Trees on networks: resolving statistical patterns of phylogenetic similarities among interacting proteins

Background  

Phylogenies capture the evolutionary ancestry linking extant species. Correlations and similarities among a set of species are mediated by and need to be understood in terms of the phylogenic tree. In a similar way it has been argued that biological networks also induce correlations among sets of interacting genes or their protein products.     

南瓜雌蕊与自花及远缘花粉的相互作用

南瓜柱头表面经去垢剂、蛋白酶及Con A处理后花粉不能萌发或花粉管生长受阻,Con A能专一地与柱头表面结合。柱头块加入培养液可促进花粉萌发。不同的远缘花粉授粉后在雌蕊不同部位受阻。在成熟南瓜雌蕊提取液中检测到血凝活性,凝集素可能参与雌蕊对远缘花粉的抑制。     

Segregation analysis indicates a major gene in the control of interleukine-5 production in humans infected with Schistosoma mansoni.

The interleukine-5 (IL-5) is a hormone of the immune system that is the main regulator of eosinopoiesis, eosinophil maturation and activation, and immunoglobulin A production. Thus, IL-5 contributes in several ways to human immune defenses against various pathogens, including helminths and infectious agents of the digestive and respiratory tracts. On the other hand, the increase in eosinophil number and the activation of these cells, which both have been related to elevated IL-5 production, are the cause of severe pathological disorders, as in asthma or hypereosinophilic syndromes. Although the immunological pathways leading to IL-5 synthesis have been identified, the reasons for the large variability observed in IL-5 production among subjects exposed to comparable antigenic stimulation are unknown. To investigate the role of genetic factors in this variability, we conducted a segregation analysis in a Brazilian population infected by the helminth parasite Schistosoma mansoni. The analysis was performed on IL-5 levels produced by blood mononuclear cells of these subjects after in vitro restimulation with either parasite extracts (IL-5/schistosomula sonicates [SS] phenotype) or a T-lymphocyte mitogen (IL-5/phytohemagglutin [PHA]). The results provide clear evidence for the segregation of a codominant major gene controlling IL-5/SS and IL-5/PHA production and accounting for 70% and 73% of the phenotypic variance, respectively; the frequency of the allele predisposing to low IL-5 production was approximately .22 for both phenotypes. No significant relationship was found between these genes and the gene controlling infection intensities by S. mansoni detected in a previous study. Linkage studies are ongoing to locate those genes that would help to characterize the genetic factors involved in pathological conditions such as severe helminth infections and allergic diseases.     

Towards the elucidation of the true impact of adipocytokines on cardiovascular risk in rheumatoid arthritis

