bluuebunny/crossref_metadata_2025 huggingface dataset:
Minireview: The Busy Road to Pheochromocytomas and Paragangliomas Has a New Member, TMEM127
Authors: Jiang Shoulei , Dahia Patricia L. M.
Published: March 2011

Characterization of the entire spectrum of cancer-associated genetic disruptions is an overarching goal of contemporary and future oncology and can inform on patient diagnosis, treatment, and surveillance. Hereditary endocrine tumors, by having the potential to reveal the cancer's primary molecular defect, have been especially informative in this realm. Within this group, pheochromocytomas and paragangliomas, neural crest-derived, catecholamine-secreting tumors have come to represent true conduits for gene discovery. About one-third of pheochromocytomas and paragangliomas are now known to result from germline mutations in one of at least eight genes that belong to a variety of functional classes. Greater understanding of the molecular signals transduced by these genes and their respective mutants has advanced our understanding of kinase signaling pathways, hypoxia regulation, and the link between metabolic disruptions and cell growth. A new susceptibility gene without homology to other functional classes has been recently identified and encodes for a three-spanner transmembrane protein, transmembrane protein 127 (TMEM127). Initial insights from in vitro and patient data suggest that this candidate tumor suppressor is linked to the endosomal system and the mechanistic target of rapamycin [formerly mammalian target of rapamycin (mTOR)] pathway, and that mutation carriers often have clinical features that are typically associated with sporadic forms of pheochromocytoma. Functional characterization of transmembrane protein 127 (TMEM127) and discovery of additional pheochromocytoma/paraganglioma susceptibility genes is likely to shed light on our understanding of these tumors and extend these insights to other cancers.
ERK-Regulated Double Cortin-Like Kinase (DCLK)-Short Phosphorylation and Nuclear Translocation Stimulate POMC Gene Expression in Endocrine Melanotrope Cells
Authors: Kuribara Miyuki , Jenks Bruce G. , Dijkmans Thomas F. , de Gouw Daan , Ouwens Debbie T. W. M. , Roubos Eric W. , Vreugdenhil Erno , Scheenen Wim J. J. M.
Published: March 2011

We tested whether double cortin-like kinase-short (DCLK-short), a microtubule-associated Ser/Thr kinase predominantly expressed in the brain, is downstream of the ERK signaling pathway and is involved in proopiomelanocortin gene (POMC) expression in endocrine pituitary melanotrope cells of Xenopus laevis. Melanotropes form a well-established model to study physiological aspects of neuroendocrine plasticity. The amphibian X. laevis adapts its skin color to the background light intensity by the release of α-MSH from the melanotrope cell. In frogs on a white background, melanotropes are inactive but they are activated during adaptation to a black background. Our results show that melanotrope activation is associated with an increase in DCLK-short mRNA and with phosphorylation of DCLK-short at serine at position 30 (Ser-30). Upon cell activation phosphorylated Ser-30-DCLK-short was translocated from the cytoplasm into the nucleus, and the ERK blocker U0126 inhibited this process. The mutation of Ser-30 to alanine also inhibited the translocation and reduced POMC expression, whereas overexpression stimulated POMC expression. This is the first demonstration of DCLK-short in a native endocrine cell. We conclude that DCLK-short is physiologically regulated at both the level of its gene expression and protein phosphorylation and that the kinase is effectively regulating POMC gene expression upon its ERK-mediated phosphorylation.
Images of Illness: How Causal Claims and Racial Associations Influence Public Preferences toward Diabetes Research Spending
Authors: Gollust Sarah E. , Lantz Paula M. , Ubel Peter A.
Published: March 2011

Despite the salience of health disparities in media and policy discourse, little previous research has investigated if imagery associating an illness with a certain racial group influences public perceptions. This study evaluated the influence of the media's presentation of the causes of type 2 diabetes and its implicit racial associations on attitudes toward people with diabetes and preferences toward research spending. Survey participants who viewed an article on genetic causation or social determinants of diabetes were more likely to support increased government spending on research than those viewing an article with no causal language, while participants viewing an article on behavioral choices were more likely to attribute negative stereotypes to people with diabetes. Participants who viewed a photo of a black woman accompanying the article were less likely to endorse negative stereotypes than those viewing a photo of a white woman, but those who viewed a photo of a glucose-testing device expressed the lowest negative stereotypes. The effect of social determinants language was significantly different for blacks and whites, lowering stereotypes only among blacks. Emphasizing the behavioral causes of diabetes, as is common in media coverage, may perpetuate negative stereotypes. While drawing attention to the social determinants that shape these behaviors could mitigate stereotypes, this strategy is unlikely to influence the public uniformly.
No Laughing Matter: The UAW and Gender Construction on Labor Radio in Fifties' America
Authors: Fones-Wolf Elizabeth
Published: March 2011

This essay analyzes the competing feminist and misogynists messages projected by the United Automobile Workers' radio program, Eye Opener, to explore the constraints that limited efforts to promote gender equity with the UAW in the fifties. In a time when gender relations were in flux, Eye Opener, for a brief time tried to include appeals to both labor feminists and males anxious about the new worlds that encroached into the work and home. Through an analysis of the program's scripts and listeners' responses, it offers insights into the contradictions facing a post-war labor movement concerned with both broadening its horizons while shoring up its members.
The Great Escape: How a Field Survived Hard Times
Authors: Fink Leon
Published: March 2011

