Shape Processing across Lateral Occipital Cortex

There are two predominant means of identifying visual areas in the human brain; retinotopy (exploiting maps of the visual field) and localisers (exploiting functional selectivity). This thesis aimed to bridge those two approaches, assessing the roles of LO-1 and LO-2; two retinotopically-defined regions that show overlap with the functionally-defined (shape selective) Lateral Occipital Complex (LOC). More generally, we asked what is the nature of the shape representation across Lateral Occipital cortex? We first probed the functional roles of LO-1 and LO-2, finding that LO-2 is the more shape-sensitive region of the pair and will respond to second order shape stimuli, whereas LO-1 may process more local cues (perhaps orientation information). Our later work then assessed neural shape representations across visual cortex, identifying two discrete representations; ‘Shape-profile’ (essentially retinotopic responses) and ‘Shape-complexity’ (responses based upon the complexity of a shape’s contour). The latter dimension captured variance in LOC, and surprisingly LO-2. This indicates that even explicit visual field maps can respond to non‑retinotopic attributes such as curvature complexity. Intriguingly, a transition between dimensions occurred around LO-1 and LO-2. Finally, we explicitly tested whether the ‘Shape-complexity’ representation may be curvature based. Our results implied that radial shape protrusions are highly salient features for Lateral Occipital cortex, but it is not necessarily the points of maximal curvature that are being responded to. Instead, we hypothesise that it is the convergent lines comorbid with curvature that neurons may be attuned to, as such lines likely represent the most salient or characteristic features in a given shape. In sum, we argue for an evolving shape representation across visual cortex, with some degree of shape sensitivity first emerging around LO-1 and LO-2. These maps may then be acting as preliminary processing stages for more selective shape tunings in LOC

Insulin processing and action in adipocytes: evidence for generation of insulin-containing vesicles by leupeptin and monensin

AbstractIncubation of adipocytes with 125I-insulin plus leupeptin or monensin, but not chloroquine, resulted in the appearance of a novel peak of 125I-insulin (modal density about 1.20 gml) on density gradient centrifugation; the appearance of the peak depended on the presence of specific insulin receptors on the cell surface. The fractions comprising this peak contained vesicles, probably originating from the Golgi apparatus, and dit not appear to be contaminated with lysosomes, mitochondria or plasma membrane. Entrapment of insulin in these vesicles per se did not prevent the activation of glucose transport, acetyl-CoA carboxylase or pyruvate dehydrogenase by insulin

Multivariate Patterns in the Human Object-Processing Pathway Reveal a Shift from Retinotopic to Shape Curvature Representations in Lateral Occipital Areas, LO-1 and LO-2

Representations in early visual areas are organized on the basis of retinotopy, but this organizational principle appears to lose prominence in the extrastriate cortex. Nevertheless, an extrastriate region, such as the shape-selective lateral occipital cortex (LO), must still base its activation on the responses from earlier retinotopic visual areas, implying that a transition from retinotopic to “functional” organizations should exist. We hypothesized that such a transition may lie in LO-1 or LO-2, two visual areas lying between retinotopically defined V3d and functionally defined LO. Using a rapid event-related fMRI paradigm, we measured neural similarity in 12 human participants between pairs of stimuli differing along dimensions of shape exemplar and shape complexity within both retinotopically and functionally defined visual areas. These neural similarity measures were then compared with low-level and more abstract (curvature-based) measures of stimulus similarity. We found that low-level, but not abstract, stimulus measures predicted V1–V3 responses, whereas the converse was true for LO, a double dissociation. Critically, abstract stimulus measures were most predictive of responses within LO-2, akin to LO, whereas both low-level and abstract measures were predictive for responses within LO-1, perhaps indicating a transitional point between those two organizational principles. Similar transitions to abstract representations were not observed in the more ventral stream passing through V4 and VO-1/2. The transition we observed in LO-1 and LO-2 demonstrates that a more “abstracted” representation, typically considered the preserve of “category-selective” extrastriate cortex, can nevertheless emerge in retinotopic regions

Modeling first impressions from highly variable facial images

The research was funded in part by an Economic and Social Research Council Studentship ES/I900748/1 (to C.A.M.S.).Peer reviewedPublisher PD

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Assessing the structure of the posterior visual pathway in bilateral macular degeneration

Abstract Macular degeneration (MD) embodies a collection of disorders causing a progressive loss of central vision. Cross-sectional MRI studies have revealed structural changes in the grey and white matter in the posterior visual pathway in MD but there remains a need to understand how such changes progress over time. To that end we assessed the posterior pathway, characterising the visual cortex and optic radiations over a ~ 2-year period in MD patients and controls. We performed cross-sectional and longitudinal analysis of the former. Reduced cortical thickness and white matter integrity were observed in patients compared to controls, replicating previous findings. While faster, neither the rate of thinning in visual cortex nor the reduction in white matter integrity during the ~ 2-year period reached significance. We also measured cortical myelin density; cross-sectional data showed this was higher in patients than controls, likely as a result of greater thinning of non-myelinated tissue in patients. However, we also found evidence of a greater rate of loss of myelin density in the occipital pole in the patient group indicating that the posterior visual pathway is at risk in established MD. Taken together, our results revealed a broad decline in grey and white matter in the posterior visual pathway in bilateral MD; cortical thickness and fractional anisotropy show hints of an accelerated rate of loss also, with larger effects emerging in the occipital pole

