CytoITMprobe: a network information flow plugin for Cytoscape

ABSTRACT: BACKGROUND: Cytoscape is a well-developed flexible platform for visualization, integration and analysis of network data. Apart from the sophisticated graph layout and visualization routines, it hosts numerous user-developed plugins that significantly extend its core functionality. Earlier, we developed a network information flow framework and implemented it as a web application, called ITM Probe. Given a context consisting of one or more user-selected nodes, ITM Probe retrieves other network nodes most related to that context. It requires neither user restriction to subnetwork of interest nor additional and possibly noisy information. However, plugins for Cytoscape with these features do not yet exist. To provide the Cytoscape users the possibility of integrating ITM Probe into their workflows, we developed CytoITMprobe, a new Cytoscape plugin. FINDINGS: CytoITMprobe maintains all the desirable features of ITM Probe and adds additional flexibility not achievable through its web service version. It provides access to ITM Probe either through a web server or locally. The input, consisting of a Cytoscape network, together with the desired origins and/or destinations of information and a dissipation coefficient, is specified through a query form. The results are shown as a subnetwork of significant nodes and several summary tables. Users can control the composition and appearance of the subnetwork and interchange their ITM Probe results with other software tools through tab-delimited files. CONCLUSIONS: The main strength of CytoITMprobe is its flexibility. It allows the user to specify as input any Cytoscape network, rather than being restricted to the pre-compiled protein-protein interaction networks available through the ITM Probe web service. Users may supply their own edge weights and directionalities. Consequently, as opposed to ITM Probe web service, CytoITMprobe can be applied to many other domains of network-based research beyond protein-networks. It also enables seamless integration of ITM Probe results with other Cytoscape plugins having complementary functionality for data analysis.     

Hyperleptinemia--non-haemodynamic risk factor for the left ventricular hypertrophy development in hypertensive overweight females

Obesity is directly and strongly associated with hypertension and left ventricular hypertrophy (LVH). Development of LVH is multifactorial, caused both by haemodynamic and non-haemodynamic factors. Hypertension is the main haemodynamic factor. Humoral mechanisms, as a non-haemodynamic factor for LVH development, have not been completely explained. The aim of this study is to determine whether hyperleptinemia can be one of humoral--non-haemodynamic factor inducing LVH together with haemodynamic factors in overweight females. The study was done on thirty six adult, overweight female patients, body mass index in range 25-30 kg/m2. Patients are nondiabetic with regular renal function. Twenty one female patients were hypertensive with left ventricular hypertrophy. Control group included fifteen hypertensive female patients without left ventricular hypertrophy. In all patients was determined glucose profile and creatinine clearance, cholesterol, triglycerides, LDL, HDL. Weight, high, circumference of the waist and hips was taken. Cardiovascular determination was done applying two-dimensional ultrasound. Serum leptin level was measured using radioimmunoassay method (RIA). Results showed that serum leptin level was significantly higher in hypertensive, overweight females with LVH. This suggests that non-haemodynamic factors, such as hyperleptinemia, participate in left ventricular hypertrophy development together with haemodynamic factors in adult hypertonic, overweight females.     

Direct interaction between SNAP-23 and L-type Ca2+ channel

During secretion, membrane-bound secretory vesicles dock and fuse at the base of porosomes in the cell plasma membrane. Among other proteins, the porosome is composed of SNAREs and Ca2+-channels. Ca2+-channels and SNAREs have been implicated in cell secretion. Several immunoprecipitation and binding studies suggest the physical interaction of the t-SNARE proteins, Syntaxin-1 and SNAP-25 with various Ca2+-channels. In this study, using yeast two-hybrid and immunoanalysis, we demonstrate for the first time, direct interaction of SNAP-23 and a L-type Ca2+-channel at the plasma membrane in pancreas.     