Inaugurating a new section, Whither Labor History? Editor Leon Fink takes note of a curious paradox: labor history appears to be thriving even as the labor movement (at least in the U.S.) is withering at the vine. How can that be? A speculative short essay focuses on how the historians themselves seem to have responded to the changing, and generally more adverse terrain of their subject in the contemporary workplace. On balance, it is suggested, the field has turned to its margins and borderlands for new subjects while returning to political economy for analytic sustenance and understanding.
p53 coordinates cranial neural crest cell growth and epithelial-mesenchymal transition/delamination processes
Authors: Rinon Ariel , Molchadsky Alina , Nathan Elisha , Yovel Gili , Rotter Varda , Sarig Rachel , Tzahor Eldad
Published: March 2011

Neural crest development involves epithelial-mesenchymal transition (EMT), during which epithelial cells are converted into individual migratory cells. Notably, the same signaling pathways regulate EMT function during both development and tumor metastasis. p53 plays multiple roles in the prevention of tumor development; however, its precise roles during embryogenesis are less clear. We have investigated the role of p53 in early cranial neural crest (CNC) development in chick and mouse embryos. In the mouse, p53 knockout embryos displayed broad craniofacial defects in skeletal, neuronal and muscle tissues. In the chick, p53 is expressed in CNC progenitors and its expression decreases with their delamination from the neural tube. Stabilization of p53 protein using a pharmacological inhibitor of its negative regulator, MDM2, resulted in reduced SNAIL2 (SLUG) and ETS1 expression, fewer migrating CNC cells and in craniofacial defects. By contrast, electroporation of a dominant-negative p53 construct increased PAX7+ SOX9+ CNC progenitors and EMT/delamination of CNC from the neural tube, although the migration of these cells to the periphery was impaired. Investigating the underlying molecular mechanisms revealed that p53 coordinates CNC cell growth and EMT/delamination processes by affecting cell cycle gene expression and proliferation at discrete developmental stages; disruption of these processes can lead to craniofacial defects.
Regulation of endoderm formation and left-right asymmetry by miR-92 during early zebrafish development
Authors: Li Nan , Wei Chunyao , Olena Abigail F. , Patton James G.
Published: March 2011

microRNAs (miRNAs) are a family of 21-23 nucleotide endogenous non-coding RNAs that post-transcriptionally regulate gene expression in a sequence-specific manner. Typically, miRNAs downregulate target genes by recognizing and recruiting protein complexes to 3′UTRs, followed by translation repression or mRNA degradation. miR-92 is a well-studied oncogene in mammalian systems. Here, using zebrafish as a model system, we uncovered a novel tissue-inductive role for miR-92 during early vertebrate development. Overexpression resulted in reduced endoderm formation during gastrulation with consequent cardia and viscera bifida. By contrast, depletion of miR-92 increased endoderm formation, which led to abnormal Kupffer's vesicle development and left-right patterning defects. Using target prediction algorithms and reporter constructs, we show that gata5 is a target of miR-92. Alteration of gata5 levels reciprocally mirrored the effects of gain and loss of function of miR-92. Moreover, genetic epistasis experiments showed that miR-92-mediated defects could be substantially suppressed by modulating gata5 levels. We propose that miR-92 is a critical regulator of endoderm formation and left-right asymmetry during early zebrafish development and provide the first evidence for a regulatory function for gata5 in the formation of Kupffer's vesicle and left-right patterning.
Fine-tuning of Hh signaling by the RNA-binding protein Quaking to control muscle development
Authors: Lobbardi Riadh , Lambert Guillaume , Zhao Jue , Geisler Robert , Kim Hyejeong R. , Rosa Frederic M.
Published: March 2011

The development of the different muscles within the somite is a complex process that involves the Hedgehog (Hh) signaling pathway. To specify the proper number of muscle cells and organize them spatially and temporally, the Hh signaling pathway needs to be precisely regulated at different levels, but only a few factors external to the pathway have been described. Here, we report for the first time the role of the STAR family RNA-binding protein Quaking A (QkA) in somite muscle development. We show in zebrafish that the loss of QkA function affects fast muscle fiber maturation as well as Hh-induced muscle derivative specification and/or morphogenesis. Mosaic analysis reveals that fast fiber maturation depends on the activity of QkA in the environment of fast fiber progenitors. We further show that Hh signaling requires QkA activity for muscle development. By an in silico approach, we screened the 3′UTRs of known Hh signaling component mRNAs for the Quaking response element and found the transcription factor Gli2a, a known regulator of muscle fate development. Using destabilized GFP as a reporter, we show that the gli2a mRNA 3′UTR is a functional QkA target. Consistent with this notion, the loss of QkA function rescued slow muscle fibers in yot mutant embryos, which express a dominant-negative Gli2a isoform. Thus, our results reveal a new mechanism to ensure muscle cell fate diversity by fine-tuning of the Hh signaling pathway via RNA-binding proteins.
PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition
Authors: Liu Li , Qi Hongying , Wang Jianquan , Lin Haifan
Published: March 2011

