Dynamic Shape Synthesis in Posterior Inferotemporal Cortex

SummaryHow does the brain synthesize low-level neural signals for simple shape parts into coherent representations of complete objects? Here, we present evidence for a dynamic process of object part integration in macaque posterior inferotemporal cortex (IT). Immediately after stimulus onset, neural responses carried information about individual object parts (simple contour fragments) only. Subsequently, information about specific multipart configurations emerged, building gradually over the course of ∼60 ms, producing a sparser and more explicit representation of object shape. We show that this gradual transformation can be explained by a recurrent network process that effectively compares parts signals across neurons to generate inferences about multipart shape configurations

Visual Attention: Bottom-Up Versus Top-Down

AbstractVisual attention is attracted by salient stimuli that ‘pop out’ from their surroundings. Attention can also be voluntarily directed to objects of current importance to the observer. What happens in the brain when these two processes interact

Twenty Years in the Trenches: A Fight for Equitable and Adequate School Funding in Ohio

Abstract This single case study examined the perceptions of William L. “Bill” Phillis, the Executive Director of the Ohio Coalition for Equity and Adequacy of School Funding, concerning an unconstitutional funding model, subsequent sociopolitical barriers, and their impact on students and school districts from underprivileged socioeconomic background within the context of the DeRolph v. State of Ohio legal battle. This research adds to the extant literature on the educational implications of the property tax and foundation model of school funding. As well, we discuss William’s insights regarding the politics, nature, and development of the current state of public school financing in Ohio. There were four emergent themes: sociopolitical sentiment and rhetoric, the plight of poorer districts, seeing a shared vision, and constitutional language and responsibility. Key findings from the study provide awareness to foster civic responsibility to effect change for inequitable and inadequate funding formulae, to encourage politicians to abandon political agendas over constitutional will, and for educators and students alike to continually advocate for a reformed system of school funding. These findings are especially relevant among under-resourced districts such as those in Appalachian Ohio. Key words: advocacy, educational leadership, equity, foundation model, school funding, single-case stud

A Sparse Object Coding Scheme in Area V4

SummarySparse coding has long been recognized as a primary goal of image transformation in the visual system [1–4]. Sparse coding in early visual cortex is achieved by abstracting local oriented spatial frequencies [5] and by excitatory/inhibitory surround modulation [6]. Object responses are thought to be sparse at subsequent processing stages [7, 8], but neural mechanisms for higher-level sparsification are not known. Here, convergent results from macaque area V4 neural recording and simulated V4 populations trained on natural object contours suggest that sparse coding is achieved in midlevel visual cortex by emphasizing representation of acute convex and concave curvature. We studied 165 V4 neurons with a random, adaptive stimulus strategy to minimize bias and explore an unlimited range of contour shapes. V4 responses were strongly weighted toward contours containing acute convex or concave curvature. In contrast, the tuning distribution in nonsparse simulated V4 populations was strongly weighted toward low curvature. But as sparseness constraints increased, the simulated tuning distribution shifted progressively toward more acute convex and concave curvature, matching the neural recording results. These findings indicate a sparse object coding scheme in midlevel visual cortex based on uncommon but diagnostic regions of acute contour curvature

RAPID PUBLICATION Responses in Area V4 Depend on the Spatial Relationship Between Stimulus and Attention

SUMMARY AND CONCLUSIONS I. We studied the spatial interaction between stimulus and attention in macaque area V4. Monkeys were required to fixate a small spot while continuously attending to a ring-shaped target within a large array of identical rings. Meanwhile, the response of the V4 cell under study was tested by flashing behaviorally irrelevant bar stimuli in the cell's classical receptive field (CRF). The location of the attended ring was varied across four positions surrounding the CRF, and the location of the bar stimulus was varied across five positions spanning the CRF. 2. Response strength depended on two aspects of the spatial relationship between the stimulus driving the cell (the bar) and the position of attention (the target ring). First, for 49% of the cells studied, responses were greater for bar stimuli near the attended ring; i.e., the receptive field profile shifted toward the attentional focus. Second, for 84% of the cells, the overall response level depended on the direction in which attention lay relative to the stimulus in the CRF (e.g., to the left, right, above, or below ) . 3. This study confirms a key prediction of spatial models of attention, which postulate enhanced processing of all stimuli near the attentional focus. It also introduces the novel finding that responses are influenced by the relative direction of attention. This result indicates that area V4 carries information about the spatial relationship between visual stimuli and attention

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

A Happy Abundance : Tales, Memoirs and More Past and Present in Wayne, Maine

https://digitalmaine.com/wayne_books/1002/thumbnail.jp

Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Background. We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods. Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. Results. Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion. Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. © 2010 Christiansen et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

A key aspect of nearly all single-cell sequencing experiments is dissociation of intact tissues into single-cell suspensions. While many protocols have been optimized for optimal cell yield, they have often overlooked the effects that dissociation can have on ex vivo gene expression. Here, we demonstrate that use of enzymatic dissociation on brain tissue induces an aberrant ex vivo gene expression signature, most prominently in microglia, which is prevalent in published literature and can substantially confound downstream analyses. To address this issue, we present a rigorously validated protocol that preserves both in vivo transcriptional profiles and cell-type diversity and yield across tissue types and species. We also identify a similar signature in postmortem human brain single-nucleus RNA-sequencing datasets, and show that this signature is induced in freshly isolated human tissue by exposure to elevated temperatures ex vivo. Together, our results provide a methodological solution for preventing artifactual gene expression changes during fresh tissue digestion and a reference for future deeper analysis of the potential confounding states present in postmortem human samples