Dominant inheritance and intra�Cfamilial variations in the association of Sturge�CWeber and Klippel�CTrenaunay�CWeber syndromes

This case report shows a genealogical study where a woman has limb hypertrophy and her son has an association of Sturge–Weber syndrome with Klippel–Trenaunay–Weber syndrome. The Sturge–Weber and Klippel–Trenaunay–Weber syndromes appear to be different manifestations of the same affliction. Familial aggregation exists and transmission may be almost imperceptible between generations. Identification of minor manifestations may prove to be a valuable contribution to genetic counseling of families and the prevention of new cases.     

Real-time single-molecule tethered particle motion analysis reveals mechanistic similarities and contrasts of Flp site-specific recombinase with Cre and λ Int

Flp, a tyrosine site-specific recombinase coded for by the selfish two micron plasmid of Saccharomyces cerevisiae, plays a central role in the maintenance of plasmid copy number. The Flp recombination system can be manipulated to bring about a variety of targeted DNA rearrangements in its native host and under non-native biological contexts. We have performed an exhaustive analysis of the Flp recombination pathway from start to finish by using single-molecule tethered particle motion (TPM). The recombination reaction is characterized by its early commitment and high efficiency, with only minor detraction from ‘non-productive’ and ‘wayward’ complexes. The recombination synapse is stabilized by strand cleavage, presumably by promoting the establishment of functional interfaces between adjacent Flp monomers. Formation of the Holliday junction intermediate poses a rate-limiting barrier to the overall reaction. Isomerization of the junction to the conformation favoring its resolution in the recombinant mode is not a slow step. Consistent with the completion of nearly every initiated reaction, the chemical steps of strand cleavage and exchange are not reversible during a recombination event. Our findings demonstrate similarities and differences between Flp and the mechanistically related recombinases λ Int and Cre. The commitment and directionality of Flp recombination revealed by TPM is consistent with the physiological role of Flp in amplifying plasmid DNA.     

Ecology and evolution of plant�Cpollinator interactions

Background

Some of the most exciting advances in pollination biology have resulted from interdisciplinary research combining ecological and evolutionary perspectives. For example, these two approaches have been essential for understanding the functional ecology of floral traits, the dynamics of pollen transport, competition for pollinator services, and patterns of specialization and generalization in plant–pollinator interactions. However, as research in these and other areas has progressed, many pollination biologists have become more specialized in their research interests, focusing their attention on either evolutionary or ecological questions. We believe that the continuing vigour of a synthetic and interdisciplinary field like pollination biology depends on renewed connections between ecological and evolutionary approaches.

Scope

In this Viewpoint paper we highlight the application of ecological and evolutionary approaches to two themes in pollination biology: (1) links between pollinator behaviour and plant mating systems, and (2) generalization and specialization in pollination systems. We also describe how mathematical models and synthetic analyses have broadened our understanding of pollination biology, especially in human-modified landscapes. We conclude with several suggestions that we hope will stimulate future research. This Viewpoint also serves as the introduction to this Special Issue on the Ecology and Evolution of Plant–Pollinator Interactions. These papers provide inspiring examples of the synergy between evolutionary and ecological approaches, and offer glimpses of great accomplishments yet to come.Key words: Floral traits, generalization and specialization, global change, male fitness, mating systems, multiple paternity, plant–pollinator networks, pollen and gene dispersal, pollinator behaviour, pollination syndromes, pollination webs, self-fertilization     

Cloud streets and land�Cwater interactions in the Amazon

Cloud streets are common feature in the Amazon Basin. They form from the combination of the vertical trade wind stress and moist convection. Here, satellite imagery, data collected during the COBRA-PARÁ (Caxiuanã Observations in the Biosphere, River and Atmosphere of Pará) field campaign, and high resolution modeling are used to understand the streets?? formation and behavior. The observations show that the streets have an aspect ratio of about 3.5 and they reach their maximum activity around 15:00 UTC when the wind shear is weaker, and the convective boundary layer reaches its maximum height. The simulations reveal that the cloud streets onset is caused by the local circulations and convection produced at the interfaces between forest and rivers of the Amazon. The satellite data and modeling show that the large rivers anchor the cloud streets producing a quasi-stationary horizontal pattern. The streets are associated with horizontal roll vortices parallel to the mean flow that organizes the turbulence causing advection of latent heat flux towards the upward branches. The streets have multiple warm plumes that promote a connection between the rolls. These spatial patterns allow fundamental insights on the interpretation of the Amazon exchanges between surface and atmosphere with important consequences for the climate change understanding.     