The nuage is a germline-specific perinuclear structure that remains functionally elusive. Recently, the nuage in Drosophila was shown to contain two of the three PIWI proteins – Aubergine and Argonaute 3 (AGO3) – that are essential for germline development. The PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and function in epigenetic regulation and transposon control. Here, we report a novel nuage component, PAPI (Partner of PIWIs), that contains a TUDOR domain and interacts with all three PIWI proteins via symmetrically dimethylated arginine residues in their N-terminal domain. In adult ovaries, PAPI is mainly cytoplasmic and enriched in the nuage, where it partially colocalizes with AGO3. The localization of PAPI to the nuage does not require the arginine methyltransferase dPRMT5 or AGO3. However, AGO3 is largely delocalized from the nuage and becomes destabilized in the absence of PAPI or dPRMT5, indicating that PAPI recruits PIWI proteins to the nuage to assemble piRNA pathway components. As expected, papi deficiency leads to transposon activation, phenocopying piRNA mutants. This further suggests that PAPI is involved in the piRNA pathway for transposon silencing. Moreover, AGO3 and PAPI associate with the P body component TRAL/ME31B complex in the nuage and transposon activation is observed in tral mutant ovaries. This suggests a physical and functional interaction in the nuage between the piRNA pathway components and the mRNA-degrading P-body components in transposon silencing. Overall, our study reveals a function of the nuage in safeguarding the germline genome against deleterious retrotransposition via the piRNA pathway.
The Arabidopsis repressor of light signaling SPA1 acts in the phloem to regulate seedling de-etiolation, leaf expansion and flowering time
Authors: Ranjan Aashish , Fiene Gabriele , Fackendahl Petra , Hoecker Ute
Published: March 2011

Plants adjust their growth and development in response to the ambient light environment. These light responses involve systemic signals that coordinate differentiation of different tissues and organs. Here, we have investigated the function of the key repressor of photomorphogenesis SPA1 in different tissues of the plant by expressing GUS-SPA1 under the control of tissue-specific promoters in a spa mutant background. We show that SPA1 expression in the phloem vasculature is sufficient to rescue the spa1 mutant phenotype in dark-grown spa mutant seedlings. Expression of SPA1 in mesophyll, epidermis or root tissues of the seedling, by contrast, has no or only slight effects. In the leaf, SPA1 expression in both the phloem and the mesophyll is required for full complementation of the defect in leaf expansion. SPA1 in phloem and mesophyll tissues affected division and expansion of cells in the epidermal layer, indicating that SPA1 induces non-cell-autonomous responses also in the leaf. Photoperiodic flowering is exclusively controlled by SPA1 expression in the phloem, which is consistent with previous results showing that the direct substrate of the COP1/SPA complex, CONSTANS, also acts in the phloem. Taken together, our results highlight the importance of phloem vascular tissue in coordinating growth and development. Because the SPA1 protein itself is incapable of moving from cell to cell, we suggest that SPA1 regulates the activity of downstream component(s) of light signaling that subsequently act in a non-cell-autonomous manner. SPA1 action in the phloem may also result in mechanical stimuli that affect cell elongation and cell division in other tissues.
Transformation of Glucose to 5-Hydroxymethyl-2-furfural by SiO2–MgCl2 Composite
Authors: Yasuda Masahide , Nakamura Yasuhisa , Matsumoto Jin , Yokoi Haruhiko , Shiragami Tsutomu
Published: March 2011

5-Hydroxymethyl-2-furfural (2a) was formed in a 70% yield by dehydration of glucose in MeCN at 140 °C in an autoclave using a composite of MgCl2 with silica gel which served as an acid catalyst under dry conditions. 10% and 32% yields of 2a were obtained from mannose and galactose, respectively.
Understanding public preferences for prioritizing health care interventions in England: Does the type of health gain matter?
Authors: Mason Helen , Baker Rachel , Donaldson Cam
Published: March 2011

Objectives:

Health care budgets are finite and decisions must be made about which interventions to provide and, by implication, which will not be provided. The aim of this study was to investigate what features of health care interventions, including the type of health gain, are important to members of the public in England in making priority-setting decisions and to understand why.

Methods:

Q methodology was used with 52 members of the public in north east England. Respondents rank ordered 36 health care interventions from those they would give highest priority to through to those they would give lowest priority to. A form of factor analysis was used to reveal a small number of shared viewpoints.

Results:

Five factors emerged: ‘life saving to maximize the size of the health gain’, ‘everyone deserves a chance at life’, ‘(potential for) own benefit’, ‘maximum benefit for (perceived) lowest cost’ and ‘quality of life and social responsibility’. There were different views about which interventions should be given priority. Respondents considered not only the type of health gain received from an intervention as important, but also the size of the health gain, who received the health gain and an individual's personal responsibility.

Conclusions:

Aspects other than health gain need to be considered when soliciting the public's views of priorities for health care interventions.
General practitioner commissioning consortia and budgetary risk: Evidence from the modelling of ‘fair share’ practice budgets for mental health
Authors: Asthana Sheena , Gibson Alex , Hewson Paul , Bailey Trevor , Dibben Chris
Published: March 2011

Objectives:

To contribute to current policy debates regarding the devolution of commissioning responsibilities to locally-based consortia of general practices in England by assessing the potential magnitude and significance of budgetary risk for commissioning units of different sizes.

