Assigning and visualizing germline genes in antibody repertoires

Identifying the germline genes involved in immunoglobulin rearrangements is an essential first step in the analysis of antibody repertoires. Based on our prior work in analysing diverse recombinant viruses, we present IgSCUEAL (Immunoglobulin Subtype Classification Using Evolutionary ALgorithms), a phylogenetic approach to assign V and J regions of immunoglobulin sequences to their corresponding germline alleles, with D regions assigned using a simple pairwise alignment algorithm. We also develop an interactive web application for viewing the results, allowing the user to explore the frequency distribution of sequence assignments and CDR3 region length statistics, which is useful for summarizing repertoires, as well as a detailed viewer of rearrangements and region alignments for individual query sequences. We demonstrate the accuracy and utility of our method compared with sequence similarity-based approaches and other non-phylogenetic model-based approaches, using both simulated data and a set of evaluation datasets of human immunoglobulin heavy chain sequences. IgSCUEAL demonstrates the highest accuracy of V and J assignment amongst existing approaches, even when the reassorted sequence is highly mutated, and can successfully cluster sequences on the basis of shared V/J germline alleles.     

Habitat suitability modelling of an invasive plant with advanced remote sensing data

Aim  Lepidium latifolium (Brassicaceae; perennial pepperweed) is a noxious Eurasian weed invading riparian and wetland areas of the western USA. Understanding which sites are most susceptible to invasion by L. latifolium will allow more efficient management of this weed. We assessed the ability of advanced remote sensing techniques to develop habitat suitability models for L. latifolium .
Location  San Francisco Bay/Sacramento-San Joaquin River Delta, California, USA.
Methods  Lepidium latifolium distribution was mapped with hyperspectral image data of Rush Ranch Open Space Preserve, providing presence/absence data to train and validate habitat models. A high-resolution light detection and ranging digital elevation model was used to derive predictor environmental variables (distance to channel, distance to upland, elevation, slope, aspect and convexity). Aggregate decision tree models were used to predict the potential distribution of this species.
Results  Lepidium latifolium infested two zones: near the marshland–upland margin and along channels within the marsh. Topographical data, which are typically strongly correlated with wetland species distributions, were relatively unimportant to L. latifolium occurrence, although relevant microtopography information, particularly relative elevation, was subsumed in the distance to channel variable. The map of potential L. latifolium distribution reveals that Rush Ranch contains considerable habitat that it is susceptible to continued invasion.
Main conclusions  Lepidium latifolium invades relatively less stressful sites along the inundation and salinity gradients. Advanced remote sensing datasets were shown to be sufficient for species distribution modelling. Remote sensing offers powerful tools that deserve wider use in ecological research and management.     

Analysis of grey matter in thalamus and basal ganglia based on EEG α3/α2 frequency ratio reveals specific changes in subjects with mild cognitive impairment

GM (grey matter) changes of thalamus and basal ganglia have been demonstrated to be involved in AD (Alzheimer''s disease). Moreover, the increase of a specific EEG (electroencephalogram) marker, α3/α2, have been associated with AD-converters subjects with MCI (mild cognitive impairment). To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to detect biomarkers (morpho-physiological) early predictive of AD and non-AD dementia. Seventy-four adult subjects with MCI underwent EEG recording and high-resolution 3D MRI (three-dimensional magnetic resonance imaging). The α3/α2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of α3/α2 ratio. GM density differences between groups were investigated using a VBM (voxel-based morphometry) technique. Subjects with higher α3/α2 ratios when compared with subjects with lower and middle α3/α2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.     

The hydrogeomorphic approach to functional assessment of riparian wetlands: evaluating impacts and mitigation on river floodplains in the U.S.A.

