Experience-dependent dendrite remodeling of GABAergic interneurons in the adult visual cortex

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 85-97).An ever increasing amount of evidence is demonstrating that structural plasticity is a diverse and ongoing feature that contributes to plasticity in the adult brain. It was previously shown that dendritic arbors of inhibitory interneurons in superficial layer 2/3 can remodel in the adult cortex. Here, we investigated the role of these structural rearrangements during experience-dependent adult plasticity. Using in vivo two photon imaging, we monitored intemeuron dendritic branch tip remodeling in response to changes in visual experience in the adult mouse visual cortex. We find that branch tip dynamics are induced by novel experiences in a stimulus-specific manner. Visual deprivation produces rearrangements that are circuit-specific and are different for branch tips extending into LI or L2/3. The weakening of dendritic input onto these cells functions to reduce levels of inhibition in local cortical circuits. This reduced inhibitory tone provides more salience to remaining instructive input, allowing more structural and functional adaptations to occur. In order to better understand how synaptic plasticity accompanies these dendritic arbor rearrangements as well as other forms of structural plasticity, we developed a method to simultaneously monitor structural and synaptic dynamics in the mammalian brain using in vivo two-photon microscopy. Structural and synaptic components can be labeled in cortical neurons of mice in a cell type and laminar specific manner through co-injection of independent lentiviral vectors at a late embryonic or early postnatal age. We demonstrate that excitatory and inhibitory post-synaptic densities can be visualized by tagging fluorescent proteins to PSD95 and Gephyrin, respectively. Finally, we show that the fluorescent proteins, Teal and Venus, can be simultaneously excited and spectrally resolved through linear unmixing so that individual structural and synaptic components can be identified and followed over time. Through this approach, the relationship between synaptic and structural plasticity can be studied in the living brain.by Jerry L. Chen.Ph.D

Unravelling the structure of the C60 and p-But-calix[8]arene complex

Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.The structure of the C60 and p-But-calix[8]arene complex has been reinvestigated, showing an unprecedented continuous layered tetragonal array of fullerenes encapsulated by calixarenes. Electron diffraction data revealed the tetragonal symmetry, with a stepped structure observed by AFM and SEM, and the thickness of the basal plane was measured by XRD, as 2 nm. The molecular simulated arrangement of fullerenes accounts for the ability to take up to ca. 11% of fullerenes C70 in place of the smaller fullerene

Test and analysis results for composite transport fuselage and wing structures

Automated tow placement (ATP) and stitching of dry textile composite preforms followed by resin transfer molding (RTM) are being investigated by researchers at NASA LaRC and Douglas Aircraft Company as cost-effective manufacturing processes for obtaining damage tolerant fuselage and wing structures for transport aircraft. The Douglas work is being performed under a NASA contract entitled 'Innovative Composites Aircraft Primary Structures (ICAPS)'. Data are presented in this paper to assess the damage tolerance of ATP and RTM fuselage elements with stitched-on stiffeners from compression tests of impacted three-J-stiffened panels and from stiffener pull-off tests. Data are also presented to assess the damage tolerance of RTM wing elements which had stitched skin and stiffeners from impacted single stiffener and three blade-stiffened compression tests and stiffener pull-off tests

Structural basis for the role of inhibition in facilitating adult brain plasticity

Although inhibition has been implicated in mediating plasticity in the adult brain, the underlying mechanism remains unclear. Here we present a structural mechanism for the role of inhibition in experience-dependent plasticity. Using chronic in vivo two-photon microscopy in the mouse neocortex, we show that experience drives structural remodeling of superficial layer 2/3 interneurons in an input- and circuit-specific manner, with up to 16% of branch tips undergoing remodeling. Visual deprivation initially induces dendritic branch retractions, and this is accompanied by a loss of inhibitory inputs onto neighboring pyramidal cells. The resulting decrease in inhibitory tone, also achievable pharmacologically using the antidepressant fluoxetine, provides a permissive environment for further structural adaptation, including addition of new synapse-bearing branch tips. Our findings suggest that therapeutic approaches that reduce inhibition, when combined with an instructive stimulus, could facilitate restructuring of mature circuits impaired by damage or disease, improving function and perhaps enhancing cognitive abilities

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research.

