Hybridization and genetic population structure of Alosa population in the United Kingdom.

Human-mediated habitat fragmentation has been proposed as the main factor driving hybridization between the sympatric migratory European shads Alosa alosa and Alosa fallax, which has co-occurred with substantial population declines in A. alosa. In river systems across Great Britain, shad are negatively affected by navigation weirs constructed in the last 150 years that impede their spawning migrations.

The changing times of Europe's largest remaining commercially harvested population of eel Anguilla anguilla L.

This study quantifies the processes involved in regulating the European eel population of Lough Neagh, a lake in Northern Ireland. The relationship between glass eel input and silver eel output for the 1923-1997 cohorts was best described by a Beverton-Holt stock recruitment model. Glass eel input time series was not complete and was thus derived from the relationship between catches elsewhere in Europe and Lough Neagh, together with the addition of stocked glass eel.

Macromolecular modeling and design in Rosetta: recent methods and frameworks.

The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities.

Utility of Covalent Labeling Mass Spectrometry Data in Protein Structure Prediction with Rosetta.

Covalent labeling mass spectrometry experiments are growing in popularity and provide important information regarding protein structure. Information obtained from these experiments correlates with residue solvent exposure within the protein in solution. However, it is impossible to determine protein structure from covalent labeling data alone.

Improving inverse docking target identification with Z-score selection.

The utilization of inverse docking methods for target identification has been driven by an increasing demand for efficient tools for detecting potential drug side-effects. Despite impressive achievements in the field of inverse docking, identifying true positives from a pool of potential targets still remains challenging. Notably, most of the developed techniques have low accuracies, limit the pool of possible targets that can be investigated or are not easy to use for non-experts due to a lack of available scripts or webserver.

Rosetta Protein Structure Prediction from Hydroxyl Radical Protein Footprinting Mass Spectrometry Data.

In recent years mass spectrometry-based covalent labeling techniques such as hydroxyl radical footprinting (HRF) have emerged as valuable structural biology techniques, yielding information on protein tertiary structure. These data, however, are not sufficient to predict protein structure unambiguously, as they provide information only on the relative solvent exposure of certain residues. Despite some recent advances, no software currently exists that can utilize covalent labeling mass spectrometry data to predict protein tertiary structure.

Antitumor Effects of Lidocaine on Human Breast Cancer Cells: An and Experimental Trial.

Aim: Retrospective studies have suggested a protective effect of regional anesthesia against recurrence after cancer surgery. But confirmation of the in vivo antitumor effects is lacking. We examined the in vitro antitumor effects of lidocaine on various breast cancer cell lines and then assessed these properties in vivo at clinically relevant concentrations.

Successful Identification of Cardiac Troponin Calcium Sensitizers Using a Combination of Virtual Screening and ROC Analysis of Known Troponin C Binders.

Calcium-dependent cardiac muscle contraction is regulated by the protein complex troponin. Calcium binds to the N-terminal domain of troponin C (cNTnC) which initiates the process of contraction. Heart failure is a consequence of a disruption of this process.

Establishment and Characterization of a Novel Cell Line, ASAN-PaCa, Derived From Human Adenocarcinoma Arising in Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Objectives: Our aim was to establish and characterize a novel pancreatic ductal adenocarcinoma cell line from a patient in whom the origin of the invasive carcinoma could be traced back to the intraductal papillary mucinous neoplasm (IPMN) precursor lesion.

Methods: The primary patient-derived tumor was propagated in immunocompromised mice for 2 generations and used to establish a continuous in vitro culture termed ASAN-PaCa. Transplantation to fertilized chicken eggs confirmed the tumorigenic potential in vivo.

Survival variability of controls and definition of imaging endpoints for longitudinal follow-up of pancreatic ductal adenocarcinoma in rats.

Background: The 3Rs guideline is the gold standard for ethics in animal experimentation. Two of those rules, namely refinement and reduction, require further improvement. The objective of this study was to define pathways to better compliance with these prerequisites.