3D organization and function of the cell: Golgi budding and vesicle biogenesis to docking at the porosome complex

Insights into the three-dimensional (3D) organization and function of intracellular structures at nanometer resolution, holds the key to our understanding of the molecular underpinnings of cellular structure-function. Besides this fundamental understanding of the cell at the molecular level, such insights hold great promise in identifying the disease processes by their altered molecular profiles, and help determine precise therapeutic treatments. To achieve this objective, previous studies have employed electron microscopy (EM) tomography with reasonable success. However, a major hurdle in the use of EM tomography is the tedious procedures involved in fixing, high-pressure freezing, staining, serial sectioning, imaging, and finally compiling the EM images to obtain a 3D profile of sub-cellular structures. In contrast, the resolution limit of EM tomography is several nanometers, as compared to just a single or even sub-nanometer using the atomic force microscope (AFM). Although AFM has been hugely successful in 3D imaging studies at nanometer resolution and in real time involving isolated live cellular and isolated organelles, it has had limited success in similar studies involving 3D imaging at nm resolution of intracellular structure-function in situ. In the current study, using both AFM and EM on aldehyde-fixed and semi-dry mouse pancreatic acinar cells, new insights on a number of intracellular structure-function relationships and interactions were achieved. Golgi complexes, some exhibiting vesicles in the process of budding were observed, and small vesicles were caught in the act of fusing with larger vesicles, possibly representing either secretory vesicle biogenesis or vesicle refilling following discharge, or both. These results demonstrate the power and scope of the combined engagement of EM and AFM imaging of fixed semi-dry cells, capable of providing a wealth of new information on cellular structure-function and interactions.     

Nuclear geometry: mitotic nucleus flares out when arrested

Studies of budding yeast arrested in mitosis outline a set of rules for nuclear envelope expansion during closed nuclear division.     

Deficiency of LKB1 in heart prevents ischemia-mediated activation of AMPKalpha2 but not AMPKalpha1

Recent studies indicate that the LKB1 is a key regulator of the AMP-activated protein kinase (AMPK), which plays a crucial role in protecting cardiac muscle from damage during ischemia. We have employed mice that lack LKB1 in cardiac and skeletal muscle and studied how this affected the activity of cardiac AMPKalpha1/alpha2 under normoxic, ischemic, and anoxic conditions. In the heart lacking cardiac muscle LKB1, the basal activity of AMPKalpha2 was vastly reduced and not increased by ischemia or anoxia. Phosphorylation of AMPKalpha2 at the site of LKB1 phosphorylation (Thr172) or phosphorylation of acetyl-CoA carboxylase-2, a downstream substrate of AMPK, was ablated in ischemic heart lacking cardiac LKB1. Ischemia was found to increase the ADP-to-ATP (ADP/ATP) and AMP-to-ATP ratios (AMP/ATP) to a greater extent in LKB1-deficient cardiac muscle than in LKB1-expressing muscle. In contrast to AMPKalpha2, significant basal activity of AMPKalpha1 was observed in the lysates from the hearts lacking cardiac muscle LKB1, as well as in cardiomyocytes that had been isolated from these hearts. In the heart lacking cardiac LKB1, ischemia or anoxia induced a marked activation and phosphorylation of AMPKalpha1, to a level that was only moderately lower than observed in LKB1-expressing heart. Echocardiographic and morphological analysis of the cardiac LKB1-deficient hearts indicated that these hearts were not overtly dysfunctional, despite possessing a reduced weight and enlarged atria. These findings indicate that LKB1 plays a crucial role in regulating AMPKalpha2 activation and acetyl-CoA carboxylase-2 phosphorylation and also regulating cellular energy levels in response to ischemia. They also provide genetic evidence that an alternative upstream kinase can activate AMPKalpha1 in cardiac muscle.     

Patterns of sexual behaviour and reported symptoms of STI/RTIs among young people in Croatia--implications for interventions' planning

