Iron regulatory proteins secure mitochondrial iron sufficiency and function.

Mitochondria supply cells with ATP, heme, and iron sulfur clusters (ISC), and mitochondrial energy metabolism involves both heme- and ISC-dependent enzymes. Here, we show that mitochondrial iron supply and function require iron regulatory proteins (IRP), cytosolic RNA-binding proteins that control mRNA translation and stability. Mice lacking both IRP1 and IRP2 in their hepatocytes suffer from mitochondrial iron deficiency and dysfunction associated with alterations of the ISC and heme biosynthetic pathways, leading to liver failure and death.

Validation of measures of biosocial precursors to borderline personality disorder: childhood emotional vulnerability and environmental invalidation.

Linehan's biosocial theory suggests that borderline personality disorder (BPD) results from a transaction of two childhood precursors: emotional vulnerability and an invalidating environment. Until recently, few empirical studies have explored relationships between these theoretical precursors and symptoms of the disorder. Psychometrically sound assessment tools are essential to this area of research.

Total and cardiovascular disease mortality predicted by metabolic syndrome is inferior relative to its components.

Objectives: This study examined the predictive role of metabolic syndrome (MetS) and its single components for total and cardiovascular disease (CVD) mortality.

Methods: We analyzed data from 3,927 participants aged 20-79 years without history of CVD, recruited for the prospective population-based Study of Health in Pomerania (SHIP). During the mean 7.

New directions in the management of chronic pain: self-regulation theory as a model for integrative clinical psychology practice.

The next generation of empirically derived clinical health psychology involves use of self-regulation theory for understanding and treating chronic pain. Temporomandibular disorders serve as a model to illustrate how increasing self-regulatory strength facilitates small, behavioral changes that positively influence the underlying physiological factors known to be important in the etiology and maintenance of chronic pain conditions. For individuals with chronic temporomandibular disorders, physical self-regulation is an integrative clinical health psychology intervention that decreases both physical and psychological symptoms via improvements in self-regulatory strength and autonomic nervous system regulation.

ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency.

Embryonic stem cells (ESCs) are pluripotent, self-renewing, and have the ability to reprogram differentiated cell types to pluripotency upon cellular fusion. Polycomb-group (PcG) proteins are important for restraining the inappropriate expression of lineage-specifying factors in ESCs. To investigate whether PcG proteins are required for establishing, rather than maintaining, the pluripotent state, we compared the ability of wild-type, PRC1-, and PRC2-depleted ESCs to reprogram human lymphocytes.

SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.

DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells.

Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators.

Polycomb Repressor Complexes (PRCs) are important regulators of embryogenesis. In embryonic stem (ES) cells many genes that regulate subsequent stages in development are enriched at their promoters for PRC1, PRC2 and Ser 5-phosphorylated RNA Polymerase II (RNAP), and contain domains of 'bivalent' chromatin (enriched for H3K4me3; histone H3 di- or trimethylated at Lys 4 and H3K27me3; histone H3 trimethylated at Lys 27). Loss of individual PRC components in ES cells can lead to gene de-repression and to unscheduled differentiation.

Electrophysiological and neurochemical techniques to investigate sensory neurons in analgesia research.

The primary afferent nociceptive neuron has recently attracted major research interest because of the cloning of very selectively expressed and well-conserved ion channel genes. All parts of the neuron, sensory terminals, axon and cell body, are accessible to validated research techniques in vitro using various isolated tissues or cells taken from laboratory animals. Single-unit recording and measuring stimulated calcitonin gene-related peptide (CGRP) release as well as patch-clamping and calcium imaging of cultured sensory neurons provide different kinds of information, and no model alone answers all questions.

Mitochondrial reactive oxygen species control T cell activation by regulating IL-2 and IL-4 expression: mechanism of ciprofloxacin-mediated immunosuppression.

