High Sensitivity to Auxin is a Common Feature of Hairy Root

The responses to auxin of Lycopersicon esculentum roots transformed by (T_l+T_r)-DNA of the Ri plasmid of agropine-type Agrobacterium rhizogenes strain 15834 and Catharanthus trichophyllus roots transformed by the (T_l+T_r)-DNA, and by T_l- or T_r- DNA alone of the same bacterial strain were compared to that of their normal counterparts. The transmembrane electrical potential difference of root protoplasts was measured as a function of the concentration of exogenous naphthalene acetic acid. The sensitivity to auxin expressed by this response was shown to be independent of the measurement conditions and of the basal polarization of isolated protoplasts. According to this electrical response, as well as to the modulation by auxin of proton excretion by root tips and root tip elongation, roots transformed by (T_l+T_r) DNA are 100 to 1000 times more sensitive to exogenous auxin than normal roots, as is the case with normal and transformed roots from Lotus corniculatus (WH Shen, A Petit, J Guern, J Tempé [1988] Proc Natl Acad Sci USA 85: 3417-3421). Further-more, transformed roots of C. trichophyllus are not modified in their sensitivity to fusicoccin, illustrating the specificity of the modification of the auxin sensitivity. Roots transformed by the T_r-DNA alone showed the same sensitivity to auxin as normal roots, whereas the roots transformed by the T_l-DNA alone exhibited an auxin sensitivity as high as the roots transformed by (T_l+T_r)-DNA. It was concluded that the high sensitivity to auxin is controlled by the T_l-DNA in agropine type Ri plasmids.     

Control Group Design,Contamination and Drop-Out in Exercise Oncology Trials: A Systematic Review

Purpose

Important considerations for exercise trials in cancer patients are contamination and differential drop-out among the control group members that might jeopardize the internal validity. This systematic review provides an overview of different control groups design characteristics of exercise-oncology trials and explores the association with contamination and drop-out rates.

Methods

Randomized controlled exercise-oncology trials from two Cochrane reviews were included. Additionally, a computer-aided search using Medline (Pubmed), Embase and CINAHL was conducted after completion date of the Cochrane reviews. Eligible studies were classified according to three control group design characteristics: the exercise instruction given to controls before start of the study (exercise allowed or not); and the intervention the control group was offered during (any (e.g., education sessions or telephone contacts) or none) or after (any (e.g., cross-over or exercise instruction) or none) the intervention period. Contamination (yes or no) and excess drop-out rates (i.e., drop-out rate of the control group minus the drop-out rate exercise group) were described according to the three design characteristics of the control group and according to the combinations of these three characteristics; so we additionally made subgroups based on combinations of type and timing of instructions received.

Results

40 exercise-oncology trials were included based on pre-specified eligibility criteria. The lowest contamination (7.1% of studies) and low drop-out rates (excess drop-out rate -4.7±9.2) were found in control groups offered an intervention after the intervention period. When control groups were offered an intervention both during and after the intervention period, contamination (0%) and excess drop-out rates (-10.0±12.8%) were even lower.

Conclusions

Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates. The present findings can be considered when designing future exercise-oncology trials.     

Sensitivity of the Breastfeeding Motivational Measurement Scale: A Known Group Analysis of First Time Mothers

Breastfeeding has immense public health value for mothers, babies, and society. But there is an undesirably large gap between the number of new mothers who undertake and persist in breastfeeding compared to what would be a preferred level of accomplishment. This gap is a reflection of the many obstacles, both physical and psychological, that confront new mothers. Previous research has illuminated many of these concerns, but research on this problem is limited in part by the unavailability of a research instrument that can measure the key differences between first-time mothers and experienced mothers, with regard to the challenges they face when breastfeeding and the instructional advice they require. An instrument was designed to measure motivational complexity associated with sustained breast feeding behaviour; the Breastfeeding Motivational Measurement Scale. It contains 51 self-report items (7 point Likert scale) that cluster into four categories related to perceived value of breast-feeding, confidence to succeed, factors that influence success or failure, and strength of intentions, or goal. However, this scale has not been validated in terms of its sensitivity to profile the motivation of new mothers and experienced mothers. This issue was investigated by having 202 breastfeeding mothers (100 first time mothers) fill out the scale. The analysis reported in this paper is a three factor solution consisting of value, midwife support, and expectancies for success that explained the characteristics of first time mothers as a known group. These results support the validity of the BMM scale as a diagnostic tool for research on first time mothers who are learning to breastfeed. Further research studies are required to further test the validity of the scale in additional subgroups.     