This paper describes some of the results of the first national-level survey on sexual behaviour and the distribution of risks to sexually transmitted infections (STIs), including human immunodeficiency virus infection (HIV), among youth in Croatia, and the nature and the extent of their vulnerability to these adverse health outcomes. The study was a cross-sectional, probability-based household survey conducted in 2005, and included 1093 respondents aged 18-24. This paper aims to describe the findings related to the knowledge of HIV transmission, key behavioural outcomes relevant for potential transmission of HIV and STIs, and correlates of genital discharge in young men and young women. More than 80% of young people know that the correct use of condoms protects against HIV and that HIV can be transmitted by someone who looks healthy. Fifty-nine percent of young men and 52.4% of young women reported using condoms during the first sexual intercourse, and 59.3% of men and 46.1% of women used condoms during the last sexual intercourse with a casual partner. This points to the gap between knowledge of condom use and the actual use of condoms as a high proportion of risky sexual contact remain unprotected. Having sexual intercourse frequently or regularly while consuming alcohol was reported by 19.2% of men and 7.6% of women. Much lower proportion are using drugs frequently or regularly during sexual intercourse (3.7% of men and 2.1% of women). Among those sexually experienced, 11.8% of men and 44.1% of women reported ever having a genital discharge. Higher presence of genital discharge in women is suggestive of reproductive tract infections that are not necessarily sexually transmitted. In the multivariate analysis, the lack of knowledge of whether chlamydial infections is an STI and having more than five partners in life were correlates of genital discharge in men, while in women the correlates included having more than five partners in life and not using condoms during the first sexual intercourse. Higher burden of STI-related symptoms was found among men who have men as sexual partners, those who paid for sex, and those with concurrent partnerships. These findings point out to the immediate need to strengthen sexual health education among young people and to the necessity for further development of other broad-based interventions to prevent adverse sexual health outcomes among both men and women, as well as those targeted towards more vulnerable subgroups.     

The role of air quality in perception of health of the local population

The research aim was to investigate and establish the perception of health among population groups with different number of industrial polluters in their living environment. Namely, the Kostrena living area (3250 inhabitants) is situated near big industrial pollutant producers: INA oil refinery Urinj, thermo power plant Rijeka, shipyard "Viktor Lenac", while in Crikvenica living area such pollutant producers do not exist. In this research 146 subjects from Kostrena participated (74 men and 72 women with age average 40.8, SD 9.2 years), and 157 subjects from Crikvenica area (79 men and 78 women with age average 39.4, SD 10.1 years). The perception of health was measured by the means of SF-36 questionnaire variables. Lung function (FEV1, FVC, FEV25/75, PEF), cardiovascular function (systolic and diastolic arterial blood pressure, heart rate were also measured, including body proportion measures by the means of waste and hip circumference and silhouette test, in order to establish the eventual objective physical health parameter difference among examined population groups. Subjects from Kostrena perceived their general health, mental health, and vitality worse than subjects from Crikvenica. Group from Kostrena felt themself more limited in their roles due to emotional problems, perceiving more pain than group from Crikvenica. On the opposite site, social functioning of subjects from Kostrena was better in comparison to Crikvenica group. No signifficant differences between groups were found in physical functioning and in role limitation due to physical problems. In addition, there were no significant differences between groups in objective physical health parameters, such as pulmonary function, arterial blood pressure, pulse, and waist to hip ratio. Subjects using sensoric systems and the mental cognition about harmful environmental factors, perceive their health worse if there are present industrial resources in their environment, even when concentration of the pollutants are within legal ranges.     

Functional analysis of Scr during embryonic and post-embryonic development in the cockroach, Periplaneta americana

The cockroach, Periplaneta americana represents a basal insect lineage that undergoes the ancestral hemimetabolous mode of development. Here, we examine the embryonic and post-embryonic functions of the hox gene Scr in Periplaneta as a way of better understanding the roles of this gene in the evolution of insect body plans. During embryogenesis, Scr function is strictly limited to the head with no role in the prothorax. This indicates that the ancestral embryonic function of Scr was likely restricted to the head, and that the posterior expansion of expression in the T1 legs may have preceded any apparent gain of function during evolution. In addition, Scr plays a pivotal role in the formation of the dorsal ridge, a structure that separates the head and thorax in all insects. This is evidenced by the presence of a supernumerary segment that occurs between the labial and T1 segments of RNAiScr first nymphs and is attributed to an alteration in engrailed (en) expression. The fact that similar Scr phenotypes are observed in Tribolium but not in Drosophila or Oncopeltus reveals the presence of lineage-specific variation in the genetic architecture that controls the formation of the dorsal ridge. In direct contrast to the embryonic roles, Scr has no function in the head region during post-embryogenesis in Periplaneta, and instead, strictly acts to provide identity to the T1 segment. Furthermore, the strongest Periplaneta RNAiScr phenotypes develop ectopic wing-like tissue that originates from the posterior region of the prothoracic segment. This finding provides a novel insight into the current debate on the morphological origin of insect wings.