bluuebunny/crossref_metadata_2025 huggingface dataset:
Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI
Authors: Poretti Andrea , Vitiello Giuseppina , Hennekam Raoul CM , Arrigoni Filippo , Bertini Enrico , Borgatti Renato , Brancati Francesco , D'Arrigo Stefano , Faravelli Francesca , Giordano Lucio , Huisman Thierry AGM , Iannicelli Miriam , Kluger Gerhard , Kyllerman Marten , Landgren Magnus , Lees Melissa M , Pinelli Lorenzo , Romaniello Romina , Scheer Ianina , Schwarz Christoph E , Spiegel Ronen , Tibussek Daniel , Valente Enza Maria , Boltshauser Eugen
Published: January 2012

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma.
Glycerol conversion to 1, 3-Propanediol is enhanced by the expression of a heterologous alcohol dehydrogenase gene in Lactobacillus reuteri
Authors: Vaidyanathan Hema , Kandasamy Vijayalakshmi , Gopal Ramakrishnan Gopi , Ramachandran KB , Jayaraman Guhan , Ramalingam Subramanian
Published: January 2012

In this work, Lactobacillus reuteri has been metabolically engineered for improving 1, 3-propanediol (1, 3-PD) production by the expression of an Escherichia coli alcohol dehydrogenase, yqhD, that is known to efficiently convert the precursor 3-hydroxypropionaldehyde (3-HPA) to 1, 3-PD. The engineered strain exhibited significantly altered formation rates for the product and other metabolites during the fermentation. An increase in the 1, 3-PD specific productivity of 34% and molar yield by 13% was achieved in the clone, relative to the native strain. A concomitant decrease in the levels of toxic intermediate, 3-HPA, was observed, with the specific productivity levels being 25% lesser than that of the native strain. Interestingly, the recombinant strain exhibited elevated rates of lactate and ethanol formation as well as reduced rate of acetate production, compared to the native strain. The preferential utilization of NADPH by YqhD with a possible decrease in the native 1, 3-PD oxidoreductase (NADH-dependent) activity, could have resulted in the diversion of surplus NADH towards increased lactate and ethanol productivities.
SEAM UPDATE: ELASTIC SIMULATIONS
Authors: Fehler Michael
Published: January 2012

SEAM is in the process of obtaining bids for elastic simulation on the SEAM elastic deepwater model that was constructed using funding from the Research Partnership to Secure Energy for America (RPSEA subcontract # 07121-2001). The model is an extension of the SEAM Phase I model that was originally constructed as a variable-density acoustic model. Parameters for shear-wave velocity have been derived in addition to tilted transverse isotropy (TTI) parameters and resistivity. A brief update on the ongoing TTI simulations and the completed controlled-source electromagnetic (CSEM) simulations is provided below.
An automatic network-extraction algorithm applied to magnetic survey data for the identification and extraction of geologic lineaments
Authors: Lee Madeline , Morris William , Harris Jeff , Leblanc George
Published: January 2012

Lineament analysis is commonly undertaken by interpreting a wide range of geoscientific data to delineate geologic structures. These structures include faults, fractures, dykes, and lithological contacts, which provide information for geologic mapping and mineral and energy exploration. We offer a simple automatic lineament analysis method that combines the principles of peak-identification algorithms typically used in geophysical data interpretation and a GIS drainage “network-extraction” algorithm commonly applied to a topographic surface. We apply this network-extraction process to a magnetic surface (grid) rather than a topographic one. The GIS approach calculates the curvature of a surface to determine whether a specific coordinate is at a minimum (trough). A simple quadratic surface is computed for a moving 3 × 3 window to determine if the local surface has the form of a dipping plane (or a trough). Continuity of troughs between adjacent kernels defines lineaments that typically correspond to streamflow pathways when analysis is carried out on a topographic surface. On a magnetic anomaly map surface, network extraction identifies magnetic lows that may represent faults that have undergone magnetite (depletion) alteration, or dykes with predominantly reversed polarity remanence. As network extraction is designed to locate troughs, it is possible to isolate normally magnetized dykes by inverting the values of a magnetic data set by to produce ridges. This modified ridge analysis method is successfully applied to three synthetic data sets, showing that network extraction offers the principal benefits of continuity in solutions to produce polylines (over isolated ridge solutions), automation for consistency and reliability, and optional amplitude thresholding.
Narrow-angle representations of the phase and group velocities and their applications in anisotropic velocity-model building for microseismic monitoring
Authors: Grechka Vladimir , Duchkov Anton A.
Published: January 2012

It is usually believed that angular aperture of seismic data should be at least 20° to allow estimation of the subsurface anisotropy. Although this is certainly true for reflection data, for which anisotropy parameters are inverted from the stacking velocities or the nonhyperbolic moveout, traveltimes of direct P- and S-waves recorded in typical downhole microseismic geometries make it possible to infer seismic anisotropy in angular apertures as narrow as about 10°. To ensure the uniqueness of such an inversion, it has to be performed in a local coordinate frame tailored to a particular data set. Because any narrow fan of vectors is naturally characterized by its average direction, we choose the axes of the local frame to coincide with the polarization vectors of three plane waves corresponding to such a direction. This choice results in a significant simplification of the conventional equations for the phase and group velocities in anisotropic media and makes it possible to predict which elements of the elastic stiffness tensor are constrained by the available data. We illustrate our approach on traveltime synthetics and then apply it to perforation-shot data recorded in a shale-gas field. Our case study indicates that isotropic velocity models are inadequate and accounting for seismic anisotropy is a prerequisite for building a physically sound model that explains the recorded traveltimes.
Glucocorticoid Receptor Signaling Is Essential for Mesoderm Formation and Muscle Development in Zebrafish
Authors: Nesan Dinushan , Kamkar Maryam , Burrows Jeffrey , Scott Ian C. , Marsden Mungo , Vijayan Mathilakath M.
Published: January 2012

