The Synthesis,Crystal and Molecular Structure,and Oxidation State of Iron Complex from Pyridoxal Isonicotinoyl Hydrazone and Ferrous Sulphate

The reaction of isonicotinoyl hydrazone of pyridoxal (PIH), a biologically active iron-carrier, with FeSO₄-7H₂0 at pH ∼ 6 generates the delta, lamda species of the N,N-trans-O,O-cis-cis coordination isomer of an iron(III) complex with iron-to-ligand ratio of 1:2. The dark red-brown crystals are monoclinic, space group C2/c, with unit-cell dimensions a = 14.487(2), b = 18.586(2), c = 27.508(4) Å, β = 102.76(3)°, and Z = 8. The coordination around the metal is distorted octahedral and involves the protonated organic ligands, which are chelated through the phenolic oxygen [Fe-O1 1.941(6), Fe-O1′ 1.938(6)], an enolic form of the carbonyl oxygen [Fe-O3 2.017(6), Fe-O3′ 2.018(6)] and the azomethinic nitrogen [Fe-N2 2.133(8), Fe-N2′ 2.133(8)]. Packing is determined by systems of N-H….O and O-H….O hydrogen bonds involving the protonated pyridoxal nitrogens, the pyridoxal hydroxymethyl group, and the [SO₄]²⁻ group. The Mössbauer spectra at different temperatures (300 K, 88 K and 4.1 K) clearly prove that the iron atom in the complex is in a high-spin trivalent state.     

The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells

Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients, the cell’s morphology changes, NF-κB pathway is activated, and their beating rate and viability decreases. These results suggest an important link between OSAS, systemic inflammatory signals and end-organ cardiovascular diseases. In this work, we confirmed and expanded these observations on a new in vitro system of beating human cardiomyocytes (CM) differentiated from human embryonic stem cells (hES). Our results show that incubation with pediatric OSAS sera, in contrast to sera from healthy children, induces over-expression of NF-κB p50 and p65 subunits, marked reduction in CMs beating rate, contraction amplitude and a strong reduction in intracellular calcium signal. The use of human CM cells derived from embryonic stem cells has not been previously reported in OSAS research. The results further support the hypothesis that NF-κB dependent inflammatory pathways play an important role in the evolution of cardiovascular morbidity in OSAS. This study uncovers a new model to investigate molecular and functional aspects of cardiovascular pathology in OSAS.     

Transient charge accumulation in a capacitive self-assembled monolayer

Charge accumulation in an organosilane monolayer self-assembled on silicon is studied using electron-spectroscopy-based chemically resolved electrical measurements (CREM). By resolving the net electrical response of the organic layer, a significant capability of holding extra charge is indicated. Quantum size effects at a molecularly thin layer and the role of competing discharge mechanisms, including defect-assisted leakage currents, are discussed.     

Detection of multiple disease indicators by an autonomous biomolecular computer

The promise of biomolecular computers is their ability to interact with naturally occurring biomolecules, enabling in the future the development of context-dependent programmable drugs. Here we show a context-sensing mechanism of a biomolecular automaton that can simultaneously sense different types of molecules, allowing future integration of biomedical knowledge on a broad range of molecular disease symptoms in the decision of a biomolecular computer to release a drug molecule.     

An evaluation of the Brief Symptom Inventory–18 using item response theory: Which items are most strongly related to psychological distress?

The psychometric structure of the Brief Symptom Inventory–18 (BSI-18; Derogatis, 2001) was investigated using Mokken scaling and parametric item response theory. Data of 487 outpatients, 266 students, and 207 prisoners were analyzed. Results of the Mokken analysis indicated that the BSI-18 formed a strong Mokken scale for outpatients and prisoners, indicating strong unidimensionality. For students, only the depression and anxiety items formed a medium Mokken scale. Parametric item response theory analyses showed that the best discriminating items came from the depression and anxiety subscales. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer

TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA PAXIP1-AS2, which had no known function. Knocking down the expression of TENT4A or CYLD, or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase η, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.