bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-27 inhibits pathophysiological intraocular neovascularization due to laser burn
Authors: Hasegawa Eiichi , Oshima Yuji , Takeda Atsunobu , Saeki Kazuko , Yoshida Hiroki , Sonoda Koh-Hei , Ishibashi Tatsuro
Published: November 2011

AMD is the most common disease leading to acquired blindness in developed countries. CNV is the foremost cause of AMD and is thought to be induced by regional inflammation as a result of age-related conformational changes of the chorioretinal interface. Here, we show that IL-27, a member of the IL-6/IL-12 cytokine family, has an angiostatic effect and regulates the development of laser-induced experimental CNV in mice. In this model, IL-27 expression increased in the damaged choroid and peaked at the 24 h-time-point. IL-27 neutralization, induced by inoculating an antagonistic antibody into the vitreous cavity, enhanced VEGF production and the extent of CNV. By contrast, the administration of rIL-27 reduced VEGF production and the extent of CNV. Mice deficient in the EBI3, which lack IL-27, also showed more CNV than C57BL/6 mice, and this was reduced by IL-27 supplementation. We additionally investigated the effect of IL-27 on the function of macrophages, which play a critical role in CNV. IL-27 did not affect macrophage migration but inhibited its VEGF production. IL-27 therefore appears to regulate CNV and is a promising candidate target for treating sight-threatening diseases caused by ocular neovascularization.
Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes
Authors: Wang Yin , Bruce Allen T. , Tu Caixia , Ma Keli , Zeng Li , Zheng Pan , Liu Yang , Liu Yan
Published: November 2011

Mutations in sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) underlie Darier disease (DD), a dominantly inherited skin disorder characterized by loss of keratinocyte adhesion (acantholysis) and abnormal keratinization (dyskeratosis) resulting in characteristic mucocutaneous abnormalities. However, the molecular pathogenic mechanism by which these changes influence keratinocyte adhesion and viability remains unknown. We show here that SERCA2 protein is extremely sensitive to endoplasmic reticulum (ER) stress, which typically results in aggregation and insolubility of the protein. Depletion of ER calcium stores is not necessary for the aggregation but accelerates the progression. Systematic analysis of diverse mutants identical to those found in DD patients demonstrated that the ER stress initiator is the SERCA2 mutant protein itself. These SERCA2 proteins were found to be less soluble, to aggregate and to be more polyubiquitinylated. After transduction into primary human epidermal keratinocytes, mutant SERCA2 aggregates elicited ER stress, caused increased numbers of cells to round up and detach from the culture plate, and induced apoptosis. These mutant induced events were exaggerated by increased ER stress. Furthermore, knockdown SERCA2 in keratinocytes rendered the cells resistant to apoptosis induction. These features of SERCA2 and its mutants establish a mechanistic base to further elucidate the molecular pathogenesis underlying acantholysis and dyskeratosis in DD.
Caveolae respond to cell stretch and contribute to stretch-induced signaling
Authors: Gervásio Othon L. , Phillips William D. , Cole Louise , Allen David G.
Published: November 2011

Caveolae are invaginations of the plasma membrane that are formed by caveolins. Caveolar membranes are also enriched in cholesterol, glycosphingolipids and signaling enzymes such as Src kinase. Here we investigate the effect of cell stretch upon caveolar dynamics and signaling. Transfection of C2 myoblasts with caveolin-3–YFP led to the formation of caveolae-like membrane pits 50–100 nm in diameter. Glycosphingolipids became immobilized and tightly packed together within caveolin-rich regions of the plasma membrane. Fluorescence resonance energy transfer (FRET) was used to assess the degree of glycosphingolipid packing. Myoblasts were subjected to a brief (1 minute) stretch on an elastic substratum. Stretch caused a reduction in glycosphingolipid FRET, consistent with a reversible unfolding of caveolar pits in response to membrane tension. Cells expressing caveolin-3–YFP also displayed an enhanced stretch-induced activation of Src kinase, as assessed by immunofluorescence. Repeated stretches resulted in the trafficking and remodeling of caveolin-3-rich membrane domains and accelerated turnover of membrane glycosphingolipids. The stretch-induced unfolding of caveolae, activation of Src and redistribution of caveolin and glycosphingolipids might reflect mechanisms of the cellular adaptation to mechanical stresses.
De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation
Authors: Chung Inn , Leonhardt Heinrich , Rippe Karsten
Published: November 2011

Telomerase-negative tumor cells use an alternative lengthening of telomeres (ALT) pathway that involves DNA recombination and repair to maintain their proliferative potential. The cytological hallmark of this process is the accumulation of promyelocytic leukemia (PML) nuclear protein at telomeric DNA to form ALT-associated PML bodies (APBs). Here, the de novo formation of a telomeric PML nuclear subcompartment was investigated by recruiting APB protein components. We show that functionally distinct proteins were able to initiate the formation of bona fide APBs with high efficiency in a self-organizing and self-propagating manner. These included: (1) PML and Sp100 as the constituting components of PML nuclear bodies, (2) telomere repeat binding factors 1 and 2 (TRF1 and TRF2, respectively), (3) the DNA repair protein NBS1 and (4) the SUMO E3 ligase MMS21, as well as the isolated SUMO1 domain, through an interacting domain of another protein factor. By contrast, the repair factors Rad9, Rad17 and Rad51 were less efficient in APB nucleation but were recruited to preassembled APBs. The artificially created APBs induced telomeric extension through a DNA repair mechanism, as inferred from their colocalization with sites of non-replicative DNA synthesis and histone H2A.X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway.
Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle
Authors: Uezumi Akiyoshi , Ito Takahito , Morikawa Daisuke , Shimizu Natsuko , Yoneda Tomohiro , Segawa Masashi , Yamaguchi Masahiko , Ogawa Ryo , Matev Miroslav M. , Miyagoe-Suzuki Yuko , Takeda Shin'ichi , Tsujikawa Kazutake , Tsuchida Kunihiro , Yamamoto Hiroshi , Fukada So-ichiro
Published: November 2011

