Edge usage, motifs and regulatory logic for cell cycling genetic networks

The cell cycle is a tightly controlled process, yet its underlying genetic network shows marked differences across species. Which of the associated structural features follow solely from the ability to impose the appropriate gene expression patterns? We tackle this question in silico by examining the ensemble of all regulatory networks which satisfy the constraint of producing a given sequence of gene expressions. We focus on three cell cycle profiles coming from baker's yeast, fission yeast and mammals. First, we show that the networks in each of the ensembles use just a few interactions that are repeatedly reused as building blocks. Second, we find an enrichment in network motifs that is similar in the two yeast cell cycle systems investigated. These motifs do not have autonomous functions, but nevertheless they reveal a regulatory logic for cell cycling based on a feed-forward cascade of activating interactions.Comment: 9 pages, 9 figures, to be published in Phys. Rev.

USE OF FREE HEMOGLOBIN AND ITS SURROGATE MARKERS TO DETECT AND MONITOR PULMONARY HYPERTENSION

A method for diagnosing and monitoring pulmonary hypertension using free hemoglobin, as well as surrogates for free hemoglobin, as markers for pulmonary hypertension. Bodily fluids, such as blood, serum, plasma, urine and/or breathe condensate may be collected and analyzed to determine the concentration of free hemoglobin or surrogates of free hemoglobin. The concentration indicates the presence or absence of pulmonary hypertension

Method of Using Carbonic Anhydrase to Detect Hemolysis

A method and a test for using carbonic anhydrase (CA), particularly CA-I or CA-II, as a biomarker ofhemolysis. The method and test detect hemolysis by determining a percentage erythrocyte hemolysis in a specimen or sample of blood based upon quantification of carbonic anhydrase present in the extracellular portion of the blood. The method and test serve to optimize therapeutic efficacy for treatments of hemolysis. Plasma carbonic anhydrase is used to determine the percentage hemolysis in plasma. Furthermore, CA is quantified with specificity to the isozyme present in the plasma

Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome

BACKGROUND: Pulmonary thromboembolism (PTE) is a common diagnosis and a leading cause of cardiovascular morbidity and mortality. A growing literature has associated PE with systemic inflammation, and global hyper-coagulability, which contribute to lung remodeling and clot recurrence. The source and mechanism of inflammation remains unstudied. In humans, inhibition of cholesterol synthesis with statins decreases biomarkers of inflammation. We test the differential effect of pulmonary vascular occlusion during mild and severe pulmonary embolism on the lung transcriptome. METHODS: Experimental PE was induced in adult male rats by injection of 25 micron polystyrene microspheres into the jugular vein. The effect of Mild PE, (2-h right ventricular systolic pressure [RVSP] normal, 18-h RVSP 44 mmHg) and Severe PE (2-h RVSP > 50 mmHg; 18-h RVSP 44 mmHg) on lungs was assessed by measuring transcriptome-wide changes in gene expression by DNA microarrays. RESULTS: Severe PE was associated with a large change in lung gene expression and in the expression of KEGG pathways and other gene functional annotation groups. Mild PE was also associated with a large number of significant changes in gene expression and in the expression of KEGG pathways and gene functional annotation groups, even after only 2 h of PE. Up-regulated pathways included increased adipocytokine, chemokine and cytokine signaling as well as cholesterol synthesis. CONCLUSIONS: Mild PE without acute pulmonary hypertension (PH) increased lung gene expression of inflammatory pathways, including increased cholesterol synthesis. These data indicate that even mild persistent pulmonary vascular occlusion is capable of inciting an inflammatory response from the lung. These data imply the detrimental effect of unresolved pulmonary obstruction from PE

Astimaton of long-term strength of oil hydrocracking reactor steels using Larson-Miller parameter

