New non-symmetrical choline kinase inhibitors.

Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. Choline kinase (ChoK) is the first enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine (PC), the major phospholipid in eukaryotic cell membranes. In the present paper, a new family of non-symmetrical monocationic compounds is developed including a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers.

Bis(carbazolyl)ureas as selective receptors for the recognition of hydrogenpyrophosphate in aqueous media.

Recognition properties of the novel bis(carbazole) tris-ureidic-based receptors 1 and 2 toward different anions have been studied by (1)H NMR and absorption and emission spectroscopy, as well as by DFT calculations. Receptor 1, in which the two urea-functionalized arms are decorated with p-nitrophenyl rings, behaves as a highly selective chromogenic molecular probe for hydrogenpyrophosphate anion in a competitive medium (acetonitrile/water, 70/30). Receptor 2, bearing two urea arms decorated with photoactive pyrenyl rings, acts as a highly selective fluorescent molecular probe for hydrogenpyrophosphate anion in either acetonitrile or an aqueous mixture (acetonitrile/water, 85/15).

A densely decorated disubstituted ferrocene as an ion-pair recognition receptor.

A functionalized 1,1'-disubstituted ferrocene acts as an electro-optical ion-pair receptor for Mg(2+), Ca(2+), Cd(2+), and Zn(2+) cations in the presence of a co-bound H2PO4(-) anion, through perturbation of the redox potential of the ferrocene unit, enhancement of the fluorescence and a noticeable colour change.

Expression of the immune regulator tripartite-motif 21 is controlled by IFN regulatory factors.

Tripartite-motif 21 (TRIM21) is an E3 ubiquitin ligase that regulates innate immune responses by ubiquitinating IFN regulatory factors (IRFs). TRIM21 is mainly found in hematopoietic cells in which its expression is induced by IFNs during viral. infections and in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome.

New steroidal 7-azaindole platinum(II) antitumor complexes.

Two new steroidal 7-azaindole-based N-donor ligands 17-α-[7-azaindole-5-ethynyl]-17-β-testosterone (ET-Haza) (1) and 17-α-[7-azaindole-5-ethynyl]-19-nortestosterone (LEV-Haza) (2), and two new DNA damaging warheads with an enhanced lipophilicity [Pt(dmba)Cl(L)] (dmba=N,N-dimethylbenzylamine-κN,κC; L=ET-Haza (3) and LEV-Haza (4)) have been prepared and characterized. Values of IC50 were calculated for complexes 3 and 4 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cis) and breast cancers (T47D). At 48 h of incubation time 3 and 4 showed very low resistance factors (RF of 1) against an A2780 cell line which has acquired resistance to cisplatin, IC50 values of the new complexes towards normal human LLC-PK1 renal cells at 48 h being about double than that of cisplatin.

Cajal-Retzius cells instruct neuronal migration by coincidence signaling between secreted and contact-dependent guidance cues.

Cajal-Retzius (CR) cells are a transient cell population of the CNS that is critical for brain development. In the neocortex, CR cells secrete reelin to instruct the radial migration of projection neurons. It has remained unexplored, however, whether CR cells provide additional molecular cues important for brain development.

Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung.

Purpose: Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.

Experimental Design: We conducted a meta-analysis of seven independent datasets containing a total of 593 human primary SCC samples to identify consensus candidate drivers in 3q26-29 amplicon.

Bulky dna adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother-child study (NewGeneris).

Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs.

Insulin-dependent H2O2 production is higher in muscle fibers of mice fed with a high-fat diet.

Insulin resistance is defined as a reduced ability of insulin to stimulate glucose utilization. C57BL/6 mice fed with a high-fat diet (HFD) are a model of insulin resistance. In skeletal muscle, hydrogen peroxide (H2O2) produced by NADPH oxidase 2 (NOX2) is involved in signaling pathways triggered by insulin.

Outbreak of multiresistant OXA-24- and OXA-51-producing Acinetobacter baumannii in an internal medicine ward.

Here we describe the clinical, microbiological, epidemiological, and molecular characterization of an outbreak of multidrug-resistant Acinetobacter baumannii (MRAB) involving 5 patients admitted to the internal medicine ward of our hospital. Over a 6-week period, 5 MRAB isolates were recovered from 5 patients, including 1 with fatal meningitis, 3 with skin and soft tissue infections, and 1 with respiratory colonization. One sample obtained during environmental monitoring in the ward was A.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls).

Dermoscopy of non-pigmented eccrine poromas: study of Mexican cases.

Background: Eccrine poroma is a benign neoplasm that can mimick a malignant neoplasm dermoscopically. The characteristic vascular pattern of this tumor has not been established.

Objective: To evaluate dermoscopic features of non-pigmented eccrine poroma in Mexican patients.

Reaction of Li/Cl phosphinidenoid complexes with a phosphite substituted ketone: access to complexes with a novel mixed-valence polycyclic P,C-ligand system.

Reaction of Li/Cl phosphinidenoid pentacarbonyltungsten(0) complexes 2a,b (R = CH(SiMe3)2, Cp*) with bifunctional phosphite-substituted ketone 3 yielded tungsten complexes 4a,b having a novel mixed-valence polycyclic P,C-cage ligand with a P–P bond. DFT calculations provide insight into an unusual product formation pathway.

Williams' neural stem cells: new model for insight into microRNA dysregulation.

Williams syndrome (WS) is a neurodevelopmental genetic disorder, due to a 7q11.23 hemizygous deletion. WS has a characteristic neurocognitive profile that includes intellectual disability (ID).

Synthesis and DFT calculations of spirooxaphosphirane complexes.

In situ formed Li/Cl phosphinidenoid complexes [Li(12-crown-4)][M(CO)5(ClPC5Me5)] 3a-c (M = Cr, Mo, W) reacted with cyclobutanone (4), cyclopentanone (5) and cyclohexanone (6) in Et2O to yield the first P-C5Me5 substituted C(3)-spirofused oxaphosphirane complexes 7a-c, 8a and 9a,a'. In the case of cyclopentanone and 1a the outcome of the reaction in THF was different: here the formation of 8a along with (anionic) phosphinoate complexes 14a and 15a was observed, the latter possess an unusual ring-opened oxaphosphirane and 2-cyclopentylidenecyclopentanone as co-ligands to the lithium cation. NMR, IR and MS data as well as single-crystal X-ray structures in the case of 7a-c, 8a, 9a and 15a are reported.

Rickettsia spp. 364D causing a cluster of eschar-associated illness, California.

We describe the clinical course of the first 3 pediatric cases infected with Rickettsia spp. 364D. Although the pathogen was identified in California ticks decades ago, only recently have human cases been documented.

Occupational exposure to immunologically active agents and risk for lymphoma: the European Epilymph case-control study.

Objectives: Allergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma.

Methods: The Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998-2004.

The mechanism of allosteric coupling in choline kinase α1 revealed by the action of a rationally designed inhibitor.

Applying a CHOK hold: Combined experimental and computational studies of the binding mode of a rationally designed inhibitor of the dimeric choline kinase α1 (CHOKα1) explain the molecular mechanism of negative cooperativity (see scheme) and how the monomers are connected. The results give insight into how the symmetry of the dimer can be partially conserved despite a lack of conservation in the static crystal structures.

Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer.

The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it's still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets.

Detection of Epstein-Barr virus and genotyping based on EBNA2 protein in Mexican patients with hodgkin lymphoma: a comparative study in children and adults.

Background: Epstein-Barr virus (EBV) is a member of the Herpesviridae family and is associated with Hodgkin lymphoma (HL). Isolates of EBV are classified according to sequence variation in the latency genes such as Epstein-Barr virus nuclear antigen (EBNA). EBNA2 contains the most divergent locus and is classified into type 1 and type 2 or EBNA2A and EBNA2B, respectively.

Galapagos III World Evolution Summit: why evolution matters.

There is no place on Earth like the Galapagos Islands and no better destination to discuss the reality of evolution. Under the theme 'Why Does Evolution Matter', the University San Francisco of Quito (USFQ), Ecuador, and its Galapagos Institute for the Arts and Sciences (GAIAS), organized the III World Evolution Summit in San Cristóbal Island. The 200-attendee meeting took place on 1 to 5 June 2013; it included 12 keynote speakers, 20 oral presentations by international scholars, and 31 posters by faculty, postdocs, and graduate and undergraduate students.

Electrical stimuli release ATP to increase GLUT4 translocation and glucose uptake via PI3Kγ-Akt-AS160 in skeletal muscle cells.

Skeletal muscle glucose uptake in response to exercise is preserved in insulin-resistant conditions, but the signals involved are debated. ATP is released from skeletal muscle by contractile activity and can autocrinely signal through purinergic receptors, and we hypothesized it may influence glucose uptake. Electrical stimulation, ATP, and insulin each increased fluorescent 2-NBD-Glucose (2-NBDG) uptake in primary myotubes, but only electrical stimulation and ATP-dependent 2-NBDG uptake were inhibited by adenosine-phosphate phosphatase and by purinergic receptor blockade (suramin).

A longitudinal follow-up of 550 mild cognitive impairment patients: evidence for large conversion to dementia rates and detection of major risk factors involved.

The most recent studies about mild cognitive impairment (MCI) are focused on the search for factors that make patients more vulnerable to conversion to dementia, mainly Alzheimer's disease (AD). The aim of this study was to determine which neuropsychological test performances, including episodic memory profiles, and genetic risk factors (APOE ε4) better predict early conversion to dementia among the four MCI subtypes. Data from 550 MCI patients were analyzed for the purpose of this study and were classified according to Petersen's criteria (2004), and also taking into account the absence (probable MCI) or presence (possible MCI) of comorbidities that could explain cognitive deficits.

Matrix and interaction effects on the magnetic properties of Co nanoparticles embedded in gold and vanadium.

The study of the magnetic properties of Co nanoparticles (with an average diameter of 10.3 nm) grown using a gas-phase aggregation source and embedded in Au and V matrices is presented. We investigate how the matrix, the number of embedded nanoparticles (counted by coverage percentage), the interparticle interactions and the complex nanoparticles/matrix interface structure define the magnetic properties of the studied systems.