Accumulation of adipocytes and collagen type-I-producing cells (fibrosis) is observed in muscular dystrophies. The origin of these cells had been largely unknown, but recently we identified mesenchymal progenitors positive for platelet-derived growth factor receptor alpha (PDGFRα) as the origin of adipocytes in skeletal muscle. However, the origin of muscle fibrosis remains largely unknown. In this study, clonal analyses show that PDGFRα+ cells also differentiate into collagen type-I-producing cells. In fact, PDGFRα+ cells accumulated in fibrotic areas of the diaphragm in the mdx mouse, a model of Duchenne muscular dystrophy. Furthermore, mRNA of fibrosis markers was expressed exclusively in the PDGFRα+ cell fraction in the mdx diaphragm. Importantly, TGF-β isoforms, known as potent profibrotic cytokines, induced expression of markers of fibrosis in PDGFRα+ cells but not in myogenic cells. Transplantation studies revealed that fibrogenic PDGFRα+ cells mainly derived from pre-existing PDGFRα+ cells and that the contribution of PDGFRα− cells and circulating cells was limited. These results indicate that mesenchymal progenitors are the main origin of not only fat accumulation but also fibrosis in skeletal muscle.
Nucleostemin inhibits TRF1 dimerization and shortens its dynamic association with the telomere
Authors: Meng Lingjun , Hsu Joseph K. , Zhu Qubo , Lin Tao , Tsai Robert Y. L.
Published: November 2011

TRF1 is a key component of the telomere-capping complex and binds double-strand telomeric DNA as homodimers. So far, it is not clear whether TRF1 dimerization coincides with its telomere binding or is actively controlled before it binds the telomere, and in the latter case, how this event might affect its telomere association. We previously found that TRF1 dimerization and its telomere binding can be increased by GNL3L, which is the vertebrate paralogue of nucleostemin (NS). Here, we show that NS and GNL3L bind TRF1 directly but competitively through two separate domains of TRF1. In contrast to GNL3L, NS prevents TRF1 dimerization through a mechanism not determined by its ability to displace TRF1-bound GNL3L. Furthermore, NS is capable of shortening the dynamic association of TRF1 with the telomere in normal and TRF2ΔBΔM-induced telomere-damaged cells without affecting the amount of telomere-bound TRF1 proteins in vivo. Importantly, NS displays a protective function against the formation of telomere-dysfunction-induced foci. This work demonstrates that TRF1 dimerization is actively and oppositely regulated by NS and GNL3L extrachromosomally. Changing the relative amount of TRF1 monomers versus dimers in the nucleoplasm might affect the dynamic association of TRF1 with the telomere and the repair of damaged telomeres.
Efficacy and safety of Aethoxysklerol® (polidocanol) 0.5%, 1% and 3% in comparison with placebo solution for the treatment of varicose veins of the lower extremities in Chinese patients (ESA-China Study)
Authors: Zhang J , Jing Z , Schliephake D E , Otto J , Malouf G M , Gu Y-Q
Published: November 2011

Objectives

To assess efficacy and safety of polidocanol (POL) versus placebo in the treatment of C1 and C2 non-saphenous varicose veins in Chinese patients.

Methods

Patients were randomly assigned to POL or placebo. POL 0.5%, 1% and 3% were administered depending on varicose vein type. Response after 12 weeks was defined as Grade 4 or 5 on a digital imaging-based five-point scale (C1 veins) or occlusion and/or absence of reflux >0.5 second (C2 veins). Safety was evaluated with a five-point scale and standard safety assessments.

Results

Two hundred and eighty-five patients were treated. POL 0.5%, 1% and 3% were each superior to placebo ( P < 0.001); response rates: 87.1% versus 13.6%, 86.4% versus 12.5% and 88.6% versus 4.3%, respectively. Significantly more POL than placebo patients were satisfied/very satisfied with treatment. POL was well tolerated, with mostly symptoms at the injection site reported.

Conclusions

Sclerotherapy with POL 0.5%, 1% and 3% was efficacious and safe in Chinese patients.
Synergy from Silence in a Combinatorial Neural Code
Authors: Schneidman Elad , Puchalla Jason L. , Segev Ronen , Harris Robert A. , Bialek William , Berry Michael J.
Published: November 2011

The manner in which groups of neurons represent events in the external world is a central question in neuroscience. Estimation of the information encoded by small groups of neurons has shown that in many neural systems, cells carry mildly redundant information. These measures average over all the activity patterns of a neural population. Here, we analyze the population code of the salamander and guinea pig retinas by quantifying the information conveyed by specific multicell activity patterns. Synchronous spikes, even though they are relatively rare and highly informative, convey less information than the sum of either spike alone, making them redundant coding symbols. Instead, patterns of spiking in one cell and silence in others, which are relatively common and often overlooked as special coding symbols, were found to be mostly synergistic. Our results reflect that the mild average redundancy between ganglion cells that was previously reported is actually the result of redundant and synergistic multicell patterns, whose contributions partially cancel each other when taking the average over all patterns. We further show that similar coding properties emerge in a generic model of neural responses, suggesting that this form of combinatorial coding, in which specific compound patterns carry synergistic or redundant information, may exist in other neural circuits.
GABAergic Synaptic Plasticity during a Developmentally Regulated Sleep-Like State inC. elegans
Authors: Dabbish Nooreen S. , Raizen David M.
Published: November 2011

