cd(II) and the 1:2 Schiff-base-type ligand 2,6-bis[1-(4-amino-1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)imino]ethylpyridine (DAPDAAU) has been chemically and structurally characterized by X-ray diffraction: the ion Cd(II) is surrounded by six nitrogen atoms from two DAPDAAU ligands which coordinates each one in a tridentate fashion through the pyridine ring (N1) and both azomethine nitrogen atoms (N5). The interaction of the Cd(II) complex (compound I) with calf-thymus DNA as observed by circular dichroism spectroscopy suggests the initial unwinding of the DNA double helix strongly depends on increasing incubation times and metal-to-nucleic acid molar ratios. Electrophoretic experiments indicate that the cadmium complex induces cleavage of the plasmid pBR322 DNA to give ulterior nicking and shortening of this molecule, as a result of the complex binding to DNA, resulting in the conclusion that compound I behaves as a chemical nuclease. Cytotoxic activity of the Cd(II) complex against selected different human cancer cell lines is specific and increases with increasing concentration of the metal compound; this fact indicates the potential antitumor character of the complex. When the culture medium is supplemented with compound I, a remarkable inhibition of the growing cell is observed, important cell degeneration appears before 48 h and abundant precipitates are formed that correspond to cell residues and denatured proteins. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Assessing effects of fishing prohibition on Posidonia oceanica seagrass meadows in the Marine Natural Reserve of Cerbère-Banyuls

The potential of alleviated fishing pressure measures established at the Marine Natural Reserve of Cerbère-Banyuls to affect phenological characters of P. oceanica, the main canopy-forming seagrass, was studied. Our results show differences in some leaf parameters between meadows under fishing prohibition measures compared to those without. In addition shallow P. oceanica meadows inside MPAs had lower non-structural carbohydrate content, yet are able to maintain themselves and, moreover, with an increased density. On the other hand, sexual reproduction was reduced inside protected areas.     

A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case–control study

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with around 9% of patients surviving >5 years. Asymptomatic in its initial stages, PDAC is mostly diagnosed late, when already a locally advanced or metastatic disease, as there are no useful biomarkers for detection in its early stages, when surgery can be curative. We have previously described a promising biomarker panel (LYVE1, REG1A, and TFF1) for earlier detection of PDAC in urine. Here, we aimed to establish the accuracy of an improved panel, including REG1B instead of REG1A, and an algorithm for data interpretation, the PancRISK score, in additional retrospectively collected urine specimens. We also assessed the complementarity of this panel with CA19-9 and explored the daily variation and stability of the biomarkers and their performance in common urinary tract cancers.Methods and findingsClinical specimens were obtained from multiple centres: Barts Pancreas Tissue Bank, University College London, University of Liverpool, Spanish National Cancer Research Center, Cambridge University Hospital, and University of Belgrade. The biomarker panel was assayed on 590 urine specimens: 183 control samples, 208 benign hepatobiliary disease samples (of which 119 were chronic pancreatitis), and 199 PDAC samples (102 stage I–II and 97 stage III–IV); 50.7% were from female individuals. PDAC samples were collected from patients before treatment. The samples were assayed using commercially available ELISAs. Statistical analyses were performed using non-parametric Kruskal–Wallis tests adjusted for multiple comparisons, and multiple logistic regression. Training and validation datasets for controls and PDAC samples were obtained after random division of the whole available dataset in a 1:1 ratio. The substitution of REG1A with REG1B enhanced the performance of the panel to detect resectable PDAC. In a comparison of controls and PDAC stage I–II samples, the areas under the receiver operating characteristic curve (AUCs) increased from 0.900 (95% CI 0.843–0.957) and 0.926 (95% CI 0.843–1.000) in the training (50% of the dataset) and validation sets, respectively, to 0.936 in both the training (95% CI 0.903–0.969) and the validation (95% CI 0.888–0.984) datasets for the new panel including REG1B. This improved panel showed both sensitivity (SN) and specificity (SP) to be >85%. Plasma CA19-9 enhanced the performance of this panel in discriminating PDAC I–II patients from controls, with AUC = 0.992 (95% CI 0.983–1.000), SN = 0.963 (95% CI 0.913–1.000), and SP = 0.967 (95% CI 0.924–1.000). We demonstrate that the biomarkers do not show significant daily variation, and that they are stable for up to 5 days at room temperature. The main limitation of our study is the low number of stage I–IIA PDAC samples (n = 27) and lack of samples from individuals with hereditary predisposition to PDAC, for which specimens collected from control individuals were used as a proxy.ConclusionsWe have successfully validated our urinary biomarker panel, which was improved by substituting REG1A with REG1B. At a pre-selected cutoff of >80% SN and SP for the affiliated PancRISK score, we demonstrate a clinically applicable risk stratification tool with a binary output for risk of developing PDAC (‘elevated’ or ‘normal’). PancRISK provides a step towards precision surveillance for PDAC patients, which we will test in a prospective clinical study, UroPanc.