Methods:

Predictive distributions of practice-level mental health care resource needs (used by the Department of Health to set ‘fair-share’ practice budgets) are aggregated to a range of hypothetical, but spatially-contiguous, consortia serving populations of up to 400,000 patients. The resulting joint distributions describe the extent to which the legitimate mental health needs of consortia populations are likely to vary. Budgetary risk is calculated as the likelihood that a consortia's resource needs will, in any given year, exceed its allocation (taken as the mean of its predictive distribution) by more than 1%, 3%, 5% or 10%. The relationship between population size and budgetary risk is then explored.

Results:

If between 500 and 600 consortia are created in England (serving 87,000 to 104,000 patients) then, in order to meet the legitimate mental health needs of their patients, each year around 15 to 26 consortia will overspend by at least 5%, and one or two by at least 10%. The budgetary risk faced by consortia serving smaller/larger populations can be read off the graphs provided.

Conclusions:

Unless steps are taken to mitigate budgetary risk, the devolution of decision-making and introduction of fixed budgets is likely to result in significant financial instability. It will be difficult to reconcile the policy objectives of devolved commissioning, best met through relatively small and fully accountable consortia, with the need for financial stability, which is best met by pooling risk across larger populations.
Studentships and fellowships
Authors: Light Kate , Harden Melissa , Wright Kath
Published: March 2011

This edition of ‘What's on the web’ reviews websites that provide information about studentship and fellowship award schemes for both clinical and non-clinical researchers. The included organizations provide funding opportunities to researchers based in the UK and elsewhere at different stages of their research careers.

If you would like to alert readers to useful web pages or suggest topics for this column, please send details to:
The Wnt5/Planar Cell Polarity Pathway Regulates Axonal Development of theDrosophilaMushroom Body Neuron
Authors: Shimizu Kazumichi , Sato Makoto , Tabata Tetsuya
Published: March 2011

Axonal development is a fundamental process for circuit formation in the nervous system and is dependent on many cellular events, including axon initiation, elongation, guidance, and branching. The molecular mechanisms underlying these events have been well studied, especially for axon guidance. In the presence of a guidance cue, the polarization of a growth cone precedes the turning response, which is one example of the diverse forms of cell polarity. Planar cell polarity (PCP) is another example of cell polarity. Although some PCP genes are required for axonal tract formation in vertebrates, it remains elusive whether these genes participate in a common PCP pathway concertedly. Here, we show that essential PCP signaling components, encoded byfrizzled(fz),strabismus(stbm),flamingo(fmi), anddishevelled(dsh), are cooperatively required for axonal targeting and branching of theDrosophilamushroom body (MB) neurons. A detailed analysis of these mutants revealed that these components were required for the correct targeting and bifurcation of axons. In addition, we suggest that Wnt5 functions as a ligand in the PCP pathway in this process.Wnt5mutants showed similar phenotypes to PCP mutants at the single-cell level and genetically interacted with PCP genes. Wnt5 was broadly expressed in the developing brain. We propose that Wnt5 and the PCP pathway concertedly regulate axonal development of the MB.
Basal Ganglia Neurons Dynamically Facilitate Exploration during Associative Learning
Authors: Sheth Sameer A. , Abuelem Tarek , Gale John T. , Eskandar Emad N.
Published: March 2011

The basal ganglia (BG) appear to play a prominent role in associative learning, the process of pairing external stimuli with rewarding responses. Accumulating evidence suggests that the contributions of various BG components may be described within a reinforcement learning model, in which a broad repertoire of possible responses to environmental stimuli are evaluated before the most profitable one is chosen. The striatum receives diverse cortical inputs, providing a rich source of contextual information about environmental cues. It also receives projections from midbrain dopaminergic neurons, whose phasic activity reflects a reward prediction error signal. These coincident information streams are well suited for evaluating responses and biasing future actions toward the most profitable response. Still lacking in this model is a mechanistic description of how initial response variability is generated. To investigate this question, we recorded the activity of single neurons in the globus pallidus internus (GPi), the primary BG output nucleus, in nonhuman primates (Macaca mulatta) performing a motor associative learning task. A subset (29%) of GPi neurons showed learning-related effects, decreasing firing during the early stages of learning, then returning to higher baseline rates as associations were mastered. On a trial-by-trial basis, lower firing rates predicted exploratory behavior, whereas higher rates predicted an exploitive response. These results suggest that, during associative learning, BG output is initially permissive, allowing exploration of a variety of responses. Once a profitable response is identified, increased GPi activity suppresses alternative responses, sharpening the response profile and encouraging exploitation of the profitable learned behavior.
Bradykinin Promotes the Chemotactic Invasion of Primary Brain Tumors
Authors: Montana Vedrana , Sontheimer Harald
Published: March 2011

Primary brain tumors, gliomas, diffusely invade the brain by active cell migration either intraparenchymal, along white matter tracts or along blood vessels. The close relationship of glioma with the vasculature assures a continuous supply of oxygen and nutrients essential for cell growth, and exposes cells to a variety growth factors, chemokines, cytokines, and kinins. Signals that attract glioma cells to blood vessels are poorly understood. It has been shown that vascular endothelial cells can initiate the bradykinin (BK) signaling cascade and two bradykinin receptors, B1 and B2, have been identified and cloned. In this study we show that glioma cells isolated from patient biopsies express bradykinin 2 receptors (B2R) whose activation causes intracellular Ca2+oscillations. Through time-lapse video-microscopy experiments we show that BK significantly enhances glioma cell migration/invasion. We further show that BK acts as a chemoattractant guiding glioma cells toward blood vessels in acute rat brain slices. The number of cells associated with blood vessels is decreased when B2R are either pharmacologically inhibited or B2R eliminated through short-hairpin RNA knockdown. These data strongly suggest that bradykinin, acting via B2R, acts as an important signal directing the invasion of glioma cells toward blood vessels. A clinically approved B2R antagonist is available that could be used as anti-invasive drug in glioma patients in the future.
Fibroblast Growth Factor Signaling Is Required for the Generation of Oligodendrocyte Progenitors from the Embryonic Forebrain
Authors: Furusho Miki , Kaga Yoshimi , Ishii Akihiro , Hébert Jean M. , Bansal Rashmi
Published: March 2011

