bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypercholesterolemic LDL receptor-deficient mice mount a neutrophilic response to tuberculosis despite the timely expression of protective immunity
Authors: Martens Gregory W , Vallerskog Therese , Kornfeld Hardy
Published: January 2012

The prevalence of hypercholesterolemia is rising in industrialized and developing countries. We reported previously that host defense against Mtb was impaired by hypercholesterolemia in ApoE−/− mice, raising the possibility that people with HC could be more vulnerable to TB. The present study examined whether TB immunity was similarly impaired in a different hypercholesterolemic model, LDL-R−/− mice, which developed comparable elevation of total serum cholesterol as ApoE−/−mice when fed HC or LC diets. Like ApoE−/− mice, LDL-R−/− mice had an exaggerated lung inflammatory response to Mtb with increased tissue necrosis. Inflammation, foamy macrophage formation, and tissue necrosis in LDL-R−/− mice increased with the degree of hypercholesterolemia. Unlike ApoE−/− mice, LDL-R−/− mice fed a HC diet mounted a timely and protective adaptive immune response that restricted mycobacterial replication comparably with WT mice. Thus, ApoE−/− and LDL-R−/− mice share a cholesterol-dependent hyperinflammatory TB phenotype but do not share the impairment of adaptive immunity found in ApoE−/− mice. The impact of hypercholesterolemia on TB immunity is more complex than appreciated by total cholesterol alone, possibly reflecting the different functional effect of specific lipoprotein particles.
Monocyte maturation, HIV susceptibility, and transmigration across the blood brain barrier are critical in HIV neuropathogenesis
Authors: Williams Dionna W , Eugenin Eliseo A , Calderon Tina M , Berman Joan W
Published: January 2012

HIV continues to be a global health crisis with more than 34 million people infected worldwide (UNAIDS: Report on the Global AIDS Epidemic 2010, Geneva, World Health Organization). HIV enters the CNS within 2 weeks of infection and establishes a spectrum of HAND in a large percentage of infected individuals. These neurologic deficits greatly impact the quality of life of those infected with HIV. The establishment of HAND is largely attributed to monocyte transmigration, particularly that of a mature CD14+CD16+ monocyte population, which is more susceptible to HIV infection, across the BBB into the CNS parenchyma in response to chemotactic signals. To enter the CNS, junctional proteins on the monocytes must participate in homo- and heterotypic interactions with those present on BMVECs of the BBB as they transmigrate across the barrier. This transmigration is responsible for bringing virus into the brain and establishing chronic neuroinflammation. While there is baseline trafficking of monocytes into the CNS, the increased chemotactic signals present during HIV infection of the brain promote exuberant monocyte transmigration into the CNS. This review will discuss the mechanisms of monocyte differentiation/maturation, HIV infectivity, and transmigration into the CNS parenchyma that contribute to the establishment of cognitive impairment in HIV-infected individuals. It will focus on markers of monocyte subpopulations, how differentiation/maturation alters HIV infectivity, and the mechanisms that promote their increased transmigration across the BBB into the CNS.
Integration of well logs for seismic-guided sand mapping in the Barail coal-shale sequence of Geleki Field
Authors: Harilal
Published: January 2012

Sandstones associated with Oligocene Barail coal-shale sequences form good reservoir facies and are oil producers in many wells of India's Geleki Field and adjoining areas. Mapping these sands using seismic attributes may lead to data that are difficult to interpret because sand-coal and shale-coal interfaces generate similar attributes. In such cases, seismic attributes may show the depositional geometry but with ambiguous lithology. The lithologic ambiguity may further be worsened by carbonaceous shales, which often occur in coal-shale sequences, and that shales may appear similar to sandstones in some log (e.g., gamma ray, resistivity, etc.) and interface properties. Integration of logs with seismic data improves lithologic discrimination and reservoir characterization. The log motifs (patterns) reinforce the interpretation of depositional environments and processes and log properties (magnitude) reduce the ambiguity in lithologic prediction. Seismic attributes and log properties can be integrated by finding interrelationships between these two types of data at control (wells) points. The interrelationships are used for seismic-guided prediction of log properties beyond the wells and generation of property volumes. The predicted volumes are interpreted in terms of lithology and other reservoir parameters (porosity, saturation, etc.).
Introduction to this special section: Near-surface measurements in exploration geophysics
Authors: Steeples Don , Kelamis Panos
Published: January 2012

