Early Relaxation Dynamics in the LC 13 T Cell Receptor in Reaction to 172 Altered Peptide Ligands: A Molecular Dynamics Simulation Study

The interaction between the T cell receptor and the major histocompatibility complex is one of the most important events in adaptive immunology. Although several different models for the activation process of the T cell via the T cell receptor have been proposed, it could not be shown that a structural mechanism, which discriminates between peptides of different immunogenicity levels, exists within the T cell receptor. In this study, we performed systematic molecular dynamics simulations of 172 closely related altered peptide ligands in the same T cell receptor/major histocompatibility complex system. Statistical evaluations yielded significant differences in the initial relaxation process between sets of peptides at four different immunogenicity levels.     

A large‐scale phylogeny of the lycophyte genus Selaginella (Selaginellaceae: Lycopodiopsida) based on plastid and nuclear loci

The lycophyte genus Selaginella alone constitutes the family Selaginellaceae, the largest of the lycophyte families. The genus is estimated to contain 700–800 species distributed on all continents except Antarctica, with highest species diversity in tropical and subtropical regions. The monophyly of Selaginella in this broad sense has rarely been doubted, whereas its intrageneric classification has been notoriously contentious. Previous molecular studies were based on very sparse sampling of Selaginella (up to 62 species) and often used DNA sequence data from one genome. In the present study, DNA sequences of one plastid (rbcL) and one nuclear (ITS) locus from 394 accessions representing approximately 200 species of Selaginella worldwide were used to infer a phylogeny using maximum likelihood, Bayesian inference and maximum parsimony methods. The study identifies strongly supported major clades and well resolves relationships among them. Major results include: (i) six deep‐level clades are discovered representing the deep splits of Selaginella; and (ii) 20 major clades representing 20 major evolutionary lineages are identified, which differ from one another in molecular, macro‐morphological, ecological and spore features, and/or geographical distribution.     

Grey mould of strawberry,a devastating disease caused by the ubiquitous necrotrophic fungal pathogen Botrytis cinerea

The fungal pathogen Botrytis cinerea causes grey mould, a commercially damaging disease of strawberry. This pathogen affects fruit in the field, storage, transport and market. The presence of grey mould is the most common reason for fruit rejection by growers, shippers and consumers, leading to significant economic losses. Here, we review the biology and epidemiology of the pathogen, mechanisms of infection and the genetics of host plant resistance. The development of grey mould is affected by environmental and genetic factors; however, little is known about how B. cinerea and strawberry interact at the molecular level. Despite intensive efforts, breeding strawberry for resistance to grey mould has not been successful, and the mechanisms underlying tolerance to B. cinerea are poorly understood and under-investigated. Current control strategies against grey mould include pre- and postharvest fungicides, yet they are generally ineffective and expensive. In this review, we examine available research on horticultural management, chemical and biological control of the pathogen in the field and postharvest storage, and discuss their relevance for integrative disease management. Additionally, we identify and propose approaches for increasing resistance to B. cinerea in strawberry by tapping into natural genetic variation and manipulating host factors via genetic engineering and genome editing.     

Are regional precipitation–productivity relationships robust to decadal-scale dry period?

降水-生产力的空间关系是否稳定不变？ 降水是全球陆地生态系统中植被生长和净初级生产力的主要驱动因素。因此,探究降水和生产力关系有助于深入了解气候变化如何改变生态系统功能。降水-生产力的空间关系在全球不同草地上非常相似,但在连续多年气候异常的情况下,这种关系是否会发生变化以及如何变化尚不清楚。本研究利用 利用中国北方温带草地长达10年低于多年平均降水的时期,基于遥感植被指数数据,量化了区域尺度上降水-植被生产力关系在持续多年的干湿期之间将如何变化。结果表明,在连续10年的干期,降水-生产力空间相关性急剧下降,而该空间关系的下降主要是由于不同草原类型对干旱的响应在空间上存在高度的异质性,即不同生态系统对干旱的响应程度存在差异。因此,如果未来气候变化进一步加剧全球草地的干旱,那么基于历史时期(平水期)得到的降水-生产力空间关系推测区域尺度植被生产力可能导致误差。     

Assessment approach for evaluating high abundance protein depletion methods for cerebrospinal fluid (CSF) proteomic analysis

Optimal proteomic analysis of human cerebrospinal fluid (CSF) requires depletion of high-abundance proteins to facilitate observation of low-abundance proteins. The performance of two immunodepletion (MARS, Agilent Technologies and ProteoSeek, Pierce Biotechnology) and one ultrafiltration (50 kDa molecular weight cutoff filter, Millipore Corporation) methods for depletion of abundant CSF proteins were compared using a graphical method to access the depth of analysis using "marker proteins" with known normal concentration ranges. Two-dimensional LC/MS/MS analysis of each depleted sample yielded 171 and 163 unique protein identifications using the MARS and ProteoSeek immunodepletion methods, respectively, while only 46 unique proteins were identified using a 50 kDa molecular weight cutoff filter. The relative abundance of the identified proteins was estimated using total spectrum counting and compared to the concentrations of 45 known proteins in CSF as markers of the analysis depth. Results of this work suggest a clear need for methodology designed specifically for depletion of high-abundance proteins in CSF, as depletion methods designed to deplete high-abundance serum proteins showed little improvement in analysis depth compared to analysis without depletion. The marker protein method should be generally useful for assessing depth of analysis in the comparison of proteomic analysis methods.     

