A three‐dimensional analysis of bilateral directional asymmetry in the human clavicle

This study presents a novel three‐dimensional analysis using statistical atlases and automated measurements to assess diaphyseal morphology of the clavicle and its relationship to muscle asymmetry. A sample of 505 individuals (285 males, 220 females) from the William McCormick Clavicle Collection was CT scanned, segmented, and added to a statistical bone atlas that captures correspondence between homologous points on the bone surfaces. Muscle attachment sites were localized on the atlas and then propagated across the entire population. Cross‐sectional contours were extracted at 5% increments along the entire bone, as well as at muscle attachment sites and the clavicle waist; maximum and minimum dimensions of each cross‐sectional contour were calculated. In addition, the entire three‐dimensional surface was examined for asymmetry by analyzing the magnitude and directional differences between homologous points across all bone surfaces in the dataset. The results confirm the existing studies on clavicle asymmetry, namely that the left clavicle is longer than the right, but the right is more robust than the left. However, the patterns of asymmetry are sexually dimorphic. Males are significantly asymmetric in all dimensions and at muscle and ligament attachment sites (P < 0.05), whereas female asymmetry is more variable. We hypothesize that this is related to absolute and relative differences in male muscle strength compared to females. However, an area with no muscle attachments on the posterior midshaft was significantly asymmetric in both sexes. We suggest that this is a curvature difference caused by opposing muscle actions at the medial and lateral ends of the bone. Am J Phys Anthropol 2012. © 2012 Wiley Periodicals, Inc.     

X-ray diffraction studies of 14-filament models of deoxygenated sickle cell hemoglobin fibers. Models based on electron micrograph reconstructions

The transforms of a large number of models of deoxygenated sickle hemoglobin fibers, related to that derived from image reconstruction of electron micrographs, have been calculated and compared with X-ray diffraction data of 15 A resolution. The model of the fiber, determined from the reconstructed image, is a helix consisting of 14 filaments that associate in a specific mode to form seven pairs, or protofilaments. Pairs were identified through the pattern of filament loss in partially disassembled fibers and by the separation between molecules, in adjacent filaments, of half a molecular diameter, along the fiber axis. An alternative mode of filament association can be derived also from the surface lattice of the reconstruction, which meets these criteria for the pairing of molecular filaments. Both pairing modes have been used in the search for structures whose transforms show the best agreement with the diffraction data. Models were generated by the systematic translation of six protofilaments, taken in symmetry related pairs, in steps of 3.5 A along the fiber axis relative to a fixed central protofilament. Each translation of a protofilament corresponds to a different fiber model, whose transform was compared with observed data. In all, over 11,000 transforms were calculated. Of all the models considered, three have been found whose residuals are minimal. At 30 A resolution, similar to that of electron micrographs, the model derived from image reconstruction and the three found through our search procedure are indistinguishable. At 15 A, however, the transforms of these models show better agreement with the observed data than the transform of the reconstructed image. Comparison of residuals shows that the model derived from the reconstructed image can be rejected with 99.5% probability relative to the model, with the same pairing scheme, found by our search procedures. The two other models, derived from the alternative pairing scheme, are also more credible than the reconstructed image, but at a lower confidence level. Each of our three models is equally acceptable. Their existence may reflect structural polymorphism of the fiber.     

A Novel Prior- and Motion-Based Compressed Sensing Method for Small-Animal Respiratory Gated CT

Low-dose protocols for respiratory gating in cardiothoracic small-animal imaging lead to streak artifacts in the images reconstructed with a Feldkamp-Davis-Kress (FDK) method. We propose a novel prior- and motion-based reconstruction (PRIMOR) method, which improves prior-based reconstruction (PBR) by adding a penalty function that includes a model of motion. The prior image is generated as the average of all the respiratory gates, reconstructed with FDK. Motion between respiratory gates is estimated using a nonrigid registration method based on hierarchical B-splines. We compare PRIMOR with an equivalent PBR method without motion estimation using as reference the reconstruction of high dose data. From these data acquired with a micro-CT scanner, different scenarios were simulated by changing photon flux and number of projections. Methods were evaluated in terms of contrast-to-noise-ratio (CNR), mean square error (MSE), streak artefact indicator (SAI), solution error norm (SEN), and correction of respiratory motion. Also, to evaluate the effect of each method on lung studies quantification, we have computed the Jaccard similarity index of the mask obtained from segmenting each image as compared to those obtained from the high dose reconstruction. Both iterative methods greatly improved FDK reconstruction in all cases. PBR was prone to streak artifacts and presented blurring effects in bone and lung tissues when using both a low number of projections and low dose. Adopting PBR as a reference, PRIMOR increased CNR up to 33% and decreased MSE, SAI and SEN up to 20%, 4% and 13%, respectively. PRIMOR also presented better compensation for respiratory motion and higher Jaccard similarity index. In conclusion, the new method proposed for low-dose respiratory gating in small-animal scanners shows an improvement in image quality and allows a reduction of dose or a reduction of the number of projections between two and three times with respect to previous PBR approaches.     

