Superantigens of gram-positive bacteria: structure-function analyses and their implications for biological activity

Just as we thought that we know everything about superantigens, new molecular and structural studies indicate that we have only just begun to unravel the secrets of these fascinating molecules. Recent structure-function analysis of superantigens from Gram-positive bacteria, with emphasis on their interaction with major histocompatibility complex molecules, could help us decipher the role of superantigens in disease, identify host factors that potentiate their effects and design drugs that specifically block their activity.     

The polyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors: a new role for old molecules?

Due to the importance of glycation in the genesis of diabetic complications, an intense search for synthetic new antiglycation agents is ongoing. However, a somewhat neglected avenue is the search for endogenous compounds that may inhibit the process and be a source of protodrugs. Based on their ubiquity, their polycationic nature, their essential role in growth, their relatively high concentrations in tissues, and their high concentrations in sperm, we hypothesized that polyamines inhibit glycation and that might be one of their so far elusive functions. In this study we demonstrate a potent antiglycation effect of physiological concentrations of the polyamines spermine and spermidine. We employed two approaches: in the first, we monitored structural changes on histones and ubiquitin in which polyamines inhibit glycation-induced dimer and polymer formation. In the second we monitored functional impairment of catalytic activity of antithrombin III and plasminogen. Protection is afforded against glycation by hexoses, trioses and dicarbonyls AGE precursors and is comparable to those of aminoguanidine and carnosine.     

Utilization of mammalian cells for efficient and reliable evaluation of specificity of antibodies to unravel the cellular function of mKIAA proteins

Complementary DNA (cDNA) clones for human KIAA genes have been isolated as long cDNAs (>4 kb) with unknown functions. To facilitate the functional analysis of these human clones, we have isolated and determined the structures of their respective mouse homologues (mKIAA genes). Furthermore, we have comprehensively raised antibodies against the translated mKIAA proteins in order to establish a platform for their functional analysis. Since the specificity of these antibodies is critical for subsequent analyses of protein function, here we introduce two assays utilizing mammalian cells to improve their evaluation. First, we have established a semi-high-throughput production of C-terminally FLAG epitope-tagged proteins for Western blotting using specially designed mammalian expression vectors. Secondly, we have utilized immunofluorescence staining of mouse cells to analyze the subcellular localization of endogenous mKIAA proteins. Importantly, these methods allow us to detect potential posttranslational modification of the mKIAA/KIAA proteins and to predict their biological function based on their subcellular localization.     

Insights from social transmission of information in rodents

Direct exposure to stimuli in their environment is not the only way that animals learn about important information. Individuals can infer fear from a social context through observation. Like humans, rats are very social animals, and may learn to infer information about their environment through their interactions with conspecifics. Here, we first review different models for social transmission of information in rodents. Second, we examine different modes of communication that are important to social learning. Then, we cover the different proximate factors that are thought to modulate the social transmission of information. Next, we identify social and environmental conditions that impact social learning, and finally, we conclude by revisiting social transmission through the lens of the Tinbergen framework.     

Peptide signaling in Hydra

Peptides play a number of crucial roles as signaling molecules in metazoans. In order to elaborate a more complete picture of the roles played by peptides in a single organism, we launched the "Hydra Peptide Project". For this project, we used Hydra magnipapillata, a species belonging to Cnidaria, one of the most basal metazoan phyla, and using a peptidomic approach, we systematically identified a number of peptide signaling molecules, their encoding genes and their functions. In this article, we report the peptides isolated from Hydra and other cnidarians, as well as their synthesis, processing and release from the cells to the target. Possible peptide signaling pathways are overviewed and finally we discuss the evolution of the peptide signaling system.     