This article shows that T cell activation-induced expression of the cytokines IL-2 and -4 is determined by an oxidative signal originating from mitochondrial respiratory complex I. We also report that ciprofloxacin, a fluoroquinolone antibiotic, exerts immunosuppressive effects on human T cells suppressing this novel mechanism. Sustained treatment of preactivated primary human T cells with ciprofloxacin results in a dose-dependent inhibition of TCR-induced generation of reactive oxygen species (ROS) and IL-2 and -4 expression.

Xanthohumol-induced transient superoxide anion radical formation triggers cancer cells into apoptosis via a mitochondria-mediated mechanism.

Oxidative stress and increased release of reactive oxygen species (ROS) are associated with apoptosis induction. Here we report ROS-mediated induction of apoptosis by xanthohumol (XN) from hops. XN at concentrations of 1.

Thermal averaging of the indirect nuclear spin-spin coupling constants of ammonia: the importance of the large amplitude inversion mode.

Analytic internal-coordinate representations are reported for two accurate ab initio spin-spin coupling surfaces of the ammonia molecule, (1)J ((15)N,H) and (2)J(H,H). Calculations were carried out at the level of the second-order polarization propagator approximation involving coupled-cluster singles and doubles amplitudes (CCSD) and using a large specialized basis set, for a total of 841 different geometries corresponding to 2523 distinct points on the (1)J ((15)N,H) and (2)J(H,H) surfaces. The results were fitted to power series expansions truncated after the fourth-order terms.

Glutaric aciduria type I and methylmalonic aciduria: simulation of cerebral import and export of accumulating neurotoxic dicarboxylic acids in in vitro models of the blood-brain barrier and the choroid plexus.

Intracerebral accumulation of neurotoxic dicarboxylic acids (DCAs) plays an important pathophysiological role in glutaric aciduria type I and methylmalonic aciduria. Therefore, we investigated the transport characteristics of accumulating DCAs - glutaric (GA), 3-hydroxyglutaric (3-OH-GA) and methylmalonic acid (MMA) - across porcine brain capillary endothelial cells (pBCEC) and human choroid plexus epithelial cells (hCPEC) representing in vitro models of the blood-brain barrier (BBB) and the choroid plexus respectively. We identified expression of organic acid transporters 1 (OAT1) and 3 (OAT3) in pBCEC on mRNA and protein level.

A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival.

Deficiency of the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase involved in isoleucine metabolism causes an organic aciduria with atypical neurodegenerative course. The disease-causing gene is HSD17B10 and encodes 17beta-hydroxysteroid dehydrogenase type 10 (HSD10), a protein also implicated in the pathogenesis of Alzheimer's disease. Here we show that clinical symptoms in patients are not correlated with residual enzymatic activity of mutated HSD10.

DNA polymorphisms and haplotype patterns of transcription factors involved in barley endosperm development are associated with key agronomic traits.

Background: Association mapping is receiving considerable attention in plant genetics for its potential to fine map quantitative trait loci (QTL), validate candidate genes, and identify alleles of interest. In the present study association mapping in barley (Hordeum vulgare L.) is investigated by associating DNA polymorphisms with variation in grain quality traits, plant height, and flowering time to gain further understanding of gene functions involved in the control of these traits.

Mass spectrometry tools for the classification and identification of bacteria.

Mass spectrometry has become an important analytical tool in biology in the past two decades. In principle, mass spectrometry offers high-throughput, sensitive and specific analysis for many applications in microbiology, including clinical diagnostics and environmental research. Recently, several mass spectrometry methods for the classification and identification of bacteria and other microorganisms, as well as new software analysis tools, have been developed.

Decreased serum TSH levels are not associated with mortality in the adult northeast German population.

Objective: Results of cohort studies on the association between decreased serum TSH levels and mortality are conflicting. Some studies demonstrated an increased mortality risk in subjects with decreased serum TSH levels, others did not. Even meta-analyses revealed contradictory results.

Mean excitation energies and energy deposition characteristics of bio-organic molecules.