Approximately one-fourth of the neurons inCaenorhabditis elegansadults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABAAreceptor agonists, indicating that postsynaptic mechanisms contribute to lethargus-dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on the behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock inC. elegansis analogous to synaptic plasticity regulated by the circadian clock in other species.
Sensory Network Dysfunction, Behavioral Impairments, and Their Reversibility in an Alzheimer's β-Amyloidosis Mouse Model
Authors: Wesson Daniel W. , Borkowski Anne H. , Landreth Gary E. , Nixon Ralph A. , Levy Efrat , Wilson Donald A.
Published: November 2011

The unique vulnerability of the olfactory system to Alzheimer's disease (AD) provides a quintessential translational tool for understanding mechanisms of synaptic dysfunction and pathological progression in the disease. Using the Tg2576 mouse model of β-amyloidosis, we show that aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-β (Aβ) deposition is restricted to the olfactory bulb (OB). Hyperactive odor-evoked activity in the piriform cortex (PCX) and increased OB–PCX functional connectivity emerged at a time coinciding with olfactory behavior impairments. This hyperactive activity persisted until later in life when the network converted to a hyporesponsive state. This conversion was Aβ-dependent, because liver-X receptor agonist treatment to promote Aβ degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior.
Emergence of Persistent Networks in Long-Term Intracranial EEG Recordings
Authors: Kramer Mark A. , Eden Uri T. , Lepage Kyle Q. , Kolaczyk Eric D. , Bianchi Matt T. , Cash Sydney S.
Published: November 2011

Over the past two decades, the increased ability to analyze network relationships among neural structures has provided novel insights into brain function. Most network approaches, however, focus on static representations of the brain's physical or statistical connectivity. Few studies have examined how brain functional networks evolve spontaneously over long epochs of continuous time. To address this, we examine functional connectivity networks deduced from continuous long-term electrocorticogram recordings. For a population of six human patients, we identify a persistent pattern of connections that form a frequency-band-dependent network template, and a set of core connections that appear frequently and together. These structures are robust, emerging from brief time intervals (∼100 s) regardless of cognitive state. These results suggest that a metastable, frequency-band-dependent scaffold of brain connectivity exists from which transient activity emerges and recedes.
Medial Temporal Lobe Function and Recognition Memory: A Novel Approach to Separating the Contribution of Recollection and Familiarity
Authors: Song Zhuang , Jeneson Annette , Squire Larry R.
Published: November 2011

Human neuroimaging studies of recognition memory have often been interpreted to mean that the hippocampus supports recollection but not familiarity. This interpretation is complicated by the fact that recollection-based decisions are typically associated with stronger memories than familiarity-based decisions. Some studies of source memory controlled for this difference in memory strength and found that hippocampal activity during learning predicted subsequent item memory strength while recollection-based memory (performance on source memory questions) was held at chance. This result suggests that the hippocampus is important for familiarity. However, a difficulty with this approach is that when source memory is assessed by asking specific, task-relevant source memory questions, participants who fail to answer the prescribed questions might nevertheless have available other (task-irrelevant) source information. Accordingly, successful item memory could still be associated with recollection. The present study used a novel method to assess item memory and source memory. Instead of responding to specific source questions, participants rated their source memory strength based on any information about the learning episode that was available to them. When subsequent source memory strength was held constant at the lowest possible level, we identified regions bilaterally in hippocampus, as well as in perirhinal cortex, where activity during learning increased as subsequent item memory increased in strength. In addition, activity in cortical regions (including prefrontal cortex) was related to source memory success independently of item memory strength. These findings suggest that activity in the hippocampus is related to the encoding of familiarity-based item memory, independent of subsequent recollection-based success.
When Attention Wanders: How Uncontrolled Fluctuations in Attention Affect Performance
Authors: Cohen Marlene R. , Maunsell John H. R.
Published: November 2011

No matter how hard subjects concentrate on a task, their minds wander (Raichle et al., 2001; Buckner et al., 2008; Christoff et al., 2009; Killingsworth and Gilbert, 2010). Internal fluctuations cannot be measured behaviorally or from conventional neurophysiological measures, so their effects on performance have been difficult to study. Previously, we measured fluctuations in visual attention using the responses of populations of simultaneously recorded neurons in macaque visual cortex (Cohen and Maunsell, 2010). Here, we use this ability to investigate how attentional fluctuations affect performance. We found that attentional fluctuations have large and complex effects on performance, the sign of which depends on the difficulty of the perceptual judgment. As expected, attention greatly improves the detection of subtle changes in a stimulus. Surprisingly, we found that attending too strongly to a particular stimulus impairs the ability to notice when that stimulus changes dramatically. Our results suggest that all previously reported measures of behavioral performance should be viewed as amalgamations of different attentional states, whether or not those studies specifically addressed attention.
PKA/AKAP1 and PP2A/Bβ2 Regulate Neuronal Morphogenesis via Drp1 Phosphorylation and Mitochondrial Bioenergetics
Authors: Dickey Audrey S. , Strack Stefan
Published: November 2011