Fibroblast growth factors (FGFs) comprise a family of developmental regulators implicated in a wide variety of neurological functions. FGF receptors 1, 2, and 3 (Fgfrs) are expressed in the embryonic forebrain, including regions overlapping with ventral sites of oligodendrocyte progenitor (OLP) generation. Although FGF signaling is known to influence the proliferation of OLPsin vitro, functions of different Fgfrsin vivoare lacking. Here, we examined single and double mutants with conditional disruption ofFgfrs, specifically in the embryonic forebrain, to investigate the effect of FGFs on the generation and proliferation of OLPsin vivo. FGF signaling, through cooperation betweenFgfr1andFgfr2but notFgfr3, is required for the initial generation of OLPs in the mouse ventral forebrain, withFgfr1being a stronger inducer thanFgfr2. In cultures derived from embryonic mutant forebrains or from normal forebrains grown in the presence of Fgfr inhibitor, a strong attenuation of OLP generation was observed, supporting the role of FGF signalingin vivo. Contrary toin vitrofindings, Fgfr1 and Fgfr2 signaling is not required for the proliferation of OLPsin vivo. Finally, failure of OLP generation in theFgfrmutants occurred without loss of sonic hedgehog (Shh) signaling; and pharmacological inhibition of either Fgfr or hedgehog signaling in parallel cultures strongly inhibited OLP generation, suggesting that Fgfrs cooperate with Shh to generate OLPs. Overall, our results reveal for the first time an essential role of FGF signalingin vivo, where the three Fgfrs differentially control the normal generation of OLPs from the embryonic ventral forebrain.
A Portable Site: A Binding Element for 17β-Estradiol Can Be Placed on Any Subunit of a Nicotinic α4β2 Receptor
Authors: Jin Xiaochun , Steinbach Joe Henry
Published: March 2011

Endogenous steroids can modulate the activity of transmitter-gated channels by directly interacting with the receptor. 17β-Estradiol potentiates activation of neuronal nicotinic α4β2 receptors by interacting with a 4 aa sequence at the extreme C terminus of the α4 subunit, but it is not known whether potentiation requires that the sequence be placed on a specific subunit (e.g., an α4 subunit that is involved in forming an acetylcholine-binding site). By using concatemers of subunits and chimeric subunits, we have found that the C-terminal domain can be moved from the α4 to the β2 subunit and still result in potentiation. In addition, the sequence can be placed on a subunit that contributes to an acetylcholine-binding site or on the structural subunit. The data indicate that this estradiol-binding element is a discrete sequence and suggest that the effect of 17β-estradiol is mediated by actions on single subunits and that the overall consequences for gating occur because of the summation of independent energetic contributions to overall gating of this receptor.
Ventral Premotor Cortex May Be Required for Dynamic Changes in the Feeling of Limb Ownership: A Lesion Study
Authors: Zeller Daniel , Gross Catharina , Bartsch Andreas , Johansen-Berg Heidi , Classen Joseph
Published: March 2011

The feeling of “body ownership” may be experimentally investigated by perceptual illusions. The “rubber hand illusion” (RHI) leads human subjects to experience an artificial hand as their own. According to functional imaging, the ventral premotor cortex (PMv) plays a key role in the integration of multisensory inputs allowing the “incorporation” of the rubber hand into body representation. However, causal structure–function relationships can only be obtained by lesion studies.

Here, we tested the RHI in 70 stroke patients and in 40 age-matched healthy controls. Additionally, asomatognosia, the unawareness of one's own body parts, was assessed in a subgroup of 64 stroke patients. Ischemic lesions were delineated on diffusion-weighted magnetic resonance images and normalized. Right-hemispheric lesions were mirrored across the midline. Voxels that might be essential for RHI and/or somatognosia were defined by voxel-based lesion-symptom mapping. Probabilistic diffusion tractography was used to identify tracts passing through these voxels.

Contralesional rubber hand illusion failure (RHIF) was observed in 18 (26%) of 70 stroke patients, an additional ipsilesional RHIF in seven of these patients. RHIF-associated lesion voxels were located subcortically adjacent to the insula, basal ganglia, and within the periventricular white matter. Tractography revealed fiber tract connections of these voxels with premotor, parietal, and prefrontal cortex. Contralesional asomatognosia was found in 18 (28%) of 64 stroke patients. In contrast to RHIF, asomatognosia-associated lesion voxels showed no connection with PMv.

