Reduced Cell Area Research Articles

2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells.

Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. T47D human breast cancer cells were treated with 2-deoxy- D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent- phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

Fibrocystin in MDCK cells: impact on cell adhesion and epithelial morphogenesis

Meeting abstract Fibrocystin (FPC), a type I membrane protein of largely unknown function, is encoded by the Pkhd1 gene, mutations of which cause autosomal recessive polycystic kidney disease (ARPKD). Among other potential functions, FPC appears to affect adhesion signaling of cells involving the FAK/Src axis. Contributions of epithelial cell adhesion and contractility to the disease process of ARPKD remain to be defined. The aim of this study is to elucidate the link between FPC function and the capacity of renal collecting duct epithelial cells to generate normal epithelia. We analyze FPC function in MDCK II renal collecting duct epithelial cells applying 3D culture conditions and micro-pattered surfaces that confine adhesion of cells to induce formation of spheroids. In this setup, establishment of polarity and lumen depend on the capacity of cells to properly control cell adhesion and actomyosin contractility. We address the impact of altered cell behavior using modulators of cell contractility and adhesion signaling. Pkhd1 siRNA-treated MDCK cells and controls were employed to analyze spheroid formation, using specific markers for polarity, cell junctions and cilia. Pkhd1 silencing strongly affects polarity and lumen formation in MDCK spheroids confirming involvement of FPC protein in cellular control of adhesion signals and establishment of polarity. Quantitative analysis of single cell adhesion reveals significant reduction in cell area and contact numbers. During spheroid formation, transient inhibition of actomyosin contractility by blebbistatin can restore epithelial morphogenesis of FPC-deficient MDCK cells. In conclusion, loss of FPC disturbs adhesion signaling, cell-cell interaction, and control of cell tension resulting in impaired epithelial morphogenesis, which can be rescued by transient reduction of cell contractility. Using a cell-based model system, we can address molecular consequences and analyze rescue strategies of FPC deficiency in collecting duct epithelia.

Variation-Aware Comparative Study of 10-nm GAA Versus FinFET 6-T SRAM Performance and Yield

This paper benchmarks the performance of gate-all-around (GAA) MOSFETs against that of optimized silicon-on-insulator FinFETs at 10-nm gate length. Variability in transistor performance due to systematic and random variations is estimated with the aid of TCAD 3-D device simulations, for both device structures. The yield of six-transistor SRAM cells implemented with these advanced MOSFET structures is then investigated via a calibrated physically based compact model. The GAA MOSFET technology is projected to provide for 0.1 V lower minimum cell operating voltage with reduced cell area.

Reactive Impedance Surface TM Mode Slow Wave for Patch Antenna Miniaturization [AMTA Corner

This paper presents a two-layer mushroom-like reactive impedance surface (RIS) and its application to patch-antenna miniaturization. A reactive impedance surface, known as a meta-substrate, has been shown to present the ability to miniaturize printed antennas when serving as the substrate for the antenna. However, the area of conventional reactiveimpedance- surface substrates is usually much larger than that of the miniaturized antenna. Here, a reactive impedance surface with very small unit-cell dimensions (a cell area reduction of 95.6%, compared to a traditional reactive impedance surface) is proposed, and utilized to design a miniaturized antenna over a reactive-impedance-surface substrate with the same size as the antenna itself. The two-layer mushroom-like reactive impedance surface is analyzed theoretically and numerically. The reflection phase diagram of the reactive-impedance-surface substrate and the reactive impedance surface/PEC parallel plate waveguide are studied to verify the analytic model. It is shown to have a high propagation constant near the resonant frequency of the reactive impedance surface. The effect of vias in the mushroom-like reactive impedance surface is also discussed. Applying the two-layer reactive-impedance-surface substrate and an optimized miniaturized patch antenna topology, several UHF-band patch antennas, working around 400 MHz, were designed and fabricated. Using this approach, a miniaturized antenna with dimensions λ0/11.4×0/11.4×}0/74, including the reactive-impedance-surface substrate, was developed.

Role of α2β1 integrins in mediating cell shape on microtextured titanium surfaces.