Mitochondrial shape is determined by fission and fusion reactions, perturbation of which can contribute to neuronal injury and disease. Mitochondrial fission is catalyzed by dynamin-related protein 1 (Drp1), a large GTPase of the dynamin family that is highly expressed in neurons and regulated by various posttranslational modifications, including phosphorylation. We report here that reversible phosphorylation of Drp1 at a conserved Ser residue by an outer mitochondrial kinase (PKA/AKAP1) and phosphatase (PP2A/Bβ2) impacts dendrite and synapse development in cultured rat hippocampal neurons. PKA/AKAP1-mediated phosphorylation of Drp1 at Ser656 increased mitochondrial length and dendrite occupancy, enhancing dendritic outgrowth but paradoxically decreasing synapse number and density. Opposing PKA/AKAP1, PP2A/Bβ2-mediated dephosphorylation of Drp1 at Ser656 fragmented and depolarized mitochondria and depleted them from dendrites, stunting dendritic outgrowth but augmenting synapse formation. Raising and lowering intracellular calcium reproduced the effects of dephospho-Drp1 and phospho-Drp1on dendrite and synapse development, respectively, while boosting mitochondrial membrane potential withl-carnitine-fostered dendrite at the expense of synapse formation without altering mitochondrial size or distribution. Thus, outer mitochondrial PKA and PP2A regulate neuronal development by inhibiting and promoting mitochondrial division, respectively. We propose that the bioenergetic state of mitochondria, rather than their localization or shape per se, is the key effector of Drp1, altering calcium homeostasis to modulate neuronal morphology and connectivity.
Diminished Top-Down Control Underlies a Visual Imagery Deficit in Normal Aging
Authors: Kalkstein Jonathan , Checksfield Kristen , Bollinger Jacob , Gazzaley Adam
Published: November 2011

Mental imagery is involved in a wide variety of cognitive abilities, including reasoning, spatial navigation, and memory. Cognitive aging is associated with impairments in these abilities, suggesting that diminished fidelity of mental images in older adults may be related to diverse cognitive deficits. However, an age-related deficit in mental imagery and its role in memory impairment is still a matter of debate. Previous human fMRI studies demonstrated that visual imagery activates representations in category-selective visual cortex via top-down control mechanisms. Here, we use fMRI to show that normal aging is associated with diminished selectivity of visual cortex activation during visual imagery, with a corresponding reduction in the selectivity of functional connections between prefrontal cortex and visual cortices. Moreover, a relationship between reduced imagery selectivity and visual memory in older adults was established. These results reveal that aging disrupts neural networks that subserve mental imagery and offers evidence of this as a factor in age-related memory decline.
Dynamic Analysis of Amyloid β-Protein in Behaving Mice Reveals Opposing Changes in ISF versus Parenchymal Aβ during Age-Related Plaque Formation
Authors: Hong Soyon , Quintero-Monzon Omar , Ostaszewski Beth L. , Podlisny Daniel R. , Cavanaugh William T. , Yang Ting , Holtzman David M. , Cirrito John R. , Selkoe Dennis J.
Published: November 2011

Growing evidence supports the hypothesis that soluble, diffusible forms of the amyloid β-peptide (Aβ) are pathogenically important in Alzheimer's disease (AD) and thus have both diagnostic and therapeutic salience. To learn more about the dynamics of soluble Aβ economyin vivo, we used microdialysis to sample the brain interstitial fluid (ISF), which contains the most soluble Aβ species in brain at steady state, in >40 wake, behaving APP transgenic mice before and during the process of Aβ plaque formation (age 3–28 months). Diffusible forms of Aβ, especially Aβ42, declined significantly in ISF as mice underwent progressive parenchymal deposition of Aβ. Moreover, radiolabeled Aβ administered at physiological concentrations into ISF revealed a striking difference in the fate of soluble Aβ in plaque-rich (vs plaque-free) mice: it clears more rapidly from the ISF and becomes more associated with the TBS-extractable pool, suggesting that cerebral amyloid deposits can rapidly sequester soluble Aβ from the ISF. Likewise, acute γ-secretase inhibition in plaque-free mice showed a marked decline of Aβ38, Aβ40, and Aβ42, whereas in plaque-rich mice, Aβ42declined significantly less. These results suggest that most of the Aβ42that populates the ISF in plaque-rich mice is derived not from new Aβ biosynthesis but rather from the large reservoir of less soluble Aβ42in brain parenchyma. Together, these and other findings herein illuminate thein vivodynamics of soluble Aβ during the development of AD-type neuropathology and after γ-secretase inhibition and help explain the apparent paradox that CSF Aβ42levels fall as humans develop AD.
Selective Inhibition of Striatal Fast-Spiking Interneurons Causes Dyskinesias
Authors: Gittis Aryn H. , Leventhal Daniel K. , Fensterheim Benjamin A. , Pettibone Jeffrey R. , Berke Joshua D. , Kreitzer Anatol C.
Published: November 2011

