The systemic administration of neural stem cells expressing an inducible and soluble form of growth arrest specific 1 inhibits mammary gland tumor growth and the formation of metastases

Background aimsMetastasis to different organs is the major cause of death in breast cancer patients. The poor clinical prognosis and lack of successful treatments for metastatic breast cancer patients demand the development of new tumor-selective therapies. Thus, it is necessary to develop treatments capable of releasing therapeutic agents to both primary tumors and metastases that avoid toxic side effects in normal tissue, and neural stem cells are an attractive vehicle for tracking tumor cells and delivering anti-cancer agents. The authorspreviously demonstrated that a soluble form of growth arrest specific 1 (GAS1) inhibits the growth of triple-negative breast tumors and glioblastoma.MethodsIn this study, the authors engineered ReNcell CX (EMD Millipore, Temecula, CA, USA) neural progenitor cells to express truncated GAS1 (tGAS1) under a tetracycline/on inducible system using lentiviral vectors.ResultsHere the authors show that treatment with ReNcell-tGAS1 in combination with tetracycline decreased primary tumor growth and inhibited the formation of metastases in tumor-bearing mice by diminishing the phosphorylation of AKT and ERK1/2 in orthotopic mammary gland tumors. Moreover, the authors observed that ReNcell-tGAS1 prolonged the survival of 4T1 tumor-bearing mice.ConclusionsThese data suggest that the delivery of tGAS1 by ReNcell cells could be an effective adjuvant for the treatment of triple-negative breast cancer.     

PEtab—Interoperable specification of parameter estimation problems in systems biology

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.     

Mechanics of the maxillary central incisor. Influence of the periodontal ligament represented by beam elements

This study aimed to evaluate the influence of loading on a maxillary central incisor with the periodontal ligament (PDL) represented by 2D elastic beam elements using a 2D finite element analysis. Two models (M) were built varying the PDL representation: Mh (homogeneous PDL) and Mht (heterogeneous PDL with beam3 elements). Stress and displacements were determined for three loading conditions (L): Ll, lingual face loading at 45° with the tooth long axis; Li, perpendicular to the incisal edge; and Lip, on the incisal edge, parallel to the tooth long axis. Evaluation was performed on ANSYS software. Lip provided lower stress variation on the tooth and support structures when compared to Ll and Li. PDL's influence on stress values was lower for Lip. Oblique loading showed stress and displacement not observed in parallel loading condition through PDL's heterogeneous representation and it is probably incompatible with the in vivo condition.     

The Deubiquitinating Enzyme AMSH1 and the ESCRT-III Subunit VPS2.1 Are Required for Autophagic Degradation in Arabidopsis

In eukaryotes, posttranslational modification by ubiquitin regulates the activity and stability of many proteins and thus influences a variety of developmental processes as well as environmental responses. Ubiquitination also plays a critical role in intracellular trafficking by serving as a signal for endocytosis. We have previously shown that the Arabidopsis thaliana ASSOCIATED MOLECULE WITH THE SH3 DOMAIN OF STAM3 (AMSH3) is a deubiquitinating enzyme (DUB) that interacts with ENDOSOMAL COMPLEX REQUIRED FOR TRANSPORT-III (ESCRT-III) and is essential for intracellular transport and vacuole biogenesis. However, physiological functions of AMSH3 in the context of its ESCRT-III interaction are not well understood due to the severe seedling lethal phenotype of its null mutant. In this article, we show that Arabidopsis AMSH1, an AMSH3-related DUB, interacts with the ESCRT-III subunit VACUOLAR PROTEIN SORTING2.1 (VPS2.1) and that impairment of both AMSH1 and VPS2.1 causes early senescence and hypersensitivity to artificial carbon starvation in the dark similar to previously reported autophagy mutants. Consistent with this, both mutants accumulate autophagosome markers and accumulate less autophagic bodies in the vacuole. Taken together, our results demonstrate that AMSH1 and the ESCRT-III-subunit VPS2.1 are important for autophagic degradation and autophagy-mediated physiological processes.     

Polygonum nepalense Meisn. avventizia nel Bellunese

Abstract

Polygonum nepalense Meisn. has been found naturalteed together with Collomia linearis Nutt. near Belluno, Northern Italy. Polygonum nepalense belongs to the Cephalophilon-Section, an annual with creeping-ascending branched stems, winged petioles and 2 rounded, basal auricles, leaf-blade ovate-triangular, somehow fleshy, ochreas tubular with a tuft of hairs at the base, peduncles glandular-pubescent; spikes globose, densely flowered, styles 2 (seldom 3), nutlets trigonous, dark-brown, about 1-1.5 mm long. This species has not been indicated yet in the Alps but is cited as a rather common one in humid localities, damp woods in mountains, tea- and chinchona-plantations in Asia and India. Abundant on the Himalaya up to 10,000 ft., known also in Bengal, Ceylon, Assam, Burma, China, Java, Formosa, Japan and Abyssinia.     

Melatonin Prevents Oxidative Stress and Hepatocyte Cell Death Induced by Experimental Cholestasis

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.     

Building Blocks for Synthesis of Oligoarabinonucleotides: Preparation of Arabinonucleoside H-Phosphonates from Protected Ribonucleosides

Abstract

A straightforward and inexpensive synthesis of arabinonucleoside H-phosphonates has been developed. Arabinonucleosides were synthesised from protected ribonucleosides via 2′-keto derivatives. Reaction conditions have been optimised for compounds bearing labile N-protections. Further protecting group manipulation and phosphonylation gave the required H-phosphonate monomers.     

Recreational boats as a vector of secondary spread for aquatic invasive species and native crustacean zooplankton

Recreational boats in tow between lakes are a known vector of the spread of aquatic invading species (AIS), but we have no test of the hypothesis that recreational boats are also a vector of secondary spread of AIS among freshwater ecosystems via in-water transport i.e., while boating between interconnected waterways. In this study, we surveyed recreational boaters travelling into Lake Simcoe (44°25′N, 79°20′W), Ontario, Canada, on their recreational activities, boat maintenance, and travel destinations, measured the degree of vessel fouling, and sampled all standing water and attached macrophytes associated with their vessels. A total of 321 zooplankton individuals comprising 15 different species were collected from the standing water in vessels, including veligers of the invasive zebra mussel Dreissena. The volume of water collected within the vessels significantly increased the number of zooplankton transported. Zooplankton species from pelagic habitats or with planktonic life stages were collected more frequently than species that occupy littoral or benthic habitats, likely reflecting the recreational activities of boaters. Patterns of boater activities, movements and hygiene habits, suggest recreational boating in the Lake Simcoe region is contributing to the spread of native and invasive species into nearby waterways. Our study validates the widespread assumption that recreational boats are an important in-water vector for the secondary spread of both native and invasive zooplankton species. Future management strategies to reduce the spread of AIS should be aimed at increasing awareness of boater hygiene practices, particularly the frequent draining of standing water.