1. The ’hydrogeomorphic‘ approach to functional assessment of wetlands (HGM) was developed as a synthetic mechanism for compensatory mitigation of wetlands lost or damaged by human activities. The HGM approach is based on: (a) classification of wetlands by geomorphic origin and hydrographic regime (b) assessment models that associate variables as indicators of function, and (c) comparison to reference wetlands that represent the range of conditions that may be expected in a particular region. In this paper, we apply HGM to riparian wetlands of alluvial rivers. 2. In the HGM classification, riverine wetlands are characterized by formative fluvial processes that occur mainly on flood plains. The dominant water sources are overbank flooding from the channel or subsurface hyporheic flows. Examples of riverine wetlands in the U.S.A. are: bottomland hardwood forests that typify the low gradient, fine texture substratum of the south-eastern coastal plain and the alluvial flood plains that typify the high gradient, coarse texture substratum of western montane rivers. 3. Assessment (logic) models for each of fourteen alluvial wetland functions are described. Each model is a composite of two to seven wetland variables that are independently scored in relation to a reference data set developed for alluvial rivers in the western U.S.A. Scores are summarized by a ’functional capacity index‘ (FCI), which is multiplied by the area of the project site to produce a dimensionless ’functional capacity unit‘ (FCU). When HGM is properly used, compensatory mitigation is based on the FCUs lost that must be returned to the riverine landscape under statutory authority. 4. The HGM approach also provides a framework for long-term monitoring of mitigation success or failure and, if failing, a focus on topical remediation. 5. We conclude that HGM is a robust and easy method for protecting riparian wetlands, which are critically important components of alluvial river landscapes.     

Factors affecting the metal ion-hydroxamate interactions II: effect of the length of the connecting chain on the Fe(III), Mo(VI) and V(V) complexation of some new desferrioxamine B (DFB) model dihydroxamic acids

Three new dihydroxamic acids (HO(CH₃)NCO-(CH₂)₂-CO-NH-(CH₂)_x-CON(CH₃)OH where the x values are 4; 3 and 2, and the compounds are abbreviated as 2,4-DIHA, 2,3-DIHA and 2,2-DIHA), containing the peptide group in a certain position to one of the two functional groups and in different distances to the other one, were synthesized and their complexation with Fe(III), Mo(VI) and V(V) was studied by pH-potentiometric, spectrophotometric and in some cases by CV methods to evaluate the redox behaviour of the Fe(III) complexes and assess their potential biological activity as siderophore models. All these compounds are structural models for the natural siderophore, desferrioxamine B (DFB). The results were compared to those of the complexes of 2,5-DIHA having the same connecting chain structure and length as DFB has, and the effects of the length of the connecting chain on the co-ordination mode and on the stability of the complexes formed were evaluated.Very similar stability of the mono-chelated complexes formed with all these dihydroxamic acids was found. All the results obtained suggest that one dihydroxamic acid (even the 2,2-DIHA) is able to complete the four coordination sites of a MoO₂ ²⁺ core forming simple mononuclear complexes. Favoured monomeric structures of the bis-chelated complexes of these dihydroxamic acids are also suggested with V(V) having the smallest ionic radius among the three metal ions studied. In the case of iron(III), however, clear indication was obtained for the slightly different complexation behaviour of 2,2-DIHA. Namely, the formation of the mononuclear bis-chelated complex with this shortest ligand seems to have sufficient strain to induce the formation of bimetallic species such as [Fe(2,2-DIHA)₂Fe)]²⁺.     

Molecular identification of Korean Trichinella isolates

Muscle larvae of Trichinella isolates from two outbreaks in Korea were analyzed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiple-PCR. All of the muscle larvae showed a band similar to that of T. spiralis larvae of the reference strain. The two Korean Trichinella isolates (isolate code ISS623 and ISS1078) might be classifiable to Trichinella spiralis.     

Role and Cost Effectiveness of PET/CT in Management of Patients with Cancer

PET/CT is a relatively new imaging technology, whose undoubted advantages are valuable in clinical oncology as well as in all fields of diagnosis, staging, and treatment. The hardware combination of anatomy and function has been the true evolution in imaging. PET using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of solid malignancies, including colon, lung, etc., but anatomic information is limited. Integrated PET/CT enables optimal anatomic delineation of PET findings and identification of FDG-negative lesions on computed tomography (CT) images and might improve preoperative staging. However, controversy still exists in relation to the application of PET/CT in clinical practice, mainly because of its high cost. It is evident that apart from additional costs, potential savings also are associated with PET/CT as a result of avoiding additional imaging examinations or invasive procedures and by helping clinicians make the optimum treatment decisions. The authors review the literature on the role of PET/CT in management of various tumors and discuss the medicoeconomic usefulness.     

