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Iron is an essential component for metabolic processes, including oxygen transport within hemoglobin, tricarboxylic acid (TCA) cycle activity, and mitochondrial energy transformation. Iron deficiency can thus lead to metabolic dysfunction and eventually result in iron deficiency anemia (IDA), which affects approximately 1.5 billion people worldwide. Using a rat model of IDA induced by phlebotomy, we studied the effects of IDA on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the liver. Furthermore, we evaluated whether the mitochondrial function evaluated by high-resolution respirometry in PBMCs reflects corresponding alterations in the liver. Surprisingly, mitochondrial respiratory capacity was increased in PBMCs from rats with IDA compared to the controls. In contrast, mitochondrial respiration remained unaffected in livers from IDA rats. Of note, citrate synthase activity indicated an increased mitochondrial density in PBMCs, whereas it remained unchanged in the liver, partly explaining the different responses of mitochondrial respiration in PBMCs and the liver. Taken together, these results indicate that mitochondrial function determined in PBMCs cannot serve as a valid surrogate for respiration in the liver. Metabolic adaptions to iron deficiency resulted in different metabolic reprogramming in the blood cells and liver tissue.

Iron is an essential co-factor for many cellular metabolic processes, and mitochondria are main sites of utilization. Iron accumulation promotes production of reactive oxygen species (ROS) via the catalytic activity of iron species. Herein, we investigated the consequences of dietary and genetic iron overload on mitochondrial function. C57/BL6N wildtype and Hfe-/- mice, the latter a genetic hemochromatosis model, received either normal diet (ND) or high iron diet (HI) for two weeks. Liver mitochondrial respiration was measured using high-resolution respirometry along with analysis of expression of specific proteins and ROS production. HI promoted tissue iron accumulation and slightly affected mitochondrial function in wildtype mice. Hepatic mitochondrial function was impaired in Hfe-/- mice on ND and HI. Compared to wildtype mice, Hfe-/- mice on ND showed increased mitochondrial respiratory capacity. Hfe-/- mice on HI showed very high liver iron levels, decreased mitochondrial respiratory capacity and increased ROS production associated with reduced mitochondrial aconitase activity. Although Hfe-/- resulted in increased mitochondrial iron loading, the concentration of metabolically reactive cytoplasmic iron and mitochondrial density remained unchanged. Our data shows multiple effects of dietary and genetic iron loading on mitochondrial function and linked metabolic pathways, providing an explanation for fatigue in iron-overloaded hemochromatosis patients and suggests iron reduction therapy for improvement of mitochondrial function.

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow guidelines of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of databases of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

OBJECTIVE:Examine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms. BACKGROUND:CSF alpha-synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha-synuclein differentiate these groups is controversial. Correlations of alpha-synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta-amyloid, tau [total, phosphorylated]) are not fully understood. The relationships of these biomarkers with PD clinical features remain unclear. METHODS:BioFIND, a cross-sectional, observational study, examines clinical and biomarker characteristics in moderate-advanced PD and matched healthy controls. We compared alpha-synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and MDS-UPDRS, motor phenotype, MoCA, and rapid eye movement sleep behavior disorder questionnaire scores in PD were examined. RESULTS:CSF alpha-synuclein was lower in PD versus controls (P = .01), controlling for age, gender, and education. Plasma and saliva alpha-synuclein did not differ between PD and controls, and alpha-synuclein did not significantly correlate among biofluids. CSF beta-amyloid1-42 was lower in PD versus controls (P

Figure S1. Images of primary neuronal cultures pre‐ and posttreatment. Figure S2. High conservation of the miR‐137 binding site in the SHANK2‐3’UTR and of miR‐137 between different species. Figure S3. Relative expression levels of miR‐137 in different human tissues. Figure S4. Uncropped Western blot pictures. Table S1. ASD risk genes which are predicted or validated miR‐137 targets. Table S2. Primers used for cloning, mutagenesis, and screening. Primer sequences are all shown in 5′→3′ orientation. Table S3. Origin of total RNA samples used to measure hsa‐miR‐137 relative expression across different tissues (see Additional file 1: Figure S2 for results). Table S4. Experimentally validated miR‐137 targets. Table S5. Gene expression analysis of 69 validated miR‐137 target genes (including SHANK2) in the CommonMind RNA sequencing data. Table S6a. Gene expression analysis of validated targets from five different control microRNAs in the CommonMind RNA sequencing data. Genes labeled in gray withstand correction for multiple testing using the Benjamini-Hochberg method and a FDR of 10%. Table S6b. Comparison of the number of differentially expressed target genes of different microRNAs between SCZ and control individuals in the CommonMind RNASeq data. Table S7. Analysis of the 3′UTR of the differentially expressed miR-137 genes in the DLPFC between SCZ and control individuals for additional putative miR-124 and miR-128 binding sites. (PDF 1417 kb)