Characterizing the upper few tens of meters of Earth materials by seismic methods other than classical refraction was virtually nonexistent in the scientific literature before 1980. This was due partly to lack of interest, but also to the limited dynamic range of analog seismographs prior to 1960 and to the limited instantaneous dynamic range of digital seismographs between 1960 and the 1980s. Furthermore, access to adequate digital processing facilities was not easily available to those outside of oil companies or major geophysical contractors until the late 1980s.
Rayleigh-wave tomography at Coronation Field, Canada: The topography effect
Authors: Haney Matthew M. , Douma Huub
Published: January 2012

Within reflection seismology, surface waves or ground roll, are often considered a form of unwanted source-generated noise. Unlike body waves, surface waves propagate exclusively in the lateral direction and are virtually insensitive to structure deeper than one wavelength. For a nominal frequency of 5 Hz and phase velocity of 500 m/s, this means that a surface wave of the Rayleigh or Love type only feels the upper 100 m of the subsurface. As a result, surface waves cannot be used for imaging deep reflectors; however, they can be used to estimate near-surface properties (Xia et al., 1999; Ross et al., 2008), in particular the shear-wave velocity. Knowledge of near-surface velocity structure in turn can be used to estimate shear-wave statics in reflection seismology. Estimating statics in the presence of laterally varying structure (i.e., obtaining the long-wavelength static component) can be challenging.
Angiotensin II Reduces Food Intake by Altering Orexigenic Neuropeptide Expression in the Mouse Hypothalamus
Authors: Yoshida Tadashi , Semprun-Prieto Laura , Wainford Richard D. , Sukhanov Sergiy , Kapusta Daniel R. , Delafontaine Patrice
Published: January 2012

Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated.
Prediabetic Nephropathy as an Early Consequence of the High-Calorie/High-Fat Diet: Relation to Oxidative Stress
Authors: Shevalye Hanna , Lupachyk Sergey , Watcho Pierre , Stavniichuk Roman , Khazim Khaled , Abboud Hanna E. , Obrosova Irina G.
Published: January 2012

This study evaluated early renal functional, structural, and biochemical changes in high-calorie/high-fat diet fed mice, a model of prediabetes and alimentary obesity. Male C57BL6/J mice were fed normal (11 kcal% fat) or high-fat (58 kcal% fat) diets for 16 wk. Renal changes were evaluated by histochemistry and immunohistochemistry, Western blot analysis, ELISA, enzymatic assays, and chemiluminometry. High-fat diet consumption led to increased body and kidney weights, impaired glucose tolerance, hyperinsulinemia, polyuria, a 2.7-fold increase in 24-h urinary albumin excretion, 20% increase in renal glomerular volume, 18% increase in renal collagen deposition, and 8% drop of glomerular podocytes. It also resulted in a 5.3-fold increase in urinary 8-isoprostane excretion and a 38% increase in renal cortex 4-hydroxynonenal adduct accumulation. 4-hydroxynonenal adduct level and immunoreactivity or Sirtuin 1 expression in renal medulla were not affected. Studies of potential mechanisms of the high-fat diet induced renal cortex oxidative injury revealed that whereas nicotinamide adenine dinucleotide phosphate reduced form oxidase activity only tended to increase, 12/15-lipoxygenase was significantly up-regulated, with approximately 12% increase in the enzyme protein expression and approximately 2-fold accumulation of 12(S)-hydroxyeicosatetraenoic acid, a marker of 12/15-lipoxygenase activity. Accumulation of periodic acid-Schiff -positive material, concentrations of TGF-β, sorbitol pathway intermediates, and expression of nephrin, CAAT/enhancer-binding protein homologous protein, phosphoeukaryotic initiation factor-α, and total eukaryotic initiation factor-α in the renal cortex were indistinguishable between experimental groups. Vascular endothelial growth factor concentrations were reduced in high-fat diet fed mice. In conclusion, systemic and renal cortex oxidative stress associated with 12/15-lipoxygenase overexpression and activation is an early phenomenon caused by high-calorie/high-fat diet consumption and a likely contributor to kidney disease associated with prediabetes and alimentary obesity.
RETURNING TO THE LIBRARY
Authors: Mack Peter
Published: January 2012