Adipo(cyto)kines are mostly produced by adipose tissue and orchestrate the adverse impact of excess adiposity on cardiovascular risk. Adipokines also contribute importantly to the pathophysiology of rheumatoid arthritis. Congruent with data reported in previous investigations, Kang and colleagues report in this issue of Arthritis Research & Therapy that adipokine concentrations are further associated with metabolic risk and inflammation and that the leptin–adiponectin ratio associates with the carotid artery resistive index in rheumatoid arthritis. Guided by evidence reported thus far on cardiovascular risk, we discuss six reasons why careful elucidation of adipokine–cardiovascular risk relations is needed in rheumatoid arthritis.In this issue of Arthritis Research & Therapy, Kang and colleagues investigate whether adipokines could link inflammation, metabolic risk factors and cardiovascular disease in rheumatoid arthritis (RA) [1]. Evidence in support of this paradigm was reported previously [2-6]. Patients with RA experience a markedly increased cardiovascular risk that is driven by metabolic risk factors and by high-grade inflammation [7]. Kang and colleagues measured adiponectin, leptin, resistin, tumor necrosis factor alpha and interleukin-6 concentrations and assessed the common carotid artery intima-media thickness, resistive index (RI) and plaque presence by high-resolution ultrasonography [1]. Concentrations of some of the adipokines related to inflammatory markers including C-reactive protein levels and the erythrocyte sedimentation rate, and to metabolic syndrome features.In a previous study by our group, leptin and adiponectin concentrations were not associated with carotid intima-media thickness and plaque [3]. In addition, the leptin–adiponectin ratio and carotid RI as markers of cardiovascular risk have not been reported in RA. For these reasons, besides the abovementioned analyses, Kang and colleagues assessed (only) the relationship of the leptin–adiponectin ratio with carotid RI. In univariate analysis, the leptin–adiponectin ratio as well as age, homeostasis model assessment for insulin resistance, waist circumference and body mass index were associated with the carotid RI. Importantly, in multivariate analysis, only age and the leptin–adiponectin ratio remained significantly related to the carotid RI. The leptin–adiponectin ratio may thus provide information about the presence of subclinical cardiovascular disease beyond that on insulin resistance as assessed by the homeostasis model of insulin resistance, as well as adiposity extent as represented by body mass index and waist circumference in RA.Adipo(cyto)kines comprise a vast range of disparate soluble bioactive proteins that are mostly secreted by adipose tissue [8]. These molecules participate in biological processes that include inflammatory responses and thereby orchestrate the adverse impact of excess adiposity on cardiovascular risk and incident type 2 diabetes [8]. Adipokines represent both adiposity extent and biological activity. RA is a prototypic inflammatory disease. In this context, ~200 recently reported investigations substantiate an important involvement of adipokines in RA activity and severity [9]. By contrast, despite the contribution of adipokines to altered cardiovascular risk in non-RA subjects and the enhanced cardiovascular risk in RA, there is a striking paucity of reported studies on the potential role of adipokines in atherogenesis in RA.A myriad of pertinent reasons exist why the role of adipokines in cardiovascular risk amongst patients with RA requires thorough elucidation. First, RA can modify adipokine production [3,9].Second, and presumably more important, the presence of autoimmunity can alter the effects of adipokines on cardiovascular risk [3,4]. In non-RA subjects, adiponectin production decreases with increasing adiposity and this adipokine has anti-inflammatory properties [8]. However, in RA adiponectin has marked proinflammatory properties [9]. In fact, in Kang and colleagues’ study the adiponectin concentrations were paradoxically positively associated with the erythrocyte sedimentation rate [1]. Whereas in non-RA subjects adiponectin improves metabolic risk and also directly inhibits atherogenesis, we reported recently that in RA, upon using comprehensive potential confounder-adjusted analysis, adiponectin concentrations associated paradoxically with high blood pressure [3,4] and in white but not black Africans with enhanced endothelial activation [4]. Endothelial activation mediates the very initial stages of atherosclerosis [3-6]. Whether such paradoxical relations represent altered effects mediated by RA or a compensatory increase in adiponectin production in the presence of heightened cardiovascular risk and in an attempt to reduce this risk needs further investigation [4].Third, conventional risk factors and disease characteristics can impact on adipokine–atherogenesis relationships in RA [5]. Resistin concentrations thus associate independently with endothelial activation in RA, but this relation is present only in those with, and not in those without, traditional risk factors, abdominal obesity, joint damage as reflected by the presence of deformed joints or prolonged disease duration [5]. This observation further supports the need for sensitivity analysis in the present context. By contrast, interleukin-6 concentrations are more consistently associated with endothelial activation in RA [6].Fourth, the effects of adipokines on cardiovascular risk require examination prior to targeting the respective molecules in an attempt to reduce disease activity and severity in RA [3]. Indeed, should the protective effect of adiponectin on cardiovascular risk be preserved amongst patients with RA, then its blockade would be expected to further enhance cardiovascular risk [3].Fifth, RA influences adiposity and its distribution, which also associates with atherosclerosis in this disease [7,10].Finally, as illustrated by the disparity in adiponectin–endothelial activation relations amongst Africans previously alluded to, population origin impacts on adipokine–cardiovascular risk relations in RA [4].A caveat of Kang and colleagues’ study is that potential confounders were not systematically identified. For example, gender, cardiovascular drug use, antirheumatic agent use and the glomerular filtration rate can all influence both the concentrations and effects of adipokines [3-6]. Nevertheless, this investigation reinforces previously reported evidence that strongly suggests an intriguing and important involvement of adipokines in RA atherogenesis.     

CARNOY: A new digital measurement tool for palynology

Quantitative data play an important role in palynological research. With the advent of digital imaging in light and electron microscopy, palynologists now have the opportunity to perform measurements faster and more precisely than ever before. Several image analysis software packages already exist for these tasks, but they are often expensive, difficult to use or not adapted to the specific needs of palynologists. After studying the daily workflow of a palynologist, we designed CARNOY, an image analysis application written from the ground up for use in palynology and morphology. CARNOY offers an easy-to-use interface and several features to make measuring easier and faster. The program can export measurements to almost every other software package for further analysis and is available for free on the Internet.