激光荧光技术及其在生物医学研究中的应用

激光荧光技术是研究生物体系结构与功能的重要手段,发展迅速,应用广泛。我们研制了用氩离子激光器作光源的多参数流式细胞光度计,荧光漂白恢复装置以及毫微秒荧光谱仪。本文对其原理、结构及其在生物医学研究中的应用作了详细的介绍。     

Dental evolution of the orang-utan in China

The main focus of this paper is to report the spatial and temporal distributions of fossil and subfossil orang-utans in south and southwest China from the late Miocene through Pliocene and Pleistocene. We will describe fossil samples and their odontometrics in order to estimate their body size through time. Furthermore we will also discuss their taxonomic status and evolutionary changes. Then, we will explore the possible reasons why and how these living fossils retreated to their present habitats.     

Continuing Professional Development for teachers

The Institute of Biology has consistently emphasised the need for teachers to have continuing professional development (CPD) opportunities and for more trust to be displayed in their professional judgements. For this reason we are delighted that we now have a flexible CPD scheme that teachers can use to plan and record their continuing development and to demonstrate their professional commitment to CPD. The IOB CPD scheme is available to all members and can help individuals prioritise their CPD needs.     

When (if ever) may doctors discuss religion with their patients?

There is ongoing debate within the bioethics literature regarding to what extent (if any) it is ethically justifiable for doctors to engage in religious discussion with their patients, in cases where patients cite religious considerations as influencing their medical decision-making. In this paper, we concede that certain forms of religious discussion between doctors and patients are morally permissible (though not necessarily morally obligatory), insofar as patients’ religious beliefs may comprise an important part of their overall wellbeing and can influence their medical decisions. However, we argue that it is not morally permissible for doctors to engage in substantive religious discussion with their patients, beyond simply inquiring about the patient's values (which may include their religious values) or referring patients to a chaplain or religious figure for further discussion. In support of this claim, we put forward two key arguments which have remained relatively unaddressed in the current debate. First, we argue that it is not practical for doctors to engage in substantive religious discussion with patients, and hence it cannot be morally obligatory for them to do so. Second, we argue that, while doctors might have a professional duty to ensure that their patient's religious interests (if any) are addressed, this does not entail that doctors themselves are the ones who should directly address these interests. Along the way, we anticipate and respond to some possible objections to these two key arguments.     

A catalog of polymorphisms falling in microRNA-binding regions of cancer genes

Recent evidence indicates that small, nonprotein-coding RNA molecules, called microRNAs (miRNAs), control cell growth, differentiation, and apoptosis, and are also involved in tumorigenesis. miRNAs can bind to the 3' untranslated regions (3'UTRs) of messenger RNAs and interfere with their translation. We hypothesized that common polymorphisms within their genes or within their targets could have an important impact for an individual's risk to develop complex diseases. In this study, we selected the 3'UTRs of 129 genes involved in pathways commonly acknowledged as important for cancer, and we identified putative miRNA-binding sites by means of specialized algorithms (PicTar, DIANA-MicroT, miRBase, miRanda, TargetScan, and MicroInspector). Then we investigated 79 single-nucleotide polymorphisms (SNPs) within the putative binding sites for their ability to affect or impair the binding with the miRNA by assessing the DeltaDeltaG, the variation of DeltaG (Gibbs free energy), through comparing the wild-type and their corresponding variant alleles. Moreover, we reported seven identified SNPs in seven pre-miRNA hairpin regions and one SNP in the mature sequence of miR-608. Considering the validation status of the SNPs and their frequencies, we found at least 23 candidate polymorphisms of biological relevance that we propose for further investigation in case-control association studies.     

Does Syntactic Alignment Effectively Influence How Speakers Are Perceived by Their Conversation Partner?

