Highlights d Three-dimensional morphologies of proprioceptive dendrites during movement are described d Drosophila larval proprioceptive neurons are tuned to direction of locomotion d ddaE responds to forward locomotion while ddaD responds to backward locomotion d Tmc channels are required for sensing movement direction

Current therapeutic angiogenesis strategies are focused on the development of biologically responsive scaffolds that can deliver multiple angiogenic cytokines and/or cells in ischemic regions. Herein, we report on a novel electrospinning approach to fabricate cytokine-containing nanofibrous scaffolds with tunable architecture to promote angiogenesis. Fiber diameter and uniformity were controlled by varying the concentration of the polymeric (i.e. gelatin) solution, the feed rate, needle to collector distance, and electric field potential between the collector plate and injection needle. Scaffold fiber orientation (random vs. aligned) was achieved by alternating the polarity of two parallel electrodes placed on the collector plate thus dictating fiber deposition patterns. Basic fibroblast growth factor (bFGF) was physically immobilized within the gelatin scaffolds at variable concentrations and human umbilical vein endothelial cells (HUVEC) were seeded on the top of the scaffolds. Cell proliferation and migration was assessed as a function of growth factor loading and scaffold architecture. HUVECs successfully adhered onto gelatin B scaffolds and cell proliferation was directly proportional to the loading concentrations of the growth factor (0–100 bFGF ng/mL). Fiber orientation had a pronounced effect on cell morphology and orientation. Cells were spread along the fibers of the electrospun scaffolds with the aligned orientation and developed a spindle-like morphology parallel to the scaffold's fibers. In contrast, cells seeded onto the scaffolds with random fiber orientation, did not demonstrate any directionality and appeared to have a rounder shape. Capillary formation (i.e. sprouts length and number of sprouts per bead), assessed in a 3-D in vitro angiogenesis assay, was a function of bFGF loading concentration (0 ng, 50 ng and 100 ng per scaffold) for both types of electrospun scaffolds (i.e. with aligned or random fiber orientation).

The nematode Caenorhabditis elegans (C. elegans) is a genetic model widely used to dissect conserved basic biological mechanisms of development and nervous system function. C. elegans locomotion is under complex neuronal regulation and is impacted by genetic and environmental factors; thus, its analysis is expected to shed light on how genetic, environmental, and pathophysiological processes control behavior. To date, computer-based approaches have been used for analysis of C. elegans locomotion; however, none of these is both high resolution and high throughput. We used computer vision methods to develop a novel automated approach for analyzing the C. elegans locomotion. Our method provides information on the position, trajectory, and body shape during locomotion and is designed to efficiently track multiple animals (C. elegans) in cluttered images and under lighting variations. We used this method to describe in detail C. elegans movement in liquid for the first time and to analyze six unc-8, one mec-4, and one odr-1 mutants. We report features of nematode swimming not previously noted and show that our method detects differences in the swimming profile of mutants that appear at first glance similar.

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Hidden Markov random field (HMRF) models are widely used for image segmentation, as they appear naturally in problems where a spatially constrained clustering scheme is asked for. A major limitation of HMRF models concerns the automatic selection of the proper number of their states, i.e., the number of region clusters derived by the image segmentation procedure. Existing methods, including likelihood- or entropy-based criteria, and reversible Markov chain Monte Carlo methods, usually tend to yield noisy model size estimates while imposing heavy computational requirements. Recently, Dirichlet process (DP, infinite) mixture models have emerged in the cornerstone of nonparametric Bayesian statistics as promising candidates for clustering applications where the number of clusters is unknown a priori; infinite mixture models based on the original DP or spatially constrained variants of it have been applied in unsupervised image segmentation applications showing promising results. Under this motivation, to resolve the aforementioned issues of HMRF models, in this paper, we introduce a nonparametric Bayesian formulation for the HMRF model, the infinite HMRF model, formulated on the basis of a joint Dirichlet process mixture (DPM) and Markov random field (MRF) construction. We derive an efficient variational Bayesian inference algorithm for the proposed model, and we experimentally demonstrate its advantages over competing methodologies.

Increasing evidence suggests that therapeutic angiogenesis strategies utilizing cytokines and stem cells are necessary to treat traumatic vascular events such as critical limb ischemia and peripheral artery disease. In this study, basic fibroblast growth factor 2 (FGF-2) and granulocyte-colony stimulating factor (G-CSF) were immobilized in fibrin matrices and codelivered in combination with unfractionated bone marrow cells. Hindlimb ischemia was induced on young (6-7 weeks) Balb/C mice, and fibrin gels containing 100 ng/mL of FGF-2 and G-CSF were implanted adjacent to the ligation points. In addition, 1×10(6) bone marrow (BM) cells were injected into five locations in the ischemic muscle immediately after ligation and artery excision. Hindlimb reperfusion was determined by Laser Doppler Perfusion Imaging and immunohistochemistry for CD31+ and smooth muscle actin-positive cells at 2, 4, and 8 weeks postsurgery to identify capillary formation and maturation. A fluorescent vessel painting technique was also utilized to determine the extent of angiogenesis and arteriogenesis in the hindlimb at 8 weeks postsurgery. The codelivery of FGF-2 and G-CSF in combination with BM cells led to enhanced therapeutic recovery in critical limb ischemia Balb/C mice after 8 weeks of treatment with 87.2% blood flow recovery and a significant increase (p<0.05) in capillary formation in comparison to growth factor delivery or BM cell administration alone.

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FK506-binding protein 51 (encoded by Fkpb51) has been associated with stress-related mental illness. To identify its function, we studied the morphological consequences of Fkbp51 deletion. Arti cial Intelligence-assist morphological analysis identi ed that Fkbp51 knock-out (KO) mice possess more elongated CA and DG but shorter in height in coronal section when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls, pharmacological manipulation experiments suggest that this may occur through regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support that FKBP51 regulates microtubule-associated protein expression. Furthermore, in the absence of differences in mRNA expression, Fkbp51 KO hippocampus exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory of Parkin by FKBP51 and signi cance of their interaction on disease onset.