Prestress and Adhesion Site Dynamics Control Cell Sensitivity to Extracellular Stiffness

This study aims at improving the understanding of mechanisms responsible for cell sensitivity to extracellular environment. We explain how substrate mechanical properties can modulate the force regulation of cell sensitive elements primarily adhesion sites. We present a theoretical and experimental comparison between two radically different approaches of the force regulation of adhesion sites that depends on their either stationary or dynamic behavior. The most classical stationary model fails to predict cell sensitivity to substrate stiffness whereas the dynamic model predicts extracellular stiffness dependence. This is due to a time dependent reaction force in response to actomyosin traction force exerted on cell sensitive elements. We purposely used two cellular models, i.e., alveolar epithelial cells and alveolar macrophages exhibiting respectively stationary and dynamic adhesion sites, and compared their sensitivity to theoretical predictions. Mechanical and structural results show that alveolar epithelial cells exhibit significant prestress supported by evident stress fibers and lacks sensitivity to substrate stiffness. On the other hand, alveolar macrophages exhibit low prestress and exhibit sensitivity to substrate stiffness. Altogether, theory and experiments consistently show that adhesion site dynamics and cytoskeleton prestress control cell sensitivity to extracellular environment with an optimal sensitivity expected in the intermediate range.     

Optimising and Communicating Options for the Control of Invasive Plant Disease When There Is Epidemiological Uncertainty

Although local eradication is routinely attempted following introduction of disease into a new region, failure is commonplace. Epidemiological principles governing the design of successful control are not well-understood. We analyse factors underlying the effectiveness of reactive eradication of localised outbreaks of invading plant disease, using citrus canker in Florida as a case study, although our results are largely generic, and apply to other plant pathogens (as we show via our second case study, citrus greening). We demonstrate how to optimise control via removal of hosts surrounding detected infection (i.e. localised culling) using a spatially-explicit, stochastic epidemiological model. We show how to define optimal culling strategies that take account of stochasticity in disease spread, and how the effectiveness of disease control depends on epidemiological parameters determining pathogen infectivity, symptom emergence and spread, the initial level of infection, and the logistics and implementation of detection and control. We also consider how optimal culling strategies are conditioned on the levels of risk acceptance/aversion of decision makers, and show how to extend the analyses to account for potential larger-scale impacts of a small-scale outbreak. Control of local outbreaks by culling can be very effective, particularly when started quickly, but the optimum strategy and its performance are strongly dependent on epidemiological parameters (particularly those controlling dispersal and the extent of any cryptic infection, i.e. infectious hosts prior to symptoms), the logistics of detection and control, and the level of local and global risk that is deemed to be acceptable. A version of the model we developed to illustrate our methodology and results to an audience of stakeholders, including policy makers, regulators and growers, is available online as an interactive, user-friendly interface at http://www.webidemics.com/. This version of our model allows the complex epidemiological principles that underlie our results to be communicated to a non-specialist audience.     

Common Garden Experiment Reveals Genetic Control of Phenotypic Divergence between Swamp Sparrow Subspecies That Lack Divergence in Neutral Genotypes

Background

Adaptive divergence between populations in the face of strong selection on key traits can lead to morphological divergence between populations without concomitant divergence in neutral DNA. Thus, the practice of identifying genetically distinct populations based on divergence in neutral DNA may lead to a taxonomy that ignores evolutionarily important, rapidly evolving, locally-adapted populations. Providing evidence for a genetic basis of morphological divergence between rapidly evolving populations that lack divergence in selectively neutral DNA will not only inform conservation efforts but also provide insight into the mechanisms of the early processes of speciation. The coastal plain swamp sparrow, a recent colonist of tidal marsh habitat, differs from conspecific populations in a variety of phenotypic traits yet remains undifferentiated in neutral DNA.