The way we talk can influence how we are perceived by others. Whereas previous studies have started to explore the influence of social goals on syntactic alignment, in the current study, we additionally investigated whether syntactic alignment effectively influences conversation partners’ perception of the speaker. To this end, we developed a novel paradigm in which we can measure the effect of social goals on the strength of syntactic alignment for one participant (primed participant), while simultaneously obtaining usable social opinions about them from their conversation partner (the evaluator). In Study 1, participants’ desire to be rated favorably by their partner was manipulated by assigning pairs to a Control (i.e., primed participants did not know they were being evaluated) or Evaluation context (i.e., primed participants knew they were being evaluated). Surprisingly, results showed no significant difference in the strength with which primed participants aligned their syntactic choices with their partners’ choices. In a follow-up study, we used a Directed Evaluation context (i.e., primed participants knew they were being evaluated and were explicitly instructed to make a positive impression). However, again, there was no evidence supporting the hypothesis that participants’ desire to impress their partner influences syntactic alignment. With respect to the influence of syntactic alignment on perceived likeability by the evaluator, a negative relationship was reported in Study 1: the more primed participants aligned their syntactic choices with their partner, the more that partner decreased their likeability rating after the experiment. However, this effect was not replicated in the Directed Evaluation context of Study 2. In other words, our results do not support the conclusion that speakers’ desire to be liked affects how much they align their syntactic choices with their partner, nor is there convincing evidence that there is a reliable relationship between syntactic alignment and perceived likeability.     

The multifaceted roles of Eph/ephrin signaling in breast cancer

Eph receptors and their membrane-bound ligands are intimately involved in the control of morphogenic processes during embryonic development and adult tissue homeostasis. By their ability to orchestrate cell migration, pattern formation and tissue integrity they are also prone to be involved in carcinogenic growth. In this review we concentrate on their involvement in the normal and carcinogenic development of the breast. In this context we summarize their multi-faceted functions as tumor suppressors, tumor promoters, angiogenic inducers and regulators of stem cell homeostasis.     

Medicine and place: an inquiry

This essay explores the various places inhabited by doctors and patients, in order to lead doctors to a more complex understanding of their patients' experiences of illness. Using Adam Haslett's "The Good Doctor" (2002), we examine what happens when doctors enter the worlds of their patients, both the literal landscapes of their patients' homes and the hidden landscapes of their minds. We illustrate the impact place has on doctors' understanding of their patients and on the patients' attitudes toward their illness. In addition, we examine how place informs readers' perceptions of both the coherence and the divide between the worlds of doctor and patient.     

The multifaceted roles of Eph/ephrin signaling in breast cancer

Eph receptors and their membrane-bound ligands are intimately involved in the control of morphogenic processes during embryonic development and adult tissue homeostasis. By their ability to orchestrate cell migration, pattern formation and tissue integrity they are also prone to be involved in carcinogenic growth. In this review we concentrate on their involvement in the normal and carcinogenic development of the breast. In this context we summarize their multi-faceted functions as tumor suppressors, tumor promoters, angiogenic inducers and regulators of stem cell homeostasis.     

Enhanced vigilance in monogamous pairs of the lizard, Tiliqua rugosa

The Australian sleepy lizard, Tiliqua rugosa, forms monogamouspairs for up to 8 weeks each spring before mating. We observedthat males had food in their mouths significantly less oftenwhen they were in pain than when they were alone. Females hadfood in the mouth independent of the presence or absence ofmales. Among females that had been feeding, indicated by foodin the mouth, we observed them feeding, as we approached, lessoften when they were in pairs than when they were alone. Amongfemales in pairs with food in their mouths, we observed themfeeding less often when their male partners were not feedingthan when their partners were feeding. This suggests that femalesare alerted to approaching danger earlier when they are in apair, and alerted earlier in a pair when their male partneris not feeding. Enhanced vigilance may be one function of pairingbehavior.     

Presynaptic glutamate receptors: physiological functions and mechanisms of action

Glutamate acts on postsynaptic glutamate receptors to mediate excitatory communication between neurons. The discovery that additional presynaptic glutamate receptors can modulate neurotransmitter release has added complexity to the way we view glutamatergic synaptic transmission. Here we review evidence of a physiological role for presynaptic glutamate receptors in neurotransmitter release. We compare the physiological roles of ionotropic and metabotropic glutamate receptors in short- and long-term regulation of synaptic transmission. Furthermore, we discuss the physiological conditions that are necessary for their activation, the source of the glutamate that activates them, their mechanisms of action and their involvement in higher brain function.     

