Lengthening the human mandible by gradual distraction.

Lengthening of the mandible by gradual distraction was performed on four young patients (average age 78 months). The amount of mandibular bone lengthening ranged from 18 to 24 mm; one patient with Nager's syndrome underwent bilateral mandibular expansion. Following the period of expansion, the patients were maintained in external fixation for an average of 9 weeks to allow ossification. The patients were followed for a minimum of 11 months to a maximum of 20 months with clinical and dental examinations as well as photographic and radiographic documentation. The technique holds promise for early reconstruction of craniofacial skeletal defects without the need for bone grafts, blood transfusion, or intermaxillary fixation.     

Matrix analysis to model the invasion of alligatorweed (Alternanthera philoxeroides) on Kentucky lakes

Aims Alligatorweed (Alternanthera philoxeroides (Mart.) Griseb.) is an invasive species indigenous to South America. With its rapid invasion of southeastern US waterways, understanding the invasiveness of this plant species is critical for providing possible mechanisms of prevention for resource managers. The aim of this project is to use a matrix model to study the invasion dynamics of alligatorweed under both terrestrial and aquatic environments. The use of this model allows for a deeper understanding of the invasiveness and life history–stage structure of alligatorweed. In particular, matrix analysis can further test the hypothesis that certain life stages of alligatorweed might be more sensitive to control and management.Methods A greenhouse experiment was conducted to study the spread of alligatorweed under both aquatic and terrestrial environments. Utilizing the growth data obtained during the summer of 2010, matrix analysis was used to model the growth of alligatorweed for six different treatments. Transition matrices were generated based on plant measurements taken at different life stages defined by the number of leaves or nodes. These matrices are population projection models whose eigenvalues represent the growth rate of alligatorweed. A high growth rate is a key feature of successful invaders. Residuals were calculated and sensitivity analysis was performed to test the accuracy of the model and importance of each life stage over the entire life cycle of alligatorweed.Important findings The results of this study indicate that in the aquatic habitat, plants at their early life cycle stage are most sensitive to potential control measures. Conversely, in the terrestrial habitat, the most sensitive stage of alligatorweed is at its late life cycle stage, characterized with large-sized plants, thus suggesting the best timing for management and eradication of this invasive species.     

Computer simulations reveal a novel nucleotide-type binding orientation for ellipticine-based anticancer c-kit kinase inhibitors

Receptor tyrosine kinase (RTK) enzymes regulate cell signaling pathways and so are an important target for cancer chemotherapy. Current inhibitors of c-kit, a key RTK stem cell factor receptor, are inactive against the most common mutated variant Asp816Val, associated with highly malignant cancers. Recent combined experimental/simulation work has highlighted the utility of the ellipticine pharmacore in inhibiting mutant c-kit, and the present simulation study applies a combination of high-level simulation tools to probe further the binding of ellipticine-based derivatives to c-kit. We find a large preference for protonation of bound ellipticine, which stabilizes the negative protein residues that coordinated ADP.Mg (2+) in the native complex. The resulting ellipticine inhibitor binding mode resembles the native nucleotide complex and serves to explain some existing experimental data on binding specificities, indicating that functionalization at the C4/C5 sites of ellipticine derivatives may be important for the design of novel nucleotide analogues that inhibit mutant c-kit.     

The role of neonatal NMDA receptor activation in defeminization and masculinization of sex behavior in the rat

Normal development of the male rat brain involves two distinct processes, masculinization and defeminization, that occur during a critical period of brain sexual differentiation. Masculinization allows for the capacity to express male sex behavior in adulthood, and defeminization eliminates or suppresses the capacity to express female sex behavior in adulthood. Despite being separate processes, both masculinization and defeminization are induced by neonatal estradiol exposure. Though the mechanisms underlying estradiol-mediated masculinization of behavior during development have been identified, the mechanisms underlying defeminization are still unknown. We sought to determine whether neonatal activation of glutamate NMDA receptors is a necessary component of estradiol-induced defeminization of behavior. We report here that antagonizing glutamate receptors during the critical period of sexual differentiation blocks estradiol-induced defeminization but not masculinization of behavior in adulthood. However, enhancing NMDA receptor activation during the same critical period mimics estradiol to permanently induce both defeminization and masculinization of sexual behavior.     

Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study

Objective To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures.Design Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home.Setting England.Participants 19 773 men and women aged 16-39 years invited to participate in screening.Main outcome measures Coverage and uptake of screening; prevalence of chlamydia.Results Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year.Conclusions Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.     