Feasibility and reliability of pancreatic cancer staging using a new confocal non-fluorescent microscopy probe: a double-blind study in rats.

Background: Surgical management of pancreatic cancer depends on tumor resectability and staging. Lymph node (LN) metastases represent an important decision-making factor when it comes to surgical treatment.

Aims: To evaluate a new in vivo, endoscopic confocal microscopy (CM) system not requiring fluorescence markers, for detection and staging of pancreatic cancer in rats.

Virotherapy of digestive tumors with rodent parvovirus: overview and perspectives.

Introduction: Toolan's H-1 parvovirus (H-1PV) exerts a cytotoxic/oncolytic effect, predominantly mediated by its non-structural protein (NS1). This rat parvovirus is harmless, unlike other parvoviruses, and its antitumor potential may be useful to clinicians as its oncolytic action appears to be true in numerous non-digestive and digestive cancers.

Areas Covered: After a brief review of parvovirus genus and biology, we summarize the proposed mechanisms to explain the cytotoxicity of H-1PV to tumors which results in dysregulation of cell transcription, cell-cycle arrest, termination of cell replication, activation of cellular stress response and induction of cell death.

Design and development of a robotized system coupled to µCT imaging for intratumoral drug evaluation in a HCC mouse model.

Hepatocellular carcinoma (HCC) is one of the most common cancer related deaths worldwide. One of the main challenges in cancer treatment is drug delivery to target cancer cells specifically. Preclinical evaluation of intratumoral drugs in orthotopic liver cancer mouse models is difficult, as percutaneous injection hardly can be precisely performed manually.

Complementary induction of immunogenic cell death by oncolytic parvovirus H-1PV and gemcitabine in pancreatic cancer.

Unlabelled: Novel therapies employing oncolytic viruses have emerged as promising anticancer modalities. The cure of particularly aggressive malignancies requires induction of immunogenic cell death (ICD), coupling oncolysis with immune responses via calreticulin, ATP, and high-mobility group box protein B1 (HMGB1) release from dying tumor cells. The present study shows that in human pancreatic cancer cells (pancreatic ductal adenocarcinoma [PDAC] cells n=4), oncolytic parvovirus H-1 (H-1PV) activated multiple interconnected death pathways but failed to induce calreticulin exposure or ATP release.

Myo-inositol trispyrophosphate-mediated hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficacy.

Hypoxia and dysfunctional tumor vessels represent a prominent feature of pancreatic cancer, being, at least in part, responsible for chemotherapy resistance and immune suppression in these tumors. We tested whether the increase of oxygen delivery induced in vivo by myo-inositol trispyrophosphate (ITPP) can reverse hypoxia, control tumor growth and improve chemotherapy response. Tumor size, metastatic development (microcomputed tomography scan follow-up) and the survival of rats and nude or NOD.

Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas.

The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA).

Increasing the oxygen load by treatment with myo-inositol trispyrophosphate reduces growth of colon cancer and modulates the intestine homeobox gene Cdx2.

Preventing tumor neovascularisation is one of the strategies recently developed to limit the dissemination of cancer cells and apparition of metastases. Although these approaches could improve the existing treatments, a number of unexpected negative effects have been reported, mainly linked to the hypoxic condition and the subsequent induction of the pro-oncogenic hypoxia inducible factor(s) resulting from cancer cells' oxygen starvation. Here, we checked in vivo on colon cancer cells an alternative approach.

Interferon γ improves the vaccination potential of oncolytic parvovirus H-1PV for the treatment of peritoneal carcinomatosis in pancreatic cancer.

