The value of an integrated approach for understanding the neocortex by combining functional characterization of single neuron activity with the underlying circuit architecture has been understood since the dawn of modern neuroscience. However, in practice, anatomical connectivity and physiology have been studied mostly separately. Following in the footsteps of previous studies that have combined physiology and anatomy in the same tissue, here we present a unique functional connectomics dataset that contains calcium imaging of an estimated 75,000 neurons from primary visual cortex (VISp) and three higher visual areas (VISrl, VISal and VISlm), that were recorded while a mouse viewed natural movies and parametric stimuli. The functional data were co-registered with electron microscopy (EM) data of the same volume which were automatically segmented, reconstructing more than 200,000 cells (neuronal and non-neuronal) and 524 million synapses. Subsequent proofreading of some neurons in this volume yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections. The largest proofread excitatory axon reached a length of 19 mm and formed 1,893 synapses, while the largest inhibitory axon formed 10,081 synapses. Here we release this dataset as an open access resource to the scientific community including a set of analysis tools that allows easy data access, both programmatically and through a web user interface.

In the preceding section various strategies to interdict postreperfusion inflammatory injury of the myocardium were proposed; effectively the strategies were aimed at specific targets such as stimuli which control cell motility, mechanisms of alteration of cell phenotype, and the induction of cell adhesion and proliferation. It is of interest to see how similar these targets would be if one were to attempt a cell biological approach to vascular injury which results in subintimal hyperplasia. In the latter, cells in the media adopt a phenotype which allows cell migration in the direction of a gradient (presumably chemotactic) which directs them to the subintima which is the site of injury. This motility is associated with the expression in these cells of non-muscle myosin and beta actin, both of which are implicated in the motility of leucocytes. Another similarity between acute inflammation and subintimal hyperplasia relates to the role of cellular adhesion as an important determinant of cell motility. As reviewed above, leucocyte motility involves cell adhesion mediated by a class of molecules termed leucocyte integrins (beta 2 integrins) which vary in their alpha subunits and share CD18 as a common beta subunit (CD11a/CD18 = LFA-1, CD11b/CD18 = Mac-1). The activation and inactivation of these integrins is associated with a high and low affinity state, and motility is effected by the cycling of high and low affinity states as well as by cytoskeleton mediated redistribution of adhesion molecules on the leucocyte membrane. In similar fashion, the migration of medial cells and macrophages to the subintima is associated with specific adhesion to extracellular matrix. This adhesion is mediated by similar classes of integrins containing varying alpha subunits and common beta subunits (in this case beta 1 or beta 3) that have been also shown to undergo activation and inactivation cycles yielding high and low affinity states. The similarities between these integrin mediated adhesion events in leucocytes and in the vascular cells is further emphasised by the fact that leucocytes also contain beta 1 integrins; in fact monocytes and T-lymphocytes express a beta 1 integrin (VLA-4) which supports transmigration out of the vascular space via its interaction with VCAM-1 as an alternative to beta 2 integrin-ICAM-1 adhesion. Substantial evidence suggests that integrin mediated adhesion also functions as a transducer of cell secretion of matrix proteins, growth factors, and cytokines from smooth muscle cells, tissue macrophages, transmigrated leucocytes, and endothelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Axon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons.

Sociopolitical development theory asserts that critical social analysis informs prosocial behaviors. We suggest that one aspect of Black adolescents’ critical social analysis development is an oppression analysis, in which Black adolescents consider (1) the importance of race to they are, (2) their personal feelings about their racial group, and (3) the experience of oppression for minority groups. The current study examined oppression analysis as a latent construct among a sample of 265 Black male adolescents in Grades 7 to 10 from three suburban districts in the Midwestern United States. Structural equation modeling revealed that received parental racial pride messages, but not school-based discrimination experiences, predicted Black male adolescents’ oppression analysis. An oppression analysis and school-based discrimination had direct effects on prosocial behaviors. Racial pride messages had an indirect effect on prosocial behaviors through oppression analysis. In addition, an oppression analysis had an indirect effect on prosocial behaviors through social-emotional skills. This research offers insight into the role of Black boys’ critical social analysis among individual and contextual factors in facilitating positive developmental outcomes.

The initial outgrowth of neurites from chick sympathetic neurons grown in vitro was investigated by time-lapse microscopy with laser-scanning and conventional light microscopes. Video-enhanced contrast, differential interference contrast optics (VECDIC) were used to monitor movements of neuronal cytoplasm, as well as the movements of small beads attached to the surface membrane, and interference reflection microscopy (IRM) was used to determine the concomitant pattern of attachment to the growth substrate (polyornithine or laminin). Related changes in the distributions of actin filaments, microtubules, and neurofilaments were determined by fluorescence labeling methods. Neurite formation on both substrates entailed invasion of the actin cores of filopodia by cytoplasm containing microtubules and neurofilaments. Small beads attached to the surface membrane surrounding the cytoplasm moved outward simultaneously with the cytoplasm. Cytoplasm invaded filopodia of neurons plated on laminin soon after attachment to the substrate or, for neurons generated in vitro, within as little as 3 min after cytokinesis. However, cytoplasm invaded filopodia of neurons grown on polyornithine only when they contacted a three-dimensional object such as another cell or a large, polyornithine-coated polystyrene bead. The observation that adhesion of filopodia to polyornithine-coated beads can initiate neurite formation is inconsistent with the commonly held view that neurite formation requires adhesion mediated by specific cell adhesion molecules. Simultaneous IRM and DIC imaging showed that cytoplasm invaded filopodia when only their tips were closely apposed to a substrate but not when they were closely apposed to a substrate along their entire lengths. These findings help to elucidate the mechanisms by which interactions between the cytoskeleton and the growth substrate initiate and produce the neuronal movements that lead to the formation of neurites.

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The objective of this study was to evaluate prospectively the outcome of 21 clinical patients treated with triple pelvic osteotomies during the year following surgery. Specific aims included documenting the time of and extent of improved limb function as measured by force plate analysis, evaluating the progression of degenerative joint disease (DJD) in the treated and untreated coxofemoral joints, and determining whether or not triple pelvic osteotomy resulted in degenerative joint changes in the ipsilateral stifle and hock. Twelve dogs were treated unilaterally and nine dogs were treated bilaterally with triple pelvic osteotomies. There were no differences in mean anteversion angles, angles of inclination, or preoperative DJD between treated hips and untreated hips. Degenerative joint disease progressed significantly in all hips regardless of treatment. Two cases developed hyperextension of their hocks after the triple pelvic osteotomies. However, no radiographic evidence of DJD was observed for any of the stifles or hocks at any observation time. A significant increase in vertical peak force (VPF) scores was noted for treated legs by two-to-three months after surgery, which continued over time. Untreated legs did not show a significant change in VPF scores over time. No differences were found in progression to higher scores when unilaterally treated legs, first-side treated legs, and second-side treated legs were compared.

Black male adolescents face unique barriers in schools that may contribute to racial disparities in educational outcomes. Their social-cognitive strengths, however, influence their confidence to be academically successful despite these barriers. This study explored whether racial academic stereotypes and racial centrality were associated with and predicted school efficacy among 103 urban Black male adolescents. Findings indicated that racial centrality had the strongest relationship with and was the strongest predictor of school efficacy. Youth mentoring programs and educators who work with urban Black male adolescents play a key role in promoting and shaping their efficacious beliefs toward their academic success.