Inhibition of insulin/IGF-1 receptor signaling protects from mitochondria-mediated kidney failure.

Mitochondrial dysfunction and alterations in energy metabolism have been implicated in a variety of human diseases. Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at the mitochondrial inner membrane. Here, we provide a link between PHB2 deficiency and hyperactive insulin/IGF-1 signaling.

Prevalence of Epileptiform Discharges in Healthy Infants.

Most studies on epileptiform discharges in young children were performed using analog electroencephalographic (EEG) recording systems and a limited numbers of electrodes that might have a lower detection rate for epileptiform discharges than modern digital recording systems. Knowing the prevalence of epileptiform discharges in healthy children is critical for a valid interpretation of findings in patients with a suspected epileptic disorder. We reviewed EEG recordings of 393 otherwise healthy children aged 12 to 60 months using digital EEG recording with respect to epileptiform discharges.

Ionic Pathways in Li13Si4 investigated by (6)Li and (7)Li solid state NMR experiments.

Local environments and dynamics of lithium ions in the binary lithium silicide Li13Si4 have been studied by (6)Li MAS-NMR, (7)Li spin-lattice relaxation time and site-resolved (7)Li 2D exchange NMR measurements as a function of mixing time. Variable temperature experiments result in distinct differences in activation energies characterizing the transfer rates between the different lithium sites. Based on this information, a comprehensive picture of the preferred ionic transfer pathways in this silicide has been developed.

Hepatotoxicity after liver irradiation in children and adolescents : results from the RiSK.

Aim: The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence.

Patients And Methods: Since 2001, irradiated children and adolescents in Germany have been prospectively documented in the "Register of Treatment-Associated Late Effects After Radiotherapy of Malignant Diseases in Childhood and Adolescence (RiSK)" using standardized forms. Toxicity was graded according to the Radiation Therapy Oncology Group (RTOG) criteria.

Accessing biological actions of Ganoderma secondary metabolites by in silico profiling.

The species complex around the medicinal fungus Ganoderma lucidum Karst. (Ganodermataceae) is widely known in traditional medicines, as well as in modern applications such as functional food or nutraceuticals. A considerable number of publications reflects its abundance and variety in biological actions either provoked by primary metabolites, such as polysaccharides, or secondary metabolites, such as lanostane-type triterpenes.

Effects of intravenous solutions on acid-base equilibrium: from crystalloids to colloids and blood components.

Intravenous fluid administration is a medical intervention performed worldwide on a daily basis. Nevertheless, only a few physicians are aware of the characteristics of intravenous fluids and their possible effects on plasma acid-base equilibrium. According to Stewart's theory, pH is independently regulated by three variables: partial pressure of carbon dioxide, strong ion difference (SID), and total amount of weak acids (ATOT).

Anisotropic dispersion and partial localization of acoustic surface plasmons on an atomically stepped surface: Au(788).

Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized.

Electrolyte shifts across the artificial lung in patients on extracorporeal membrane oxygenation: interdependence between partial pressure of carbon dioxide and strong ion difference.

Purpose: Partial pressure of carbon dioxide (PCO2), strong ion difference (SID), and total amount of weak acids independently regulate pH. When blood passes through an extracorporeal membrane lung, PCO2 decreases. Furthermore, changes in electrolytes, potentially affecting SID, were reported.

Positive or negative fructose breath test results do not predict response to fructose restricted diet in children with recurrent abdominal pain: results from a prospective randomized trial.

Objectives: To perform a prospective, blinded, randomized interventional trial in patients with recurrent abdominal pain. The primary endpoint was to determine the abdominal pain intensity after 2 weeks of fructose restricted diet. Secondary endpoints were changes of pain frequency and a secondary symptom score (SSS).

Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study.

Purpose: Fertility impairment and recovery after haematopoietic stem cell transplantation (HSCT) have been reported in both sexes, but little is known about how they develop over time. Our aim was to describe the dynamics of fertility impairment and recovery after HSCT.

Methods: We retrieved treatment and fertility data for up to 12 years of 361 paediatric patients with malignant and non-malignant diseases from seven European centres.

[Overcoming language barriers with telephone interpreters: first experiences at a German children's hospital].

Language barriers in the care for patients with limited German language proficiency contribute to impaired quality of care, more frequent medical errors and decreased patient satisfaction. However, professional interpreters are not systematically used in Germany. We conducted a pilot study in a German paediatric hospital to explore the demand for an interpreter by conducting a survey among parents and to test the use of telephone interpreters.

DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling.

Prohibitins form large protein and lipid scaffolds in the inner membrane of mitochondria that are required for mitochondrial morphogenesis, neuronal survival, and normal lifespan. Here, we have defined the interactome of PHB2 in mitochondria and identified DNAJC19, mutated in dilated cardiomyopathy with ataxia, as binding partner of PHB complexes. We observed impaired cell growth, defective cristae morphogenesis, and similar transcriptional responses in the absence of either DNAJC19 or PHB2.

Discovery and pharmacological characterization of a novel small molecule inhibitor of phosphatidylinositol-5-phosphate 4-kinase, type II, beta.

Phosphatidylinositol-5-phosphate 4-kinase, type II, beta (PIP5K2B) is linked to the pathogenesis of obesity, insulin resistance and diabetes. Here, we describe the identification of a novel pyrimidine-2,4-diamine PIP5K2B inhibitor, designated SAR088. The compound was identified by high-throughput screening and subsequently characterized in vitro and in vivo.

