Neha Uppal

Stabilization of Enzymes in Silk Films

Material systems are needed that promote stabilization of entrained molecules, such as enzymes or therapeutic proteins, without destroying their activity. We demonstrate that the unique structure of silk fibroin protein, when assembled into the solid state, establishes an environment that is conducive to the stabilization of entrained proteins. Enzymes (glucose oxidase, lipase, and horseradish peroxidase) entrapped in these films over 10 months retained significant activity, even when stored at 37 degrees C, and in the case of glucose oxidase did not lose any activity. Further, the mode of processing of the silk protein into the films could be correlated to the stability of the enzymes. The relationship between processing and stability offers a large suite of conditions within which to optimize such stabilization processes. Overall, the techniques reported here result in materials that stabilize enzymes to an extent, without the need for cryoprotectants, emulsifiers, covalent immobilization, or other treatments. Further, these systems are amenable to optical applications and characterization, environmental distribution without refrigeration, are ingestible, and offer potential use in vivo, because silk materials are biocompatible and FDA approved, degradable with proteases, and currently used in biomedical devices.

Insoluble and Flexible Silk Films Containing Glycerol

We directly prepared insoluble silk films by blending with glycerol and avoiding the use of organic solvents. The ability to blend a plasticizer like glycerol with a hydrophobic protein like silk and achieve stable material systems above a critical threshold of glycerol is an important new finding with importance for green chemistry approaches to new and more flexible silk-based biomaterials. The aqueous solubility, biocompatibility, and well-documented use of glycerol as a plasticizer with other biopolymers prompted its inclusion in silk fibroin solutions to assess impact on silk film behavior. Processing was performed in water rather than organic solvents to enhance the potential biocompatibility of these biomaterials. The films exhibited modified morphologies that could be controlled on the basis of the blend composition and also exhibited altered mechanical properties, such as improved elongation at break, when compared with pure silk fibroin films. Mechanistically, glycerol appears to replace water in silk fibroin chain hydration, resulting in the initial stabilization of helical structures in the films, as opposed to random coil or beta-sheet structures. The use of glycerol in combination with silk fibroin in materials processing expands the functional features attainable with this fibrous protein, and in particular, in the formation of more flexible films with potential utility in a range of biomaterial and device applications.

Von Economo neurons: Clinical and evolutionary perspectives

Von Economo neurons (VENs) are projection neurons located in layer V of the anterior cingulate and frontoinsular cortex that are increasingly attracting the interest of the scientific community as many studies point to their involvement in neuropsychiatric conditions. In this review we provide a critical appraisal of both historic and recent literature on VENs that highlights the importance of clinicopathological studies in areas of research where animal models are not available. Current data suggest that VENs represent a specialized neuronal type with a characteristic morphology that evolved only in a restricted number of species most likely from a population of pyramidal neurons present in ancestral mammals in the context of specific adaptive pressures. VENs, which evolved among primates only in the hominoid lineage, are particularly vulnerable in neuropsychiatric conditions characterized by deficits in social skills and emotional function. Moreover, recent evidence on the neurochemical profile, morphologic features, and laminar and regional distribution of VENs suggests that this intriguing neuronal population could be critically involved in autonomic regulation.

Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism

Autism is a neurodevelopmental disorder characterized by deficits in social interaction and social communication, as well as by the presence of repetitive and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior frontal cortex, which are involved in language processing, imitation function, and sociality processing networks, have been implicated in this complex disorder. Using a stereologic approach, this study aims to explore the presence of neuropathological differences in areas 44 and 45 in patients with autism compared to age- and hemisphere-matched controls. Based on previous evidence in the fusiform gyrus, we expected to find a decrease in the number and size of pyramidal neurons as well as an increase in volume of layers III, V, and VI in patients with autism. We observed significantly smaller pyramidal neurons in patients with autism compared to controls, although there was no difference in pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in the pathology of autism. Our results also support previous studies that have shown specific cellular neuropathology in autism with regionally specific reduction in neuron size, and provide further evidence for the possible involvement of the mirror neuron system, as well as impairment of neuronal networks relevant to communication and social behaviors, in this disorder.

