Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.

Neglected tropical diseases (NTDs) are a group of diseases that, besides prevailing in poverty conditions, contribute to the maintenance of social inequality, being a strong barrier to a country development. Schistosomiasis, a NTD, is a tropical and subtropical disease caused by the trematode Schistosoma mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum (China, Indonesia, the Philippines), mekongi (several districts of Cambodia and the Lao People's Democratic Republic), intercalatum and guianensis (areas of tropical rainforests in Central Africa) and hematobium (Middle East Africa, Corsica, France) whose adult forms inhabit the mesenteric vessels of the host, while the intermediate forms are found in the aquatic gastropod snails of the genus Biomphalaria. Currently, praziquantel (PZQ) is the first line drug chosen for the treatment of schistosomiasis according to the World Health Organization (WHO) Model List of Essential Medicines, 2015.

Survival and prognostic factors after adjuvant iodine-labeled lipiodol for hepatocellular carcinoma: a retrospective analysis of 106 patients over 20 years.

Objective: Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up.

Methods: All patients treated with I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study.

New Ulvan-Degrading Polysaccharide Lyase Family: Structure and Catalytic Mechanism Suggests Convergent Evolution of Active Site Architecture.

Ulvan is a complex sulfated polysaccharide biosynthesized by green seaweed and contains predominantly rhamnose, xylose, and uronic acid sugars. Ulvan-degrading enzymes have only recently been identified and added to the CAZy ( www.cazy.

Depolymerization of Pseudomonas stutzeri exopolysaccharide upon fermentation as a promising production process of antibacterial compounds.

Many researchers have focused on high molecular weight (M) exopolysaccharides (EPS) as a source of potentially bioactive lower M derivatives. Therefore, it is of interest to find means for efficient and safe production of depolymerized-polymer derivatives. Exopolysaccharide-depolymerization products (EDP) varying in molecular weight were recovered from fermentative depolymerization of a native EPS produced by Pseudomonas stutzeri AS22.

94 β-Decay Half-Lives of Neutron-Rich _{55}Cs to _{67}Ho: Experimental Feedback and Evaluation of the r-Process Rare-Earth Peak Formation.

The β-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of β-decay half-lives are observed at neutron-number N=97 for _{58}Ce, _{59}Pr, _{60}Nd, and _{62}Sm, and N=105 for _{63}Eu, _{64}Gd, _{65}Tb, and _{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure.

SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle.

Key Points: Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent.

Band instability in near-critical fluids subjected to vibration under weightlessness.

Periodical patterns (bands) developing at the interface of two immiscible fluids under vibration parallel to interface are observed under zero-gravity conditions. Fluids are slightly below their liquid-vapor critical point where they behave in a scaled, universal manner. In addition, liquid and vapor densities are close and surface tension is very low.

RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo.

Fibroblasts are a main player in the tumor-inhibitory microenvironment. Upon tumor initiation and progression, fibroblasts can lose their tumor-inhibitory capacity and promote tumor growth. The molecular mechanisms that underlie this switch have not been defined completely.

Active wideband higher-order raypath separation in multipath environment.

Multiple raypaths propagation is caused by reflection and refraction at the surface and the bottom of the water column. In this study, an active wideband higher-order separation is proposed, which enables the separation of raypaths interrupted by colored noise (as traditionally found in ocean environments) in the angle-vs-time domain. A comparative study shows that the proposed algorithm achieves a more accurate separation than other algorithms.

Oil-in-microgel strategy for enzymatic-triggered release of hydrophobic drugs.

Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-d-glucosamine and d-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified.

An iron(iii)-centred ferric wheel Fe⊂{Fe} with a siloxane-based bis-salicylidene Schiff base.

A new iron(iii)-centred ferric wheel Fe⊂{Fe} of the formula [Fe(HL)(NCS)](ClO)·10HO, where HL = N,N'-bis(3-carboxylsalicylidene)-1,3-bis(3-aminopropyl)tetramethyldisiloxane, was synthesised and fully characterised. Fe Mössbauer spectra indicate the presence of high spin (S = 5/2) Fe cations adopting a slightly different coordination environment in agreement with the X-ray diffraction structure. There are competing antiferromagnetic exchange interactions along the rim (J = -1.

Effect of reproductive ageing on pregnant mouse uterus and cervix.