基于Flp重组酶介导的盒式交换HPRT位点定点转基因研究

Exchange plasmid pF-HPRT-F3 and Flp expression plasmid pCMV-Flp were constructed and then introduced using electroporation system into F18 ES cell line, which have an exchange cassette F-Neo-F3 at HPRT locus. After HAT selection, HAT resistant clones were obtained. Then G418 sensitivity test and Southern blotting were carried out to screen RMCE recombinants. The results indicated that RMCE had taken place in three of 12 HAT resistant clones. The frequency is 25%. The result demonstrates that it is realizable to introduce transgene to HPRT locus by using Flp recombinase mediated cassette exchange reaction.     

Reproductive Experience and the Response of Female Sprague�CDawley Rats to Fear and Stress

The present work examines the relationship between reproductive experience (comprising breeding, parturition, and lactation) and the behavioral and hormonal processes of fear and stress in the female laboratory rat. Previous research has indicated that reproductive experience functions to decrease the female''s stress response in potentially harmful environments, thereby providing her with numerous survival benefits, including decreased fearfulness, increased aggression, and refined hunting skills. This study was designed to determine how nulliparous (no reproductive experience), primiparous (1 reproductive experience) and multiparous (at least 2 reproductive experiences) rats respond to a Pavlovian paradigm of learned fear, involving the pairing of a neutral stimulus (conditioned stimulus) with an aversive stimulus (unconditioned stimulus). We report evidence that reproductive experience is linked with fear-response and anxiety-like behaviors. Our findings indicate that reproductive experience has an additive effect: primiparous mothers showed a different response to the paradigm of conditioned fear not only compared with those of nulliparous rats as well as multiparous mothers. Assessing the complex interconnections among the behavioral and physiologic measures recorded in this study, multidimensional scaling confirmed a clear separation among the 3 groups of rats in terms of the behavioral and physiologic responses to the experimental paradigm, supporting the conclusion that reproductive experience influences the maternal mind.Stress, fear, and lack of adequate stimuli can constitute a serious problem for laboratory animals. Although several studies have investigated various social and environmental changes to improve the health of laboratory animals, the literature on husbandry regimen and reproductive experience is scarce.^{3,23,44,56,58} Pregnancy and lactation represent the quintessence of change in mammals.^13,38 Reproduction entails high physiologic costs, especially in small mammals like rodents, including increased energy and nutrient demands, making the connection between husbandry and health in laboratory rats even more compelling.⁴⁹ Extensive neuroendocrine and behavioral modifications ensure mothers the flexibility to meet their own survival needs with the survival of their offspring in most environmental contingencies.^30,46 The long-term effects of these changes on the somatic and psychologic development of infants are well-known and pervasive in most mammals: from immediate infant survival to the ability to cope with stress during adulthood.^5,7,22,26,43 Several studies have indicated that the long-term consequences on mothers themselves are as compelling. Although some authors have found a significant decrease in cell proliferation in the dentate gyrus of the hippocampus in primiparous and multiparous rats during the postpartum period, associated with temporary impaired learning skills,¹⁵ others have found that motherhood can improve spatial cognition, learning and memory,^9,27,33,42 through mechanisms based on increased glucocorticoid production.^31,41 The combination of improved behavioral performances and increased physiologic stress in mothers is hardly surprising considering that the sequence of modifications during pregnancy involves, as a cascade of events, the whole body and shapes the inherently plastic central nervous system to cope with the extra challenges of providing for offspring. At the pinnacle of its fruition, the maternal brain is responsible for a complex set of behaviors that mold mothers in every aspect of their life.^28,29 In this scenario, we expect that empirical examinations of laboratory female rats with differential reproductive experience would yield significant differences in both the fear and stress response of maternal and virgin rats. Because stress and fear can impair the health of research animals and, if not controlled for, confound results obtained in experimental data, it is important to evaluate how reproductive experience can modify both stress and fear responses. Previous studies have indicated that, when confronted with a stressful stimulus, maternal rats display fewer stress-related behaviors than do nonmaternal rats.