The results point to a role of PMv and its connections in mediating changes in the sense of limb ownership driven by multisensory stimulation.
Neuronal Mechanisms and Attentional Modulation of Corticothalamic Alpha Oscillations
Authors: Bollimunta Anil , Mo Jue , Schroeder Charles E. , Ding Mingzhou
Published: March 2011

Field potential oscillations in the ∼10 Hz range are known as the alpha rhythm. The genesis and function of alpha has been the subject of intense investigation for the past 80 years. Whereas early work focused on the thalamus as the pacemaker of alpha rhythm, subsequent slice studies revealed that pyramidal neurons in the deep layers of sensory cortices are capable of oscillating in the alpha frequency range independently. How thalamic and cortical generating mechanisms in the intact brain might interact to shape the organization and function of alpha oscillations remains unclear. We addressed this problem by analyzing laminar profiles of local field potential and multiunit activity (MUA) recorded with linear array multielectrodes from the striate cortex of two macaque monkeys performing an intermodal selective attention task. Current source density (CSD) analysis was combined with CSD–MUA coherence to identify intracortical alpha current generators and assess their potential for pacemaking. Coherence and Granger causality analysis was applied to delineate the patterns of interaction among different alpha current generators. We found that (1) separable alpha current generators are located in superficial, granular, and deep layers, with both layer 4C and deep layers containing primary local pacemaking generators, suggesting the involvement of the thalamocortical network, and (2) visual attention reduces the magnitude of alpha oscillations as well as the level of alpha interactions, consistent with numerous reports of occipital alpha reduction with visual attention in human EEG. There is also indication that alpha oscillations in the lateral geniculate cohere with those in V1.
Localization of Cortical Phase and Amplitude Dynamics during Visual Working Memory Encoding and Retention
Authors: Palva Satu , Kulashekhar Shrikanth , Hämäläinen Matti , Palva J. Matias
Published: March 2011

Several studies show that the amplitudes of human brain oscillations are modulated during the performance of visual working memory (VWM) tasks in a load-dependent manner. Less is known about the dynamics and identities of the cortical regions in which these modulations take place, and hence their functional significance has remained unclear. We used magnetoencephalography and electroencephalography together with minimum norm estimate-based source modeling to study the dynamics of ongoing brain activity during a parametric VWM task. Early stimulus processing and memory encoding were associated with a memory load-dependent spread of neuronal activity from occipital to temporal, parietal, and frontal cortical regions. During the VWM retention period, the amplitudes of oscillations in theta/alpha- (5–9 Hz), high-alpha- (10–14 Hz), beta- (15–30 Hz), gamma- (30–50 Hz), and high-gamma- (50–150 Hz) frequency bands were suppressed below baseline levels, and yet, in frontoparietal regions, load dependently strengthened. However, in occipital and occipitotemporal structures, only beta, gamma, and high-gamma amplitudes were robustly strengthened by memory load. Individual behavioral VWM capacity was predicted by both the magnitude of the N1 evoked response component in early visual regions and by the amplitudes of frontoparietal high-alpha and high-gamma band oscillations. Thus, both early stimulus processing and late retention period activities may influence the behavioral outcome in VWM tasks. These data support the notion that beta- and gamma-band oscillations support the maintenance of object representations in VWM whereas alpha-, beta-, and gamma-band oscillations together contribute to attentional and executive processing.
A Parallel Functional Topography between Medial and Lateral Prefrontal Cortex: Evidence and Implications for Cognitive Control
Authors: Taren Adrienne A. , Venkatraman Vinod , Huettel Scott A.
Published: March 2011

The dorsomedial and dorsolateral prefrontal cortices (dmPFC and dlPFC) together support cognitive control, with dmPFC responsible for monitoring performance and dlPFC responsible for adjusting behavior. The dlPFC contains a topographic organization that reflects complexity of control demands, with more anterior regions guiding increasingly abstract processing. Recent evidence for a similar gradient within dmPFC suggests the possibility of parallel, hierarchical organization. Here, we measured connectivity between functional nodes of dmPFC and dlPFC using resting-state functional magnetic resonance imaging in humans. We found a posterior-to-anterior connectivity gradient; posterior dmPFC maximally connected to posterior dlPFC and anterior dmPFC maximally connected to anterior dlPFC. This parallel topographic pattern replicated across three independent datasets collected on different scanners, within individual participants, and through both point-to-point and voxelwise analyses. We posit a model of cognitive control characterized by hierarchical interactions—whose level depends on current environmental demands—between functional subdivisions of medial and lateral PFC.
An Intrinsic Neural Oscillator in the Degenerating Mouse Retina
Authors: Borowska Joanna , Trenholm Stuart , Awatramani Gautam B.
Published: March 2011

The loss of photoreceptors during retinal degeneration (RD) is known to lead to an increase in basal activity in remnant neural networks. To identify the source of activity, we combined two-photon imaging with patch-clamp techniques to examine the physiological properties of morphologically identified retinal neurons in a mouse model of RD (rd1). Analysis of activity inrd1ganglion cells revealed sustained oscillatory (∼10 Hz) synaptic activity in ∼30% of all classes of cells. Oscillatory activity persisted after putative inputs from residual photoreceptor, rod bipolar cell, and inhibitory amacrine cell synapses were pharmacologically blocked, suggesting that presynaptic cone bipolar cells were intrinsically active. Examination of presynapticrd1ON and OFF bipolar cells indicated that they rested at relatively negative potentials (less than −50 mV). However, in approximately half the cone bipolar cells, low-amplitude membrane oscillation (∼5 mV, ∼10 Hz) were apparent. Such oscillations were also observed in AII amacrine cells. Oscillations in ON cone bipolar and AII amacrine cells exhibited a weak apparent voltage dependence and were resistant to blockade of synaptic receptors, suggesting that, as in wild-type retina, they form an electrically coupled network. In addition, oscillations were insensitive to blockers of voltage-gated Ca2+channels (0.5 mmCd2+and 0.5 mmNi2+), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in therd1retina that is likely to drive synaptic activity in downstream circuits.
Common and Distinct Mechanisms of Cognitive Flexibility in Prefrontal Cortex
Authors: Kim Chobok , Johnson Nathan F. , Cilles Sara E. , Gold Brian T.
Published: March 2011