Fast-spiking interneurons (FSIs) can exert powerful control over striatal output, and deficits in this cell population have been observed in human patients with Tourette syndrome and rodent models of dystonia. However, a direct experimental test of striatal FSI involvement in motor control has never been performed. We applied a novel pharmacological approach to examine the behavioral consequences of selective FSI suppression in mouse striatum. IEM-1460, an inhibitor of GluA2-lacking AMPARs, selectively blocked synaptic excitation of FSIs but not striatal projection neurons. Infusion of IEM-1460 into the sensorimotor striatum reduced the firing rate of FSIs but not other cell populations, and elicited robust dystonia-like impairments. These results provide direct evidence that hypofunction of striatal FSIs can produce movement abnormalities, and suggest that they may represent a novel therapeutic target for the treatment of hyperkinetic movement disorders.
Matrix Metalloproteinase-9 and Stromal Cell-Derived Factor-1 Act Synergistically to Support Migration of Blood-Borne Monocytes into the Injured Spinal Cord
Authors: Zhang Haoqian , Trivedi Alpa , Lee Jung-Uek , Lohela Marja , Lee Sang Mi , Fandel Thomas M. , Werb Zena , Noble-Haeusslein Linda J.
Published: November 2011

The infiltration of monocytes into the lesioned site is a key event in the inflammatory response after spinal cord injury (SCI). We hypothesized that the molecular events governing the infiltration of monocytes into the injured cord involve cooperativity between the upregulation of the chemoattractant stromal cell-derived factor-1 (SDF-1)/CXCL12 in the injured cord and matrix metalloproteinase-9 (MMP-9/gelatinase B), expressed by infiltrating monocytes. SDF-1 and its receptor CXCR4 mRNAs were upregulated in the injured cord, while macrophages immunoexpressed CXCR4. When mice, transplanted with bone marrow cells from green fluorescent protein (GFP) transgenic mice, were subjected to SCI, GFP+ monocytes infiltrated the cord and displayed gelatinolytic activity.In vitrostudies confirmed that SDF-1α, acting through CXCR4, expressed on bone marrow-derived macrophages, upregulated MMP-9 and stimulated MMP-9-dependent transmigration across endothelial cell monolayers by 2.6-fold. There was a reduction in F4/80+ macrophages in spinal cord-injured MMP-9 knock-out mice (by 36%) or wild-type mice, treated with the broad-spectrum MMP inhibitor GM6001 (by 30%). Mice were adoptively transferred with myeloid cells and treated with the MMP-9/-2 inhibitor SB-3CT, the CXCR4 antagonist AMD3100, or a combination of both drugs. While either drug resulted in a 28–30% reduction of infiltrated myeloid cells, the combined treatment resulted in a 45% reduction, suggesting that SDF-1 and MMP-9 function independently to promote the trafficking of myeloid cells into the injured cord. Collectively, these observations suggest a synergistic partnership between MMP-9 and SDF-1 in facilitating transmigration of monocytes into the injured spinal cord.
Fórmulas DRIS para o diagnóstico nutricional de pomares de cupuaçueiros
Authors: Wadt Paulo Guilherme Salvador , Dias Jairo Rafael Machado , Perez Daniel Vidal , Lemos Cleigiane de Oliveira
Published: November 2011

O objetivo foi avaliar o desempenho das fórmulas DRIS na avaliação do estado nutricional de pomares de cupuaçu. Análises foliares de 153 pomares comerciais localizados no distrito de Nova Califórnia, Porto Velho, Brasil, foram usadas para comparar os diagnósticos proporcionados pelas fórmulas de Beaufils, usando-se relações bivariadas log-transformadas e adotando-se o critério do Potencial de Resposta à Adubação para a interpretação dos índices DRIS. Foram avaliadas a coincidência do diagnóstico obtido pelas diferentes fórmulas, a frequência de ocorrência de cada nutriente nos diferentes tipos de estado nutricional e feita a análise multivariada para discriminar os diagnósticos entre as fórmulas adotadas. Os resultados sugerem que as fórmulas DRIS de Beaufils e de Jones são semelhantes entre si, sendo a fórmula de Wadt et al. distinta das demais, considerando-se todas as comparações realizadas entre as três fórmulas. No momento, os resultados não permitem a escolha de qualquer uma destas fórmulas como a mais indicada para adoção em programas de recomendação de adubação.
Eficiência do uso da água das culturas do milho e do feijão-caupi sob sistemas de plantio exclusivo e consorciado no semiárido brasileiro
Authors: Souza Luciana Sandra Bastos de , Moura Magna Soelma Beserra de , Sediyama Gilberto Chohaku , Silva Thieres George Freire da
Published: November 2011

O objetivo deste trabalho foi analisar a resposta produtiva, a eficiência do uso de água e a viabilidade econômica de cultivos de milho e de feijão-caupi em sistemas de plantio exclusivo e consorciado na região semiárida do Nordeste brasileiro. O experimento foi desenvolvido no município de Petrolina (PE). As culturas, nos diferentes sistemas de plantio (exclusivo e consorciado), foram submetidas a cinco lâminas de irrigação, aplicadas logo após o pendoamento no milho e na fase de floração do feijão-caupi aos 40 dias depois da semeadura. Combinando as configurações de sistema de cultivo e as diferentes lâminas de irrigação, as culturas do milho e do feijão-caupi foram submetidas a 15 tratamentos distintos. Para avaliar o desempenho das culturas nos diferentes tratamentos foram utilizados indicadores que consideram a resposta produtiva da cultura e o desempenho de aplicação de água no sistema de produção. Estes foram calculados por meio de dados de rendimento total, da relação entre os preços da produção comercial de grãos e da lâmina de água aplicada ao sistema. A produtividade de grãos das culturas do milho e feijão-caupi em resposta à disponibilidade hídrica no solo foi menor no plantio consorciado, em relação ao plantio exclusivo. Mesmo assim, em termos econômicos a adoção do consórcio foi mais vantajosa.
Cento e vinte anos de totais extremos de precipitação pluvial máxima diária em Campinas, Estado de São Paulo: análises estatísticas
Authors: Blain Gabriel Constantino
Published: November 2011