^32,57One common method of examining the animal''s reaction to a threatening environment is to use a Pavlovian model of learned fear. The neural circuitry of learned fear, involving the association of a conditioned stimulus or context with an unconditioned stimulus, is of particular interest because learned fear processes involve multiple cognitive functions including predicting, representing, and defining relationships between events.⁴⁵ The literature discussing the neural correlates of learned fear is vast and, further, agrees that the amygdala is the central brain structure responsible for learned fear. In fact, bilateral damage to the amygdala seriously impairs Pavlovian fear conditioning.^8,53 Studies conducted in developing rats revealed that different nuclei of the amygdala process sensory information of different modalities, mediate unconditioned freezing behavior, and may be involved in developmental changes in the fear response in young rats.¹⁴ Research elucidating a relationship or lack thereof between reproductive experience and changes in fear response is limited presently.^19,55 Examinations of unconditioned fear and maternal experience have suggested that an attenuated stress response and an overall decrease in fearfulness provides numerous survival benefits, such as enhanced and increased hunting and gathering skills, exploration, social awareness, and aggression, to the female rat.^21,37,50,51 Because survivability is dependent upon the prediction and appropriate response to threatening stimuli, this research paradigm can provide pertinent information about the animal''s fitness, thus providing critical information on both the health of animals and the quality of experimental data.Pregnancy, lactation, and the complex behavioral repertoire comprising maternal care constitute an expensive metabolic and genetic investment that is pivotal to species survival.^11,52 Alterations of the female brain due to occurrences of several cycles of pup exposure are reflected in many aspects of maternal life, including fear responses, activation of the hypothalamic–pituitary–adrenal axis, and anxiety.¹⁰ In the present work, we assessed whether reproductive experience plays a specific role on fear response and how this response activates the hypothalamic–pituitary–adrenal axis and interacts with anxiety-related behaviors in rats. We also assessed whether these effects are additive, that is, whether multiparous mothers (2 or more pregnancies) have a different fear response than do primiparous mothers (only 1 pregnancy). On the basis of information provided by previous studies, we hypothesized that during the retention–testing trials of the conditioning model, maternal subjects (primiparous and multiparous groups) would express fewer fear-related (freezing) behaviors than would nonmaternal subjects (nulliparous group). We further hypothesized that the maternal groups would express anxiety-related behaviors less frequently than would the nonmaternal group during the retention–testing trials. In addition, we speculated that the nulliparous group would exhibit significantly higher activation of the hypothalamic–pituitary–adrenal axis than would the reproductive groups (primiparous and multiparous), as measured by corticosterone concentrations after the fear-conditioning training trials.     

Waves affect predator�Cprey interactions between fish and benthic invertebrates

Little is known about the effects of waves on predator-prey interactions in the littoral zones of freshwaters. We conducted a set of mesocosm experiments to study the differential effects of ship- and wind-induced waves on the foraging success of littoral fish on benthic invertebrates. Experiments were conducted in a wave tank with amphipods (Gammarus roeseli) as prey, and age-0 bream (Abramis brama, B0), age-0 and age-1 dace (Leuciscus leuciscus, D0 and D1) as predators. The number of gammarids suspended in the water column was higher in the wave treatments compared to a no-wave control treatment, especially during pulse waves mimicking ship-induced waves in comparison to continuous waves mimicking wind-induced waves. The resulting higher prey accessibility in the water column was differently exploited by the three types of predatory fish. D0 and D1 showed significantly higher foraging success in the pulse wave treatment than in the continuous and control treatments. The foraging success of D0 appears to be achieved more easily, since significantly higher swimming activity and more foraging attempts were recorded only for D1 under the wave treatments. In contrast, B0 consumed significantly fewer gammarids in both wave treatments than in the control. Hence, waves influenced predator-prey interactions differently depending on wave type and fish type. It is expected that regular exposure to ship-induced waves can alter littoral invertebrate and fish assemblages by increasing the predation risk for benthic invertebrates that are suspended in the water column, and by shifting fish community compositions towards species that benefit from waves.     