REMO: A new protocol to refine full atomic protein models from C‐alpha traces by optimizing hydrogen‐bonding networks

Protein structure prediction approaches usually perform modeling simulations based on reduced representation of protein structures. For biological utilizations, it is an important step to construct full atomic models from the reduced structure decoys. Most of the current full atomic model reconstruction procedures have defects which either could not completely remove the steric clashes among backbone atoms or generate final atomic models with worse topology similarity relative to the native structures than the reduced models. In this work, we develop a new protocol, called REMO, to generate full atomic protein models by optimizing the hydrogen‐bonding network with basic fragments matched from a newly constructed backbone isomer library of solved protein structures. The algorithm is benchmarked on 230 nonhomologous proteins with reduced structure decoys generated by I‐TASSER simulations. The results show that REMO has a significant ability to remove steric clashes, and meanwhile retains good topology of the reduced model. The hydrogen‐bonding network of the final models is dramatically improved during the procedure. The REMO algorithm has been exploited in the recent CASP8 experiment which demonstrated significant improvements of the I‐TASSER models in both atomic‐level structural refinement and hydrogen‐bonding network construction. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

Dimorphism of right–left asymmetry in the female genitalia of the brachypterous grasshopper Parapodisma mikado (Orthoptera: Acrididae)

Several insects exhibit morphological asymmetry in the mouthparts or genitalia. In a part of species with asymmetric genitalia, two mirror‐image forms of the genitalia are reported to occur in a population. This dimorphism, called chiral dimorphism, is usually observed in male genitalia, but its examples in female genitalia are very limited. Here, we report that the females of the brachypterous grasshopper Parapodisma mikado are equipped with an asymmetric sclerite in the copulatory bursa, and that two mirror‐image forms of the sclerite occur in local populations. This dimorphism was detected in all of seven populations examined, and the ratio of the two forms was approximately 2:1 for the right : left forms. In one population, the ratio of the two forms did not vary among three consecutive years. Thus, chiral dimorphism in the female genitalia is kept almost constant spatiotemporally. Mating experiments indicated that the direction of female genitalia did not affect the direction to which the males twist their abdomen (right or left side) during mating or the duration of mating. We propose two hypotheses, a neutral developmental mechanism and sexual conflict, for the maintenance of chiral dimorphism in the genitalia of P. mikado females.     

Factors Influencing Superimposition Error of 3D Cephalometric Landmarks by Plane Orientation Method Using 4 Reference Points: 4 Point Superimposition Error Regression Model

Superimposition has been used as a method to evaluate the changes of orthodontic or orthopedic treatment in the dental field. With the introduction of cone beam CT (CBCT), evaluating 3 dimensional changes after treatment became possible by superimposition. 4 point plane orientation is one of the simplest ways to achieve superimposition of 3 dimensional images. To find factors influencing superimposition error of cephalometric landmarks by 4 point plane orientation method and to evaluate the reproducibility of cephalometric landmarks for analyzing superimposition error, 20 patients were analyzed who had normal skeletal and occlusal relationship and took CBCT for diagnosis of temporomandibular disorder. The nasion, sella turcica, basion and midpoint between the left and the right most posterior point of the lesser wing of sphenoidal bone were used to define a three-dimensional (3D) anatomical reference co-ordinate system. Another 15 reference cephalometric points were also determined three times in the same image. Reorientation error of each landmark could be explained substantially (23%) by linear regression model, which consists of 3 factors describing position of each landmark towards reference axes and locating error. 4 point plane orientation system may produce an amount of reorientation error that may vary according to the perpendicular distance between the landmark and the x-axis; the reorientation error also increases as the locating error and shift of reference axes viewed from each landmark increases. Therefore, in order to reduce the reorientation error, accuracy of all landmarks including the reference points is important. Construction of the regression model using reference points of greater precision is required for the clinical application of this model.     

