CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver

IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells have been implicated in immune-mediated liver diseases, but the molecular basis for their recruitment and positioning within the liver is unknown.

Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors

GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we need to understand the interaction of such compounds with the benzodiazepine-binding pocket. With this aim, we mutated residues located in the benzodiazepine-binding site individually to cysteine. These mutated receptors were combined with benzodiazepine site ligands carrying a cysteine reactive group in a defined position. Proximal apposition of reaction partners will lead to a covalent reaction. We describe here such proximity-accelerated chemical coupling reactions of alpha(1)S205C and alpha(1)T206C with a diazepam derivative modified at the C-3 position with a reactive isothiocyanate group (-NCS). We also provide new data that identify alpha(1)H101C and alpha(1)N102C as exclusive sites of the reaction of a diazepam derivative where the -Cl atom is replaced by a -NCS group. Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors.

Relative positioning of classical benzodiazepines to the γ2-subunit of GABAA receptors.

GABAA receptors are the major inhibitory neurotransmitter receptors in the brain. Benzodiazepine exert their action via a high affinity-binding site at the α/γ subunit interface on some of these receptors. Diazepam has sedative, hypnotic, anxiolytic, muscle relaxant, and anticonvulsant effects. It acts by potentiating the current evoked by the agonist GABA. Understanding specific interaction of benzodiazepines in the binding pocket of different GABAA receptor isoforms might help to separate these divergent effects. As a first step, we characterized the interaction between diazepam and the major GABAA receptor isoform α1β2γ2. We mutated several amino acid residues on the γ2-subunit assumed to be located near or in the benzodiazepine binding pocket individually to cysteine and studied the interaction with three ligands that are modified with a cysteine-reactive isothiocyanate group (-NCS). When the reactive NCS group is in apposition to the cysteine residue this leads to a covalent reaction. In this way, three amino acid residues, γ2Tyr58, γ2Asn60, and γ2Val190 were located relative to classical benzodiazepines in their binding pocket on GABAA receptors.

Ultrasound-guided needle positioning in sensory nerve conduction study of the sural nerve

OBJECTIVES: To evaluate the usefulness of ultrasound imaging to improve the positioning of the recording needle for nerve conduction studies (NCS) of the sural nerve. METHODS: Orthodromic NCS of the sural nerve was performed in 44 consecutive patients evaluated for polyneuropathy. Ultrasound-guided needle positioning (USNP) was compared to conventional "blind" needle positioning (BNP), electrically guided needle positioning (EGNP), and to recordings with surface electrodes (SFN). RESULTS: The mean distance between the needle tip and the nerve was 1.1 mm with USNP compared to 5.1 mm with BNP (p<0.0001). The mean amplitude of the sensory nerve action potential (SNAP) was 21 microV with USNP and 11 microV with BNP (p<0.0001). Compared to BNP, nerve-needle distances and SNAP amplitudes did not improve with EGNP. SNAP amplitudes recorded with SFN were significantly smaller than with BNP, EGNP and USNP. CONCLUSION: Ultrasound increases the precision of needle positioning markedly, compared to conventional methods. The amplitude of the recorded SNAP is usually clearly greater using USNP. In addition, USNP is faster, less painful and less dependent on the patient. SIGNIFICANCE: USNP is superior to BNP, EGNP, and SFN in accurate measurement of SNAP amplitude. It has a potential use in the routine near-nerve needle sensory NCS of pure sensory nerves.

Fulfilled and missed requirements for online reservation systems: an empirical investigation of Austrian and Swiss hotels

Temporal data are a core element of a reservation. In this paper we formulate 10 requirements and 14 sub-requirements for handling temporal data in online hotel reservation systems (OHRS) from a usability viewpoint. We test the fulfillment of these requirements for city and resort hotels in Austria and Switzerland. Some of the requirements are widely met; however, many requirements are fulfilled only by a surprisingly small number of hotels. In particular, numerous systems offer options for selecting data which lead to error messages in the next step. A few screenshots illustrate flaws of the systems. We also draw conclusions on the state of applying software engineering principles in the development of Web pages.

Microsurgical and laser ablation analysis of leaf positioning and dorsoventral patterning in tomato

Leaves are arranged according to regular patterns, a phenomenon referred to as phyllotaxis. Important determinants of phyllotaxis are the divergence angle between successive leaves, and the size of the leaves relative to the shoot axis. Young leaf primordia are thought to provide positional information to the meristem, thereby influencing the positioning of new primordia and hence the divergence angle. On the contrary, the meristem signals to the primordia to establish their dorsoventral polarity, which is a prerequisite for the formation of a leaf blade. These concepts originate from classical microsurgical studies carried out between the 1920s and the 1970s. Even though these techniques have been abandoned in favor of genetic analysis, the resulting insights remain a cornerstone of plant developmental biology. Here, we employ new microsurgical techniques to reassess and extend the classical studies on phyllotaxis and leaf polarity. Previous experiments have indicated that the isolation of an incipient primordium by a tangential incision caused a change of divergence angle between the two subsequent primordia, indicating that pre-existing primordia influence further phyllotaxis. Here.. we repeat these experiments and compare them with the results of laser ablation of incipient primordia. Furthermore. we explore to what extent the different pre-existing primordia influence the size and position of new organs. and hence phyllotaxis. We propose that the two youngest primordia (P-1 and P-2) are sufficient for the approximate positioning of the incipient primordium (I-1), and therefore for the perpetuation of the generative spiral, whereas the direct contact neighbours of I-1 (P-2 and P-3) control its delimitation and hence its exact size and position. Finally. we report L I specific cell ablation experiments suggesting that the meristem L-1 layer is essential for the dorsoventral patterning of leaf primordia.

