Midface position after LeFort III advancement

Nineteen of 30 patients who had midface advancement procedures between 1972 and 1980 had sufficient cephalometric data to be included in this retrospective study. The position of the midface in relation to the cranium and mandible was evaluated immediately postoperatively and for a period of 2 to 11 years (mean 5.8 years). At 1 year, midface position after LeFort III advancement was stable in 12 of 19 patients. Of these 12 patients, 8 showed some evidence of downward and/or forward movement of the midface. The remaining 7 patients showed a minor degree of midface relapse in the first year of follow-up. In 15 of 19 patients, at 2 years or more postoperatively, the final position of the midface was either at, anterior to, or inferior to its immediate postoperative location. Correction of exorbitism remained stable in all but one patient, who required a second advancement of the orbital segment. Three patients required subsequent LeFort I osteotomy to correct class III occlusion. Prognathism was determined to be secondary to mandibular growth, not midface relapse.     

Differentiation properties of renal collecting duct cells in culture

In the present study, we were particularly interested in distinguishing specific patterns of structural and functional proteins in the collecting duct system of neonatal and adult kidneys and in cultured renal collecting duct epithelia in order to ascertain the degree of differentiation in the cultures. We studied the distribution of specific renal collecting duct cell markers using morphological, immunohistochemical and biochemical procedures. Cultured renal collecting duct epithelium undergoes maturation in vitro. Examples of morphological differentiation include the appearance of cilia and microvilli at the apical cell pole, and a basement membrane at the basal aspect of the epithelium. Tight junctions with five to seven strands separate the wide intercellular spaces from the apical cell surface. Physiological maturation from a 'leaky' to a 'tight' epithelium is evident from the acquisition of the alpha-subunit of Na/K-ATPase and the development of a high transepithelial potential difference and resistance. Biochemical differentiation is revealed by the expression of specific proteins. The simple-epithelium cytokeratins, PKK1 and PKK2, which are typical intracellular-matrix proteins of mature collecting duct epithelium, maintain the same distribution in cell culture as in neonatal and adult kidneys. An indicator of maturation in vitro is the expression of the collecting duct-specific proteins, PCD2 and PCD3. Newly developed monoclonal antibodies against these antigens reacted similarly with cultured cells and cells of the mature collecting duct system, but they did not label the embryonic ampullae in the cortex of neonatal rabbit kidneys. In contrast, a third collecting duct-specific protein, PCD1, is not expressed by the cultured cells, which indicates the retention of an embryonic characteristic in vitro. Embryonic collecting duct ampullae of the neonatal kidney in situ contain laminin during their development. Laminin is, however, absent in cultured collecting duct epithelium. Biochemical stimulation of the adenylate cyclase system by arginine vasopressin resulted in a twofold stimulation of the enzyme activity. This degree of stimulation is similar to that found in maturing kidneys of neonatal rabbits and indicates another embryonic feature of the cultures.     

Relationship between ligand binding and conformational change of macromolecules in the two-state allosteric model

The relationship between the binding function $\text{Y}$ and the state function $\text{R}$ of an oligomeric protein has been analysed for the general two-state allosteric model. It is shown that this relation is determined by the numerical values of the inherent parameters of the model. The shape of the function $\text{Y}\text{= f (}\text{R}\text{)}$ can therefore be strictly concave, strictly convex or inverse sigmoidal according to the conditions. In the two-state allosteric model only a dimeric protein can display a linear relationship between $\text{Y}$ and $\text{R}$.In the paper general criteria for the estimation of the state function $\text{R}$ from experimentally obtained conformational parameters are discussed.     

Electromyographic Permutation Entropy Quantifies Diaphragmatic Denervation and Reinnervation