This essay reflects on the different uses that its author has made of the Warburg Institute Library, first as a student, resident in the Library for two years, then as a visitor on day-long research trips from Warwick, and most recently as director of the Institute. After describing how the Library shelves can be accessed now electronically and discussing the arrangements of the opening sections of the fourth floor (history) and the second floor (comparative literature, poetics, and rhetoric), the essay concludes with comments on the future of the Library.
UNPACKING THE WARBURG LIBRARY
Authors: Kraye Jill
Published: January 2012

Against the backdrop of Walter Benjamin's famous essay, “Unpacking My Library” (1931), this article, by the Librarian of the Warburg Institute, tells the story of the many times that the Warburg Library has been packed and unpacked. First it was the private collection of Aby Warburg, later a public institution, originally in Hamburg (in the 1920s) and then in London from 1933 to the present. This essay also explores the various ways in which books have been — and continue to be — acquired by the Warburg Library, including publication (both individual and institutional), donation, recommendation, and purchase. Each of these methods is not only discussed but also examined in light of Benjamin's account of the acquisition of his own library. Moreover, Benjamin's view that collections lose their meaning when they cease to be personal is challenged by the example of the Warburg Library, which has been transformed from a private collection containing around 15,000 books in 1911 to a public institution today housing over 350,000 volumes, while still maintaining its unique character.
SPEAKING OF LILLIPUT?
Authors: Kaufmann Thomas DaCosta
Published: January 2012

This essay, part of a special issue on the Warburg Institute and Library, offers personal recollections of scholars whom the author encountered there as a student in the early 1970s, including E. H. Gombrich, Otto Kurz, Michael Baxandall, Frances Yates, D. P. Walker, A. I. Sabra, Michael Podro, Michael Screech, Arnaldo Momigliano, and Nikolaus Pevsner. The author's focus is on differences between the milieu of the Kulturwissenschaftliche Bibliothek Warburg, as it had been in Hamburg, and the ethos of the Warburg Institute in London. The key document for establishing this contrast is an anonymous review — by Edgar Wind — attacking Gombrich's biography of Aby Warburg, which was published in 1970. Wind found the new Warburg circle “Lilliputian” in comparison with the old Hamburg circle, to which he had belonged. This essay disputes Wind's finding, based on its author's own experience, as well as on his sympathy with the reasoned empirical approach of Gombrich, Baxandall, and others at the London Warburg to issues that Aby Warburg had raised when the Library was in Germany.
Preeclampsia: multiple approaches for a multifactorial disease
Authors: Pennington Kathleen A. , Schlitt Jessica M. , Jackson Daniel L. , Schulz Laura C. , Schust Danny J.
Published: January 2012

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and excess protein excretion in the urine. It is an important cause of maternal and fetal morbidity and mortality worldwide. The disease is almost exclusive to humans and delivery of the pregnancy continues to be the only effective treatment. The disorder is probably multifactorial, although most cases of preeclampsia are characterized by abnormal maternal uterine vascular remodeling by fetally derived placental trophoblast cells. Numerous in vitro and animal models have been used to study aspects of preeclampsia, the most common being models of placental oxygen dysregulation, abnormal trophoblast invasion, inappropriate maternal vascular damage and anomalous maternal-fetal immune interactions. Investigations into the pathophysiology and treatment of preeclampsia continue to move the field forward, albeit at a frustratingly slow pace. There remains a pressing need for novel approaches, new disease models and innovative investigators to effectively tackle this complex and devastating disorder.
The NIH Undiagnosed Diseases Program: bonding scientists and clinicians
Authors: Gahl William A. , Boerkoel Cornelius F. , Boehm Manfred
Published: January 2012