We suggest a method for determination of the mean excitation energies of several biomolecules, such as amino acids, using a Bragg-like sum rule developed for molecular fragments or functional groups. Because the fragment composition of many bio-organic molecules is very similar, we find that many of them, including the amino acids, have similar mean excitation energies (approximately 70 eV, which is interestingly close to the mean excitation energy of the major component of a cell: namely, water). Differences in amino acid mean excitation energies arise from variation of the side chains (-R); addition of -CH(2)- groups decreases the mean excitation energy.

Structural trends of 77Se-1H spin-spin coupling constants and conformational behavior of 2-substituted selenophenes.

Experimental measurements and second-order polarization propagator approach (SOPPA) calculations of (77)Se-(1)H spin-spin coupling constants together with theoretical energy-based conformational analysis in the series of 2-substituted selenophenes have been carried out. A new basis set optimized for the calculation of (77)Se-(1)H spin-spin coupling constants has been introduced by extending the aug-cc-pVTZ-J basis for selenium. Most of the spin-spin coupling constants under study, especially vicinal (77)Se-(1)H couplings, demonstrated a remarkable stereochemical behavior with respect to the internal rotation of the substituent in the 2-position of the selenophene ring, which is of major importance in the stereochemical studies of the related organoselenium compounds.

Runx proteins regulate Foxp3 expression.

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells.

Long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam] as a possible model to study renal disease in methylmalonic acidurias.

Dysfunction of proximal tubules resulting in tubulointerstitial nephritis and chronic renal failure is a frequent long-term complication of methylmalonic acidurias. However, the underlying pathomechanisms have not yet been extensively studied owing to the lack of suitable in vitro and in vivo models. Application of hydroxycobalamin[c-lactam] has been shown to inhibit the metabolism of hydroxycobalamin and, thereby, to induce methylmalonic aciduria in rats, oligodendrocytes, and rat hepatocytes.

Benchmarking second order methods for the calculation of vertical electronic excitation energies: valence and Rydberg states in polycyclic aromatic hydrocarbons.

The performance of the six second order linear response methods RPA(D), SOPPA, SOPPA(CCSD), CIS(D), CC2, and CCSD, which include either noniterative or iterative doubles contributions, has been studied in calculations of vertical excitation energies. The benchmark set consisted of 39 valence and 76 Rydberg states of benzene and five polycyclic aromatic hydrocarbons. As reference values we have used the results of the corresponding calculations with the third order method CCSDR(3), which includes noniterative triples contributions.

Quantification of target proteins using hydrogel antibody arrays and MALDI time-of-flight mass spectrometry (A2M2S).

Mass spectrometry-based analysis techniques are widely applied in proteomics. This study presents a novel method for quantitative multiplex candidate protein profiling. It applies immunocapture of differentially labeled protein complements on hydrogel antibody arrays and subsequent quantification by MS.

Analysis of isotope effects in NMR one-bond indirect nuclear spin-spin coupling constants in terms of localized molecular orbitals.

We recently showed, by analyzing contributions from localized molecular orbitals, that the anomalous deuterium isotope effect in the one-bond indirect nuclear spin-spin coupling constant of methane, also called the unexpected differential sensitivity, can be explained by the transfer of s-orbital character from the stretched bond to the other unchanged bonds [ChemPhysChem, 2008, 9, 1259]. We now extend this analysis of isotope effects to the molecules BH(4)(-), NH(4)(+), SiH(4), H(2)O and NH(3) in order to test our conclusions on a wider rage of XH(4) compounds and to investigate whether the lone-pair orbitals are really responsible for the absence of a similar effect in water and ammonia as proposed earlier [J. Chem.

Familiality and molecular genetics of attention networks in ADHD.

Indices from a more elementary neuropsychological level might be useful in the search for genes for complex psychiatric disorders, such as ADHD. In this study we investigated systematically whether attentional performance as measured with the Attention Network Test (ANT) is suited for the identification of endophenotypes of ADHD. Attentional performance in affected sib pairs with ADHD (n = 181) was compared to unaffected control siblings (n = 121).