Spontaneous reinnervation after diaphragmatic paralysis due to trauma, surgery, tumors and spinal cord injuries is frequently observed. A possible explanation could be collateral reinnervation, since the diaphragm is commonly double-innervated by the (accessory) phrenic nerve. Permutation entropy (PeEn), a complexity measure for time series, may reflect a functional state of neuromuscular transmission by quantifying the complexity of interactions across neural and muscular networks. In an established rat model, electromyographic signals of the diaphragm after phrenicotomy were analyzed using PeEn quantifying denervation and reinnervation. Thirty-three anesthetized rats were unilaterally phrenicotomized. After 1, 3, 9, 27 and 81 days, diaphragmatic electromyographic PeEn was analyzed in vivo from sternal, mid-costal and crural areas of both hemidiaphragms. After euthanasia of the animals, both hemidiaphragms were dissected for fiber type evaluation. The electromyographic incidence of an accessory phrenic nerve was 76%. At day 1 after phrenicotomy, PeEn (normalized values) was significantly diminished in the sternal (median: 0.69; interquartile range: 0.66–0.75) and mid-costal area (0.68; 0.66–0.72) compared to the non-denervated side (0.84; 0.78–0.90) at threshold p<0.05. In the crural area, innervated by the accessory phrenic nerve, PeEn remained unchanged (0.79; 0.72–0.86). During reinnervation over 81 days, PeEn normalized in the mid-costal area (0.84; 0.77–0.86), whereas it remained reduced in the sternal area (0.77; 0.70–0.81). Fiber type grouping, a histological sign for reinnervation, was found in the mid-costal area in 20% after 27 days and in 80% after 81 days. Collateral reinnervation can restore diaphragm activity after phrenicotomy. Electromyographic PeEn represents a new, distinctive assessment characterizing intramuscular function following denervation and reinnervation.     

Scale-dependence in species-area relationships

Species-area relationships (SARs) are among the most studied phenomena in ecology, and are important both to our basic understanding of biodiversity and to improving our ability to conserve it. But despite many advances to date, our knowledge of how various factors contribute to SARs is limited, searches for single causal factors are often inconclusive, and true predictive power remains elusive. We believe that progress in these areas has been impeded by 1) an emphasis on single-factor approaches and thinking of factors underlying SARs as mutually exclusive hypotheses rather than potentially interacting processes, and 2) failure to place SAR-generating factors in a scale-dependent framework. We here review mathematical, ecological, and evolutionary factors contributing to species-area relationships, synthesizing major hypotheses from the literature in a scale-dependent context. We then highlight new research directions and unanswered questions raised by this scale-dependent synthesis.     

Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder

Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community.     

Citizen Science Program Shows Urban Areas Have Lower Occurrence of Frog Species,but Not Accelerated Declines

Understanding the influence of landscape change on animal populations is critical to inform biodiversity conservation efforts. A particularly important goal is to understand how urban density affects the persistence of animal populations through time, and how these impacts can be mediated by habitat provision; but data on this question are limited for some taxa. Here, we use data from a citizen science monitoring program to investigate the effect of urbanization on patterns of frog species richness and occurrence over 13 years. Sites surrounded by a high proportion of bare ground (a proxy for urbanization) had consistently lower frog occurrence, but we found no evidence that declines were restricted to urban areas. Instead, several frog species showed declines in rural wetlands with low-quality habitat. Our analysis shows that urban wetlands had low but stable species richness; but also that population trajectories are strongly influenced by vegetation provision in both the riparian zone and the wider landscape. Future increases in the extent of urban environments in our study area are likely to negatively impact populations of several frog species. However, existing urban areas are unlikely to lose further frog species in the medium term. We recommend that landscape planning and management focus on the conservation and restoration of rural wetlands to arrest current declines, and the revegetation of urban wetlands to facilitate the re-expansion of urban-sensitive species.     

Drosophila Embryos as Model Systems for Monitoring Bacterial Infection in Real Time

Drosophila embryos are well studied developmental microcosms that have been used extensively as models for early development and more recently wound repair. Here we extend this work by looking at embryos as model systems for following bacterial infection in real time. We examine the behaviour of injected pathogenic (Photorhabdus asymbiotica) and non-pathogenic (Escherichia coli) bacteria and their interaction with embryonic hemocytes using time-lapse confocal microscopy. We find that embryonic hemocytes both recognise and phagocytose injected wild type, non-pathogenic E. coli in a Dscam independent manner, proving that embryonic hemocytes are phagocytically competent. In contrast, injection of bacterial cells of the insect pathogen Photorhabdus leads to a rapid ‘freezing’ phenotype of the hemocytes associated with significant rearrangement of the actin cytoskeleton. This freezing phenotype can be phenocopied by either injection of the purified insecticidal toxin Makes Caterpillars Floppy 1 (Mcf1) or by recombinant E. coli expressing the mcf1 gene. Mcf1 mediated hemocyte freezing is shibire dependent, suggesting that endocytosis is required for Mcf1 toxicity and can be modulated by dominant negative or constitutively active Rac expression, suggesting early and unexpected effects of Mcf1 on the actin cytoskeleton. Together these data show how Drosophila embryos can be used to track bacterial infection in real time and how mutant analysis can be used to genetically dissect the effects of specific bacterial virulence factors.