Surface microroughness plays an important role in determining osteoblast behavior on titanium. Previous studies have shown that osteoblast differentiation on microtextured titanium substrates is dependent on alpha-2 beta-1 (α2β1) integrin signaling. This study used focused ion beam milling and scanning electron microscopy, combined with three-dimensional image reconstruction, to investigate early interactions of individual cells with their substrate and the role of integrin α2β1 in determining cell shape. MG63 osteoblast-like cells on sand blasted/acid etched (SLA) Ti surfaces after 3 days of culturing indicated decreased cell number, increased cell differentiation, and increased expression of mRNA levels for α1, α2, αV, and β1 integrin subunits compared to cells on smooth Ti (PT) surfaces. α2 or β1 silenced cells exhibited increased cell number and decreased differentiation on SLA compared to wild-type cells. Wild-type cells on SLA possessed an elongated morphology with reduced cell area, increased cell thickness, and more apparent contact points. Cells on PT exhibited greater spreading and were relatively flat. Silenced cells possessed a morphology and phenotype similar to wild-type cells grown on PT. These observations indicate that surface microroughness affects cell response via α2β1 integrin signaling, resulting in a cell shape that promotes osteoblastic differentiation.

Non-overlapping activities of ADF and cofilin-1 during the migration of metastatic breast tumor cells.

BackgroundADF/cofilin proteins are key modulators of actin dynamics in metastasis and invasion of cancer cells. Here we focused on the roles of ADF and cofilin-1 individually in the development of polarized migration of rat mammary adenocarcinoma (MTLn3) cells, which express nearly equal amounts of each protein. Small interference RNA (siRNA) technology was used to knockdown (KD) the expression of ADF and cofilin-1 independently.ResultsEither ADF KD or cofilin KD caused cell elongation, a reduction in cell area, a decreased ability to form invadopodia, and a decreased percentage of polarized cells after 180 s of epidermal growth factor stimulation. Moreover, ADF KD or cofilin KD increased the rate of cell migration and the time of lamellipodia protrusion but through different mechanisms: lamellipodia protrude more frequently in ADF KD cells and are more persistent in cofilin KD cells. ADF KD cells showed a significant increase in F-actin aggregates, whereas cofilin KD cells showed a significant increase in prominent F-actin bundles and increased cell adhesion. Focal adhesion area and cell adhesion in cofilin KD cells were returned to control levels by expressing exogenous cofilin but not ADF. Return to control rates of cell migration in ADF KD cells was achieved by expression of exogenous ADF but not cofilin, whereas in cofilin KD cells, expression of cofilin efficiently rescued control migration rates.ConclusionAlthough ADF and cofilin have many redundant functions, each of these isoforms has functional differences that affect F-actin structures, cell adhesion and lamellipodial dynamics, all of which are important determinants of cell migration.

A Vertex Model of Drosophila Ventral Furrow Formation

Ventral furrow formation in Drosophila is an outstanding model system to study the mechanisms involved in large-scale tissue rearrangements. Ventral cells accumulate myosin at their apical sides and, while being tightly coupled to each other via apical adherens junctions, execute actomyosin contractions that lead to reduction of their apical cell surface. Thereby, a band of constricted cells along the ventral epithelium emerges which will form a tissue indentation along the ventral midline (the ventral furrow). Here we adopt a 2D vertex model to simulate ventral furrow formation in a surface view allowing easy comparison with confocal live-recordings. We show that in order to reproduce furrow morphology seen in vivo, a gradient of contractility must be assumed in the ventral epithelium which renders cells more contractile the closer they lie to the ventral midline. The model predicts previous experimental findings, such as the gain of eccentric morphology of constricting cells and an incremental fashion of apical cell area reduction. Analysis of the model suggests that this incremental area reduction is caused by the dynamical interplay of cell elasticity and stochastic contractility as well as by the opposing forces from contracting neighbour cells. We underpin results from the model through in vivo analysis of ventral furrow formation in wildtype and twi mutant embryos. Our results show that ventral furrow formation can be accomplished as a “tug-of-war” between stochastically contracting, mechanically coupled cells and may require less rigorous regulation than previously thought.SummaryFor the developmental biologist it is a fascinating question how cells can coordinate major tissue movements during embryonic development. The so-called ventral furrow of the Drosophila embryo is a well-studied example of such a process when cells from a ventral band, spanning nearly the entire length of the embryo, undergo dramatic shape change by contracting their tips and then fold inwards into the interior of the embryo. Although numerous genes have been identified that are critical for ventral furrow formation, it is an open question how cells work together to elicit this tissue rearrangement. We use a computational model to mimic the physical properties of cells in the ventral epithelium and simulate the formation of the furrow. We find that the ventral furrow can form through stochastic self-organisation and that previous experimental observations can be readily explained in our model by considering forces that arise when cells execute contractions while being coupled to each other in a mechanically coherent epithelium. The model highlights the importance of a physical perspective when studying tissue morphogenesis and shows that only a minimal genetic regulation may be required to drive complex processes in embryonic development.