Glucocorticoid receptor (GR) signaling is thought to play a key role in embryogenesis, but its specific developmental effects remain unclear. Cortisol is the primary ligand for GR activation in teleosts, and in zebrafish (Danio rerio), the prehatch embryo content of this steroid is of maternal origin. Using early zebrafish developmental stages, we tested the hypothesis that GR signaling is critical for embryo growth and hatching. In zebrafish, maternal GR mRNA is degraded quickly, followed by zygotic synthesis of the receptor. GR protein is widely expressed throughout early development, and we were able to knockdown this protein using morpholino oligonucleotides. This led to a more than 70% reduction in mRNA abundance of matrix metalloproteinase-13 (mmp13), a glucocorticoid-responsive gene. The GR morphants displayed delayed somitogenesis, defects in somite and tail morphogenesis, reduced embryo size, and rarely survived after hatch. This correlated with altered expression of myogenic markers, including myogenin, myostatin, and muscle-specific myosin heavy chain and troponin genes. A key finding was a 70–90% reduction in the mRNA abundance of bone morphogenetic proteins (BMP), including bmp2a, bmp2b, and bmp4 in GR morphants. Bioinformatics analysis confirmed multiple putative glucocorticoid response elements upstream of these BMP genes. GR morphants displayed reduced expression of BMP-modulated genes, including eve1 and pax3. Zebrafish GR mRNA injection rescued the GR morphant phenotype and reversed the disrupted expression of BMP and myogenic genes. Our results for the first time indicate that GR signaling is essential for zebrafish muscle development, and we hypothesize a role for BMP morphogens in this process.
Norepinephrine, Active Norepinephrine Transporter, and Norepinephrine-Metabolism Are Involved in the Generation of Reactive Oxygen Species in Human Ovarian Granulosa Cells
Authors: Saller S. , Merz-Lange J. , Raffael S. , Hecht S. , Pavlik R. , Thaler C. , Berg D. , Berg U. , Kunz L. , Mayerhofer A.
Published: January 2012

The neurotransmitter norepinephrine (NE) is derived from the sympathetic nervous system and may be involved in the regulation of ovarian functions. Ovarian innervation increases in patients with polycystic ovarian syndrome (PCOS), prompting us to readdress a role of NE in the human ovary. In vitro fertilization-derived granulosa cells (GC), follicular fluids (FF), and ovarian sections were studied. NE was found in FF and freshly isolated GC, yet significantly lower levels of NE were detected in samples from PCOS patients. Furthermore, the metabolite normetanephrine was detected in FF. Together this suggests cellular uptake and metabolism of NE in GC. In accordance, the NE transporter and NE-metabolizing enzymes [catechol-o-methyltransferase (COMT) and monoamine oxidase A] were found in GC, COMT in GC and thecal cells of large human antral follicles in vivo and in cultured GC. Cellular uptake and metabolism of NE also occurred in cultured GC, events that could be blocked pharmacologically. NE, in the range present in FF, is unlikely to affect GC via activation of typical α- or β-receptors. In line with this assumption, it did not alter phosphorylation of MAPK. However, NE robustly induced the generation of reactive oxygen species (ROS). This action occurred even when receptors were blocked but was prevented by blockers of NE transporter, COMT, and monoamine oxidase A. Thus, NE contributes to the microenvironment of preovulatory human follicles and is lower in PCOS. By inducing the production of ROS in GC, NE is linked to ROS-regulated events, which are emerging as crucial factors in ovarian physiology, including ovulation.
GLP-1 Receptor Agonists and the Thyroid: C-Cell Effects in Mice Are Mediated via the GLP-1 Receptor and not Associated with RET Activation
Authors: Madsen Lars Wichmann , Knauf Jeffrey A. , Gotfredsen Carsten , Pilling Andrew , Sjögren Ingrid , Andersen Søren , Andersen Lene , Sietske de Boer Anne , Manova Katia , Barlas Afsar , Vundavalli Sushil , Nyborg Niels C. Berg , Bjerre Knudsen Lotte , Moelck Anne Marie , Fagin James A.
Published: January 2012

Liraglutide and exenatide are glucagon-like peptide receptor (GLP-1R) agonists used in the treatment of type 2 diabetes. Both molecules have been associated with the development of thyroid C-cell tumors after lifetime exposure in rodents. Previously, it has been reported that these tumors are preceded by increased plasma calcitonin and C-cell hyperplasia. We can now document that the murine C-cell effects are mediated via GLP-1R. Thus, 13 wk of continuous exposure to GLP-1R agonists was associated with marked increases in plasma calcitonin and in the incidence of C-cell hyperplasia in wild-type mice. In contrast, similar effects were not seen in GLP-1R knockout mice. Human C-cell cancer is often caused by activating mutations in the rearranged-during-transfection (RET) protooncogene. We developed an immunohistochemical method to assess RET activation in tissues. Liraglutide dosing to mice was not found to activate RET. Further evaluation of the signaling pathways demonstrated that liraglutide increased ribosomal S6, but not MAPK kinase, phosphorylation. These observations are consistent with effects of GLP-1R agonists on rodent C cells being mediated via mammalian target of rapamycin activation in a RET- and MAPK-independent manner.
“IS DURABILITY ITSELF NOT ALSO A MORAL QUALITY?”
Authors: Baxandall Michael
Published: January 2012

