Acute Complexin Knockout Abates Spontaneous and Evoked Transmitter Release

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Evaluation of a DC pulsed magnetic tracking system in neurosurgical navigation: technique, accuracies, and influencing factors]

Navigation systems are useful instruments in cranial neurosurgery. For specification of position, so-called sensor-based navigation techniques use: (a) a signal emitter that generates a defined electromagnetic field in the area of the operation site; and (b) small sensors that detect the position of various operating instruments in the electromagnetic field. For a long time, owing to a lack of clinical data and long-term studies, electromagnetic systems have been regarded as error-prone and imprecise. With the development of a pulsed direct current (DC) technique, precision levels can now be reached that are comparable with those of established optical and mechanical measuring procedures. However, it must be noted that the influence on the measuring accuracy within the operating field increases with increasing susceptibility of the various metals used in the operating theatre (titanium相似文献   

Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts

Metabolic profiling, metabolomic and metabonomic studies mainly involve the multicomponent analysis of biological fluids, tissue and cell extracts using NMR spectroscopy and/or mass spectrometry (MS). We summarize the main NMR spectroscopic applications in modern metabolic research, and provide detailed protocols for biofluid (urine, serum/plasma) and tissue sample collection and preparation, including the extraction of polar and lipophilic metabolites from tissues. 1H NMR spectroscopic techniques such as standard 1D spectroscopy, relaxation-edited, diffusion-edited and 2D J-resolved pulse sequences are widely used at the analysis stage to monitor different groups of metabolites and are described here. They are often followed by more detailed statistical analysis or additional 2D NMR analysis for biomarker discovery. The standard acquisition time per sample is 4-5 min for a simple 1D spectrum, and both preparation and analysis can be automated to allow application to high-throughput screening for clinical diagnostic and toxicological studies, as well as molecular phenotyping and functional genomics.     

House-level risk factors associated with the colonization of broiler flocks with Campylobacter spp. in Iceland, 2001 – 2004

Background

The most predominant beta2-integrin lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alphaLbeta2), expressed on all leukocytes, is essential for many adhesive functions of the immune system. Interestingly, RTX toxin-producing bacteria specifically target this leukocyte beta2-integrin which exacerbates lesions and disease development.

Results

This study reports the sequencing of the wild boar beta2-integrin CD11a and CD18 cDNAs. Predicted CD11a and CD18 subunits share all the main structural characteristics of their mammalian homologues, with a larger interspecies conservation for the CD18 than the CD11a. Besides these strong overall similarities, wild boar and domestic pig LFA-1 differ by 2 (CD18) and 1 or 3 (CD11a) substitutions, of which one is located in the crucial I-domain (CD11a, E168D).

Conclusion

As most wild boars are seropositive to the RTX toxin-producing bacterium Actinobacillus pleuropneumoniae and because they have sustained continuous natural selection, future studies addressing the functional impact of these polymorphisms could bring interesting new information on the physiopathology of Actinobacillus pleuropneumoniae-associated pneumonia in domestic pigs.     

Optimal sampling time selection for parameter estimation in dynamic pathway modeling

Systems Biology is an emerging research area, which considers mathematical representations of inter- and intra-cellular dynamics. Among the many research problems that have been addressed, dynamic modeling of signal transduction pathways has received increasing attention. The usual approach to represent intra-cellular dynamics are nonlinear, usually ordinary, differential equations. The purpose of the models is to test and generate hypothesis of specific pathways and it is therefore required to estimate model parameters from experimental data. The experiments to generate data are complex and expensive, as a consequence of which the time series available are usually rather short, with few if any replicates. Almost certainly, not all variables one would like to include in a model can be measured. Parameter estimation is therefore an important research problem in Systems Biology and the focus of this paper. In particular, we are interested in optimizing the sampling time selection in order to minimize the variance of the parameter estimation error. With few sampling time points feasible, their selection is of practical importance in experimental design. Finally, the theoretical results are supported with an application.     