丝氨酸/精氨酸富集蛋白与肿瘤发生

富含丝氨酸和精氨酸的SR蛋白（serine/arginine-rich protein）是重要的剪接因子家族,广泛参与RNA加工过程,包括剪接、出核、稳定性及翻译。近年来的研究发现,SR蛋白家族成员大多在肿瘤组织中存在异常表达,有些SR蛋白甚至能够作为原癌基因,通过调控肿瘤相关基因的选择性剪接而参与细胞转化和肿瘤发生。本文综述了SR蛋白的不同成员在肿瘤发生中的作用及其调控肿瘤相关基因的机制,以期为相关肿瘤的研究与诊治提供新思路和新靶点。     

Plasma and scales levels of interleukin 18 in comparison with other possible clinical and laboratory biomarkers of psoriasis activity

The aim of the study was to assess plasma and scales levels of interleukin (IL) 18 collected from psoriatic patients with different disease activity. IL-18 concentrations were measured using an enzyme immunoassay in the plasma and scales of 34 patients with chronic plaque type psoriasis. IL-18 levels were analysed with respect to plasma-transforming growth factor β₁ (TGF-β₁), the disease duration and the duration of the present relapse, and psoriasis area and severity index (PASI). Plasma IL-18 concentration varied from 90 to 1300 pg ml^-1 and means (368.2±42.4 pg ml^-1) were significantly elevated in comparison with healthy controls (205.9±31.8 pg ml^-1). The presence of IL-18 was also demonstrated in scales from skin lesions. Treatment caused a significant decrease of plasma IL-18 concentration to 250.2±13.8 pg ml^-1. There was a significant correlation between plasma IL-18 levels and PASI values (r=0.554). There was no correlation between IL-18 concentration in scales and PASI, between IL-18 concentrations in plasma and scales, and between plasma IL-18 and the disease duration or duration of present relapse. Plasma TGF-β₁ concentration demonstrated a significant correlation with PASI (r=0.353), but not with IL-18 levels in plasma (r=0.063) and scales (0.141). The sum of plasma levels of IL-18 and TGF-β₁ divided by the optimal coefficient demonstrated a statistically significant correlation with the highest r-value. The findings confirm an association between plasma IL-18 concentration and psoriasis severity. Moreover, it was shown that combined measurement of IL-18 and TGF-β₁ in plasma can be considered as a possible biomarker of psoriasis activity.     

Fundamental Principles for CAD-based Ecological Assessments (9 pp)

Background Aims, and Scope. As products are, directly and indirectly, main sources for ecological impact, the overall enhancement of products' ecological behaviour is an important contribution to the protection of the Earth's biosphere. This is especially important in a world where the major economical system is based on a constant rise in industrial production, consumption, and disposal of products. The true ecological performance of a product can only be determined by consideration of the impact arising from the entire lifecycle, and by including all known impacts into the assessments. The state of technology provides a standardized framework for such life cycle assessments (LCA) in the ISO 14040 series (see ISO 1997), and numerous databases and software tools are available to support the conduction of LCA. To integrate ecological indicators into decisions of everyday product development, as natural as it is the case today with finite items, design, and costs, indicators based on a consideration of the product's entire life have to be generated with little effort and in short time. Methods This article describes the fundamental principles of a technology designed to integrate lifecycle information into common 3-dimensional product models, like the ones used within modern Computer Aided Design (CAD) systems. Thereby, ecological assessments can be effectively undertaken during product development, where most of the environmental lock-in of a product is defined (see Lewis et al. 2001). Overall effects of alterations in materials or other product properties can be assessed instantly, supporting on the spot decisions to reach an improved product design. Results Next to an information model that manages the product and process representation, the research on which this article is based also deals with the calculation of resulting indicators, database access to ecological indicators, a graphical user interface, and a synchronisation tool for the CAD system Pro/Engineer . The developed concepts have been implemented as a prototype software and validated in different stages. Conclusions The concepts described in this article are a foundation for tools that integrate ecological assessments into everyday product development, on the basis of 3-dimensional CAD systems. Reuse of existing CAD data, an improved understanding of the assessment structure by product developers, and an automated calculation of resulting indicators are approaches to largely enhance the efficiency of product-related ecological assessments.     