Centering on his relationship with Gertrud Bing from 1958 until her death in 1964 — as well as, to a lesser extent, on his relationship with Ernst Gombrich — the author recalls his informal induction during those years into a tradition of thought and an intellectual climate that Aby Warburg had embodied in the Institute and Library that he founded in Hamburg. The Institute is described as existing, during the late 1950s and early 1960s in London, less as a formal institution than as the interaction of some two dozen émigrés with what the author describes as “the intention of the books” and the Library's “frame of mind.” The essay — which is a somewhat revised excerpt from the author's memoir Episodes: A Memorybook (2010) — goes on to detail various habits of classification in the Warburg Library's arrangement and to show how these have entailed assumptions about how the human world works.
UNE MACHINE À PENSER
Authors: Ginzburg Carlo
Published: January 2012

The author describes his research experience in the 1960s, as an apprentice historian, in the Warburg Library. His work on witchcraft trials in early modern Italy, he argues, was deeply affected by the Library's unique character. Aby Warburg's law of the “good neighbour” (the book we need is placed next to the one we are looking for) is illustrated through a specific example: the encounter with a forgotten tract dealing with some anomalous Bavarian witchcraft trials — a book that would have been very difficult (if not impossible) to come across anywhere but Warburg's Library.
RECONCEIVING THE WARBURG LIBRARY AS A WORKING MUSEUM OF THE MIND
Authors: Stafford Barbara Maria
Published: January 2012

Received opinion holds that it would be more efficient, hence more economical, to compress and thus dissolve the holdings of the Warburg Institute Library into an overarching university library system. This essay argues two points: first, that we should not be automatically persuaded by the popular and largely unexamined goal of efficiency; and second, that the Library indeed requires its own space but that that space must now be reconceived. In line with Aby Warburg's belief that the past should engage the present by expanding and refreshing it, the Warburg Institute Library's rare and singular collections are less about the books and more about the uniqueness of the content and what it does. This essay proposes that what makes the Library vital to today's networked epistemology is the insights that its volumes provide to the varieties of human ordering, organization, formatting, and categorization—visibly exhibited in the spatial arrangement of its holdings. As its users have long felt, the Warburg is more than a library: it is a complex physical space demonstrating the formal evolution or framing of human thought. The Warburg should thus be reconceived as a “house museum” (à la, perhaps, the Soane Museum in London) along these lines.
International Portfolio Allocation under Model Uncertainty
Authors: Benigno Pierpaolo , Nisticò Salvatore
Published: January 2012

This paper revisits an old argument, hedging real exchange rate risk, as an explanation of the international home bias in equity. In a dynamic model, the relevant risk to be hedged is the long-run risk as opposed to the short-run risk. Domestic equity is indeed a good hedge with respect to long-run real-exchange-rate risk. Two new frameworks are able to explain a large share of the observed US home bias: a model with Hansen-Sargent preferences in which agents fear model misspecification and a model with Epstein-Zin preferences. These two models are also immune to the risk-free rate puzzle. (JEL C58, F31, G11, G15)
The Optimal Conduct of Monetary Policy with Interest on Reserves
Authors: Kashyap Anil K , Stein Jeremy C
Published: January 2012

In a world with interest on reserves, the central bank has two distinct tools that it can use to raise the short-term policy rate: it can either increase the interest it pays on reserve balances, or it can reduce the quantity of reserves in the system. We argue that by using both of these tools together, and by broadening the scope of reserve requirements, the central bank can simultaneously pursue two objectives: it can manage the inflation-output tradeoff using a Taylor-type rule, and it can regulate the externalities created by socially excessive short-term debt issuance on the part of financial intermediaries. (JEL E43, E52, E58, G21)
How Does The US Government Finance Fiscal Shocks?
Authors: Berndt Antje , Lustig Hanno , Yeltekin Şevin
Published: January 2012

We develop a method for identifying and quantifying the fiscal channels that help finance government spending shocks. We define fiscal shocks as surprises in defense spending and show that they are more precisely identified when defense stock data are used in addition to aggregate macroeconomic data. Our results show that in the postwar period, about 9 percent of the US government's unanticipated spending needs were financed by a reduction in the market value of debt and more than 70 percent by an increase in primary surpluses. Additionally, we find that long-term debt is more effective at absorbing fiscal risk than short-term debt. (JEL E62, H56, and H63)
Insulin resistance induces medial artery calcification in fructose-fed rats
Authors: Zhou Ye-bo , Zhang Jing , Cai Yan , Teng Xu , Duan Xiao-hui , Song Jun-qiu , Du Jie , Tang Chao-shu , Qi Yong-fen
Published: January 2012