Right‐ and left‐handed three‐helix proteins. I. Experimental and simulation analysis of differences in folding and structure

Despite the large number of publications on three‐helix protein folding, there is no study devoted to the influence of handedness on the rate of three‐helix protein folding. From the experimental studies, we make a conclusion that the left‐handed three‐helix proteins fold faster than the right‐handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three‐helix proteins (four right‐handed and four left‐handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary‐structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left‐handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right‐handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three‐helix proteins (238 right‐ and 94 left‐handed). From our analysis, we found that the left‐handed three‐helix proteins have some less‐dense packing that should result in faster folding for some proteins as compared to the case of right‐handed proteins.Proteins 2013; © 2013 Wiley Periodicals, Inc.     

Flower visitor communities are similar on remnant and reconstructed tallgrass prairies despite forb community differences

One common goal of habitat restoration and reconstruction is to reinstate the biodiversity found at intact reference sites. However, few researchers have examined whether these practices reinstate communities of flower‐visiting insects. This is unfortunate, as anthropogenically mediated declines in flower visitors, including bees (the primary pollinators for most terrestrial ecosystems), beetles, flies, and butterflies, have been reported worldwide. Biodiversity declines may be especially severe in North America's tallgrass prairie, a once‐vast grassland that has experienced severe destruction and degradation due to agricultural conversion. As such, we assessed the structure of forb and flower‐visiting insect communities as a whole and two subsets of the flower visitor community—bees and phytophagous beetles—across five tallgrass prairie remnants and five reconstructed prairies (former crop fields) in Kansas from 2013 to 2015. Remnant prairies had significantly higher forb diversity and differed significantly in forb composition, compared to reconstructed prairies. Despite the dissimilarities in forb community structure, there were no differences in flower visitor diversity or abundance between remnants and reconstructed prairies. However, when considered separately, bee communities exhibited significantly greater variability in composition on reconstructed prairies, likely due to the abundance of generalist bee species visiting non‐native legumes at two reconstructed prairies. Our work provides evidence that prairie habitat reconstruction is a valuable tool for reestablishing flower‐visiting insect communities and also emphasizes the considerable role that non‐native species may play in structuring grassland plant–bee interactions.     

A cracking complication: Displacement of existing clavicle fracture complicating subcutaneous implantable cardioverter defibrillator implantation

An 18 year old male with an incompletely healed clavicle fracture presented with unexplained syncope. Subsequent investigations were consistent with a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). A subcutaneous implantable cardioverter-defibrillator (S-ICD) was successfully implanted and defibrillation threshold (DFT) testing performed as per standard protocol. Shortly following the procedure, the patient complained of pain and swelling over the left clavicle. A radiograph revealed aggravation and displacement of the underlying clavicle fracture. Surgical reduction and internal fixation was performed one week later.     

Applying PyRosetta molecular energies to separate properly oriented protein models from mirror models,obtained from contact maps

Reconstructing protein structure based on contact maps leads to two types of models: properly oriented models and mirror models. This is due to the fact that contact maps do not include information on protein chirality. Therefore, both types of model orientations share the same contact map and are geometrically allowed. In this work, we verified the hypothesis that some of the energy terms calculated by PyRosetta could be useful to distinguish between properly oriented and mirror models. We studied 440 models of all-alpha protein domains reconstructed manually from their contact maps, where 50 % of the models were properly oriented and 50 % had mirror orientation. We showed that dihedral angles and energy terms, based on the probability of specific geometrical arrangement of the residues, differed significantly for properly oriented and mirror models.     

Accuracy and reproducibility of CFD predicted wall shear stress using 3D ultrasound images

Computational fluid dynamics (CFD) flow simulation techniques have the potential to enhance our understanding of how haemodynamic factors are involved in atherosclerosis. Recently, 3D ultrasound has emerged as an alternative to other 3D imaging techniques, such as magnetic resonance angiography (MRA). The method can be used to generate realistic vascular geometry suitable for CFD simulations. In order to assess accuracy and reproducibility of the procedure from image acquisition to reconstruction to CFD simulation, a human carotid artery bifurcation phantom was scanned three times using 3D ultrasound. The geometry was reconstructed and flow simulations were carried out on the three sets as well as on a model generated using computer aided design (CAD) from the geometric information given by the manufacturer. It was found that the three reconstructed sets showed good reproducibility as well as satisfactory quantitative agreement with the CAD model. Analyzing two selected locations probably representing the 'worst cases,' accuracy comparing ultrasound and CAD reconstructed models was estimated to be between 7.2% and 7.7% of the maximum instantaneous WSS and reproducibility comparing the three scans to be between 8.2% and 10.7% of their average maximum.     