Methods and Principal Findings

Here we use an experimental approach to demonstrate that phenotypic divergence between ecologically separated populations of swamp sparrows is the result of local adaptation despite the lack of divergence in neutral DNA. We find that morphological (bill size and plumage coloration) and life history (reproductive effort) differences observed between wild populations were maintained in laboratory raised individuals suggesting genetic divergence of fitness related traits.

Conclusions and Significance

Our results support the hypothesis that phenotypic divergence in swamps sparrows is the result of genetic differentiation, and demonstrate that adaptive traits have evolved more rapidly than neutral DNA in these ecologically divergent populations that may be in the early stages of speciation. Thus, identifying evolutionarily important populations based on divergence in selectively neutral DNA could miss an important level of biodiversity and mislead conservation efforts.     

A Note on the Sensitivity of Chlorine-stressed Bifidobacteria to Nalidixic Acid

Bifidobacterium adolescentis , normally resistant to 200 μg/ml nalidixic acid, became sensitive to 10 μg/ml nalidixic acid after 15 min exposure to chlorinated sewage effluent (0–08 mg/1000 ml of residual chlorine). After exposure to 0.7 mg/1000 ml of residual chlorine, Bifidobacterium adolescentis became sensitive to 5 μg/ml nalidixic acid.     

解放军疾控所SPF动物房的工艺设计

解放军疾病预防控制所,为履行职能和任务,在业务办公大楼12层建设了SPF动物实验设施,面积约240 m^2。文章介绍了作者的设计思路和建设方案。同时还介绍了SPF动物房的建设经验。     

以花背蟾蜍为材料进行发育生物学综合性实验的设计

在基础性实验课程的基础上,以花背蟾蜍为材料,根据实验室的实际情况,设计4个单元的综合性实验,以期为发育生物学的综合性实验设计及开放实验项目提供参考.同时,学生在完成实验操作的过程中,能独立进行实验准备和设计,实践多项实验技术,可增强学生的科研兴趣,培养学生的创新能力.     

A Network Flow-Based Method to Predict Anticancer Drug Sensitivity

Predicting anticancer drug sensitivity can enhance the ability to individualize patient treatment, thus making development of cancer therapies more effective and safe. In this paper, we present a new network flow-based method, which utilizes the topological structure of pathways, for predicting anticancer drug sensitivities. Mutations and copy number alterations of cancer-related genes are assumed to change the pathway activity, and pathway activity difference before and after drug treatment is used as a measure of drug response. In our model, Contributions from different genetic alterations are considered as free parameters, which are optimized by the drug response data from the Cancer Genome Project (CGP). 10-fold cross validation on CGP data set showed that our model achieved comparable prediction results with existing elastic net model using much less input features.     

High Affinity Peptide Inhibitors of the Hepatitis C Virus NS3-4A Protease Refractory to Common Resistant Mutants

Hepatitis C virus (HCV) NS3-4A protease is essential for viral replication. All current small molecular weight drugs against NS3-4A are substrate peptidomimetics that have a similar binding and resistance profile. We developed inhibitory peptides (IPs) capping the active site and binding via a novel “tyrosine” finger at an alternative NS3-4A site that is of particular interest for further HCV drug development. The peptides are not cleaved due to a combination of geometrical constraints and impairment of the oxyanion hole function. Selection and optimization through combinatorial phagemid display, protein crystallography, and further modifications resulted in a 32-amino acid peptide with a K_i of 0.53 nm. Inhibition of viral replication in cell culture was demonstrated by fusion to a cell-penetrating peptide. Negligible susceptibility to known (A156V and R155K) resistance mutations of the NS3-4A protease was observed. This work shows for the first time that antiviral peptides can target an intracellular site and reveals a novel druggable site on the HCV protease.