The Lantern Vol. 4, No. 1, December 1935

• A Challenge to All • The Tree • College With a Purpose • Midnight Clouds • Exultation • Pagan Festival • Ah Childhood! • From Brain to Brawn • Pictures in the Sky • Winds • In Absolution • Clouds in a Hot, Red Sky • Out of Douche and Latin • Satan Calls a Conference • Emptiness • A Portly Gentleman Intrudeshttps://digitalcommons.ursinus.edu/lantern/1014/thumbnail.jp

Assessing functional reorganization in visual cortex with simulated retinal lesions

Macular degeneration (MD) causes central vision loss, removing input to corresponding representations in the primary visual cortex. There is disagreement concerning whether the cortical regions deprived of input can remain responsive, and the source of reported cortical responses is still debated. To simulate MD in controls, normally sighted participants viewed a bright central disk to adapt the retina, creating a transient 'retinal lesion' during a functional MRI experiment. Participants viewed blocks of faces, scrambled faces and uniform grey stimuli, either passively or whilst performing a one-back task. To assess the impact of the simulated lesion, participants repeated the paradigm using a more conventional mean luminance simulated scotoma without adaptation. Our results suggest our attempt to create a more realistic simulation of a lesion did not impact on responses in the representation of the simulated lesion. While most participants showed no evidence of stimulus-driven activation within the lesion representation, a few individuals (22%) exhibited responses similar to a participant with juvenile MD who completed the same paradigm (without adaptation). Reliability analysis showed that responses in the representation of the lesion were generally consistent irrespective of whether positive or negative. We provide some evidence that peripheral visual stimulation can also produce responses in central representations in controls while performing a task. This suggests that the 'signature of reorganization of visual processing', is not found solely in patients with retinal lesions, consistent with the idea that activity may be driven by unmasked top-down feedback

Prehospital 12-Lead Electrocardiogram within 60 Minutes Differentiates Proximal versus Nonproximal Left Anterior Descending Artery Myocardial Infarction

<p>Introduction: Acute anterior myocardial infarctions caused by proximal left anterior descending (LAD) artery occlusions are associated with a higher morbidity and mortality. Early identification of high-risk patients via the 12-lead electrocardiogram (ECG) could assist physicians and emergency response teams in providing early and aggressive care for patients with anterior ST-elevation myocardial infarctions (STEMI). Approximately 25% of US hospitals have primary percutaneous coronary intervention (PCI) capability for the treatment of acute myocardial infarctions. Given the paucity of</p> <p>hospitals capable of PCI, early identification of more severe myocardial infarction may prompt</p> <p>emergency medical service routing of these patients to PCI-capable hospitals. We sought to determine if the 12 lead ECG is capable of predicting proximal LAD artery occlusions.</p> <p>Methods: In a retrospective, post-hoc analysis of the Pre-Hospital Administration of Thrombolytic Therapy with Urgent Culprit Artery Revascularization pilot trial, we compared the ECG findings of</p> <p>proximal and nonproximal LAD occlusions for patients who had undergone an ECG within 180 minutes of symptom onset.</p> <p>Results: In this study, 72 patients had anterior STEMIs, with ECGs performed within 180 minutes of symptom onset. In patients who had undergone ECGs within 60 minutes (n¼35), the mean sum of ST elevation (STE) in leads V1 through V6 plus ST depression (STD) in leads II, III, and aVF was 19.2 mm for proximal LAD occlusions and 11.7 mm for nonproximal LAD occlusions (P¼0.007). A sum STE in V1 through V6 plus STD in II, III, and aVF of at least 17.5 mm had a sensitivity of 52.3%, specificity of 92.9%, positive predictive value of 91.7%, and negative predictive value of 56.5% for proximal LAD occlusions. When the ECG was performed more than 60 minutes after symptom onset (n¼37), there was no significant difference in ST-segment deviation between the 2 groups.</p> <p>Conclusion: The sum STE (V1-V6) and STD (II, III, aVF) on a 12-lead ECG can be used to predict proximal LAD occlusions if performed within the first hour of symptom onset. This should be considered a high-risk finding and may prompt prehospital direction of such patients to PCI-capable hospitals. [West J Emerg Med. 2011;12(4):408–413.]</p

Characterization of an Aggregated Three-Dimensional Cell Culture Model by Multimodal Mass Spectrometry Imaging

Mass spectrometry imaging (MSI) is an established analytical tool capable of defining and understanding complex tissues by determining the spatial distribution of biological molecules. Three-dimensional (3D) cell culture models mimic the pathophysiological environment of in vivo tumors and are rapidly emerging as a valuable research tool. Here, multimodal MSI techniques were employed to characterize a novel aggregated 3D lung adenocarcinoma model, developed by the group to mimic the in vivo tissue. Regions of tumor heterogeneity and the hypoxic microenvironment were observed based on the spatial distribution of a variety of endogenous molecules. Desorption electrospray ionization (DESI)-MSI defined regions of a hypoxic core and a proliferative outer layer from metabolite distribution. Targeted metabolites (e.g., lactate, glutamine, and citrate) were mapped to pathways of glycolysis and the TCA cycle demonstrating tumor metabolic behavior. The first application of imaging mass cytometry (IMC) with 3D cell culture enabled single-cell phenotyping at 1 μm spatial resolution. Protein markers of proliferation (Ki-67) and hypoxia (glucose transporter 1) defined metabolic signaling in the aggregoid model, which complemented the metabolite data. Laser ablation inductively coupled plasma (LA-ICP)-MSI analysis localized endogenous elements including magnesium and copper, further differentiating the hypoxia gradient and validating the protein expression. Obtaining a large amount of molecular information on a complementary nature enabled an in-depth understanding of the biological processes within the novel tumor model. Combining powerful imaging techniques to characterize the aggregated 3D culture highlighted a future methodology with potential applications in cancer research and drug development