Homologous control of protein signaling networks

In a previous paper we introduced a method called augmented sparse reconstruction (ASR) that identifies links among nodes of ordinary differential equation networks, given a small set of observed trajectories with various initial conditions. The main purpose of that technique was to reconstruct intracellular protein signaling networks.In this paper we show that a recursive augmented sparse reconstruction generates artificial networks that are homologous to a large, reference network, in the sense that kinase inhibition of several reactions in the network alters the trajectories of a sizable number of proteins in comparable ways for reference and reconstructed networks. We show this result using a large in-silico model of the epidermal growth factor receptor (EGF-R) driven signaling cascade to generate the data used in the reconstruction algorithm.The most significant consequence of this observed homology is that a nearly optimal combinatorial dosage of kinase inhibitors can be inferred, for many nodes, from the reconstructed network, a result potentially useful for a variety of applications in personalized medicine.     

Evolution of the climatic niche in scaly tree ferns (Cyatheaceae,Polypodiopsida)

Although climatic niche conservatism has been assumed by a large number of studies focused on climatic niche evolution, there are examples of climatic niche diversification and adaptation to changing climates. In this article, we reconstruct a climatic niche of scaly tree ferns (Cyatheaceae) using a rigorous analytical procedure which combines climatic niche modelling with reconstruction of continuous characters given a phylogenetic hypothesis. To estimate the limits to climatic niches of species, we used climate envelope modelling and ordination. Ancestral climatic niches of species were reconstructed by maximum likelihood and least‐squares analyses. We observed a trend towards niche conservatism with occasional events of niche transformations in scaly tree ferns. We discuss the implications of our study with respect to the potential and limitations for applications of niche modelling to evolutionary studies. We suggest that future studies of evolution of climatic niches could be considerably improved by employing approaches enabling reconstruction of continuous response to climatic gradients. Further progress may also be achieved by exploring models of character evolution other than the Brownian motion model. © 2010 The Linnean Society of London, Botanical Journal of the Linnean Society, 2011, 165 , 1–19.     

Structural analysis of theridiid spider's testicular cyst using 3D reconstruction rendering

A three dimensional reconstruction technique was used for the analysis of a theridiid spider's (Achaearanea tepidariorum) testicular cyst. Although microscopic techniques have greatly improved, most of the information gathered is still based on two‐dimensional images. Particularly in spiders, it is very difficult to count the exact number of sperm in a single cyst, since their spermatogenetic processes takes place within the spherical cysts through the flagellar coiling process. Since morphological features of spider sperm provide detailed information on the whole spermatogenetic processes, we analyzed the exact number of germ cells per cyst in A. tepidariorum through a three‐dimensional image reconstruction technique. For image processing, serially sectioned histological images were scanned using a light microscope and 3D rendering images were reconstructed from these sections. Based on the three dimensional image analysis of the testicular cyst, the number of secondary spermatocytes per cyst was calculated to be 32 (2⁵). Therefore the total number of sperm produced from a single cyst can be calculated as 64 (2⁶), which indicates that a single spermatogonium undergoes four mitotic divisions and an additional two meiotic divisions to produce mature spermatozoa.     

Morpho-Functional Analysis Using Procrustes Superimposition by Static Reference

In conventional geometric morphometric analyses of limb long bones, differences in the evolutionary capacity of articular surfaces and non-articular structures often remain unrecognised. It can be shown that areas of high spatial variance dominate shape data, which is problematic for the functional interpretation of limb long bone shape. We herein introduce Procrustes superimposition by static reference (PSSR), a novel analysis strategy that aims to facilitate morpho-functional inference. This procedure exploits the spatial constraint of some reference structures (in our case, articular surfaces) for the superimposition of other subareas (e.g. muscle attachment sites) in relation to that static reference. PSSR allows for the transformation of raw scan data, enabling researchers to extract geometric models of two- and three-dimensional substructures that cannot effectively be integrated with landmarks. As we demonstrate by a simple model analysis for one muscle attachment site, this procedure can yield measures of direct functional relevance. Multivariate analysis of an extensive set of subareas indicates how this type of data relates to conventional shape coordinates. The shape evolution of xenarthran humeri, which has previously been subject to a detailed study (Milne et al., J Zool 278(1):48–56, 2009), serves as a test case. The concept of a variance-based separation of landmark subsets expands mathematical methods by incorporating knowledge about evolutionary constraints. PSSR could therefore find application far beyond the intuitive case study of long bone shape.     