3D bloodstain pattern analysis: ballistic reconstruction of the trajectories of blood drops and determination of the centres of origin of the bloodstains

For crime scene investigation in cases of homicide, the pattern of bloodstains at the incident site is of critical importance. The morphology of the bloodstain pattern serves to determine the approximate blood source locations, the minimum number of blows and the positioning of the victim. In the present work, the benefits of the three-dimensional bloodstain pattern analysis, including the ballistic approximation of the trajectories of the blood drops, will be demonstrated using two illustrative cases. The crime scenes were documented in 3D, using the non-contact methods digital photogrammetry, tachymetry and laser scanning. Accurate, true-to-scale 3D models of the crime scenes, including the bloodstain pattern and the traces, were created. For the determination of the areas of origin of the bloodstain pattern, the trajectories of up to 200 well-defined bloodstains were analysed in CAD and photogrammetry software. The ballistic determination of the trajectories was performed using ballistics software. The advantages of this method are the short preparation time on site, the non-contact measurement of the bloodstains and the high accuracy of the bloodstain analysis. It should be expected that this method delivers accurate results regarding the number and position of the areas of origin of bloodstains, in particular the vertical component is determined more precisely than using conventional methods. In both cases relevant forensic conclusions regarding the course of events were enabled by the ballistic bloodstain pattern analysis.

Influence of rhBMP-2 on bone formation and osseointegration in different implant systems after sinus-floor elevation. An in vivo study on sheep

Several studies have reported certain bone morphogenic proteins (BMPs) to have positive effects on bone generation. Although some investigators have studied the effects of human recombinant BMP (rhBMP-2) in sinus augmentation in sheep, none of these studies looked at the placement of implants at the time of sinus augmentation. Furthermore, no literature could be found to report on the impact that different implant systems, as well as the positioning of the implants had on bone formation if rhBMP-2 was utilized in sinus-lift procedures.

The effect of different implant neck configurations on soft and hard tissue healing: a randomized-controlled clinical trial

Objective: To compare the soft and hard tissue healing and remodeling around tissue-level implants with different neck configurations after at least 1 year of functional loading. Material and methods: Eighteen patients with multiple missing teeth in the posterior area received two implants inserted in the same sextant. One test (T) implant with a 1.8 mm turned neck and one control (C) implant with a 2.8 mm turned neck were randomly assigned. All implants were placed transmucosally to the same sink depth of approximately 1.8 mm. Peri-apical radiographs were obtained using the paralleling technique and digitized. Two investigators blinded to the implant type-evaluated soft and hard tissue conditions at baseline, 6 months and 1 year after loading. Results: The mean crestal bone levels and soft tissue parameters were not significantly different between T and C implants at all time points. However, T implants displayed significantly less crestal bone loss than C implants after 1 year. Moreover, a frequency analysis revealed a higher percentage (50%) of T implants with crestal bone levels 1–2 mm below the implant shoulder compared with C implants (5.6%) 1 year after loading. Conclusion: Implants with a reduced height turned neck of 1.8 mm may, indeed, lower the crestal bone resorption and hence, may maintain higher crestal bone levels than do implants with a 2.8 mm turned neck, when sunk to the same depth. Moreover, several factors other than the vertical positioning of the moderately rough SLA surface may influence crestal bone levels after 1 year of function.

Treatment of soft tissue recessions at titanium implants using a resorbable collagen matrix: a pilot study

OBJECTIVES: To histologically assess the effectiveness of a porcine-derived collagen matrix (CM) and a subepithelial connective tissue graft (CTG) for the coverage of single mucosal recessions at osseointegrated dental implants. MATERIALS AND METHODS: Chronic-type mucosal Miller Class I-like recessions (mean clinical defect height: 0.67 ± 0.33-1.16 ± 0.19 mm) were established at the buccal aspect of titanium implants with platform switch in six beagle dogs. The defects were randomly allocated to either (1) coronally advanced flap surgery (CAF) + CM, (2) CAF + CTG or (3) CAF alone. At 12 weeks, histomorphometrical measurements were made (e.g.) between the implant shoulder (IS) and the mucosal margin (PM) and IS and the outer contour of the adjacent soft tissue (mucosal thickness [MT]). RESULTS: All treatment procedures investigated were associated with an almost complete soft tissue coverage of the defect area (i.e. coronal positioning of PM relative to IS). Mean IS-PM and MT values tended to be increased in both CAF + CM (1.04 ± 0.74 mm/0.71 ± 0.55 mm) and CAF + CTG (0.88 ± 1.23 mm/0.62 ± 0.66 mm) groups when compared with CAF (0.16 ± 0.28 mm/0.34 ± 0.23 mm) alone. These differences, however, did not reach statistical significance. CONCLUSIONS: Within the limits of this pilot study, it was concluded that all treatment procedures investigated were effective in covering soft tissue recessions at titanium implants.