Long term experimental drought alters community plant trait variation,not trait means,across three semiarid grasslands

Plant and Soil - Mechanisms by which soil pH affects rice growth await further elucidation. We have used a Systems Biology approach to elucidate the nature of the damage caused by extreme pH to...     

Opportunistic testing of medically underserved women for cervical cancer in South Africa

OBJECTIVE: To determine the yield of opportunistic Pap smears taken in an unscreened and medically underserved population in the Transkei Region of South Africa. STUDY DESIGN: Cross-sectional study of 22,160 cervical cytology specimens from an unscreened population attending gynecologic outpatient clinics between January 1990 and December 1996. RESULTS: The overall prevalence of atypical squamous cells of uncertain significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL) was, respectively, 34.7%, 8.3% and 2.4%. The ASCUS: SIL ratio was 3:1. The prevalence of invasive squamous cell carcinoma was 1.6%. The yield of opportunistic Pap smears was 10.7% including only LSIL and HSIL. CONCLUSION: The pathologic process of precursor lesions of cervical cancer appears to start at an early age since > 20% of cases are diagnosed before the age of 30 years. In the absence of a national screening program, opportunistic testing of medically underserved women needs to be maintained and encouraged.     

C3 woody plant expansion in a C4 grassland: are grasses and shrubs functionally distinct?

The expansion of C(3) shrubs into C(4)-dominated tallgrass prairies represents a fundamental shift in growth-form dominance accompanied by changes in resource acquisition and use. We assessed these changes by comparing the ecophysiological traits of the dominant C(4) grass Andropogon gerardii, with traits of three C(3) invasive shrub species, Cornus drummondii, Prunus americana, and Rhus glabra. We tested the hypothesis that ecophysiological traits of the shrubs would be similar within this growth form but distinct from grasses and that these species would conform to the two-layer soil water model. Photosynthetic rates in R. glabra were similar to A. gerardii and higher than in the other two shrubs, while water use efficiency was markedly greater in A. gerardii. Among all species, midday xylem pressure potentials (XPP) were distinctly lower (70%) for P. americana, but were similar among the other species. Predawn XPP was related to soil water at shallow depths for A. gerardii (r(2) = 0.59) and P. americana (r(2) = 0.62), and to deeper soil moisture for R. glabra (r(2) = 0.63); there was no relationship for C. drummondii at any soil depth. Thus, a simple two-layer soil water model for partitioning shrub/grass resource acquisition was not appropriate for this grassland. We conclude that these shrubs could not be considered functional equivalents from an ecophysiological perspective, nor were they, as a group, distinct from A. gerardii in resource acquisition and use.     

Thermodynamics of HMGB1 interaction with duplex DNA

The high mobility group protein HMGB1 is a small, highly abundant protein that binds to DNA in a non-sequence-specific manner. HMGB1 consists of 2 DNA binding domains, the HMG boxes A and B, followed by a short basic region and a continuous stretch of 30 glutamate or aspartate residues. Isothermal titration calorimetry was used to characterize the binding of HMGB1 to the double-stranded model DNAs poly(dAdT).(dTdA) and poly(dGdC).(dCdG). To elucidate the contribution of the different structural motifs to DNA binding, calorimetric measurements were performed comparing the single boxes A and B, the two boxes plus or minus the basic sequence stretch (AB(bt) and AB), and the full-length HMGB1 protein. Thermodynamically, binding of HMGB1 and all truncated constructs to duplex DNA was characterized by a positive enthalpy change at 15 degrees C. From the slopes of the temperature dependence of the binding enthalpies, heat capacity changes of -0.129 +/- 0.02 and -0.105 +/- 0.05 kcal mol(-1) K(-1) were determined for box A and full-length HMGB1, respectively. Significant differences in the binding characteristics were observed using full-length HMGB1, suggesting an important role for the acid tail in modulating DNA binding. Moreover, full-length HMGB1 binds differently these two DNA templates: binding to poly(dAdT).(dTdA) was cooperative, had a larger apparent binding site size, and proceeded with a much larger unfavorable binding enthalpy than binding to poly(dGdC).(dCdG).     

Thermodynamics of the high-affinity interaction of TCF4 with beta-catenin

The formation of a complex between beta-catenin and members of the TCF/LEF family of high-mobility group proteins is a key regulatory event in the wnt-signaling pathway, essential for embryonal development as well as the growth of normal and malignant colon epithelium. We have characterized the binding of TCF4 to human beta-catenin by steady-state intrinsic fluorescence quenching experiments, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Binding studies in solution and in heterogeneous phase showed that TCF4 binds reversibly to beta-catenin with an affinity (KB) of 3(+/-1) 10(8) M(-1). Site-directed mutagenesis, together with calorimetric measurements, revealed that residue D16 in TCF4 plays a crucial role in high-affinity binding. Mutation of this residue to alanine resulted in a decrease of KB by two orders of magnitude as well as a significant reduction in binding enthalpy. Binding of TCF4 to beta-catenin gave rise to a large negative enthalpy change at 25 degrees C (-29.7 kcal/mol). Binding enthalpies were strongly temperature dependent, which resulted in the determination of a large heat capacity change upon binding of -1.5 kcal/(mol K). The molecular events that take place upon complex formation are discussed using the measured thermodynamic data together with the crystal structure of the beta-catenin arm repeat region/TCF complex.