Osteogenic differentiation of vascular smooth muscle cells (VSMCs) results in medial artery calcification, which is common in diabetes, but the pathogenesis is poorly understood. We aimed to explore the pathophysiological roles of insulin resistance (IR) on medial artery calcification in rats with 10% fructose in drinking water. After 12 weeks of fructose feeding, rats showed severe IR, with increased levels of fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Fructose-fed rats showed aortic calcification, increased aortic calcium deposition and irregular elastic fibers in the medial layer of the vessel wall. Moreover, plasma phosphorus concentration, calcium × phosphorus product and alkaline phosphatase (ALP) activity, and aortic calcium content and ALP activity were significantly increased. Fructose feeding increased mRNA levels of osteopontin, type III sodium-dependent phosphate co-transporter, bone morphogenetic protein-2 and the key transcription factor core binding factor alpha 1 in aortic tissue and downregulated mRNA levels of osteoprotegerin and matrix γ-carboxyglutamic acid protein. Fructose feeding decreased protein levels of smooth-muscle lineage markers and induced severe lipid peroxidation injury. IR induced by high fructose feeding could evoke osteogenic transdifferentiation of VSMCs and promote vascular calcification.
Prohibitin Reduces Mitochondrial Free Radical Production and Protects Brain Cells from Different Injury Modalities
Authors: Zhou Ping , Qian Liping , D'Aurelio Marilena , Cho Sunghee , Wang Gang , Manfredi Giovanni , Pickel Virginia , Iadecola Costantino
Published: January 2012

Prohibitin is an essential mitochondrial protein that has been implicated in a wide variety of functions in many cell types, but its role in neurons remains unclear. In a proteomic screen of rat brains in which ischemic tolerance was induced by electrical stimulation of the cerebellar fastigial nucleus, we found that prohibitin is upregulated in mitochondria. This observation prompted us to investigate the role of prohibitin in neuronal death and survival. We found that prohibitin is upregulated also in the ischemic tolerance induced by transient ischemiain vivo, or oxygen–glucose deprivation in neuronal cultures. Cell fractionation and electron-microscopic immunolabeling studies demonstrated that prohibitin is localized to neuronal mitochondria. Upregulation of prohibitin in neuronal cultures or hippocampal slices was markedly neuroprotective, whereas prohibitin gene silencing increased neuronal vulnerability, an effect associated with loss of mitochondrial membrane potential and increased mitochondrial production of reactive oxygen species. Prohibitin upregulation was associated with reduced production of reactive oxygen species in mitochondria exposed to the complex I inhibitor rotenone. In addition, prohibitin protected complex I activity from the inhibitory effects of rotenone. These observations, collectively, establish prohibitin as an endogenous neuroprotective protein involved in ischemic tolerance. Prohibitin exerts beneficial effects on neurons by reducing mitochondrial free radical production. The data with complex I activity suggest that prohibitin may stabilize the function of complex I. The protective effect of prohibitin has potential translational relevance in diseases of the nervous system associated with mitochondrial dysfunction and oxidative stress.
Alteration of Synaptic Network Dynamics by the Intellectual Disability Protein PAK3
Authors: Dubos Aline , Combeau Gaelle , Bernardinelli Yann , Barnier Jean-Vianney , Hartley Oliver , Gaertner Hubert , Boda Bernadett , Muller Dominique
Published: January 2012

Several gene mutations linked to intellectual disability in humans code for synaptic molecules implicated in small GTPase signaling. This is the case of the Rac/Cdc42 effector p21-activated kinase 3 (PAK3). The mechanisms responsible for the intellectual defects and the consequences of the mutation on the development and wiring of brain networks remain unknown. Here we show that expression of PAK3 mutants, suppression of PAK3, or inhibition of PAK3 function in rat hippocampal slice cultures interfere with activity-mediated spine dynamics. Inhibition of PAK3 resulted in two main alterations: (1) an increased growth of new, unstable spines, occurring in clusters, and mediated by activity; and (2) an impairment of plasticity-mediated spine stabilization interfering with the formation of persistent spines. Additionally, we find that PAK3 is specifically recruited by activity from dendrites into spines, providing a new mechanism through which PAK3 could participate in the control of both spine stabilization and local spine growth. Together, these data identify a novel function of PAK3 in regulating activity-mediated rearrangement of synaptic connectivity associated with learning and suggest that defects in spine formation and refinement during development could account for intellectual disability.
A Conditioning Lesion Protects Axons from Degeneration via the Wallenda/DLK MAP Kinase Signaling Cascade
Authors: Xiong Xin , Collins Catherine A.
Published: January 2012

Axons are vulnerable components of neuronal circuitry, and neurons are equipped with mechanisms for responding to axonal injury. A highly studied example of this is the conditioning lesion, in which neurons that have been previously injured have an increased ability to initiate new axonal growth (Hoffman, 2010). Here we investigate the effect of a conditioning lesion on axonal degeneration, which occurs in the distal stump after injury, and also occurs in neuropathies and neurodegenerative disorders (Coleman, 2005). We found thatDrosophilamotoneuron axons that had been previously injured had an increased resiliency to degeneration. This requires the function of a conserved axonal kinase, Wallenda (Wnd)/DLK, and a downstream transcription factor. Because axonal injury leads to acute activation of Wnd (Xiong et al., 2010), and overexpression studies indicate that increased Wnd function is sufficient to promote protection from degeneration, we propose that Wnd regulates an adaptive response to injury that allows neurons to cope with axonal stress.
GABA Is Excitatory in Adult Vasopressinergic Neuroendocrine Cells
Authors: Haam Juhee , Popescu Ion R. , Morton Linda A. , Halmos Katalin C. , Teruyama Ryoichi , Ueta Yoichi , Tasker Jeffrey G.
Published: January 2012