O objetivo do trabalho foi descrever, com base na distribuição geral dos valores extremos (GEV), a probabilidade de ocorrência associada aos totais máximos anuais de precipitação pluvial diária (Preabs), observados na localidade de Campinas entre 1890 e 2009, verificando também qual método, máxima verossimilhança ou momentos-L, resultam no melhor desempenho da GEV no referido propósito. Após verificação estatística da inexistência de significativas correlações seriais, tendências e periodicidades, observou-se que a GEV pode ser utilizada na descrição das probabilidades associadas aos dados de Preabs, na localidade de Campinas. O método da máxima verossimilhança mostrou-se, por meio do teste Lilliefors e de gráficos Quantil-Quantil, o melhor algoritmo para estimação dos parâmetros da GEV. Verificou-se ganho de energia no sinal temporal da série analisada após 1990. Essa característica espectral, também verificada entre 1920 e 1935, indica concentração dos valores mais elevados de Preabs nos referidos períodos.
Perfil de humor de mulheres com fibromialgia
Authors: Brandt Ricardo , Fonseca Alessandra Bertinatto Pinto , Oliveira Lays Guimarães Amorim de , Steffens Ricardo de Azevedo Klumb , Viana Maick da Silveira , Andrade Alexandro
Published: November 2011

OBJETIVO: O objetivo deste estudo foi verificar o perfil dos estados de humor de mulheres com fibromialgia, bem como analisar sua associação com características sociodemográficas e clínicas. MÉTODOS: Cento e seis participantes responderam ao Questionário Sociodemográfico e Clínico (QSDC) e à Escala de Humor de Brunel (BRUMS). O QSDC é constituído por perguntas sobre dados pessoais e aspectos clínicos, enquanto o BRUMS avalia o humor por meio de seis fatores, a saber: tensão, depressão, raiva, vigor, fadiga e confusão mental. Os dados foram tratados com estatística descritiva e por meio dos testes de Kruskal-Wallis e Mann-Whitney. RESULTADOS: As variáveis negativas do humor estiveram em níveis elevados, em especial a tensão, a depressão, a fadiga e a confusão mental, enquanto o vigor esteve baixo. Verificou-se ainda que as participantes mais jovens que trabalham com diagnóstico de depressão e, principalmente, as que possuíam maior número de sintomas relacionados à fibromialgia apresentavam humor mais deprimido do que seus pares. CONCLUSÃO: Mulheres com fibromialgia apresentaram tendência de humor deprimido, sendo que essa característica se apresentou associada a fatores sociodemográficos e clínicos.
Treinamento físico intervalado como ferramenta na terapia cognitivo-comportamental do transtorno de pânico
Authors: Sardinha Aline , Araújo Claudio Gil Soares de , Nardi Antonio Egidio
Published: November 2011

Este trabalho consiste no relato da utilização de um programa de exercícios físicos aeró-bicos intervalados no contexto da terapia cognitivo-comportamental em um caso de transtorno de pânico e agorafobia. São descritos os procedimentos utilizados, bem como os resultados positivos obtidos na redução da ansiedade cardíaca e na ansiedade cotidiana em relação a situações que exigem esforço físico.
Aplicação dos testes de padrão temporal em crianças com gagueira desenvolvimental persistente
Authors: Silva Rosimeire da , Oliveira Cristiane Moço Canhetti de , Cardoso Ana Cláudia Vieira
Published: November 2011

OBJETIVO: caracterizar e comparar o desempenho das crianças com diagnóstico de gagueira nos testes de padrão temporal, com crianças sem queixas e/ou sinais de transtornos psiquiátricos ou neurológicos, dificuldades de fala, audição, linguagem e/ou aprendizagem. MÉTODO: participaram 30 crianças entre 9 e 12 anos de idade, de ambos os gêneros, divididas em dois grupos: GI - 15 crianças com gagueira desenvolvimental persistente; GII - 15 crianças sem queixas e/ou sinais de transtornos psiquiátricos ou neurológicos, dificuldades de fala, audição, linguagem e/ou aprendizagem. Para avaliação do processamento auditivo temporal, foi aplicado os Testes Tonais de Padrão de Frequência (PPS-Pitch Pattern Sequence Test) e Testes Tonais de Padrão de Duração (DPS - Duration Pattern Sequence Test). RESULTADOS: o grupo II apresentou desempenho superior no teste de padrão de frequência e de padrão de duração quando comparado ao grupo I. Os resultados indicaram que houve diferença estatisticamente significante entre os grupos estudados. CONCLUSÃO: os participantes do grupo I apresentaram desempenho alterado nos testes de padrão temporal, o que indica que existe relação entre a gagueira e o transtorno do processamento auditivo.
Desempenho, características da carcaça, digestibilidade aparente dos nutrientes, metabolismo de nitrogênio e parâmetros ruminais de cordeiros alimentados com rações contendo polpa cítrica úmida semidespectinada e/ou polpa cítrica desidratada
Authors: Rodrigues Gustavo Henrique , Susin Ivanete , Pires Alexandre Vaz , Nussio Luiz Gustavo , Gentil Renato Shinkai , Ferreira Evandro Maia , Biehl Marcos Vinicius , Ribeiro Michele Ferreira
Published: November 2011