Purification and functional assessment of smooth muscle cells derived from mouse embryonic stem cells.

ObjectiveTo obtain a pure population of smooth muscle cells (SMC) derived from mouse embryonic stem cells (ESC) and further assess their functions.MethodsA vector, expressing both puromycin resistance gene (puror) and enhanced green fluorescent protein (EGFP) gene driven by smooth muscle 22α (SM22α) promoter, named pSM22α-puror-IRES2-EGFP was constructed and used to transfect ESC. Transgenic ESC (Tg-ESC) clones were selected by G418 and identified by PCR amplification of puror gene. The characteristics of Tg-ESC were detected by alkaline phosphatase (ALP) staining, SSEA-1 immunofluorescence and teratoma formation test in vivo. After induction of SMC differentiation by all-trans retinoic acid, differentiated Tg-ESC were treated with 10 µg/mL puromycin for three days to obtain purified SMC (P-SMC). Percentage of EGFP+ cells in P-SMC was assessed by flow cytometer. Expressions of smooth muscle specific markers were detected by immunostaining and Western blotting. Proliferation, migration and contractility of P-SMC were analyzed by growth curve, trans-well migration assay, and carbachol treatment, respectively. Finally, both P-SMC and unpurified SMC (unP-SMC) were injected into syngeneic mouse to see teratoma development.ResultsTg-ESC clone was successfully established and confirmed by PCR detection of puror gene in its genomic DNA. The Tg-ESC was positive for ALP staining, SSEA-1 staining and formed teratoma containing tissues derived from three germ layers. After retinoic acid induction, large amount of EGFP positive cells outgrew from differentiated Tg-ESC. Three days of puromycin treatment produced a population of P-SMC with an EGFP+ percentage as high as 98.2% in contrast to 29.47% of unP-SMC. Compared with primary mouse vascular smooth muscle cells (VSMC), P-SMC displayed positive, but lowered expression of SMC-specific markers including SM α-actin and myosin heavy chain (SM-MHC) detected either, by immunostaining, or immunoblotting, accelerated proliferation, improved migration (99.33 ± 2.04 vs. 44.00 ± 2.08 migrated cells/field, P < 0.05), and decreased contractility in response to carbachol (7.75 ± 1.19 % vs. 16.50 ± 3.76 % in cell area reduction, P < 0.05). In vivo injection of unP-SMC developed apparent teratoma while P-SMC did not.ConclusionsWe obtained a pure population of ESC derived SMC with less mature (differentiated) phenotypes, which will be of great use in research of vascular diseases and in bio-engineered vascular grafts for regenerative medicine.

Proteinase-activated receptor-2 modulates human macrophage differentiation and effector function

Proteinase-activated receptor-2 (PAR-2) was shown to influence immune regulation; however, its role in human macrophage subset development and function has not been addressed. Here, PAR-2 expression and activation was investigated on granulocyte macrophage (GM)-CSF(M1) and macrophage (M)-CSF(M2) macrophages. In both macrophages, the PAR-2-activating peptide, SLIGKV, increased PAR-2 expression and regulated TNF-α and IL-10 secretion in a manner similar to LPS. In addition, HLA-DR on M1 cells also increased. Monocytes matured to an M1 phenotype in the presence of SLIGKV had reduced cell area, and released less TNF-α after LPS challenge compared with vehicle (P < 0.05, n = 3). Cells matured to an M2 phenotype with SLIGKV also had a reduced cell area and made significantly more TNF-α after LPS exposure compared to vehicle (P < 0.05, n = 3) with reduced IL-10 secretion (P < 0.05, n = 3). Thus, PAR-2 activation on macrophage subsets regulates HLA-DR and PAR-2 surface expression, and drives cytokine production. In contrast, PAR-2 activation during M1 or M2 maturation induces altered cell morphology and skewing of phenotype, as evidenced by cytokine secretion. These data suggest a complex role for PAR-2 in macrophage biology and may have implications for macrophage-driven disease in which proteinase-rich environments can influence the immune process directly.