Neuronal excitability in the adult brain is controlled by a balance between synaptic excitation and inhibition mediated by glutamate and GABA, respectively. While generally inhibitory in the adult brain, GABAAreceptor activation is excitatory under certain conditions in which the GABA reversal potential is shifted positive due to intracellular Cl−accumulation, such as during early postnatal development and brain injury. However, the conditions under which GABA is excitatory are generally either transitory or pathological. Here, we reveal GABAergic synaptic inputs to be uniformly excitatory in vasopressin (VP)-secreting magnocellular neurons in the adult hypothalamus under normal conditions. The GABA reversal potential (EGABA) was positive to resting potential and spike threshold in VP neurons, but not in oxytocin (OT)-secreting neurons. The VP neurons lacked expression of the K+-Cl−cotransporter 2 (KCC2), the predominant Cl−exporter in the adult brain. TheEGABAwas unaffected by inhibition of KCC2 in VP neurons, but was shifted positive in OT neurons, which express KCC2. Alternatively, inhibition of the Na+-K+-Cl−cotransporter 1 (NKCC1), a Cl−importer expressed in most cell types mainly during postnatal development, caused a negative shift inEGABAin VP neurons, but had no effect on GABA currents in OT neurons. GABAAreceptor blockade caused a decrease in the firing rate of VP neurons, but an increase in firing in OT neurons. Our findings demonstrate that GABA is excitatory in adult VP neurons, suggesting that the classical excitation/inhibition paradigm of synaptic glutamate and GABA control of neuronal excitability does not apply to VP neurons.
Cross-Frequency Phase–Phase Coupling between Theta and Gamma Oscillations in the Hippocampus
Authors: Belluscio Mariano A. , Mizuseki Kenji , Schmidt Robert , Kempter Richard , Buzsáki György
Published: January 2012

Neuronal oscillations allow for temporal segmentation of neuronal spikes. Interdependent oscillators can integrate multiple layers of information. We examined phase–phase coupling of theta and gamma oscillators in the CA1 region of rat hippocampus during maze exploration and rapid eye movement sleep. Hippocampal theta waves were asymmetric, and estimation of the spatial position of the animal was improved by identifying the waveform-based phase of spiking, compared to traditional methods used for phase estimation. Using the waveform-based theta phase, three distinct gamma bands were identified: slow gammaS(gammaS; 30–50 Hz), midfrequency gammaM(gammaM; 50–90 Hz), and fast gammaF(gammaF; 90–150 Hz or epsilon band). The amplitude of each sub-band was modulated by the theta phase. In addition, we found reliable phase–phase coupling between theta and both gammaSand gammaMbut not gammaFoscillators. We suggest that cross-frequency phase coupling can support multiple time-scale control of neuronal spikes within and across structures.
Why Do Axons Differ in Caliber?
Authors: Perge János A. , Niven Jeremy E. , Mugnaini Enrico , Balasubramanian Vijay , Sterling Peter
Published: January 2012

CNS axons differ in diameter (d) by nearly 100-fold (∼0.1–10 μm); therefore, they differ in cross-sectional area (d2) and volume by nearly 10,000-fold. If, as found for optic nerve, mitochondrial volume fraction is constant with axon diameter, energy capacity would rise with axon volume, also asd2. We asked, given constraints on space and energy, what functional requirements set an axon's diameter? Surveying 16 fiber groups spanning nearly the full range of diameters in five species (guinea pig, rat, monkey, locust, octopus), we found the following: (1) thin axons are most numerous; (2) mean firing frequencies, estimated for nine of the identified axon classes, are low for thin fibers and high for thick ones, ranging from ∼1 to >100 Hz; (3) a tract's distribution of fiber diameters, whether narrow or broad, and whether symmetric or skewed, reflects heterogeneity of information rates conveyed by its individual fibers; and (4) mitochondrial volume/axon length rises ≥d2. To explain the pressure toward thin diameters, we note an established law of diminishing returns: an axon, to double its information rate, must more than double its firing rate. Since diameter is apparently linear with firing rate, doubling information rate would more than quadruple an axon's volume and energy use. Thicker axons may be needed to encode features that cannot be efficiently decoded if their information is spread over several low-rate channels. Thus, information rate may be the main variable that sets axon caliber, with axons constrained to deliver information at the lowest acceptable rate.
Disrupted-in-Schizophrenia 1 (DISC1) Is Necessary for the Correct Migration of Cortical Interneurons
Authors: Steinecke André , Gampe Christin , Valkova Christina , Kaether Christoph , Bolz Jürgen
Published: January 2012