O objetivo neste estudo foi avaliar os efeitos da substituição parcial da polpa cítrica desidratada (PCD) pela polpa cítrica úmida semidespectinada in natura (PCUD), silagem de polpa cítrica úmida semidespectinada (PCUDS) ou silagem de polpa cítrica úmida semidespectinada adicionada de benzoato de sódio (PCUDS+B) sobre o desempenho, as características da carcaça, a digestibilidade aparente dos nutrientes, os parâmetros ruminais e o metabolismo de nitrogênio. Na avaliação de desempenho, 64 cordeiros Santa Inês foram alimentados com rações contendo 95% de concentrado e 5% de bagaço de cana-de-açúcar in natura durante 56 dias. O delineamento experimental utilizado foi o de blocos completos casualizados (BCC). A dieta controle continha 69,5% de PCD e foi substituída em 30% na matéria seca (MS) pela PCUD, PCUDS ou PCUDS+B. Não houve diferença no consumo de MS, no ganho médio diário de peso e nas características das carcaças. No entanto, a eficiência alimentar dos cordeiros alimentados com PCUD foi maior que a daqueles alimentados com PCD. No ensaio de metabolismo, 16 borregos Santa Inês, canulados no rúmen, foram distribuídos em BCC e alimentados com rações contendo 85% de concentrado e 15% de bagaço de cana-de-açúcar in natura. A dieta controle continha 75,3% de PCD e foi substituída em 30% na MS pela PCUD, PCUDS ou PCUDS+B. Não houve diferença nos coeficientes de digestibilidade da MS, matéria orgânica e proteína bruta. O coeficiente de digestibilidade da fibra em detergente neutro, porém foi maior para a PCUD comparado à PCD. A concentração de amônia no fluido ruminal foi maior para as rações contendo PCD em comparação àquelas com PCUDS e PCUDS+B. No entanto, para os demais parâmetros ruminais não foi verificado efeito dos tratamentos. A PCUD in natura ou ensilada pode substituir parcialmente a PCD em rações com alta proporção de concentrado para cordeiros em confinamento.
O conceito de reabsorções dentárias ou As reabsorções dentárias não são multifatoriais, nem complexas, controvertidas ou polêmicas!
Authors: Consolaro Alberto
Published: November 2011

Os mecanismos das reabsorções dentárias são conhecidos e suas causas bem definidas. Clinicamente são assintomáticas e não induzem alterações pulpares, periapicais e periodontais, sendo geralmente consequências delas. As reabsorções dentárias são alterações locais e adquiridas e não representam manifestações dentárias de doenças sistêmicas. As reabsorções dentárias ocorrem quando as estruturas de proteção dos dentes em relação à remodelação óssea são eliminados, especialmente os cementoblastos e restos epiteliais de Malassez.
Primary Vitreoretinal Lymphoma: A Report from an International Primary Central Nervous System Lymphoma Collaborative Group Symposium
Authors: Chan Chi-Chao , Rubenstein James L. , Coupland Sarah E. , Davis Janet L. , Harbour J. William , Johnston Patrick B. , Cassoux Nathalie , Touitou Valerie , Smith Justine R. , Batchelor Tracy T. , Pulido Jose S.
Published: November 2011

Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous. Conversely, 65%–90% of PVRL patients develop CNS lymphoma. Consequently, PVRL is often fatal because of ultimate CNS association. Current PVRL animal models are limited and require further development. Typical clinical findings include vitreous cellular infiltration (lymphoma and inflammatory cells) and subretinal tumor infiltration as determined using dilated fundoscopy, fluorescent angiography, and optical coherent tomography. Currently, PVRL is most often diagnosed using both histology to identify lymphoma cells in the vitreous or retina and immunohistochemistry to indicate monoclonality. Additional adjuncts in diagnosing PVRL exist, including elevation of interleukin-10 levels in ocular fluids and detection of IgH or T-cell receptor gene rearrangements in malignant cells. The optimal therapy for PVRL is not defined and requires the combined effort of oncologists and ophthalmologists. PVRL is sensitive to radiation therapy and exhibits high responsiveness to intravitreal methotrexate or rituximab. Although systemic chemotherapy alone can result in high response rates in patients with PVRL, there is a high relapse rate. Because of the disease rarity, international, multicenter, collaborative efforts are required to better understand the biology and pathogenesis of PVRL as well as to define both diagnostic markers and optimal therapies.
Transflective blue‐phase liquid‐crystal display with corrugated electrode structure
Authors: Cui Jian‐Peng , Wang Qiong‐Hua , Zhou Feng
Published: November 2011

Abstract— A transflective polymer‐stabilized blue‐phase liquid‐crystal display (BP‐LCD) with a corrugated electrode structure is proposed. To balance the optical phase retardation between the transmissive (T) and reflective (R) regions, two device structures are proposed. The first device structure has the same inclination angles but different cell gaps in the T and R regions. And the second device structure has the same cell gap but different inclination angles in the T and R regions. Both of the device structures can obtain well‐matched VT and VR curves. This display exhibits low operating voltage, high optical efficiency, and a wide viewing angle.
A new class of bookshelf bistable siloxane modified ferroelectric LC materials with electrical repairability in an LCoS configuration
Authors: Xu Huan , Moore John R. , Crossland William A. , Clapp Terry V. , Hannington Jonathan P. , Nishida Fumi
Published: November 2011