BackgroundThe long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman's life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention.Main textDespite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland's structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals-including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols-and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers.ConclusionsAn integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective

Activin Limits Progenitor Capability by Promoting Epithelial Cell Differentiation in the Mammary Gland

Transforming growth factor beta (TGF-beta) and activin utilize common signaling pathways, via smad2/3 and smad4, to mediate tumor suppression by effecting cell cycle arrest and apoptosis. Differences in temporal expression patterns suggest that each cytokine has specific roles in mammary gland development. Activin is expressed during pregnancy and lactation and is required for branching and lactogenesis, implying a role in mammary gland maturation. In contrast, TGF-beta is expressed during involution during mammary gland regression and functions to re-organize the mammary epithelial content to the non-lactating state. Previously, we found that TGF-beta and activin do share common signaling pathways allowing both cytokines to restrict the growth of mammary epithelial cells. However, extended exposure to TGF-beta (5ng/ml; 14 days) causes epithelial to mesencymal transition (EMT). The TGF-beta-treated cells were de-differentiated with loss of both luminal and basal markers. Activin treatment (50ng/ml; 14 days) did not activate EMT. Rather, activin promotes luminal epithelial differentiation with increased expression of prolactin receptor and luminal keratins. Therefore, to test the hypothesis that activin-treatment promotes luminal differentiation and decreases the proportion of progenitor cells in the epithelial population, we compared mammosphere forming capability in vitro and performed limiting dilution experiments in vivo by transplanting 50,000 or 500,000 pre-treated cells into cleared mouse mammary fat pads. The mammosphere assay showed that secondary mammospheres were significantly decreased in the activin-treated cells compared to both the control and TGF-beta treated cells. Tumor incidence between activin-treated and control cells were similar for transplants of 50,000 cells, but tumor incidence was significantly greater in TGF-beta-treated transplants. However, the activin-treated cells had poor outgrowth potential at both 50,000 and 500,000 cells relative to control. We conclude that activin may have the potential to reduce the stem cell population by promoting epithelial cell differentiation

A Survey on Deep Learning in Medical Image Registration: New Technologies, Uncertainty, Evaluation Metrics, and Beyond

Over the past decade, deep learning technologies have greatly advanced the field of medical image registration. The initial developments, such as ResNet-based and U-Net-based networks, laid the groundwork for deep learning-driven image registration. Subsequent progress has been made in various aspects of deep learning-based registration, including similarity measures, deformation regularizations, and uncertainty estimation. These advancements have not only enriched the field of deformable image registration but have also facilitated its application in a wide range of tasks, including atlas construction, multi-atlas segmentation, motion estimation, and 2D-3D registration. In this paper, we present a comprehensive overview of the most recent advancements in deep learning-based image registration. We begin with a concise introduction to the core concepts of deep learning-based image registration. Then, we delve into innovative network architectures, loss functions specific to registration, and methods for estimating registration uncertainty. Additionally, this paper explores appropriate evaluation metrics for assessing the performance of deep learning models in registration tasks. Finally, we highlight the practical applications of these novel techniques in medical imaging and discuss the future prospects of deep learning-based image registration

An automated growth enclosure for metabolic labeling of Arabidopsis thaliana with 13C-carbon dioxide - an in vivo labeling system for proteomics and metabolomics research

<p>Abstract</p> <p>Background</p> <p>Labeling whole <it>Arabidopsis (Arabidopsis thaliana) </it>plants to high enrichment with ¹³C for proteomics and metabolomics applications would facilitate experimental approaches not possible by conventional methods. Such a system would use the plant's native capacity for carbon fixation to ubiquitously incorporate ¹³C from ¹³CO₂gas. Because of the high cost of ¹³CO₂it is critical that the design conserve the labeled gas.</p> <p>Results</p> <p>A fully enclosed automated plant growth enclosure has been designed and assembled where the system simultaneously monitors humidity, temperature, pressure and ¹³CO₂concentration with continuous adjustment of humidity, pressure and ¹³CO₂levels controlled by a computer running LabView software. The enclosure is mounted on a movable cart for mobility among growth environments. <it>Arabidopsis </it>was grown in the enclosure for up to 8 weeks and obtained on average >95 atom% enrichment for small metabolites, such as amino acids and >91 atom% for large metabolites, including proteins and peptides.</p> <p>Conclusion</p> <p>The capability of this labeling system for isotope dilution experiments was demonstrated by evaluation of amino acid turnover using GC-MS as well as protein turnover using LC-MS/MS. Because this 'open source' <it>Arabidopsis </it>¹³C-labeling growth environment was built using readily available materials and software, it can be adapted easily to accommodate many different experimental designs.</p