Lack of CFTR in a cystic fibrosis pig model disrupts airway smooth muscle development

To better understand the pathogenesis of cystic fibrosis (CF) lung disease, we recently generated CFTR‐targeted pigs. CF pigs develop lung disease typical of human CF. An unexpected finding at birth, prior to the onset of infection and inflammation, was that CF tracheas have a reduced lumen area, irregularly developed airway cartilage, and airway smooth muscle (ASM) with prominent appearing bundles. We hypothesized that these abnormal‐appearing ASM bundles were due to differences in ASM proliferation. To test this hypothesis, tracheas were harvested at birth for histological examination. Despite a reduction in tracheal ASM area in CF, we found that ASM cell density was increased in CF (CF: 0.52±0.06 vs. non‐CF: 0.39±0.02 cells/100 μm2). To investigate if cell proliferation was increased in CF, we stained for the proliferation marker Ki‐67 and found reduced Ki‐67 positive cells in CF (CF: 0.04%±0.01 vs. non‐CF: 0.1%±0.01). This decrease was associated with a reduction in CF ASM cell area (197±19 vs. 259±14 μm2). Finally, electron microscopic studies revealed that at birth CF ASM has a contracted appearance, likely accounting for the reduced cell area. These data suggest that CFTR is important in ASM development and might explain, in part, the increased incidence of airway hyper‐responsiveness in human CF.This work was supported, in part, by the American Asthma Foundation (Sandler).

A Cell-Level Biomechanical Model of Drosophila Dorsal Closure

We report a model describing the various stages of dorsal closure of Drosophila. Inspired by experimental observations, we represent the amnioserosa by 81 hexagonal cells that are coupled mechanically through the position of the nodes and the elastic forces on the edges. In addition, each cell has radial spokes representing actin filaments on which myosin motors can attach and exert contractile forces on the nodes, the attachment being controlled by a signaling molecule. Thus, the model couples dissipative cell and tissue motion with kinetic equations describing the myosin and signal dynamics. In the early phase, amnioserosa cells oscillate as a result of coupling among the chemical signaling, myosin attachment/detachment, and mechanical deformation of neighboring cells. In the slow phase, we test two ratcheting mechanisms suggested by experiments: an internal ratchet by the apical and junctional myosin condensates, and an external one by the supracellular actin cables encircling the amnioserosa. Within the range of parameters tested, the model predictions suggest the former as the main contributor to cell and tissue area reduction in this stage. In the fast phase of dorsal closure, cell pulsation is arrested, and the cell and tissue areas contract consistently. This is realized in the model by gradually shrinking the resting length of the spokes. Overall, the model captures the key features of dorsal closure through the three distinct phases, and its predictions are in good agreement with observations.

Comparative Economic Analysis of Concentrating Solar Technologies

One of the noted benefits of concentrating photovoltaics (PV) is the reduced cell area which results in reduction of the overall system cost. A variety of studies have looked at the cost for concentrating PV systems and made comparisons to concentrating solar thermal power plants, typically resulting in concentrating solar thermal power having lower system costs. Recently, a widespread design space was assessed for the potential efficiency improvements possible with a coupled hybrid PV/thermal solar energy system for electricity generation. The analysis showed that modest efficiency improvements could be made but no assessment of the economic impact was made. Although modest efficiency gains can be made, such a hybrid system requires more components than one of the conventional stand alone concentrating solar power plant on its own resulting in significantly different system costs. As a result, we look to compare the overall system costs of three different solar power technologies: concentrating PV, concentrating solar thermal, and the concentrating hybrid approach. Additionally, we will focus on documenting the necessary hybrid efficiencies to make a hybrid system competitive as well as the feasibility and means for achieving these efficiencies.

Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans

Diabetes frequently develops in patients with pancreatic disorders. We aimed to determine the lower threshold of beta cell area for diabetes manifestation as well as the impact of insulin sensitivity on glucose homoeostasis in patients with pancreatic diabetes. Eighty-two patients undergoing pancreatic surgery underwent pre-operative oral glucose challenge. Fractional pancreatic beta cell area was determined, and indices of insulin sensitivity and beta cell function were calculated. HbA1c and glucose levels were similar in patients with high and intermediate beta cell area, but were significantly higher in those with the lowest beta cell area (p < 0.0001). Insulin secretion was reduced only in patients with the lowest beta cell area (p < 0.001). The relative beta cell deficits at the onset of diabetes and impaired glucose tolerance were 64% and 21%, respectively, based on 2 h glucose levels. Deteriorating insulin sensitivity was associated with a small increase in the incidence of diabetes. In conclusion, pancreatic diabetes probably develops after a reduction in beta cell area of ~65%. Post-challenge glucose excursions are much more closely related to pancreatic beta cell area than to fasting glycaemia, thereby underlining the usefulness of the OGTT in patients with pancreatic disorders.

