Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model

Objective: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model. Methods: In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D re-constructions, and a 3D-CT cephalometric analysis were performed. Results: The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used. Conclusions: None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed. Copyright (c) 2006 S. Karger AG, Basel

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

A Target-Based High Throughput Screen Yields Trypanosoma brucei Hexokinase Small Molecule Inhibitors with Antiparasitic Activity

African sleeping sickness is a disease found in sub-Saharan Africa that is caused by the single-celled parasite Trypanosoma brucei. The drugs used widely now to treat infections are 50 years old and notable for their toxicity, emphasizing the need for development of new therapeutics. In the search for potential drug targets, researchers typically focus on enzymes or proteins that are essential to the survival of the infectious agent while being distinct enough from the host to avoid accidental targeting of the host enzyme. This work describes our research on one such trypanosome enzyme, hexokinase, which is a protein that the parasite requires to make energy. Here we describe the results of our search for inhibitors of the parasite enzyme. By screening 220,223 compounds for anti-hexokinase activity, we have identified new inhibitors of the parasite enzyme. Some of these are toxic to trypanosomes while having no effect on mammalian cells, suggesting that they may hold promise for the development of new anti-parasitic compounds

Fluoro-edenitic fibres in the sputum of subjects from Biancavilla (Sicily): a pilot study

BACKGROUND: An excess of mortality for malignant neoplasms of the pleura in Biancavilla, promoted an investigation for pleural mesothelioma, disclosing 17 cases. As the absence of known sources of asbestos exposure, a local stone quarry, located near the inhabited area, used for the extraction of building materials, was investigated. Amphibolic fibres were found in the quarry and identified as fluoro-edenite "new end-member of the edenite / fluoro-edenite series" and recognized as the fluoro-edenite holotype by International Mineralogical Association – Commission on New Minerals and Mineral Names. A pilot study was performed to verify the feasibility of using spontaneous sputum as an exposure indicator for these fibres, in a context in which the use of aerosol-induced sputum technique would not be easily accepted. METHODS: Hypothesizing a behaviour of the new fibre analogous to that of asbestos, the determination of the free fibres and the ferruginous bodies in spontaneous sputum was carried out. Phase Contrast Optical Microscope and an Environmental Scanning Electron Microscope fitted with X-ray energy dispersive analysis system (micro-analysis) were used to examine the samples. The criteria for inclusion in the study were: 1) subjects hospitalized for exacerbation of chronic obstructive pulmonary disease symptoms, 2) age ≥ 45 years, 3) residence in Biancavilla for at least 30 years. RESULTS: The preliminary findings are related to 12 subjects (7 females and 5 males). Uncoated fibres (with length > 5 μm, diameter < 3 μm, aspect ratio 3.1) and ferruginous bodies were searched. Six out of twelve subjects (4 females, 2 males) had at least one of the three samples positive for the presence of fluoro-edenite, confirmed by micro-analysis. The fibre concentration found in the sputum ranged from 0.04 to 10 fibres/g; the length from 20 to 40 μm, the diameter was < 0.5 μm. No ferruginous bodies were found in any of the samples. The four women with a positive sample were housewives. Of the two men with a positive sample, one was a farmer and the other a mason. Therefore, it may be assumed that the exposure to fluoro-edenitic fibres was mainly environmental. CONCLUSION: The occurrence of the pleural mesothelioma cases and the presence of fluoro-edenitic fibres in spontaneous sputum, evidence the need to study the biological activity of fluoro-edenitic fibres and the implementation of epidemiological monitoring systems

New Forearm Elements Discovered of Holotype Specimen Australovenator wintonensis from Winton, Queensland, Australia

New skeletal elements are reported of the holotype specimen Australovenator wintonensis, from the type locality, near Winton, central western Queensland. New elements include left and right humeri, right radius, right radiale, right distal carpal 1, near complete right metacarpal I, left manual phalanx II-1, left manual phalanx II-2, near complete left manual phalanx II-3 and a left manual phalanx III-3. These new elements combined with those previously described are compared against other neovenatorids

Influence of Microbial Biofilms on the Preservation of Primary Soft Tissue in Fossil and Extant Archosaurs