Background: In patients with systemic sclerosis (SSc) borderline mean pulmonary arterial pressures (mPAP; 21-24 mmHg at rest) are a frequent finding and could represent an intermediate stage between normal pulmonary pressuresand manifest pulmonary hypertension (PH) [1]. The objective of[for full text, please go to the a.m. URL], 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Cultivation of truffles in managed orchards has become an important agricultural alternative in rural Mediterranean regions. The declines of wild Tuber melanosporum throughout its natural range, its high market value and the development of nursery and cultivation techniques have encouraged its successful cultivation during the last several decades. We present here the state of the art of black truffle cultivation, habitat requirements of the fungus, cultivation techniques and descriptions of the mycorrhizae of four important Tuber species. Additionally we provide recent research findings with special implications for truffle cultivation and a brief review of truffle culinary products. In the last section we address the developing Truffle Sector in Southwest Turkey. This project is co-funded by the European Union and the Republic of Turkey

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data., Author summary A lot of attention has been paid to Latino heterogeneity related to individual proportions of Native American, European and African ancestry. The importance of the type of Native American ancestry for health, however, has hardly been studied. Here we examined genetic data from 2,039 admixed Chileans to investigate possible associations between top causes of death and the two major types of Native American ancestry in Chile. Our findings demonstrate the necessity of suitable surrogates for ancestry estimation which mirror the actual composition of the study population, and the advantage of considering fine-scale Latino heterogeneity for unraveling of disease etiology and personalized healthcare.

"Die häufigsten Erkrankungen in entwickelten Ländern sind Herz- Kreislaufkrankheiten, Tumorleiden, Stoffwechsel-, Autoimmun- und psychiatrische Erkrankungen. Diese werden als komplexe Krankheiten bezeichnet, da ihre Entstehung sowohl von genetischen als auch von nicht genetischen, von außen einwirkenden Faktoren beeinflusst wird. Viele dieser Krankheiten zeigen deutliche Unterschiede zwischen Männern und Frauen sowohl im Hinblick auf die Neuerkrankungsrate als auch auf den Krankheitsverlauf. Als Erklärungen werden Unterschiede in den soziokulturellen Rollen von Männern und Frauen und daraus resultierend die Exposition gegenüber unterschiedlichen Risikofaktoren diskutiert. Kürzlich fand man durch genetische Studien für einige Krankheiten Hinweise auf unterschiedliche prädisponierende Gene bei Männern und Frauen. Diese Gene entwickeln ihre Wirkung auf die Krankheit nur auf dem Hintergrund eines Geschlechts. Geschlechterabhängige Präventions- und Therapiemaßnahmen für diese Erkrankungen erscheinen notwendig. Dieser Beitrag beschäftigt sich mit den genetischen Aspekten des geschlechterabhängigen Erkrankungsrisikos. Wir schildern Beispiele für geschlechtsspezifische Assoziationen sowohl beim Menschen als auch im Tierversuch und diskutieren methodische Probleme sowie mögliche biologische Mechanismen." (Autorenreferat) "The most frequent conditions affecting populations in developed countries are cardiovascular diseases, tumours, metabolic disorders, autoimmune and psychiatric diseases. All these disorders belong to the category of complex diseases, as their development is influenced by genetic as well as non-genetic factors. Many of these disorders arise with a marked sex/gender bias regarding incidence and/or progression. Differences in the sociocultural roles of men and women resulting in exposition towards different risk factors have been discussed as being causative. Recently, genetic studies have revealed that different genes might predispose men and women towards specific complex diseases. These genes display effects on disease risk preponderantly in one sex. Therefore, sex-/gender-dependent disease prevention measures and therapies appear to be necessary. This article focuses on the genetic aspects of differential disease risks of men and women. We present examples of sex-specific association in humans and in model organisms and discuss possible biological mechanisms and methodological problems." (author's abstract)