Dynamics of fertility impairment in childhood brain tumour survivors.

Purpose: Fertility impairment and recovery after chemo- and radiotherapy have been reported in both male and female childhood cancer survivors, but little is known about the dynamics. Our aim, therefore, was to describe the development of fertility impairment and possible recovery in childhood brain tumour survivors.

Methods: In this longitudinal study, we included 144 survivors, who were treated in two German paediatric oncology centres between 2000 and 2005.

1,2-N-migration in a gold-catalysed synthesis of functionalised indenes by the 1,1-carboalkoxylation of ynamides.

Unique α-hemiaminal ether gold carbene intermediates were accessed by a gold-catalysed 1,1-carboalkoxylation strategy and evolved through a highly selective 1,2-N-migration. This skeletal rearrangement gave functionalised indenes, and isotopic labelling confirmed the rare C-N bond cleavage of the ynamide moiety. The effect of substituents on the migration has been explored, and a model is proposed to rationalise the observed selectivity.

SPG7 variant escapes phosphorylation-regulated processing by AFG3L2, elevates mitochondrial ROS, and is associated with multiple clinical phenotypes.

Mitochondrial production of reactive oxygen species (ROS) affects many processes in health and disease. SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes. SPG7 is cleaved and activated by AFG3L2 upon assembly.

Thienoquinolines as novel disruptors of the PKCε/RACK2 protein-protein interaction.

Ten protein kinase C (PKC) isozymes play divergent roles in signal transduction. Because of sequence similarities, it is particularly difficult to generate isozyme-selective small molecule inhibitors. In order to identify such a selective binder, we derived a pharmacophore model from the peptide EAVSLKPT, a fragment of PKCε that inhibits the interaction of PKCε and receptor for activated C-kinase 2 (RACK2).

Loss of the m-AAA protease subunit AFG₃L₂ causes mitochondrial transport defects and tau hyperphosphorylation.

The m-AAA protease subunit AFG₃L₂ is involved in degradation and processing of substrates in the inner mitochondrial membrane. Mutations in AFG₃L₂ are associated with spinocerebellar ataxia SCA28 in humans and impair axonal development and neuronal survival in mice. The loss of AFG₃L₂ causes fragmentation of the mitochondrial network.

Cardiotoxicity and oncological treatments.

Background: Cardiotoxic and other side effects limit the usefulness of treatments for cancer.

Method: This article is based on pertinent articles that were retrieved by a selective search in PubMed and other databases, and on the guidelines of the European Society of Cardiology, the Association of Scientific Medical Societies in Germany, and the European Society of Medical Oncology.

Results: Prospective studies have shown that some treatments for cancer are cardiotoxic.

Low-dose chest computed tomography for quantitative and visual anatomical analysis in patients with acute respiratory distress syndrome.

Purpose: Chest computed tomography (CT) is a fundamental tool for the characterization of acute respiratory distress syndrome (ARDS). Its frequent use is, however, hindered by the associated radiation exposure. The aim of the present study was to evaluate, in patients with ARDS, the accuracy of quantitative and visual anatomical lung analysis performed on low-dose CT.

The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission.

Mitochondrial fusion and structure depend on the dynamin-like GTPase OPA1, whose activity is regulated by proteolytic processing. Constitutive OPA1 cleavage by YME1L and OMA1 at two distinct sites leads to the accumulation of both long and short forms of OPA1 and maintains mitochondrial fusion. Stress-induced OPA1 processing by OMA1 converts OPA1 completely into short isoforms, inhibits fusion, and triggers mitochondrial fragmentation.

Dynamic survey of mitochondria by ubiquitin.

Ubiquitin is a post-translational modifier with proteolytic and non-proteolytic roles in many biological processes. At mitochondria, it performs regulatory homeostatic functions and contributes to mitochondrial quality control. Ubiquitin is essential for mitochondrial fusion, regulates mitochondria-ER contacts, and participates in maternal mtDNA inheritance.

Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis.

Familial Alzheimer's disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia with unclear pathophysiology. A Colombian kindred carrying the PS1-E280A mutation is the largest known cohort of PS1-FAD patients.

Stress-induced OMA1 activation and autocatalytic turnover regulate OPA1-dependent mitochondrial dynamics.

The dynamic network of mitochondria fragments under stress allowing the segregation of damaged mitochondria and, in case of persistent damage, their selective removal by mitophagy. Mitochondrial fragmentation upon depolarisation of mitochondria is brought about by the degradation of central components of the mitochondrial fusion machinery. The OMA1 peptidase mediates the degradation of long isoforms of the dynamin-like GTPase OPA1 in the inner membrane.

StAR enhances transcription of genes encoding the mitochondrial proteases involved in its own degradation.

Steroidogenic acute regulatory protein (StAR) is essential for steroid hormone synthesis in the adrenal cortex and the gonads. StAR activity facilitates the supply of cholesterol substrate into the inner mitochondrial membranes where conversion of the sterol to a steroid is catalyzed. Mitochondrial import terminates the cholesterol mobilization activity of StAR and leads to mounting accumulation of StAR in the mitochondrial matrix.