The human ability to flexibly alternate between tasks represents a central component of cognitive control. Neuroimaging studies have linked task switching with a diverse set of prefrontal cortex (PFC) regions, but the contributions of these regions to various forms of cognitive flexibility remain largely unknown. Here, subjects underwent functional brain imaging while they completed a paradigm that selectively induced stimulus, response, or cognitive set switches in the context of a single task decision performed on a common set of stimuli. Behavioral results indicated comparable reaction time costs associated with each switch type. Domain-general task-switching activation was observed in the inferior frontal junction and posterior parietal cortex, suggesting core roles for these regions in switching such as updating and representing task sets. In contrast, multiple domain-preferential PFC activations were observed across lateral and medial PFC, with progressively more rostral regions recruited as switches became increasingly abstract. Specifically, highly abstract cognitive set switches recruited anterior-PFC regions, moderately abstract response switches recruited mid-PFC regions, and highly constrained stimulus switches recruited posterior-PFC regions. These results demonstrate a functional organization across lateral and medial PFC according to the level of abstraction associated with acts of cognitive flexibility.
Inflammatory Pain Unmasks Heterosynaptic Facilitation in Lamina I Neurokinin 1 Receptor-Expressing Neurons in Rat Spinal Cord
Authors: Torsney Carole
Published: March 2011

Central sensitization in inflammatory pain conditions results in behavioral mechanical hypersensitivity. Specifically, C-fiber-driven spinal hyperexcitability enables A fibers to gain access to specific spinal circuitry, via heterosynaptic facilitatory mechanisms, to mediate mechanical hypersensitivity. However, the precise circuitry engaged is not known. Lamina I neurokinin 1 (NK1) receptor expressing (NK1R+) dorsal horn neurons, many of which are projection neurons, are required for the development of this hypersensitivity and are therefore likely to be a component of this circuitry. To investigate, whole-cell patch-clamp recordings were made from lamina I NK1R+neurons in the spinal cord slice preparation with attached dorsal root, obtained from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation. EPSCs were recorded in response to electrical stimulation of the dorsal root. Control neurons predominantly received monosynaptic C-fiber input (69%) with a smaller proportion receiving monosynaptic Aδ-fiber input (28%). In contrast, CFA inflammation significantly increased the incidence (by twofold) and magnitude (by 75% in a subset) of monosynaptic Aδ-fiber but not monosynaptic C-fiber-evoked responses. Aβ-fiber input to lamina I NK1R+neurons was minimal, polysynaptic in nature, and unaltered by CFA inflammation. Additional examination of control neurons revealed that a proportion received silent monosynaptic Aδ-fiber input, suggesting that these may provide the substrate for the novel Aδ inputs observed in CFA inflammation. This inflammation induced unmasking and strengthening of monosynaptic Aδ drive to lamina I NK1R+neurons may contribute to the heterosynaptic facilitatory mechanisms underlying mechanical hyperalgesia in inflammatory pain.
Automatische Kommissionierung geometrisch unterschiedlicher Artikel
Authors: Bruns Rainer , Cleves Björn
Published: March 2011

Die Kommissionierung ist bedingt durch den hohen Anteil manueller Tätigkeiten der größte Kostenfaktor im Lagerumfeld. Zur Automatisierung der Hauptaufgaben eines Kommissionierers Erfassen und Erkennen von Artikeln werden Ansätze der industriellen Bildverarbeitung und der künstlichen Intelligenz aufgegriffen. Die Handhabung der Artikel wird durch ein am Lehrstuhl entwickeltes Greiferprinzip realisiert.
Hitler und der Juliputsch 1934 in Österreich. Eine Fallstudie zur nationalsozialistischen Außenpolitik in der Frühphase des Regimes
Authors: Bauer Kurt
Published: March 2011

Vorspann

Der Juliputsch von 1934 ist ein zentrales Ereignis der österreichischen und auch der deutschen Geschichte. Entsprechend gut ist es dokumentiert und erforscht. Eine der wichtigsten Fragen ist aber bis heute ungeklärt: Wie kam es überhaupt zu diesem frühen Versuch einer nationalsozialistischen Machtergreifung in Österreich? Und welche Rolle hat Hitler bei alldem gespielt? Mittlerweile sind so viele Quellen bekannt und auch systematisch ediert, dass hier erstmals überzeugend nachgewiesen werden kann, dass Hitler von Anfang an alle Fäden in der Hand hielt und dass auch in diesem Fall mitnichten von einem „schwachen Diktator“ die Rede sein kann.
Perfil epidemiológico dos pacientes em terapia renal substitutiva no Brasil, 2000-2004
Authors: Cherchiglia Mariangela Leal , Machado Elaine Leandro , Szuster Daniele Araújo Campo , Andrade Eli Iola Gurgel , Acúrcio Francisco de Assis , Caiaffa Waleska Teixeira , Sesso Ricardo , Guerra Junior Augusto A , Queiroz Odilon Vanni de , Gomes Isabel Cristina
Published: March 2011