Neuropathology of the Anterior Midcingulate Cortex in Young Children With Autism

Abstract The anterior cingulate cortex, which is involved in cognitive and affective functioning, is important in investigating disorders in which individuals exhibit impairments in higher-order functions. In this study, we examined the anterior midcingulate cortex (aMCC) at the cellular level in patients with autism and in controls. We focused our analysis on layer V of the aMCC because it contains von Economo neurons, specialized cells thought to be involved in emotional expression and focused attention. Using a stereologic approach, we determined whether there were neuropathologic changes in von Economo neuron number, pyramidal neuron number, or pyramidal neuron size between diagnostic groups. When the groups were subdivided into young children and adolescents, pyramidal neuron and von Economo neuron numbers positively correlated with autism severity in young children, as measured by the Autism Diagnostic Interview—Revised. Young children with autism also had significantly smaller pyramidal neurons than their matched controls. Because the aMCC is involved in decision-making during uncertain situations, decreased pyramidal neuron size may reflect a potential reduction in the functional connectivity of the aMCC.

Neuropathology of the posteroinferior occipitotemporal gyrus in children with autism

BackgroundWhile most neuropathologic studies focus on regions involved in behavioral abnormalities in autism, it is also important to identify whether areas that appear functionally normal are devoid of pathologic alterations. In this study we analyzed the posteroinferior occipitotemporal gyrus, an extrastriate area not considered to be affected in autism. This area borders the fusiform gyrus, which is known to exhibit functional and cellular abnormalities in autism.FindingsNo studies have implicated posteroinferior occipitotemporal gyrus dysfunction in autism, leading us to hypothesize that neuropathology would not occur in this area. We indeed observed no significant differences in pyramidal neuron number or size in layers III, V, and VI in seven pairs of autism and controls.ConclusionsThese findings are consistent with the hypothesis that neuropathology is unique to areas involved in stereotypies and social and emotional behaviors, and support the specificity of the localization of pathology in the fusiform gyrus.

Von Economo Neurons

Von Economo neurons (VENs) are projection neurons located in layer V of the anterior cingulate and frontoinsular cortex that have recently attracted the interest of the neuroscience community. Several studies have pointed to their complex evolutionary history and to their involvement in many neurological and psychiatric illnesses. Current evidence suggests that VENs represent a specialized neuronal type with a characteristic morphology that is present in several species across mammalian orders and most likely represent a population of pyramidal neurons present in ancestral mammals in the context of specific adaptive pressures. Within primates, VENs are observed only in the anthropoid lineage and are particularly vulnerable in human neuropsychiatric conditions characterized by deficits in social skills and emotional function. Moreover, recent evidence on the neurochemical phenotype, morphological features, and laminar and regional distribution of VENs suggests that this intriguing neuronal population could be critically involved in autonomic regulation.

Discrete Cortical Neuropathology in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are the most inheritable of psychiatric disorders, although precise genetic alterations have only been identified in about 20% of cases. The major impact of the condition on the development and social integration of affected children has led to a marked increase in research efforts focusing on the possible roles of neuropathological processes underlying it. This chapter provides an overview of the literature on the cortical neuropathology of ASD. Postmortem studies are pivotal for cell-level exploration, especially in the context of brain regions which consistently show altered patterns of activation in functional magnetic resonance imaging studies. Cortical alterations known to occur in ASD are reviewed, including abnormalities in neuronal morphology, neurotransmitter systems, and cytoarchitectural organization. We focus in particular on abnormalities of the prefrontal cortex, the inferior frontal cortex, fusiform gyrus, the insular cortex, the cingulate cortex, and the hippocampus.

Erratum to: Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism

The online version of the original article can be found underdoi:10.1007/s00401-012-0976-6.S. Jacot-Descombes N. Uppal B. Wicinski M. Santos P. R. Hof (&)Fishberg Department of Neuroscience, Mount Sinai Schoolof Medicine, One Gustave L. Levy Place, Box 1065,New York, NY 10029, USAe-mail: patrick.hof@mssm.eduJ. SchmeidlerDepartment of Psychiatry, Mount Sinai School of Medicine,New York, NY 10029, USAN. UppalSeaver Autism Center, Mount Sinai School of Medicine,New York, NY 10029, USAS. Jacot-Descombes M. Santos P. GiannakopoulosDepartment of Mental Health and Psychiatry, UniversityHospitals and School of Medicine, Geneva, SwitzerlandP. GiannakopoulosDepartment of Psychiatry, University of Lausanne Schoolof Medicine, Lausanne, SwitzerlandH. HeinsenMorphological Brain Research Unit, Department of Psychiatry,Psychosomatics, and Psychotherapy, University of Wuerzburg,Wuerzburg, GermanyC. SchmitzDepartment of Neuroanatomy, School of Medicine,Ludwig-Maximilians University, Munich, Germany