The trans-Pacific zipper effect: disjunct sister taxa and matching geological outlines that link the Pacific margins

Aim To combine analyses of trans‐Pacific sister taxa with geological evidence in order to test the hypothesis of the existence of a Panthalassa superocean. Location The study is concerned with taxa, both fossil and extant, from East Asia, Australia, New Zealand, South America and North America. Methods Phylogenetic and distributional analyses of trans‐Pacific biota were integrated with geological evidence from the Pacific and circum‐Pacific regions. Results A series of recent biogeographical analyses delineates a zipper‐like system of sister areas running up both margins of the Pacific, with each section of western North and South America corresponding to a particular section from East Asia/Australia/New Zealand. These sister areas coincide neatly with a jigsaw‐like fit provided by the matching Mesozoic coastlines that bracket the Pacific. Main conclusions The young age (<200 Myr) of oceanic crust, the matching Mesozoic circum‐Pacific outlines, and a corresponding system of interlocking biogeographical sister areas provide three independent avenues of support for a closed Pacific in the Upper Triassic–Lower Jurassic. The hypothesis of the existence and subsequent subduction of the pre‐Pacific superocean Panthalassa is not only unnecessary, it conflicts with this evidence. Panthalassa‐based paleomaps necessitate the invention of dozens of additional hypotheses of species‐dependent, trans‐oceanic dispersal events, often involving narrow‐range taxa of notoriously limited vagility, in order to explain repeated examples of the same biogeographical pattern. Removing the vanished‐superocean hypothesis reunites both the matching geological outlines and all the disjunct sister taxa. In brief, what appears to be a multi‐era tangle of convoluted, trans‐oceanic distributions on Panthalassa‐based paleomaps is actually a relatively simple biogeographical pattern that is explainable by a single vicariant event: the opening and expansion of the Pacific.     

Comparing Denitrification Estimates for a Texas Estuary by Using Acetylene Inhibition and Membrane Inlet Mass Spectrometry

Characterizing denitrification rates in aquatic ecosystems is essential to understanding how systems may respond to increased nutrient loading. Thus, it is important to ensure the precision and accuracy of the methods employed for measuring denitrification rates. The acetylene (C₂H₂) inhibition method is a simple technique for estimating denitrification. However, potential problems, such as inhibition of nitrification and incomplete inhibition of nitrous oxide reduction, may influence rate estimates. Recently, membrane inlet mass spectrometry (MIMS) has been used to measure denitrification in aquatic systems. Comparable results were obtained with MIMS and C₂H₂ inhibition methods when chloramphenicol was added to C₂H₂ inhibition assay mixtures to inhibit new synthesis of denitrifying enzymes. Dissolved-oxygen profiles indicated that surface layers of sediment cores subjected to the MIMS flowthrough incubation remained oxic whereas cores incubated using the C₂H₂ inhibition methods did not. Analysis of the microbial assemblages before and after incubations indicated significant changes in the sediment surface populations during the long flowthrough incubation for MIMS analysis but not during the shorter incubation used for the C₂H₂ inhibition method. However, bacterial community changes were also small in MIMS cores at the oxygen transition zone where denitrification occurs. The C₂H₂ inhibition method with chloramphenicol addition, conducted over short incubation intervals, provides a cost-effective method for estimating denitrification, and rate estimates are comparable to those obtained by the MIMS method.     

Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells.

Prostate cancer metastasis to bone marrow involves initial adhesion of tumor cells to the bone marrow endothelium, followed by transmigration and proliferation within the marrow. Rapid, specific adhesion of highly metastatic prostate adenocarcinoma cells (PC3M-LN4) to bone marrow endothelial cell (BMEC) lines requires a pericellular hyaluronan (HA) matrix and correlates with dramatically up-regulated HA synthase (HAS) expression. Non-metastatic prostate tumor cells (LNCaP) do not assemble a HA matrix, adhere poorly to BMECs, and express normal levels of HAS. Preferential bone metastasis of prostate carcinoma cells may therefore be facilitated by tumor cell HA biosynthesis. In this report, HAS gene expression was manipulated to investigate the direct impact of prostate tumor cell HA production on adhesion to BMECs. PC3M-LN4 cells stably transfected with antisense HAS2 and HAS3 failed to form pericellular matrices. Adhesion of these transfectants to BMECs was significantly diminished, comparable to the low level exhibited by LNCaP cells. Upon transfection with full-length HAS2 or HAS3, the non-adherent LNCaP cells retained pericellular HA and adhered to BMECs. The results of this study are consistent with a model in which HA matrix formation, BMEC adhesion, and metastatic potential are mediated by HAS expression.