Disrupted-in-Schizophrenia 1(DISC1) is a prominent susceptibility gene for major psychiatric disorders. Previous work indicated that DISC1 plays an important role during neuronal proliferation and differentiation in the cerebral cortex and that it affects the positioning of radial migrating pyramidal neurons. Here we show that in mice, DISC1 is necessary for the migration of the cortical interneurons generated in the medial ganglionic eminence (MGE). RT-PCR,in situhybridizations, and immunocytochemical data revealed expression of DISC1 transcripts and protein in MGE-derived cells. To study the possible functional role of DISC1 during tangential migration, we performedin uteroandex uteroelectroporation to suppress DISC1 in the MGEin vivoandin vitro. Results indicate that after DISC1 knockdown, the proportion of tangentially migrating MGE neurons that reached their cortical target was strongly reduced. In addition, there were profound alterations in the morphology of DISC1-deficient neurons, which exhibited longer and less branched leading processes than control cells. These findings provide a possible link between clinical studies reporting alterations of cortical interneurons in schizophrenic patients and the current notion of schizophrenia as a neurodevelopmental disorder.
Neural Prediction Errors Reveal a Risk-Sensitive Reinforcement-Learning Process in the Human Brain
Authors: Niv Yael , Edlund Jeffrey A. , Dayan Peter , O'Doherty John P.
Published: January 2012

Humans and animals are exquisitely, though idiosyncratically, sensitive to risk or variance in the outcomes of their actions. Economic, psychological, and neural aspects of this are well studied when information about risk is provided explicitly. However, we must normally learn about outcomes from experience, through trial and error. Traditional models of such reinforcement learning focus on learning about the mean reward value of cues and ignore higher order moments such as variance. We used fMRI to test whether the neural correlates of human reinforcement learning are sensitive to experienced risk. Our analysis focused on anatomically delineated regions of a priori interest in the nucleus accumbens, where blood oxygenation level-dependent (BOLD) signals have been suggested as correlating with quantities derived from reinforcement learning. We first provide unbiased evidence that the raw BOLD signal in these regions corresponds closely to a reward prediction error. We then derive from this signal the learned values of cues that predict rewards of equal mean but different variance and show that these values are indeed modulated by experienced risk. Moreover, a close neurometric–psychometric coupling exists between the fluctuations of the experience-based evaluations of risky options that we measured neurally and the fluctuations in behavioral risk aversion. This suggests that risk sensitivity is integral to human learning, illuminating economic models of choice, neuroscientific models of affective learning, and the workings of the underlying neural mechanisms.
Gene Genealogies Within a Fixed Pedigree, and the Robustness of Kingman’s Coalescent
Authors: Wakeley John , King Léandra , Low Bobbi S , Ramachandran Sohini
Published: January 2012

We address a conceptual flaw in the backward-time approach to population genetics called coalescent theory as it is applied to diploid biparental organisms. Specifically, the way random models of reproduction are used in coalescent theory is not justified. Instead, the population pedigree for diploid organisms—that is, the set of all family relationships among members of the population—although unknown, should be treated as a fixed parameter, not as a random quantity. Gene genealogical models should describe the outcome of the percolation of genetic lineages through the population pedigree according to Mendelian inheritance. Using simulated pedigrees, some of which are based on family data from 19th century Sweden, we show that in many cases the (conceptually wrong) standard coalescent model is difficult to reject statistically and in this sense may provide a surprisingly accurate description of gene genealogies on a fixed pedigree. We study the differences between the fixed-pedigree coalescent and the standard coalescent by analysis and simulations. Differences are apparent in recent past, within ∼ <log2(N) generations, but then disappear as genetic lineages are traced into the more distant past.
An ORFan No More: The Bacteriophage T4 39.2 Gene Product, NwgI, Modulates GroEL Chaperone Function
Authors: Ang Debbie , Georgopoulos Costa
Published: January 2012

Bacteriophages are the most abundant biological entities in our biosphere, characterized by their hyperplasticity, mosaic composition, and the many unknown functions (ORFans) encoded by their immense genetic repertoire. These genes are potentially maintained by the bacteriophage to allow efficient propagation on hosts encountered in nature. To test this hypothesis, we devised a selection to identify bacteriophage-encoded gene(s) that modulate the host Escherichia coli GroEL/GroES chaperone machine, which is essential for the folding of certain host and bacteriophage proteins. As a result, we identified the bacteriophage RB69 gene 39.2, of previously unknown function and showed that homologs of 39.2 in bacteriophages T4, RB43, and RB49 similarly modulate GroEL/GroES.

Production of wild-type bacteriophage T4 Gp39.2, a 58-amino-acid protein, (a) enables diverse bacteriophages to plaque on the otherwise nonpermissive groES or groEL mutant hosts in an allele-specific manner, (b) suppresses the temperature-sensitive phenotype of both groES and groEL mutants, (c) suppresses the defective UV-induced PolV function (UmuCD) of the groEL44 mutant, and (d) is lethal to the host when overproduced. Finally, as proof of principle that Gp39.2 is essential for bacteriophage growth on certain bacterial hosts, we constructed a T4 39.2 deletion strain and showed that, unlike the isogenic wild-type parent, it is incapable of propagating on certain groEL mutant hosts. We propose a model of how Gp39.2 modulates GroES/GroEL function.
Micro-organic Light-emitting Devices Fabricated by Room-temperature Curing Nanoimprint Lithography Using Diamond Molds
Authors: Ishikawa Ippei , Okuno Taisuke , Kiyohara Shuji , Taguchi Yoshio , Sugiyama Yoshinari , Omata Yukiko , Kurashima Yuichi
Published: January 2012