Coevolutionary analyses of the relationships between piroplasmids and their hard tick hosts

Host–parasite coevolution is a key driver of biological diversity. To examine the evolutionary relationships between piroplasmids and their hard tick hosts, we calculated the molecular clock and conducted phylogenetic analyses of both groups. Based on our results, we conclude that the divergence time of piroplasmids (~56 Mya) is later than divergence time of their hard tick hosts (~86 Mya). From analyses of the evolution of both piroplasmid and vector lineages and their association, we know that hard ticks transmit piroplasmids with high genus specificity and low species specificity.     

Migration of monocytes after intracerebral injection

Recently, we monitored green fluorescent protein (GFP)-expressing monocytes after injection at the entorhinal cortex lesion (ECL) site in mice. We followed their migration out of the central nervous system (CNS) along olfactory nerve fibers penetrating the lamina cribrosa, within the nasal mucosa, and their subsequent appearance within the deep cervical lymph nodes (CLN), with numbers peaking at day 7. This is the same route activated T cells use for reaching the CLN, as we have shown before. Interestingly, GFP cells injected into the brain and subsequently found in the CLN exhibited ramified morphologies, which are typical of microglia and dendritic cells. To gain more insight into immunity and regeneration within the CNS we want to monitor injected monocytes using magnetic resonance imaging (MRI) after labeling with very small superparamagnetic iron oxide particles (VSOP). Due to their small size, nanoparticles have huge potential for magnetic labeling of different cell populations and their MRI tracking in vivo. So far we have verified that incubation with VSOP particles does not alter their migration pattern after ECL.     

Migration of monocytes after intracerebral injection

Recently, we monitored green fluorescent protein (GFP)-expressing monocytes after injection at the entorhinal cortex lesion (ECL) site in mice. We followed their migration out of the central nervous system (CNS) along olfactory nerve fibers penetrating the lamina cribrosa, within the nasal mucosa, and their subsequent appearance within the deep cervical lymph nodes (CLN), with numbers peaking at day 7. This is the same route activated T cells use for reaching the CLN, as we have shown before. Interestingly, GFP cells injected into the brain and subsequently found in the CLN exhibited ramified morphologies, which are typical of microglia and dendritic cells. To gain more insight into immunity and regeneration within the CNS we want to monitor injected monocytes using magnetic resonance imaging (MRI) after labeling with very small superparamagnetic iron oxide particles (VSOP). Due to their small size, nanoparticles have huge potential for magnetic labeling of different cell populations and their MRI tracking in vivo. So far we have verified that incubation with VSOP particles does not alter their migration pattern after ECL.     

Three-dimensional orientation in desert ants: context-independent memorisation and recall of sloped path segments

Desert ants (Cataglyphis fortis) navigate by a combination of path integration and landmark-based route memories. Their ability to correct sloped path segments to their ground distances enables them to orientate accurately even in undulating terrain. In this study, we tested whether or not ants incorporate vertical components of an itinerary into their route memory in similar ways as they do with visual landmarks and horizontal changes of direction. In two separate experiments, we trained desert ants to walk over artificial hills and later tested their acceptance of slopes within novel contexts. In the first paradigm, ants had to traverse a hill only on their outbound run, but not on their homebound trip. In a follow-up experiment, we confronted ramp-trained animals with descents in a completely new temporal and spatial context. The animals transferred their newly acquired acceptance of slopes from the outbound to the homebound run as well as to novel foraging trips. Cataglyphis obviously dissociates the experience of sloped path segments from the original context in which they appeared, thus reducing their significance as a navigational aid.