Abstract— Investigation of siloxane‐based ferroelectric liquid crystals (Si‐FLCs) has revealed chevron‐free long‐term bistable behavior and, unusually, an easy regeneration of bistable performance after damage (e.g., by mechanical shock). The properties are intrinsically related to the chemical structure of the oligosiloxane materials. The phenomena result from the coupling of siloxane and organic moieties that causes nano‐phase segregation, which essentially reduces the correlation of tilting from adjacent layers and also generates weak anchoring by decoupling the bulk structure from the strong surface anchoring. A method of regenerating a condition with bistable performance by an electric field (without mechanical and heat treatment) is established. An in‐house Si‐FLC over a silicon (Si‐FLCoS) device is demonstrated, which exhibits good memory effects without chevron defects and a repair function for regenerating bistability in case of damage.
Narrow‐gap field‐sequential TN‐LCD with and without nanoparticle doping
Authors: Kobayashi Shunsuke , Kundu Brindaban , Miyama Tomohiro , Shiraishi Yukihide , Sawai Hiroya , Toshima Naoki , Okita Masaya , Takeuchi Kiyofumi , Takatsu Haruyoshi
Published: November 2011

Abstract— The fabrication and demonstration of field‐sequential‐color (FSC) LCDs using modules of narrow‐gap twisted‐nematic (NTN) LCDs with and without doping of newly synthesized PγCyD‐ZrO2 nanoparticles is reported. Two types of FSC‐LCDs are demonstrated: one is a direct multiplexed NTN‐LCD and the other is TFT driven. The advantages of FSC‐LCDs include their high legibility even under direct sunlight, and the mechanism for the doping of nanoparticles in LCDs is discussed.
High‐performance white OLEDs with high color‐rendering index for next‐generation solid‐state lighting
Authors: Komoda Takuya , Ide Nobuhiro , Varutt Kittichungchit , Yamae Kazuyuki , Tsuji Hiroya , Matsuhisa Yuko
Published: November 2011

Abstract— Several white‐OLED structures with a high color‐rendering index (CRI) were investigated for lighting applications. A two‐unit fluorescent/phosphorescent hybrid white OLED achieved an excellent CRI of 95, high luminous efficacy of 37 lm/W, and long lifetime of over 40,000 hours at 1000 cd/m2. White‐OLED lighting panels of 8 × 8 cm for high‐luminance operation were fabricated, and a stable emission at 3000 cd/m2 was confirmed. Quite a small variation in chromaticity in a different directions was achieved by using an optimized optical device structure. With a light‐outcoupling substrate, a higher efficacy of 56 lm/W, high CRI of 91, and longer half‐decay lifetime of over 150,000 hours at 1000 cd/m2 was achieved. All‐phosphorescent white OLEDs placed on the light‐outcoupling substrate show a high CRI of 85 and higher efficacy of 65 lm/W with a fairly good half‐decay lifetime of over 30,000 hours. With a further voltage reduction and a high‐index spherical extractor, 128 lm/W at 1000 cd/m2 has been achieved.
Blockade of MUC1 Expression by Glycerol Guaiacolate Inhibits Proliferation of Human Breast Cancer Cells
Authors: Smith J.S. , Colon J. , Madero-Visbal R. , Isley B. , Konduri S.D. , Baker C.H.
Published: November 2011

We sought to determine whether administration of glycerol guaiacolate at an optimal biological dose inhibits human breast cancer cell growth. Human breast cancer MCF-7 and ZR-75-1 cells were treated with glycerol guaiacolate and the therapeutic efficacy and biological activity of this drug was investigated on breast cancer cell growth. MCF-7 cells were injected into the mammary fat pad of overectamized female athymic nude mice. Ten days later, animals were treated with daily intraperitoneal injections of glycerol guaiacolate for six weeks. Tumor size and volume was monitored and immunohistochemical analysis on MUC1, p21 and ki-67 was performed. Glycerol guaiacolate decreased breast cancer cell growth in a dose-dependent manner, decreased cell migration, and caused G1 cell cycle arrest. Our results demonstrate that glycerol guaiacolate inhibits MUC1 protein and mRNA expression levels and significantly increased p21 expression in human breast cancer cells as well as induced PARP cleavage. Similarly, glycerol guaiacolate inhibited breast tumor growth in vivo as well as enhanced p21 expression and decreased breast tumor cell proliferation (ki-67 expression). Collectively, our results demonstrate that glycerol guaiacolate decreased MUC1 expression and enhanced cell growth inhibition by inducing p21 expression in breast cancer cells. These findings suggest that glycerol guaiacolate may provide a novel and effective approach for the treatment of human breast cancer.
Silver nanoparticles sintering at low temperature on a copper substrate: In situ characterization under inert atmosphere and air
Authors: Sopousek J. , Bursik J. , Zalesak J. , Pesina Z.
Published: November 2011

Silver nanoparticles (Ag-NPs) were prepared by wet synthesis. The Ag-NPs
suspension and the copper substrate plate were used for a preparation of
substrate-nanoparticle-substrate samples. The sandwich like samples Cu/Ag/Cu
were prepared and investigated in-situ at the isothermal external conditions
(IEC) and inside apparatus for simultaneous thermal analysis STA409 (DSC).
The in-situ results of the electrical resistance were recorded during the
Cu/Ag/Cu (IEC) sample preparation and heat treatment. Thermal effects of the
Ag-NPs sintering between copper substrates were measured by differential
scanning calorimetry (DSC) under different atmospheres. The prepared Cu/Ag/Cu
sandwich samples were characterised by means of both optical and electron
microscopy. The process of the low temperature sintering inside calorimeter
of the Ag-NPs was monitored using both thermogravimetry (TG) and DSC
technique under inert gas and under synthetic air. The exothermic heat effect
of nanosilver sintering was evaluated.