Organic light-emitting devices (OLEDs) have attracted a lot of attention as a next generation display. In this study, we fabricated the micro-OLEDs by room-temperature curing nanoimprint lithography (RTC-NIL) using diamond molds. The diamond has superior durability and was used as mold material for RTC-NIL. The diamond molds have been fabricated by electron cyclotron resonance (ECR) oxygen ion shower with polysiloxane oxide mask in the electron beam (EB) lithography technology. We fabricated the diamond mold pattern with 10 μm-square dot. The diamond molds have been used to form an insulating layer in micro-OLEDs. The optimum thickness of N,N’-Diphenyl-N,N’-di(m-tolyl)benzidine (TPD) [hole transport layer],Tris(8-quinolinolato)aluminum (Alq3) [electron transport layer] and aluminum (Al) [cathode] were 40 nm, 40 nm and 200 nm, respectively. We succeeded in formation of insulating layer in micro-OLEDs and operation of micro-OLEDs with 10 μm-square-dot by RTC-NIL using diamond molds.
Enhanced Wettability of Nanocrystalline Diamond Films for Biocoating Applications
Authors: Yang Jason H. C. , Teii Kungen
Published: January 2012

Nanocrystalline diamond (NCD) films are prepared from Ar-rich/N2/CH4 and Ar-rich/H2/CH4 mixtures by microwave plasma-enhanced chemical vapor deposition, and further treated by microwave hydrogen and oxygen plasma exposures separately to enhance the wetting property. The hydrogen plasma treatment has small effect on the surface roughness, while the oxygen plasma treatment forms fine protrusions on the film surface. Results show that the wettability of the hydrogen plasma treated NCD film is nearly constant or little improvement as the polar component of the apparent surface free energy is close to the as-deposit NCD film. In contrast, the wettability of the oxygen plasma treated NCD film is improved dramatically such that the contact angle is reduced from 92º and 4.7º to almost 0º for water and 1-bromonaphthalene, respectively, and the polar component increases significantly to 34 mJ/m2. The low contact angle suggests that the film is considerably a cell adhesive friendly surface, which is essential in maintaining multicellular structure, and thus making it a favorable wetting surface for biological and biomedical applications.
Photomodulated Rayleigh Scattering from Single Semiconductor Nanowires
Authors: Montazeri Mohammad , Wade Aaron , Fickenscher Melodie , Jackson Howard E. , Smith Leigh M. , Yarrison-Rice Jan M. , Gao Qiang , Tan H. Hoe , Jagadish Chennupati
Published: January 2012

We demonstrate the newly developed technique Photomodulated Rayleigh Scattering spectroscopy in order to probe the electronic band structure of single semiconductor nanowires. We show that both the electronic transition energies and nanowire diameter can be measured simultaneously and with high accuracy in a single non-destructive measurement. We demonstrate our results for zincblende GaAs as well as wurtzite InP nanowires where we probed the band gaps and transition energies at both room and low temperatures. This technique should advance the study of optical properties of single nanowires as well as other types of nanostructures.
Photoconductivity of ZnO Nanowires Decorated with CdSe Quantum Dots
Authors: Hou Dongchao , Dev Apurba , Frank Kristian , Rosenauer Andreas , Voss Tobias
Published: January 2012

A hybrid assembly was built using ZnO nanowire (NW) arrays and colloidal CdSe quantum dots (QDs) stabilized by 3-mercaptopropionic acid (MPA). The QDs were chemically linked to the nanowires through the bonds formed between the outgoing carboxyl groups of the QD stabilizers and the zinc ions on the nanowire surface. An efficient clustering attachment of the QDs was achieved via partial removal of the stabilizers of the QDs. The photoconductivity of the NW/QD assembly was investigated by selective excitation of the CdSe QDs. Oxygen desorption from the nanowire surface enhances the photoconductivity and a model involving electron transfer between the QDs and the nanowires is proposed to explain the experimental results.
Thermoelectric Properties of p and n-type Nanocrystalline Silicon Nanowires with High Doping Levels
Authors: Suriano F. , Ferri M. , Solmi S. , Belsito L. , Roncaglia A. , Romano E. , Narducci D. , Cerofolini G.
Published: January 2012

An experimental investigation about the thermoelectric properties of heavily doped p ad n-type nanocrystalline silicon nanowires (NWs) is described. The NWs are produced with low cost CMOS compatible processes, highly customizable in terms of cross-section and placement, which enables the fabrication of both stacked NWs in nearly vertical arrays within nanostructured templates built with SiO2/Si3N4 thin films and individual, freestanding NWs suited for thermal conductivity measurements. The cross-section dimensions of the investigated NWs range between 30 and 120 nm in size and up to about 2 cm in length. The structure of the NWs, as shown by SEM/TEM observations, is nanocrystalline with average size of the nanocrystals in one dimension that is comparable with the nanowire diameter. On the NWs, Seebeck coefficient, electrical resistivity and thermal conductivity have been measured, yielding thermoelectric figure of merit (ZT) values of 0.2 at 300 K for the best case.
The role of the New Trauma and Injury Severity Score (NTRISS) for survival prediction
Authors: Domingues Cristiane de Alencar , Sousa Regina Marcia Cardoso de , Nogueira Lilia de Souza , Poggetti Renato Sérgio , Fontes Belchor , Muñoz Daniele
Published: January 2012

