Gender differences in the long-term effects of perinatal hypoxia on pulmonary circulation in rats.

Hampl, Vá clav, Jana Bíbová , Ivana Oštá dalová , Viera Pový šilová , and Jan Herget. Gender differences in the long-term effects of perinatal hypoxia on pulmonary circulation in rats. Am J Physiol Lung Cell Mol Physiol 285: L386-L392, 2003. First published April 11, 2003 10.1152/ ajplung.00389.2002-Some effects of perinatal hypoxia on pulmonary circulation are permanent. Since pulmonary vascular sensitivity to hypoxia in adults differs between sexes, we hypothesized that gender-based variability also exists in the long-term effects of perinatal hypoxia. Rats spent 1 wk before and 1 wk after birth in hypoxia (12% O2) and then lived in normoxia. When adult, females, but not males, with the perinatal experience of hypoxia had right ventricle hypertrophy. To assess the role of sex hormones, some rats were gonadectomized in ether anesthesia as newborns. Compared with intact, perinatally normoxic controls, muscularization of peripheral pulmonary vessels in adulthood was augmented in perinatally hypoxic, neonatally gonadectomized males (by 85%) and much more so in females (by 533%). Pulmonary artery pressure was elevated in perinatally hypoxic, neonatally gonadectomized females (24.4 Ϯ 1.7 mmHg) but not males (17.2 Ϯ 0.6 mmHg). Gonadectomy in adulthood had no effect. We conclude that female pulmonary circulation is more sensitive to late effects of perinatal hypoxia, and these effects are blunted by the presence of ovaries during maturation. sexual variability; ovaries; pulmonary hypertension; right ventricular hypertrophy; newborn CHRONIC HYPOXIA is a well-defined, clinically important cause of pulmonary hypertension. With restoration of normoxia, hypoxic pulmonary hypertension is completely reversible (17). However, if the hypoxic exposure occurs at around the time of birth, the recovery is incomplete, and subtle yet significant alterations of the pulmonary circulation persist well into adulthood. Although characterized variously in different studies, these changes can be summarized as an increased susceptibility to the development of pulmonary hypertension later in life In 1997, Barer et al. (1) noticed in a preliminary report that the late effects of perinatal hypoxia appear more prominent in female than in male rats. In agreement with this observation, resting pulmonary arterial blood pressure (PAP) and/or pulmonary vascular resistance in adults were slightly but significantly elevated in studies of perinatal hypoxia where pooled male and female rats were studied (10, 19) but not in experiments on males only (14). The present study was, therefore, designed to test the hypothesis that the long-term effects of perinatal hypoxia on pulmonary circulation differ between genders and that the presence of gonads during maturation plays a prominent role in this variability. The results were reported in a preliminary form (13). METHODS The project in this study was reviewed and approved by the Animal Studies Committee of the Charles University Second Medical School. All procedures conformed to the European Community and National Institutes of Health guidelines for the use of experimental animals. Wistar rats were purchased from Anlab (Prague, Czech Republic). To analyze the specific, late effects of perinatal hypoxia and gonadectomy on pulmonary circulation, three experiments were performed (1 main and 2 supplementary). Their overall design is schematically illustrated in Main experiment: perinatal hypoxia and neonatal gonadectomy. In the main experiment, adult rats were divided into groups based on gender, history of perinatal hypoxia, and gonadal status. This resulted in four male and four female groups in the main experiment: 1) perinatally normoxic with intact gonads; 2) perinatally normoxic gonadectomized as newborns; 3) perinatally hypoxic with intact gonads; and 4) perinatally hypoxic gonadectomized as newborns. In fact, the groups with the intact gonads consisted of rats that did not undergo any surgery and rats serving as sham surgery controls. Since we did not find any significant differences between sham-operated and nonoperated rats, their data were pooled to enhance clarity by reducing the large number of groups. Perinatal hypoxia and gonadectomy. The rats were exposed to perinatal hypoxia as previously describe

A database of naturally occurring human urinary peptides and proteins for use in clinical applications

Owing to its availability, ease of collection and correlation with (patho-) physiology, urine is an attractive source for clinical proteomics. However, the lack of comparable datasets from large cohorts has greatly hindered development in this field. Here we report the establishment of a high resolution proteome database of naturally occurring human urinary peptides and proteins - ranging from 800-17,000 Da - from over 3,600 individual samples using capillary electrophoresis coupled to mass spectrometry, yielding an average of 1,500 peptides per sample. All processed data were deposited in an SQL database, currently containing 5,010 relevant unique urinary peptides that serve as classifiers for diagnosis and monitoring of diseases, including kidney and vascular diseases. Of these, 352 have been sequenced to date. To demonstrate the applicability of this database, two examples of disease diagnosis were provided: For renal damage diagnosis, patients with a specific renal disease were identified with high specificity and sensitivity in a blinded cohort of 131 individuals. We further show definition of biomarkers specific for immunosuppression and complications after transplantation (Kaposi's sarcoma). Due to its high information content, this database will be a powerful tool for the validation of biomarkers for both renal and non-renal diseases

A search for resonances decaying into a Higgs boson and a new particle X in the XH→qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson ($H$) and a new particle ($X$) is reported, utilizing 36.1 fb$^{-1}$ of proton-proton collision data at $\sqrt{s} =$ 13 TeV collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle $X$ is assumed to decay to a pair of light quarks, and the fully hadronic final state $XH \rightarrow q\bar q'b\bar b$ is analysed. The search considers the regime of high $XH$ resonance masses, where the $X$ and $H$ bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of $XH$ mass versus $X$ mass is scanned for evidence of a signal, over a range of $XH$ resonance mass values between 1 TeV and 4 TeV, and for $X$ particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of $XH$ and $X$ masses, on the production cross-section of the $XH\rightarrow q\bar q'b\bar b$ resonance

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

A survey of the ATP-binding cassette (ABC) gene superfamily in the salmon louse (Lepeophtheirus salmonis)

Salmon lice,Lepeophtheirus salmonis(Krøyer, 1837), are fish ectoparasites causing significant economic damage in the mariculture of Atlantic salmon,Salmo salarLinnaeus, 1758. The control ofL.salmonisat fish farms relies to a large extent on treatment with anti-parasitic drugs. A problem related to chemical control is the potential for development of resistance, which inL.salmonisis documented for a number of drug classes including organophosphates, pyrethroids and avermectins. The ATP-binding cassette (ABC) gene superfamily is found in all biota and includes a range of drug efflux transporters that can confer drug resistance to cancers and pathogens. Furthermore, some ABC transporters are recognised to be involved in conferral of insecticide resistance. While a number of studies have investigated ABC transporters inL.salmonis, no systematic analysis of the ABC gene family exists for this species. This study presents a genome-wide survey of ABC genes inL.salmonisfor which, ABC superfamily members were identified through homology searching of theL.salmonisgenome. In addition, ABC proteins were identified in a reference transcriptome of the parasite generated by high-throughput RNA sequencing (RNA-seq) of a multi-stage RNA library. Searches of both genome and transcriptome allowed the identification of a total of 33 genes / transcripts coding for ABC proteins, of which 3 were represented only in the genome and 4 only in the transcriptome. Eighteen sequences were assigned to ABC subfamilies known to contain drug transporters,i.e. subfamilies B (4 sequences), C (11) and G (2). The results suggest that the ABC gene family ofL.salmonispossesses fewer members than recorded for other arthropods. The present survey of theL.salmonisABC gene superfamily will provide the basis for further research into potential roles of ABC transporters in the toxicity of salmon delousing agents and as potential mechanisms of drug resistance

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies