Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner

Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1–26.2), estimated fetal weight (measured by ultrasound during 18–25th weeks and >25th weeks) and birth weight were measured in 7987 mother–child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations me

Radiation–Induced Signaling Results in Mitochondrial Impairment in Mouse Heart at 4 Weeks after Exposure to X-Rays

BACKGROUND: Radiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk of cardiovascular disease in the survivors decades after the treatment. The mechanisms that underlie the radiation damage remain poorly understood so far. Previous data show that impairment of mitochondrial oxidative metabolism is directly linked to the development of cardiovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the radiation-induced in vivo effects on cardiac mitochondrial proteome and function were investigated. C57BL/6N mice were exposed to local irradiation of the heart with doses of 0.2 Gy or 2 Gy (X-ray, 200 kV) at the age of eight weeks, the control mice were sham-irradiated. After four weeks the cardiac mitochondria were isolated and tested for proteomic and functional alterations. Two complementary proteomics approaches using both peptide and protein quantification strategies showed radiation-induced deregulation of 25 proteins in total. Three main biological categories were affected: the oxidative phophorylation, the pyruvate metabolism, and the cytoskeletal structure. The mitochondria exposed to high-dose irradiation showed functional impairment reflected as partial deactivation of Complex I (32%) and Complex III (11%), decreased succinate-driven respiratory capacity (13%), increased level of reactive oxygen species and enhanced oxidation of mitochondrial proteins. The changes in the pyruvate metabolism and structural proteins were seen with both low and high radiation doses. CONCLUSION/SIGNIFICANCE: This is the first study showing the biological alterations in the murine heart mitochondria several weeks after the exposure to low- and high-dose of ionizing radiation. Our results show that doses, equivalent to a single dose in radiotherapy, cause long-lasting changes in mitochondrial oxidative metabolism and mitochondria-associated cytoskeleton. This prompts us to propose that these first pathological changes lead to an increased risk of cardiovascular disease after radiation exposure

POSSIBILITIES OF FINANCIAL SUPPORT TO SMALL AND MEDIUM HOTEL COMPANIES IN SERBIA

Small and medium hotel companies in the majority of developed tourist countries have dominant role in hotel industry. The same situation is with Serbia. An important precondition for successful business of a hotel is accepting and applying basic pillars of marketing concept i.e. satisfying needs and expectations of guests in order to achieve profit. Small hotel companies have specific problems in their daily business. Top priority in management and surviving of hotels is cash, because fixed costs are very dominant so hotels earmark more resources for them than for marketing. This means higher engagement and involvement of the state in further development of small and medium hotel companies in Serbia. The state should provide favourable subsidized credit lines for small and medium hotel companies in Serbia, through appropriate support programmes.small and medium hotel companies; financial support; support programme.

POSSIBILITIES OF FINANCIAL SUPPORT TO SMALL AND MEDIUM HOTEL COMPANIES IN SERBIA

Abstract: Small and medium hotel companies in the majority of developed tourist countries have dominant role in hotel industry. The same situation is with Serbia. An important precondition for successful business of a hotel is accepting and applying basic pillars of marketing concept i.e. satisfying needs and expectations of guests in order to achieve profit. Small hotel companies have specific problems in their daily business. Top priority in management and surviving of hotels is cash, because fixed costs are very dominant so hotels earmark more resources for them than for marketing. This means higher engagement and involvement of the state in further development of small and medium hotel companies in Serbia. The state should provide favourable subsidized credit lines for small and medium hotel companies in Serbia, through appropriate support programmes

Formal specification and verification of the OSI session layer using the Calculus of Communicating Systems (CCS)

This document describes the application of formal methods to concurrent software systems, specifically communication protocols. The chosen formal method is Milner\u27s process algebra called the Calculus of Communicating Systems (CCS). We applied CCS to the specification and verification of the Open Systems Interconnection (OSI) Session Layer (SL). We modeled the Session Layer service and Session Layer protocol in CCS, and verified it using CCS\u27s automated model checker, the Edinburgh Concurrency Workbench (CWB). We verified that the protocol specification satisfies the service specification. We also formally embedded CCS in the first-order formal language Larch, using the automated theorem prover Penelope. We tested the embedding by specifying and verifying a simple two-slot buffer example. We compared the automated tools by specifying a portion of the Session Layer and verifying it using Penelope

Hyperacetylation of Cardiac Mitochondrial Proteins Is Associated with Metabolic Impairment and Sirtuin Downregulation after Chronic Total Body Irradiation of ApoE -/- Mice

Chronic exposure to low-dose ionizing radiation is associated with an increased risk of cardiovascular disease. Alteration in energy metabolism has been suggested to contribute to radiation-induced heart pathology, mitochondrial dysfunction being a hallmark of this disease. The goal of this study was to investigate the regulatory role of acetylation in heart mitochondria in the long-term response to chronic radiation. ApoE-deficient C57Bl/6J mice were exposed to low-dose-rate (20 mGy/day) gamma radiation for 300 days, resulting in a cumulative total body dose of 6.0 Gy. Heart mitochondria were isolated and analyzed using quantitative proteomics. Radiation-induced proteome and acetylome alterations were further validated using immunoblotting, enzyme activity assays, and ELISA. In total, 71 proteins showed peptides with a changed acetylation status following irradiation. The great majority (94%) of the hyperacetylated proteins were involved in the TCA cycle, fatty acid oxidation, oxidative stress response and sirtuin pathway. The elevated acetylation patterns coincided with reduced activity of mitochondrial sirtuins, increased the level of Acetyl-CoA, and were accompanied by inactivation of major cardiac metabolic regulators PGC-1 alpha and PPAR alpha. These observations suggest that the changes in mitochondrial acetylation after irradiation is associated with impairment of heart metabolism. We propose a novel mechanism involved in the development of late cardiac damage following chronic irradiation