OBJETIVO: Descrever o perfil epidemiológico e clínico de pacientes em terapia renal substitutiva, identificando fatores associados ao risco de morte. MÉTODOS: Estudo observacional, prospectivo não concorrente, a partir de dados de 90.356 pacientes da Base Nacional em Terapias Renais Substitutivas, no Brasil. Foi realizado relacionamento determinístico-probabilístico do Sistema de Autorização de Procedimentos de Alta Complexidade/Custo e do Sistema de Informação de Mortalidade. Foram incluídos todos os pacientes incidentes que iniciaram diálise entre 1/1/2000 e 31/12/2004, acompanhados até a morte ou final de 2004. Idade, sexo, região de residência, doença renal primária, causa do óbito foram analisados. Ajustou-se um modelo de riscos proporcionais para identificar fatores associados ao risco de morte. RESULTADOS: Ocorreu um aumento médio de 5,5% na prevalência de pacientes em terapia enquanto a incidência manteve-se estável no período. Hemodiálise foi a modalidade inicial predominante (89%). A maioria dos pacientes era do sexo masculino, com idade média de 53 anos, residente na região Sudeste, e apresentava causa indeterminada como principal causa básica da doença renal crônica, seguida da hipertensão, diabetes e glomerulonefrites. Desses pacientes, 7% realizou transplante renal e 42% evoluiu para o óbito. Os pacientes em diálise peritoneal eram mais idosos e apresentavam maior prevalência de diabetes. Entre os não transplantados, 45% foi a óbito e, entre os transplantados, 7%. No modelo final de riscos proporcionais de Cox, o risco de mortalidade foi associado com o aumento da idade, sexo feminino, ter diabetes, residir nas regiões Norte e Nordeste, diálise peritoneal como modalidade de entrada e não ter realizado transplante renal. CONCLUSÕES: Houve aumento da prevalência de pacientes em terapia renal no Brasil. Pacientes com idade avançada, diabetes, do sexo feminino, residentes nas regiões Norte e Nordeste e sem transplante renal apresentam maior risco de morte.
QUADAS e STARD: avaliação da qualidade de estudos de acurácia de testes diagnósticos
Authors: Oliveira Maria Regina Fernandes de , Gomes Almério de Castro , Toscano Cristiana Maria
Published: March 2011

OBJETIVO: Comparar duas abordagens baseadas em critérios do Quality Assessment of Diagnostic Accuracy Studies (QUADAS) e do Standards for Reporting Studies of Diagnostic Accuracy (STARD) na avaliação de qualidade de estudos de validação do teste rápido OptiMal®, para diagnóstico de malária. MÉTODOS: Foi realizada busca de artigos de validação do teste rápido na base bibliográfica Medline acessada pelo PubMed, no ano de 2007. Treze artigos foram recuperados na busca. Foram combinados 12 critérios do QUADAS e três do STARD para comparação com os critérios do QUADAS isoladamente. Foi considerado que artigos de regular a boa qualidade atenderiam pelo menos 50% dos critérios do QUADAS. RESULTADOS: Dos 13 artigos recuperados, 12 cumpriram pelo menos 50% dos critérios do QUADAS, e apenas dois atenderam à combinação dos critérios. Considerando-se a combinação dos dois critérios (> 6 QUADAS e > 3STARD), dois estudos (15,4%) apresentaram boa qualidade metodológica. A seleção de artigos usando a combinação proposta variou de dois a oito artigos, dependendo do número de itens considerados como ponto de corte. CONCLUSÕES: A combinação do QUADAS com o STARD tem o potencial de conferir maior rigor nas avaliações da qualidade de artigos publicados sobre validação de testes diagnósticos em malária, por incorporar a checagem de informações relevantes não alcançáveis pelo uso do QUADAS isoladamente.
Mortalidade por câncer de mama e câncer de colo do útero em município de porte médio da Região Sudeste do Brasil, 1980-2006
Authors: Rodrigues Anselmo Duarte , Bustamante-Teixeira Maria Teresa
Published: March 2011

Analisar a tendência da mortalidade por câncer de mama e câncer de colo do útero em mulheres residentes no Município de Juiz de Fora, Minas Gerais, Brasil, no período de 1980 a 2006. Os dados sobre os óbitos foram obtidos do Sistema de Informação sobre Mortalidade; as taxas de mortalidade específicas foram calculadas por idade e padronizadas pela população mundial. Para análise de tendência, foram aplicados modelos de regressão polinomial. O câncer de mama foi a principal causa de óbito entre as neoplasias na população de mulheres residentes no município, enquanto o câncer de colo do útero oscilou entre a segunda e a quarta causa no período do estudo. A análise de tendência mostrou queda da mortalidade por câncer de colo do útero (p = 0,001) e tendência de crescimento na mortalidade por câncer de mama (p = 0,035) ao longo dos anos da série. A mortalidade por câncer de mama e colo do útero no Município de Juiz de Fora sugere um processo de transição epidemiológica em andamento, com tendência crescente na mortalidade por câncer de mama e persistência de taxas elevadas por câncer de colo do útero.