Regression model,artificial neural network,and cost estimation for biosorption of Ni(II)-ions from aqueous solutions by Potamogeton pectinatus

This study investigated the application of Potamogeton pectinatus for Ni(II)-ions biosorption from aqueous solutions. FTIR spectra showed that the functional groups of –OH, C–H, –C = O, and –COO– could form an organometallic complex with Ni(II)-ions on the biomaterial surface. SEM/EDX analysis indicated that the voids on the biosorbent surface were blocked due to Ni(II)-ions uptake via an ion exchange mechanism. For Ni(II)-ions of 50 mg/L, the adsorption efficiency recorded 63.4% at pH: 5, biosorbent dosage: 10 g/L, and particle-diameter: 0.125–0.25 mm within 180 minutes. A quadratic model depicted that the plot of removal efficiency against pH or contact time caused quadratic-linear concave up curves, whereas the curve of initial Ni(II)-ions was quadratic-linear convex down. Artificial neural network with a structure of 5 – 6 – 1 was able to predict the adsorption efficiency (R²: 0.967). The relative importance of inputs was: initial Ni(II)-ions > pH > contact time > biosorbent dosage > particle-size. Freundlich isotherm described well the adsorption mechanism (R²: 0.974), which indicated a multilayer adsorption onto energetically heterogeneous surfaces. The net cost of using P. pectinatus for the removal of Ni(II)-ions (4.25 ± 1.26 mg/L) from real industrial effluents within 30 minutes was 3.4 $USD/m³.     

候选结核疫苗的评价模型

卡介苗作为目前唯一批准使用的预防结核疫苗,由于无法提供充足的保护力,目前结核病依然是严重危害人类健康的传染病,因此筛选优质候选疫苗迫在眉睫.所有候选疫苗进入临床试验前必须评价其安全性、免疫原性以及有效性.评价结果在一定程度上也预示候选疫苗在人体的免疫作用,也是目前评价候选疫苗是否优于传统卡介苗的依据.论述候选结核疫苗临...     

植物碱性亮氨酸拉链（bZIP）蛋白的研究进展（一）——结构、分类、分布和同源性分析

植物碱性亮氨酸拉链（bZIP)蛋白在高等植物中广泛存在,对基因表达与调控起重要作用。本简要介绍了植物bZIP蛋白的结构之后,概述了植物bZIP蛋白的分类和分布。最后,以模式植物、主要农作物及蔬菜等为例,对它们的同源性进行了详细的描述和分析。     

Mechanisms of the antinociceptive action of (?) Epicatechin obtained from the hydroalcoholic fraction of Combretum leprosum Mart & Eic in rodents