Silvana Debernardi and colleagues establish a clinical risk score and a biomarker panel for early detection of pancreatic cancer.     

The real-life value of ST2 monitoring during heart failure decompensation: impact on long-term readmission and mortality

Context: Prognostic value of ST2 levels and dynamics has not been investigated in acute heart failure (AHF) using prospective real-life measurements.

Objective: The objective of this study is to investigate the prognostic value of ST2 in AHF.

Methods: ST2 levels were determined at admission (n?=?182) and discharge (n?=?85). Primary endpoint was the composite of all-cause death and HF rehospitalisation at one year.

Results: Discharge ST2 (HR 2.42 [95% CI 1.46–4], p?=?0.001) and ΔST2 (HR 2.32 [95% CI 1.21–4.57], p?=?0.01) but not admission ST2, remained independently prognostic for the primary endpoint after comprehensive multivariable adjustment. ST2 significantly improved prognosis stratification on top of clinical variables and NTproBNP.

Conclusions: Routine clinical use of discharge ST2 and ST2 dynamics provide independent prognostic information.     

Analysis of formin functions during cytokinesis using specific inhibitor SMIFH2

The phragmoplast separates daughter cells during cytokinesis by constructing the cell plate, which depends on interaction between cytoskeleton and membrane compartments. Proteins responsible for these interactions remain unknown, but formins can link cytoskeleton with membranes and several members of formin protein family localize to the cell plate. Progress in functional characterization of formins in cytokinesis is hindered by functional redundancies within the large formin gene family. We addressed this limitation by employing Small Molecular Inhibitor of Formin Homology 2 (SMIFH2), a small-molecule inhibitor of formins. Treatment of tobacco (Nicotiana tabacum) tissue culture cells with SMIFH2 perturbed localization of actin at the cell plate; slowed down both microtubule polymerization and phragmoplast expansion; diminished association of dynamin-related proteins with the cell plate independently of actin and microtubules; and caused cell plate swelling. Another impact of SMIFH2 was shortening of the END BINDING1b (EB1b) and EB1c comets on the growing microtubule plus ends in N. tabacum tissue culture cells and Arabidopsis thaliana cotyledon epidermis cells. The shape of the EB1 comets in the SMIFH2-treated cells resembled that of the knockdown mutant of plant Xenopus Microtubule-Associated protein of 215 kDa (XMAP215) homolog MICROTUBULE ORGANIZATION 1/GEMINI 1 (MOR1/GEM1). This outcome suggests that formins promote elongation of tubulin flares on the growing plus ends. Formins AtFH1 (A. thaliana Formin Homology 1) and AtFH8 can also interact with EB1. Besides cytokinesis, formins function in the mitotic spindle assembly and metaphase to anaphase transition. Our data suggest that during cytokinesis formins function in: (1) promoting microtubule polymerization; (2) nucleating F-actin at the cell plate; (3) retaining dynamin-related proteins at the cell plate; and (4) remodeling of the cell plate membrane.

Formins regulate phragmoplast expansion, microtubule turnover rate, actin nucleation, and cell plate membrane remodeling during cytokinesis.     

Localization of Nickel in Tissues of Streptanthus polygaloides Gray (Cruciferae) and Endemic Nickel Hyperaccumulators from California

The genus Streptanthus Nutt. is one of the most important indicators of ultramafic floras in western North America. This genus contains taxa that are endemic or tolerant of ultramafic soils. Streptanthus polygaloides is an annual nickel hyperaccumulator strictly confined to ultramafic soils throughout the Californian Sierra Nevada foothills. Nickel concentration in S. polygaloides populations was evaluated by elemental microanalysis using inductively coupled plasma mass spectrometry (ICP-MS). Representative samples of S. polygaloides roots, stems, leaves, flowers, and fruits were studied by scanning electron microscopy (SEM) coupled to an energy-dispersive X-ray probe (SEM-EDX). Results show Ni accumulation values between 0.09 and 1.18 %, and a distribution pattern similar to that observed in other Ni hyperaccumulator taxa, with the leaf epidermis accumulating the largest concentrations.