The objective of this study was to verify if replacing the Injury Severity Score (ISS) by the New Injury Severity Score (NISS) in the original Trauma and Injury Severity Score (TRISS) form would improve the survival rate estimation. This retrospective study was performed in a level I trauma center during one year. ROC curve was used to identify the best indicator (TRISS or NTRISS) for survival probability prediction. Participants were 533 victims, with a mean age of 38±16 years. There was predominance of motor vehicle accidents (61.9%). External injuries were more frequent (63.0%), followed by head/neck injuries (55.5%). Survival rate was 76.9%. There is predominance of ISS scores ranging from 9-15 (40.0%), and NISS scores ranging from 16-24 (25.5%). Survival probability equal to or greater than 75.0% was obtained for 83.4% of the victims according to TRISS, and for 78.4% according to NTRISS. The new version (NTRISS) is better than TRISS for survival prediction in trauma patients.
Levantamento epidemiológico dos acidentes motociclísticos atendidos em um Centro de Referência ao Trauma de Sergipe
Authors: Vieira Rita de Cássia Almeida , Hora Edilene Curvelo , Oliveira Daniel Vieira de , Vaez Andréia Centenaro
Published: January 2012

O trauma por acidentes motociclísticos atinge um grande número de vítimas e se constitui um grave problema de saúde pública no Brasil. Trata-se de um estudo documental com abordagem quantitativa que objetivou levantar dados epidemiológicos de 554 vítimas de acidentes motociclísticos atendidos nos meses de setembro e outubro de 2006 em um centro de referência ao trauma de Sergipe. As análises dos resultados evidenciaram predominância de homens (82,7%) com idade média de 27,78 anos que deram entrada no turno da noite (45,9%), domingo (27,3%), que tiveram como lesão as escoriações (n=169), nas regiões da cabeça, face e pescoço. Permaneceram no hospital até 12 horas (76%), evoluindo para alta. Dos casos registrados, 14,6% tinham suspeita de ingestão alcoólica e 19,3% não utilizavam capacete durante o acidente.
Qualidade de vida de adultos com lesão medular: um estudo com WHOQOL-bref
Authors: França Inacia Sátiro Xavier de , Coura Alexsandro Silva , França Eurípedes Gil de , Basílio Narjara Neumann Vieira , Souto Rafaela Queiroga
Published: January 2012

Objetivou-se avaliar a qualidade de vida (QV) de adultos com lesão medular e identificar os domínios que podem influir na qualidade de vida. Para coletar os dados utilizou-se o WHOQOL-bref e um questionário com variáveis sociodemográficas. Participaram 47 sujeitos com média de idade de 42,95 anos, 91,5% do sexo masculino e 8,5% do feminino. Os domínios obtiveram os escores: físico (58,59%), psicológico (63,82%), social (68,79%) e ambiental (55,20%). Por meio de regressão linear múltipla, verificou-se a correlação dos escores dos domínios com a percepção da QV: físico (p < 0,187), psicológico (p < 0,399), social (p < 0,000) e ambiental (p < 0,008). Concluiu-se que a maioria (55,3%) dos participantes está insatisfeita com a QV e que os domínios social e ambiental apresentaram maior correlação com a QV.
Úlcera por pressão em pacientes submetidos à cirurgia: incidência e fatores associados
Authors: Scarlatti Kelly Cristina , Michel Jeanne Liliane Marlene , Gamba Mônica Antar , Gutiérrez Maria Gaby Rivero de
Published: January 2012

As úlceras por pressão constituem um dos principais indicadores da qualidade do cuidado na assistência perioperatória. Este é um estudo longitudinal, do tipo série de casos, com o objetivo de estimar a incidência de úlceras por pressão em pacientes submetidos a cirurgias de médio e grande portes; classificá-las segundo estágio e localização, verificar a associação das variáveis sexo, idade, índice de massa corpórea, comorbidades, posição cirúrgica, tempo cirúrgico, anestesia e uso de dispositivos de posicionamento com a presença ou ausência de úlceras por pressão. Os dados foram coletados em 2007, em São Paulo, com 199 pacientes, dos quais 20,6% apresentaram úlceras por pressão, 98,6% nos estágios I e II, com localização predominante no tronco frontal (35,1%). As variáveis: posição, tempo cirúrgico, anestesia geral e uso de dispositivos apresentaram associação estatística significativa. Concluiu-se que a incidência de úlceras por pressão em pacientes cirúrgicos é elevada, demandando ações que visem à redução desse tipo de lesão.
Tecnologia na terapia intensiva e suas influências nas ações do enfermeiro
Authors: Silva Rafael Celestino da , Ferreira Márcia de Assunção
Published: January 2012

Objetivou-se identificar as representações sociais de enfermeiros sobre a tecnologia aplicada em cuidados intensivos, e relacioná-las aos seus modos de agir no cuidado do paciente. Pesquisa qualitativa, cujo referencial teórico-metodológico foi o das representações sociais. Realizou-se entrevistas com 24 enfermeiros, observação sistemática e análise de conteúdo temática. Os resultados se organizaram em três categorias sobre o desconhecimento da linguagem tecnológica, estratégias de aproximação, seu domínio e sua aplicação. O saber/conhecimento necessário para o manuseio da tecnologia, e o tempo de experiência do seu manejo orientam as representações sociais dos enfermeiros, incidindo nas suas ações de cuidado. Conclui-se que a política de contratação de pessoal para trabalhar em cenário de terapia intensiva deve considerar as experiências e a formação especializada dos enfermeiros.