ABSTRACT: BACKGROUND: The mechanisms of the antinociceptive activity of () epicatechin (EPI), a compound isolated from the hydroalcoholic fraction of Combreum leprosum Mart & Eicher. METHODS: were assessed in the model of chemical nociception induced by glutamate (20 mumol/paw). To evaluate the mechanisms involved, the animals , male Swiss mice (25-30 g), received EPI (50 mg/kg p.o.) after pretreatment with naloxone (2 mg/kg s.c. opioid antagonist), glibenclamide (2 mg/kg s.c. antagonist K + channels sensitive to ATP), ketanserin (0.3 mg/kg s.c. antagonist of receptor 5-HT2A), yoimbine (0.15 mg/kg s.c. alpha2 adrenergic receptor antagonist), pindolol (1 mg/kg s.c. 5-HT1a/1b receptor antagonist), atropine (0.1 mg/kg s.c. muscarinic antagonist) and caffeine (3 mg/kg s.c. adenosine receptor antagonist), ondansetron (0.5 mg/kg s.c. for 5-HT3 receptor) and L-arginine (600 mg/kg i.p.). RESULTS: The antinociceptive effect of EPI was reversed by pretreatment with naloxone and glibenclamide, ketanserin, yoimbine, atropine and pindolol, which demonstrates the involvement of opioid receptors and potassium channels sensitive to ATP, the serotoninergic (receptor 5HT1A and 5HT2A), adrenergic (receptor alpha 2) and cholinergic (muscarinic receptor) systems in the activities that were observed. The effects of EPI, however, were not reversed by pretreatment with caffeine, L-arginine or ondansetron, which shows that there is no involvement of 5HT3 receptors or the purinergic and nitrergic systems in the antinociceptive effect of EPI. In the Open Field and Rotarod test, EPI had no significant effect, which shows that there was no central nervous system depressant or muscle relaxant effect on the results. CONCLUSIONS: This study demonstrates that the antinociceptive activity of EPI in the glutamate model involves the participation of the opioid system, serotonin, adrenergic and cholinergic.     

核仁小RNA与肺癌

核仁小RNA（small nucleolar RNA, snoRNA）是一类定位于核仁内的短链非编码RNA,在多种RNA的加工修饰过程中发挥重要作用。随着人们对基因组认识的深入,snoRNA等非编码RNA的结构及功能已成为研究的热点。近年来有研究表明,snoRNA与肺癌的发生发展有密切关系。本文结合国内外snoRNA与肺癌相关的最新研究结果,在总结snoRNA的基本结构和功能的基础上,对snoRNA在肺癌发生发展中的特点以及在肺癌的诊断和治疗中潜在应用价值进行综述,以期为后续相关的研究提供参考。     

F NMR studies of solvent exposure and peptide binding to an SH3 domain

¹⁹F NMR was used to study topological features of the SH3 domain of Fyn tyrosine kinase for both the free protein and a complex formed with a binding peptide. Metafluorinated tyrosine was biosynthetically incorporated into each of 5 residues of the G48M mutant of the SH3 domain (i.e. residues 8, 10, 49 and 54 in addition to a single residue in the linker region to the C-terminal polyhistidine tag). Distinct ¹⁹F NMR resonances were observed and subsequently assigned after separately introducing single phenylalanine mutations. ¹⁹F NMR chemical shifts were dependent on protein concentration above 0.6 mM, suggestive of dimerization via the binding site in the vicinity of the tyrosine side chains. ¹⁹F NMR spectra of Fyn SH3 were also obtained as a function of concentration of a small peptide (2-hydroxynicotinic-NH)–Arg–Ala–Leu–Pro–Pro–Leu–Pro-diaminopropionic acid –NH₂, known to interact with the canonical polyproline II (PPII) helix binding site of the SH3 domain. Based on the ¹⁹F chemical shifts of Tyr8, Tyr49, and Tyr54, as a function of peptide concentration, an equilibrium dissociation constant of 18 ± 4 μM was obtained. Analysis of the line widths suggested an average exchange rate, k_ex, associated with the peptide–protein two-site exchange, of 5200 ± 600 s^− 1 at a peptide concentration where 96% of the FynSH3 protein was assumed to be bound. The extent of solvent exposure of the fluorine labels was studied by a combination of solvent isotope shifts and paramagnetic effects from dissolved oxygen. Tyr54, Tyr49, Tyr10, and Tyr8, in addition to the Tyr on the C-terminal tag, appear to be fully exposed to the solvent at the metafluoro position in the absence of binding peptide. Tyr54 and, to some extent, Tyr10 become protected from the solvent in the peptide bound state, consistent with known structural data on SH3–domain peptide complexes. These results show the potential utility of ¹⁹F-metafluorotyrosine to probe protein–protein interactions in conjunction with paramagnetic contrast agents.