Досліджено високотемпературну тривалу міцність та швидкість усталеної повзучості у водні та на повітрі корпусної теплостійкої сталі типу 2,25Cr-1Mo. Сталь досліджували у вихідному стані та після їх високотемпературної деградації в наводнювальному середовищі за технологічних умов експлуатації реактора гідрокрекінгу нафти впродовж 6∙104 год у вигляді зразків-свідків. Виявлено, що незалежно від стану (вихідний чи після деградації) теплостійкої сталі її швидкість усталеної повзучості у водні вища ніж на повітрі. Встановлено, що вплив підвищення температури випроб зростає зі зниженням рівня напружень. Вплив деградації сталі на швидкість повзучості суттєво переважає вплив водню. Аналіз тривалої міцності сталі 2,25Cr-1Mo у водні з використанням температурно-часового параметра Ларсона-Міллера показав, що у вихідному стані вона має значний запас міцності, а після 6∙104 год експлуатації в реакторі її тривала міцність суттєво знижується, але ще не виходить з безпечного діапазону.The high temperature long-term strength and steady creep rate in hydrogen and in air of heat-resistant 2,25 Cr–1Mo steel were investigated. The steel was tested in the initial state and after high-temperature degradation in hydrogenated environment under working conditions of hydrocracking reactor service for 6•104 hours as the specimen-witnesses. It was revealed for both virgin and degraded heat-resistant steel that the steady creep rate in hydrogen is higher than in air. The effect of temperature increase enhances with the stress level decrease. Steel degradation effect on the creep rate prevails over the hydrogen influence. Analysis of long-term strength of 2,25 Cr–1Mo steel in hydrogen using temperature-time Larson-Miller parameter showed a huge safety margin of steel in the initial state, and after 6•104 hours of operation in a reactor its long-term strength reduced substantially, but not yet out of the safe range

Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats

Right ventricular (RV) dysfunction is associated with poor clinical outcome following pulmonary embolism (PE). Previous studies in our laboratory show that influx of neutrophils contributes to acute RV damage seen in an 18 h rat model of PE. The present study describes the further progression of inflammation over 6 weeks and compares the neutrophil and monocyte responses. The RV outflow tract became white in colour by day 1 with influx of neutrophils (tissue myeloperoxidase activity increased 17-fold) and mononuclear cells with characteristics of M1 phenotype (high in Ccl20, Cxcl10, CcR2, MHCII, DNA microarray analysis). Matrix metalloproteinase activities were increased and tissue was thinned to produce a translucent appearance in weeks 1 through 6 in 40% of hearts. RV contractile function was significantly reduced at 6 weeks of PE. In this later phase, there was accumulation of myofibroblasts, the presence of mononuclear cells with M2 characteristics (high in scavenger mannose receptors, macrophage galactose lectin 1, PDGFR1, PDGFRβ), enrichment of the subendocardial region of the RV outflow tract with neovesels (α-smooth muscle immunohistochemistry) and deposition of collagen fibres (picrosirius red staining) beginning scar formation. Thus, while neutrophil response is associated with the early, acute inflammatory events, macrophage cells continue to be present during the proliferative phase and initial deposition of collagen in this model, changing from the M1 to the M2 phenotype. This suggests that the macrophage cell response is biphasic

Built environment change and change in BMI and waist circumference: Multi‐ethnic S tudy of A therosclerosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109571/1/oby20873.pd

Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

BackgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.MethodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.ResultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.ConclusionsAV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD

The origin of pine pollen grains captured from air at Calypsobyen, Svalbard

Spitsbergen is the largest island in the Svalbard Archipelago (Norway) that has been permanently populated. The harsh Arctic climate prevents development of large vascular plants such as trees. A two-year aerobiological survey was conducted within the framework of two consecutive polar expeditions (2014 and 2015) in Spitsbergen (Calypsobyen, Bellsund). The air quality was measured continuously from June/July to August using a 7-day volumetric air sampler, Tauber trap and moss specimens. Collected air samples and gravimetric pollen deposits were processed following transfer to sterile laboratory conditions and analyzed with the aid of light microscopy. Days when pine pollen grains were detected in the air were selected for further analysis. Clusters of back-trajectories, computed using the Hybrid Single Particle Lagrangian Integrated Trajectory model in combination with ArcGIS software as well as the Flextra trajectory model, showed the movement of air masses to the sampling location at Hornsund, and thus indicated the likely origin of pollen grains. The GlobCover 2009 and CORINE Land Cover 2012 datasets were employed to establish the distribution of coniferous forests in the areas of interest. Conclusions were drawn based on the analyses of the circulation of air masses, using visualization of global weather conditions forecast to supercomputers. For the first time, we have demonstrated that pine pollen grains occurring in pine-free Spitsbergen, could originate from numerous locations, including Scandinavia, Iceland, Siberia and northern Canada. Pollen grains were transported via air masses for distances exceeding ~2000 km. Both air samples and gravimetric pollen deposits revealed the same pattern of Pinus pollen distributio