Collective and single cell behavior in epithelial contact inhibition

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing, and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition." The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured Madin-Darby canine kidney cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size, and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition.

Concentrating PV/T Hybrid System for Simultaneous Electricity and Usable Heat Generation: A Review

Photovoltaic (PV) power generation is one of the attractive choices for efficient utilization of solar energy. Considering that the efficiency and cost of PV cells cannot be significantly improved in near future, a relatively cheap concentrator to replace part of the expensive solar cells could be used. The photovoltaic thermal hybrid system (PV/T), combining active cooling with thermal electricity and providing both electricity and usable heat, can enhance the total efficiency of the system with reduced cell area. The effect of nonuniform light distribution and the heat dissipation on the performance of concentrating PV/T was discussed. Total utilization of solar light by spectral beam splitting technology was also introduced. In the last part, we proposed an integrated compound parabolic collector (CPC) plate with low precision solar tracking, ensuring effective collection of solar light with a significantly lowered cost. With the combination of beam splitting of solar spectrum, use of film solar cell, and active liquid cooling, efficient and full spectrum conversion of solar light to electricity and heat, in a low cost way, might be realized. The paper may offer a general guide to those who are interested in the development of low cost concentrating PV/T hybrid system.

Identification by SNP Analysis of a Major Role for Cayetana Blanca in the Genetic Network of Iberian Peninsula Grapevine Varieties

AIMS: To measure Langerhans9 cells in skin of patients treated by bone marrow transplantation who developed chronic graft versus host disease (GvHD); to determine whether the reduction in Langerhans9 cells resulted directly from the GvHD or from other factors, such as the immunosuppressive regimens used in bone marrow transplant patients. PATIENTS AND METHODS: Lesional and nonlesional skin specimens from nine patients with lichen planus-like lesions and three patients with sclerodermoid lesions were studied. Control skin specimens were taken from three patients undergoing breast reduction surgery. The number of Langerhans9 cells/mm2 and the area of Langerhans9 cells as a percentage of total epidermis were measured by counting cells labelled with antihuman CD1a. RESULTS: A significant reduction in Langerhans9 cell area and number were found in specimens with lesions (area 3.5%; number 507/mm2) compared with specimens without lesions (8.42%; 2375/mm2). In contrast, Langerhans9 cell area and number in skin without lesions were similar to controls (10.26%; 2968/mm2). CONCLUSIONS: Langerhans9 cells were significantly reduced in skin with lesions of chronic GvHD but not in skin without lesions from the same patient, suggesting that the reduction is a direct consequence of GvHD and not linked to immunosuppressive drugs or late effects of conditioning regimens. In long term bone marrow transplant recipients, Langerhans9 cells are derived mainly from the donor cells; therefore, this result suggests the occurrence of autoreactive phenomenon in chronic GvHD.