The effect of sample size on the accuracy of species distribution models: considering both presences and pseudo‐absences or background sites

Most high‐performing species distribution modelling techniques require both presences, and either absences or pseudo‐absences or background points. In this paper, we explore the effect of sample size, towards developing improved strategies for modelling. We generated 1800 virtual species with three levels of prevalence using ten modelling techniques, while varying the number of training presences (NTP) and the number of random points (NRP representing pseudo‐absences or background sites). For five of the ten modelling techniques we built two versions of models: one with an equal total weight (ETW) setting where the total weight for pseudo‐absence is equivalent to the total weight for presence, and another with an unequal total weight (UTW) setting where the total weight for pseudo‐absence is not required to be equal to the total weight for presence. We compared two strategies for NRP: a small multiplier strategy (i.e. setting NRP at a few times as large as NTP), and a large number strategy (i.e. using numerous random points). We produced ensemble models (by averaging the predictions from 30 models built with the same set of training presences and different sets of random points in equivalent numbers) for three NTP magnitudes and two NRP strategies. We found that model accuracy altered as NRP increased with four distinct patterns of performance: increasing, decreasing, arch‐shaped and horizontal. In most cases ETW improved model performance. Ensemble models had higher accuracy than the corresponding single models, and this improvement was pronounced when NTP was low. We conclude that a large NRP is not always an appropriate strategy. The best choice for NRP will depend on the modelling techniques used, species prevalence and NTP. We recommend building ensemble models instead of single models, using the small multiplier strategy for NRP with ETW, especially when only a small number of species presence records are available.     

Left‐right asymmetry in the chick embryo requires core planar cell polarity protein Vangl2

Consistent left‐right patterning is a fascinating and biomedically important problem. In the chick embryo, it is not known how cells determine their position (left or right) relative to the primitive streak, which is required for subsequent asymmetric gene expression cascades. We show that the subcellular localization of Vangl2, a core planar cell polarity (PCP) protein, is consistently polarized, giving cells in the blastoderm a vector pointing toward the primitive streak. Moreover, morpholino‐mediated loss‐of‐function of Vangl2 by electroporation into chicks at very early stages randomizes the normally left‐sided expression of Sonic hedgehog. Strikingly, Vangl2 morpholinos also induce a desynchronization of asymmetric gene expression within the left and right domains of Hensen's node. These data reveal the existence of polarized planar cell polarity protein localization in gastrulating chick and demonstrate that the PCP pathway is functionally required for normal asymmetry in the chick upstream of Sonic hedgehog. These data suggest a new and widely applicable class of models for the spread and coordination of left‐right patterning information in the embryonic blastoderm. genesis 47:719–728, 2009. © 2009 Wiley‐Liss, Inc.     

Quantitative study on exact reconstruction sampling condition by verifying solution uniqueness in limited-view CT

In limited-view computed tomography reconstruction, iterative image reconstruction with sparsity-exploiting methods, such as total variation (TV) minimization, inspired by compressive sensing, potentially claims large reductions in sampling requirements. However, a quantitative notion of this claim is non-trivial because of the ill-defined reduction in sampling achieved by the sparsity-exploiting method. In this paper, exact reconstruction sampling condition for limited-view problem is studied by verifying the uniqueness of solution in TV minimization model. Uniqueness is tested by solving a convex optimization problem derived from the sufficient and necessary condition of solution uniqueness. Through this method, the sufficient sampling number of exact reconstruction is quantified for any fixed phantom and settled geometrical parameter in the limited-view problem. This paper provides a reference to quantify the sampling condition. Three phantoms are tested to study the sampling condition of limited view exact reconstruction in this paper. The experiment results show the quantified sampling number and indicate that an object would be accurately reconstructed as the scanning range becomes narrower by increasing sampling number. The increased samplings compensate for the deficiency of the projection angle. However, the lower bound of the scanning range corresponding to three different phantoms are presented, in which an exact reconstruction cannot be obtained once the projection angular is narrowed to this extent no matter how to increase sampling.