Key Points: Older pregnant women have a greater risk of operative delivery, still birth and post-term induction. This suggests that maternal age can influence the timing of birth and processes of parturition. We have found that increasing maternal age in C57BL/6J mice is associated with prolongation of gestation and length of labour.

Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

Background: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms).

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine.

Alterations to mitochondrial fatty-acid use in skeletal muscle after chronic exposure to hypoxia depend on metabolic phenotype.

We investigated the effects of chronic hypoxia on the maximal use of and sensitivity of mitochondria to different substrates in rat slow-oxidative (soleus, SOL) and fast-glycolytic (extensor digitorum longus, EDL) muscles. We studied mitochondrial respiration in situ in permeabilized myofibers, using pyruvate, octanoate, palmitoyl-carnitine (PC), or palmitoyl-coenzyme A (PCoA). The hypophagia induced by hypoxia may also alter metabolism.

Receptor Tyrosine Kinases: Translocation Partners in Hematopoietic Disorders.

Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation.

Room Temperature Magnetic Switchability Assisted by Hysteretic Valence Tautomerism in a Layered Two-Dimensional Manganese-Radical Coordination Framework.

The manganese-nitronyl-nitroxide two-dimensional coordination polymer {[Mn(NITIm)]ClO} (1) (NITImH = 2-(2-imidazolyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-3-oxide-1-oxyl) undergoes an unusual hysteretic thermo-induced valence tautomeric transition near room temperature, during which the manganese(II) ions are oxidized to manganese(III) and two of the three deprotonated radicals (NITIm) are reduced to their diamagnetic aminoxyl form (denoted NIT). Upon cooling, the high-temperature species {[Mn(NITIm)]ClO} (1) turns into the low-temperature species {[Mn(NIT)(NITIm)]ClO} (1) around 274 K, while on heating the process is reversed at about 287 K. This valence tautomeric phenomenon is supported by temperature-dependent magnetic susceptibility measurements, differential scanning calorimetry (DSC), crystal structure determination, UV-vis absorption, X-ray absorption (XAS), and emission (XES) and electron paramagnetic resonance (EPR) spectroscopies in the solid state.

Morphological and functional imaging of neck paragangliomas.

Objective: To review the optimal techniques for localization and characterization of neck paragangliomas (PGL).

Material And Methods: Systematic review of the literature from the PubMed/Medline database.

Results: Neck PGL are hypervascular tumours essentially arising from paraganglionic tissue situated at the carotid bifurcation (carotid body) and along the vagus nerve.

Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for Efficient Cell Cycle Progression.

Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The alpha Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development.

Functional Characterization of a Central Core Disease RyR1 Mutation (p.Y4864H) Associated with Quantitative Defect in RyR1 Protein.

Background: Central Core Disease (CCD) is a congenital myopathy often resulting from a mutation in RYR1 gene. Mutations in RyR1 can increase or decrease channel activity, or induce a reduction in the amount of protein. The consequences of a single mutation are sometimes multiple and the analysis of the functional effects is complex.

MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion.

Cancer cells are permanently being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an increase of drug efflux.

Simultaneous observation of asymmetric speed-dependent capillary force hysteresis and slow relaxation of a suddenly stopped moving contact line.

We report direct atomic-force-microscope measurements of capillary force hysteresis (CFH) and relaxation of a circular moving contact line (CL) formed on a long micron-sized hydrophobic fiber intersecting a liquid-air interface. By using eight different liquid interfaces with varying solid-liquid molecular interactions, we find a universal behavior of the asymmetric speed dependence of CFH and CL relaxation. A unified model based on force-assisted barrier crossing is used to connect the mesoscopic measurements of CFH and CL relaxation with the energy barrier height E_{b} and size λ associated with the surface defects.

Common functions of the chloroplast and mitochondrial co-chaperones cpDnaJL (CDF1) and mtDnaJ (PAM16) in protein import and ROS scavenging in Arabidopsis thaliana.

As semi-autonomous cell organelles that contain only limited coding information in their own DNA, chloroplasts and mitochondria must import the vast majority of their protein constituents from the cytosol. Respective protein import machineries have been identified that mediate the uptake of chloroplast and mitochondrial proteins and interact with molecular chaperones of the HEAT-SHOCK PROTEIN (HSP) 70 family operating as import motors. Recent work identified unexpected new functions of 2 DnaJ co-chaperones in mitochondrial and chloroplast protein translocation and suggest a common mechanism of reactive oxygen species (ROS) scavenging that shall be discussed here.