Dissecting physiological roles of estrogen receptor alpha and beta with potent selective ligands from structure-based design

The distinct roles of the two estrogen receptor (ER) isotypes, ERalpha and ERbeta, in mediating the physiological responses to estrogens are not completely understood. Although knockout animal experiments have been aiding to gain insight into estrogen signaling, additional information on the function of ERalpha and ERbeta will be provided by the application of isotype-selective ER agonists. Based on the crystal structure of the ERalpha ligand binding domain and a homology model of the ERbeta-ligand binding domain, we have designed steroidal ligands that exploit the differences in size and flexibility of the two ligand binding cavities. Compounds predicted to bind preferentially to either ERalpha or ERbeta were synthesized and tested in vitro using radio-ligand competition and transactivation assays. This approach directly led to highly ER isotype-selective (approximately 200-fold) and potent ligands. To unravel physiological roles of the two receptors, in vivo experiments with rats were conducted using the ERalpha- and ERbeta-selective agonists in comparison to 17beta-estradiol. The ERalpha agonist induced uterine growth, caused bone-protective effects, reduced LH and FSH plasma levels, and increased angiotensin I, whereas the ERbeta agonist did not at all or only at high doses lead to such effects, despite high plasma levels. It can thus be concluded that estrogen effects on the uterus, pituitary, bone, and liver are primarily mediated via ERalpha. Simultaneous administration of the ERalpha and ERbeta ligand did not lead to an attenuation of ERalpha-mediated effects on the uterus, pituitary, and liver parameters.     

Somatotopic representation of action words in human motor and premotor cortex

Since the early days of research into language and the brain, word meaning was assumed to be processed in specific brain regions, which most modern neuroscientists localize to the left temporal lobe. Here we use event-related fMRI to show that action words referring to face, arm, or leg actions (e.g., to lick, pick, or kick), when presented in a passive reading task, differentially activated areas along the motor strip that either were directly adjacent to or overlapped with areas activated by actual movement of the tongue, fingers, or feet. These results demonstrate that the referential meaning of action words has a correlate in the somatotopic activation of motor and premotor cortex. This rules out a unified "meaning center" in the human brain and supports a dynamic view according to which words are processed by distributed neuronal assemblies with cortical topographies that reflect word semantics.     

Activin redux: specification of mesodermal pattern in Xenopus by graded concentrations of endogenous activin B

Mesoderm formation in the amphibian embryo occurs through an inductive interaction in which cells of the vegetal hemisphere of the embryo act on overlying equatorial cells. The first candidate mesoderm-inducing factor to be identified was activin, a member of the transforming growth factor type beta family, and it is now clear that members of this family are indeed involved in mesoderm and endoderm formation. In particular, Derrière and five nodal-related genes are all considered to be strong candidates for endogenous mesoderm-inducing agents. Here, we show that activin, the function of which in mesoderm induction has hitherto been unclear, also plays a role in mesoderm formation. Inhibition of activin function using antisense morpholino oligonucleotides interferes with mesoderm formation in a concentration-dependent manner and also changes the expression levels of other inducing agents such as Xnr2 and Derrière. This work reinstates activin as a key player in mesodermal patterning. It also emphasises the importance of checking for polymorphisms in the 5' untranslated region of the gene of interest when carrying out antisense morpholino experiments in Xenopus laevis.     

The impact of species concept on biodiversity studies

Species are defined using a variety of different operational techniques. While discussion of the various methodologies has previously been restricted mostly to taxonomists, the demarcation of species is also crucial for conservation biology. Unfortunately, different methods of diagnosing species can arrive at different entities. Most prominently, it is widely thought that use of a phylogenetic species concept may lead to recognition of a far greater number of much less inclusive units. As a result, studies of the same group of organisms can produce not only different species identities but also different species range and number of individuals. To assess the impact of different definitions on conservation issues, we collected instances from the literature where a group of organisms was categorized both under phylogenetic and nonphylogenetic concepts. Our results show a marked difference, with surveys based on a phylogenetic species concept showing more species (48%) and an associated decrease in population size and range. We discuss the serious consequences of this trend for conservation, including an apparent change in the number of endangered species, potential political fallout, and the difficulty of deciding what should be conserved.