Background: Mineralized and permineralized bone is the most common form of fossilization in the vertebrate record. Preservation of gross soft tissues is extremely rare, but recent studies have suggested that primary soft tissues and biomolecules are more commonly preserved within preserved bones than had been presumed. Some of these claims have been challenged, with presentation of evidence suggesting that some of the structures are microbial artifacts, not primary soft tissues. The identification of biomolecules in fossil vertebrate extracts from a specimen of Brachylophosaurus canadensis has shown the interpretation of preserved organic remains as microbial biofilm to be highly unlikely. These discussions also propose a variety of potential mechanisms that would permit the preservation of soft-tissues in vertebrate fossils over geologic time. Methodology/Principal Findings: This study experimentally examines the role of microbial biofilms in soft-tissue preservation in vertebrate fossils by quantitatively establishing the growth and morphology of biofilms on extant archosaur bone. These results are microscopically and morphologically compared with soft-tissue extracts from vertebrate fossils from the Hell Creek Formation of southeastern Montana (Latest Maastrichtian) in order to investigate the potential role of microbial biofilms on the preservation of fossil bone and bound organic matter in a variety of taphonomic settings. Base

Ethnobotany of the Samburu of Mt. Nyiru, South Turkana, Kenya

Traditional plant use is of extremely high importance in many societies, and prevalent in African communities. This knowledge is however dwindling rapidly due to changes towards a more Western lifestyle. The influence of modern tourism cannot be neglected in this context. This paper examines the plant use of the Samburu of the Mt. Nyiru area in Northern Kenya. The Samburu pastoralists of Kenya are still amongst the most traditional communities of the country and have retained most of their knowledge about the use of a large part of the plants in their environment for a wide variety of purposes. The results indicate that the local population has a very high knowledge of the plants in their surroundings, and attributes a purpose to a large percentage of the plants found. 448 plant species were collected, identified and their Samburu names and traditional uses recorded. 199 species were reported as of "no use". The high proportion of 249 plant species however had some traditional use: The highest number (180 species) was used as fodder, followed by 80 species that had medicinal use. Firewood (59 species), construction (42 species), tools (31 species), food (29 species) and ceremonial use (19 species) ranked far behind. Traditionally the Samburu attribute most illnesses to the effect of pollutants that block or inhibit digestion. This can include "polluted" food, contagion through sick people as well as witchcraft. In most cases the treatment of illness involves herbal purgatives to cleanse the patient. There are however frequent indications of plant use for common problems like wounds, parasites, body aches and burns. The change from a nomadic to a more sedentary lifestyle, often observed in other areas of the country, has affected the Samburu of remote Mt. Nyiru to a much lesser extent and did so far not lead to a major loss of traditional plant knowledge. However, overgrazing and over-exploitation of plant resources have already led to a decline of the plant material available

Eggs of the copepod Acartia tonsa Dana require hypoxic conditions to tolerate prolonged embryonic development arrest

Additional file 1. Raw data and calculations for all experiments as well as an overview of experiments in this study

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open

Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells

Cyr61 has been reported to participate in the development and progression of various cancers; however, its role in prostate cancer (PCa) still remains poorly understood. In this study, we explored the function of Cyr61 in a series of malignant PCa cell lines, including LnCap, Du145, and PC3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays demonstrated that Cyr61 was essential for the proliferation of PCa cells. Soft agar assay and xenograft analysis showed that downregulation of Cyr61 suppressed the tumorigenicity of Du145 cells both in vitro and in vivo. Either silencing the cellular Cyr61 by RNA interference or neutralising the endogenous Cyr61 by antibody inhibited the migration of Du145 cells. In contrast, purified protein of Cyr61 promoted the migration of LnCap cells in a dose-dependent manner. These results suggested that Cyr61 was involved in the migration of PCa cells. We also observed the accumulation of mature focal adhesion complexes associated with the impaired migration through Cyr61 downregulation. Also, further studies showed that Cyr61 regulated the level of activated Rac1 as well as its downstream targets, including phosphorylated JNK, E-cadherin, and p27kip1, which are key molecules involved in cell growth, migration, and invasion. The in vivo mouse tail vein injection experiment revealed that Cyr61 affected the metastatic capacity of Du145 cells, suggesting that Cyr61 was required for prostate tumour metastasis. Altogether, our results demonstrated that Cyr61 played an important role in the tumorigenicity and metastasis of PCa cells, which will benefit the development of therapeutic strategy for PCas