Common Sub-expression Sharing을 사용한 저면적 FFT 프로세서 구조

이 논문에서는 저면적 256-point FFT 구조를 제안한다. 저면적 구현을 위하여 CSD(Canonic Signed Digit) 곱셈기 방식을 채택하여 구현하였다. CSD 곱셈기 방식을 효율적으로 적용하기 위해서는 곱셈연산의 가지 수가 적어야 하는데, 여러 알고리즘을 조사한 결과 Radix-<TEX>$4^2$</TEX> 알고리즘이 곱셈연산의 가지 수가 적음을 발견하였다. 따라서 제안 구조는 Radix-<TEX>$4^2$</TEX> DIF 알고리즘과 CSD 곱셈기 방식을 사용하였다. 즉 Radix-<TEX>$4^2$</TEX> 알고리즘을 사용하여 4개의 스테이지에서 사용되는 곱셈연산의 가지 수를 최소화한 후에 각각의 곱셈연산 블록은 CSD 곱셈기를 사용하여 구현하였다. CSD 곱셈기 구현에서 공통패턴을 공유하여 덧셈기의 수를 줄일 수 있는 CSS(Common Sub-expression Sharing) 기술을 사용하여 구현면적을 더욱 감소시켰다. 제안된 FFT 구조를 Verilog-HDL 코딩 후 합성하여 구현한 결과, Radix-4를 사용한 구조와 비교하여 복소 곱셈기 부분의 29.9%의 cell area 감소를 보였고 전체적인 256-point FFT 구조에 대한 비교에서는 12.54% cell area 감소를 보였다. In this paper, a low-area 256-point FFT structure is proposed. For low-area implementation CSD(Canonic Signed Digit) multiplier method is chosen. Because multiplication type should be less for efficient CSD multiplier application to the FFT structure, the Radix-<TEX>$4^2$</TEX> algorithm is chosen for those purposes. After, in the proposed structure, the number of multiplication type is minimized in each multiplication block, the CSD multipliers are applied for implementation of multiplication. Furthermore, in CSD multiplier implementation, cell-area is more reduced through common sub-expression sharing(CSS). The Verilog-HDL coding result shows 29.9% cell area reduction in the complex multiplication part and 12.54% cell area reduction in overall 256-point FFT structure comparison with those of the conventional structure.

Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia

The habenular complex is composed of important relay nuclei linking the limbic forebrain to the midbrain and brain stem nuclei. Based on clinical observations, experiments with animals and theoretical considerations, it has been speculated that this brain area might be involved in psychiatric diseases (i.e. schizophrenia and depression). However, evidence in favour of this hypothesis is still lacking because the human habenular complex has rarely been studied with regard to mental illness. We examined habenular volumes in post-mortem brains of 17 schizophrenia patients, 14 patients with depression (six patients with major depression and eight patients with bipolar depression) and 13 matched controls. We further determined the neuronal density, cell number and cell area of the medial habenular nuclei of the same cohorts using a counting box and a computer-assisted instrument. Significantly reduced habenular volumes of the medial and lateral habenula were estimated in depressive patients in comparison to normal controls and schizophrenia patients. We also found a reduction in neuronal cell number and cell area in depressive patients for the right side compared to controls and schizophrenia patients. No such changes were seen in schizophrenia. Our anatomical data argue against prominent structural alterations of the habenular nuclei in schizophrenia but demonstrate robust alterations in depressive patients. We are currently applying immunohistochemical markers to better characterize neuronal subpopulations of this brain region in schizophrenia and depression.

Osteoblast response to dimethacrylate composites varying in composition, conversion and roughness using a combinatorial approach

Dimethacrylate polymers and composites are seeing increased usage in orthopedics. As these applications require the material to integrate with the surrounding tissues, direct contact cytotoxicity assays should be used to assess the biocompatibility. This study utilized a combinatorial testing platform to evaluate the cell response to dimethacrylate composites with a variety of properties on a single sample. MC3T3-E1 pre-osteoblasts were cultured directly on composites with varying filler content, filler type, degree of conversion (DC), and surface topography. Cell viability, density, and area depended on an interplay of the material properties, with low DC causing a reduction in cell area but having minimal effect on cell viability, high filler content causing an increase in cell density, and filler content/type altering the surface roughness as a function of DC. The combinatorial testing platform successfully quantified the effects of numerous material properties on several aspects of the osteoblast response.

Evidence Group I mGluR Drugs Modulate the Activation Profile of Lipopolysaccharide-Exposed Microglia in Culture

Metabotropic glutamate receptors (mGluRs) may play a role in modulating microglial activation, but group I mGluRs have received little attention. This study aimed to investigate the effects of group I mGluR selective ligands, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), in lipopolysaccharide (LPS; 50 ng/ml)-activated rat microglial cultures. (S)-3,5-DHPG (150 microM) significantly reduced (approximately 20-60%) the LPS-mediated production of nitrite (NO2(-)), tumour necrosis factor alpha (TNF-alpha), and L-glutamate (Glu) at 24 and 72 h. Image analysis revealed increases in both cell area and number, with larger amoeboid microglia (with retracted processes) formed following 2 h LPS exposure. This cellular population was absent after addition of (S)-3,5-DHPG, an effect antagonised by AIDA, and a concomitant reduction in cell area was also found. Taken together, these biochemical and morphological observations suggest that (S)-3,5-DHPG reduces microglial activation, indicating a role for group I mGluRs in modulating microglial function.