Zum Schutz der Gesundheit und der Sicherheit der Arbeitnehmer verlangt Artikel 4a der Richtlinie 89/655/EWG vom Arbeitgeber, dafür zu sorgen, dass bestimmte Arbeitsmittel durch eine befähigte Person geprüft werden. Die Richtlinie ist in Deutschland mit der Betriebssicherheitsverordung (BetrSichV) umgesetzt worden. Das Bundesministerium für Arbeit und Soziales (BMAS) beabsichtigt eine Weiterentwicklung der BetrSichV und des Regelwerkes der Technischen Regeln für Betriebssicherheit. Die Studie soll Erkenntnisse gewinnen zur Umsetzung des Artikel 4a der Richtlinie in anderen EU-Mitgliedstaaten. Die vorliegende Rechtsvergleichung stellt dar, wie in Dänemark, Frankreich, den Niederlanden und dem Vereinigten Königreich die Prüfungen nach Artikel 4a der Richtlinie unter Berücksichtigung des nationalen Rechtssystems umgesetzt wurden und legt dar, ob in diesen EU-Mitgliedsstaaten Parallelen zu den zwingend vorgeschriebenen Prüfungen gemäß dem 3. Abschnitt der BetrSichV bestehen.

Golden to dark brown c1avate to cylindl'ical mycorrhizae, often arranged in grapelike c1usters. The pseudoparenchyrnatous epidermoid pmper manlle is covered with a plectenchymatous net of hyphae from which smooth-walled, dense, short, non-ramifying qstidia elnerge. Middle mantle ceHs are polygonal with rounded rather than angular l~orners., This l'eSeal'Cll was SlIppol'led hy lhe Departament de Medi Ambient, Generalitat de Calalllnya, lhe Comunital de Trehall deis Pil'inclIs, Grant W ITT-CTP2000-3, and thc scholarship 2002¡'!00071110 I..M,S. I'rom Dircccit1 General de Recerca, Deparlamenl d'Universitals, Recerca i Societat de la Inlúrmaeiú, G,'neralitat de Catalunya.

La versió en paper del document disposa del text capiculat en català i en castellà 134 p. El objetivo de esta monografía es determinar las zonas de Cataluña más adecuadas para el cultivo de la trufa negra (Tuber melanosporum Vitt.). Para conseguir este objetivo, se han considerado los rangos de valores adecuados para el desarrollo de la trufa negra de los parámetros seleccionados; la precipitación media anual, la precipitación de los meses de verano, la temperatura media anual, la temperatura media del mes más frio, la temperatura media del mes más cálido, el pH y la textura. A partir del Atlas Climático Digital de Cataluña, del Modelo Digital del Terreno y de analíticas de suelos de diferentes localizaciones de Cataluña, se ha cartografiado la aptitud para el cultivo de la trufa negra. Cataluña dispone de 1.582.662 ha aptas para el cultivo de la trufa negra, 506.804 de las cuales necesitarían la aplicación de riegos de soporte o aportaciones de enmiendas calcáreas al suelo. De éstas 1.582.662 ha, 375.007 ha son terrenos que se dedican a cultivos de secano donde son necesarias las subvenciones de la Plítica Agraria Comunitaria para hacerlos rentables, o que han sufrido incendios forestales. El cambio climático global comportará un descenso de la superficie apta para el cultivo de la trufa negra del 14% para el año 2040.

Informe para el Centro de Investigación Forestal de Valonsadero, Soria. 68 p.

Objective This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). Methods Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. Results Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). Conclusion The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.

Background: Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPEH). The objective of this study was to evaluate right heart size and function assessed by echocardiography during long term treatment with riociguat. Methods: Patients who started riociguat treatment (1.0–2.5 mg tid) within the trials phase II, PATENT, PATENTplus, EAS, CHEST and continued treatment for 3–12 months were included in this study. Echocardiography was analysed off-line at baseline, after 3, 6 and 12 months by investigators who were blinded to clinical data. Last and baseline observation carried forward method (LOCF, BOCF) were performed as sensitivity analysis. Results: Seventy-one patients (45% PAH, 55% CTEPH; 53.5% female; 60 ± 13 years, mean pulmonary arterial pressure 46 ± 10 mmHg, mean PVR 700 ± 282dynes·sec·cm-5) were included. After 6 months, RA and RV area, RV thickness tricuspid regurgitation velocity showed a significant reduction. After 12 months, patients receiving riociguat therapy showed a significant reduction in right atrial (− 2.6 ± 4.4 cm2, 95% CI -3.84, − 1.33; p