Oncolytic viruses with their capacity to specifically replicate in and kill tumor cells emerged as a novel class of cancer therapeutics. Rat oncolytic parvovirus (H-1PV) was used to treat different types of cancer in preclinical settings and was lately successfully combined with standard gemcitabine chemotherapy in treating pancreatic ductal adenocarcinoma (PDAC) in rats. Our previous work showed that the immune system and particularly the release of interferon-gamma (IFNγ) seem to mediate the anticancer effect of H-1PV in that model.

[Contribution of microCT structural imaging to preclinical evaluation of hepatocellular carcinoma chemotherapeutics on orthotopic graft in ACI rats].

Animal experimentation is a prerequisite for preclinical evaluation of treatments such as chemotherapy. It's strictly regulated with the purpose of reducing the number of experimental animal as well as their pain. Small animal imaging should provide a painless longitudinal follow up of tumor progression on a single animal.

Myo-InositolTrisPyroPhosphate treatment leads to HIF-1α suppression and eradication of early hepatoma tumors in rats.

Myo-inositol trispyrophosphate (ITPP), a synthetic allosteric effector of hemoglobin, increases the regulated oxygen-releasing capacity of red blood cells (RBCs), leading to suppression of hypoxia-inducible factor 1α (HIF-1α) and to down-regulation of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF). As a consequence, tumor growth is markedly affected. The effect of weekly intravenous injection of ITPP on an orthotopic, syngenic rat hepatocellular carcinoma (HCC) model was compared to that for untreated animals and animals subjected to conventional Doxorubicin chemotherapy.

Immune cells participate in the oncosuppressive activity of parvovirus H-1PV and are activated as a result of their abortive infection with this agent.

Treatment of cancers by means of viruses, that specifically replicate in (oncotropism) and kill (oncolysis) neoplastic cells, is increasingly gaining acceptance in the clinic. Among these agents, parvoviruses have been shown to possess not only direct oncolytic but also immunomodulating properties, serving as an adjuvant to prime the immune system to react against infected tumors. Here, we aimed to establish whether immunomodulating mechanisms participate in the recently reported therapeutic potential of parvoviruses against pancreatic carcinoma.

Climate change and the green energy paradox: the consequences for twaite shad Alosa fallax from the River Severn, U.K.

A stock-recruitment model with a temperature component was used to estimate the effect of an increase in temperature predicted by climate change projections on population persistence and distribution of twaite shad Alosa fallax. An increase of 1 and 2° C above the current mean summer (June to August) water temperature of 17·8° C was estimated to result in a three and six-fold increase in the population, respectively. Climate change is also predicted to result in an earlier commencement to their spawning migration into fresh water.

Feasibility and reliability of pancreatic cancer staging using fiberoptic confocal fluorescence microscopy in rats.

Background & Aims: Surgical management of pancreatic cancer depends on tumor resectability and staging. This study evaluated a new in vivo technique, fiberoptic confocal fluorescence microscopy (FCFM), for detection and staging of pancreatic tumors in rats.

Methods: FCFM was used with a protease-activated fluorescent marker (ProSense; VisEn Medical Inc, Woburn, MA) for in vivo imaging of solid organs (1.

Oncolytic rat parvovirus H-1PV, a candidate for the treatment of human lymphoma: In vitro and in vivo studies.

The incidence of lymphomas developing in both immunocompetent and immunosuppressed patients continues to steadily increase worldwide. Current chemotherapy and immunotherapy approaches have several limitations, such as severe side toxicity and selection of resistant cell variants. Autonomous parvoviruses (PVs), in particular the rat parvovirus H-1PV, have emerged as promising anticancer agents.

Improvement of gemcitabine-based therapy of pancreatic carcinoma by means of oncolytic parvovirus H-1PV.

Unlabelled: Pancreatic carcinoma is a gastrointestinal malignancy with poor prognosis. Treatment with gemcitabine, the most potent chemotherapeutic against this cancer up to date, is not curative, and resistance may appear. Complementary treatment with an oncolytic virus, such as the rat parvovirus H-1PV, which is infectious but nonpathogenic in humans, emerges as an innovative option.