Co-clustering phenome�Cgenome for phenotype classification and disease gene discovery

Understanding the categorization of human diseases is critical for reliably identifying disease causal genes. Recently, genome-wide studies of abnormal chromosomal locations related to diseases have mapped >2000 phenotype–gene relations, which provide valuable information for classifying diseases and identifying candidate genes as drug targets. In this article, a regularized non-negative matrix tri-factorization (R-NMTF) algorithm is introduced to co-cluster phenotypes and genes, and simultaneously detect associations between the detected phenotype clusters and gene clusters. The R-NMTF algorithm factorizes the phenotype–gene association matrix under the prior knowledge from phenotype similarity network and protein–protein interaction network, supervised by the label information from known disease classes and biological pathways. In the experiments on disease phenotype–gene associations in OMIM and KEGG disease pathways, R-NMTF significantly improved the classification of disease phenotypes and disease pathway genes compared with support vector machines and Label Propagation in cross-validation on the annotated phenotypes and genes. The newly predicted phenotypes in each disease class are highly consistent with human phenotype ontology annotations. The roles of the new member genes in the disease pathways are examined and validated in the protein–protein interaction subnetworks. Extensive literature review also confirmed many new members of the disease classes and pathways as well as the predicted associations between disease phenotype classes and pathways.     

Environment�CKHV�Ccarp�Chuman linkage as a model for environmental diseases

To predict outbreaks of infectious disease and to prevent epidemics, it is essential not only to conduct pathological studies but also to understand the interactions between the environment, pathogen, host and humans that cause and spread infectious diseases. Outbreaks of mass mortality in carp caused by Cyprinid herpesvirus 3 (CyHV-3), formerly known as koi herpesvirus (KHV), disease have occurred worldwide since the late 1990s. We proposed an environment?CKHV?Ccarp?Chuman linkage as a conceptual model for ??environmental diseases?? and specify research subjects that might be necessary to construct and shape this linkage.     

基于Flp重组酶介导的盒式交换HPRT位点定点转基因研究

以电穿孔转染法将构建的交换质粒pF-HPRT-F3和Flp表达载体pCMV-Flp共转染已在基因组HPRT位点整合有交换盒F-Neo-F3结构的ES细胞F18,经HAT筛选得到HAT抗性ES细胞克隆;G418敏感性试验和基因组Southern杂交表明,所分析的12个HAT抗性克隆中有3个克隆发生了预期的盒式交换重组,转基因定点整合的相对效率为25%.这一结果表明,Flp重组酶是可以在HPRT位点有效地介导盒式交换反应的,我们提出的利用Flp重组酶介导的盒式交换反应建立基于HPRT位点的转基因定点整合体系的策略是可行的.     

Bottom�Cup attention: pulsed PCA transform and pulsed cosine transform

In this paper we propose a computational model of bottom–up visual attention based on a pulsed principal component analysis (PCA) transform, which simply exploits the signs of the PCA coefficients to generate spatial and motional saliency. We further extend the pulsed PCA transform to a pulsed cosine transform that is not only data-independent but also very fast in computation. The proposed model has the following biological plausibilities. First, the PCA projection vectors in the model can be obtained by using the Hebbian rule in neural networks. Second, the outputs of the pulsed PCA transform, which are inherently binary, simulate the neuronal pulses in the human brain. Third, like many Fourier transform-based approaches, our model also accomplishes the cortical center-surround suppression in frequency domain. Experimental results on psychophysical patterns and natural images show that the proposed model is more effective in saliency detection and predict human eye fixations better than the state-of-the-art attention models.