The majority of the biomedical research workforce and funds are focused on studying common diseases and the development of drugs to treat them. However, some of the most remarkable discoveries in physiology and medicine are uncovered by studying rare conditions, because the importance of certain molecular mechanisms is revealed only when their dysfunction results in disease. In 2008, the National Institutes of Health (NIH) launched the NIH Undiagnosed Diseases Program (UDP), which recruits and selects patients who suffer from diseases of unknown etiology, and studies their causes at the clinical, genetic and cellular levels. In this Editorial, we discuss how the UDP has enabled the discovery of several new diseases and disease mechanisms through collaborations between clinical and basic science teams, using the power of both clinical medicine and biological models. Establishing programs with similar infrastructure at other centers around the world could help to benefit patients, their families and the entire medical community, by enhancing research productivity for rare and novel diseases.
Stories of the Twentieth Century for the Twenty-First
Authors: Gourinchas Pierre-Olivier , Obstfeld Maurice
Published: January 2012

A key precursor of twentieth-century financial crises in emerging and advanced economies alike was the rapid buildup of leverage. Those emerging economies that avoided leverage booms during the 2000s also were most likely to avoid the worst effects of the twenty-first century's first global crisis. A discrete-choice panel analysis using 1973–2010 data suggests that domestic credit expansion and real currency appreciation have been the most robust and significant predictors of financial crises, regardless of whether a country is emerging or advanced. For emerging economies, however, higher foreign exchange reserves predict a sharply reduced probability of a subsequent crisis. (JEL E44, F34, F44, G01, G21, O19)
Concentrations of toxic and essential elements in Lebanese bread
Authors: Bou Khouzam Rola , Pohl Pawel , Al Ayoubi Baydaa , Jaber Farouk , Lobinski Ryszard
Published: January 2012

Concentrations of 20 minor, trace, and ultratrace elements relevant to human health (Ag, Al, As, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Ni, Pb, Sb, Se, Si, Sn, V, and Zn) were determined in three varieties of Lebanese bread (white and brown double loaf bread, Saj bread) sampled at five geographical regions (Grand Beirut, South of Lebanon, North of Lebanon, Mount of Lebanon, and Beka’a) during the wet and dry seasons. The analyses were carried out by double-focusing sector-field inductively coupled plasma-mass spectrometry (DF-SF-ICP-MS). The data were discussed in terms of nutritional elements supplied by type of bread, the risk of contamination by toxic elements (As, Cd, Pb) owing to the manufacturing process, and variations related to geographic distribution and seasonal sampling.
Central Adaptation to Odorants Depends on PI3K Levels in Local Interneurons of the Antennal Lobe
Authors: Acebes Angel , Devaud Jean-Marc , Arnés Mercedes , Ferrús Alberto
Published: January 2012

We have previously shown that driving PI3K levels up or down leads to increases or reductions in the number of synapses, respectively. Using these tools to assay their behavioral effects inDrosophila melanogaster, we showed that a loss of synapses in two sets of local interneurons,GH298andkrasavietz, leads to olfaction changes toward attraction or repulsion, while the simultaneous manipulation of both sets of neurons restored normal olfactory indexes. We show here that olfactory central adaptation also requires the equilibrated changes in both sets of local interneurons. The same genetic manipulations directed to projection (GH146) or mushroom body (201Y,MB247) neurons did not affect adaptation. Also, we show that the equilibrium is a requirement for the glomerulus-specific size changes which are a morphological signature of central adaptation. Since the two sets of local neurons are mostly, although not exclusively, inhibitory (GH298) and excitatory (krasavietz), we interpret that the normal phenomena of sensory perception, measured as an olfactory index, and central adaptation rely on an inhibition/excitation ratio.
Preservation of Cone Photoreceptors after a Rapid yet Transient Degeneration and Remodeling in Cone-OnlyNrl−/−Mouse Retina
Authors: Roger Jerome E. , Ranganath Keerthi , Zhao Lian , Cojocaru Radu I. , Brooks Matthew , Gotoh Norimoto , Veleri Shobi , Hiriyanna Avinash , Rachel Rivka A. , Campos Maria Mercedes , Fariss Robert N. , Wong Wai T. , Swaroop Anand
Published: January 2012

Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor neural retina leucine zipper (NRL). The loss ofNrl(Nrl−/−) in mice results in a retina with predominantly S-opsin-containing cones that exhibit molecular and functional characteristics of wild-type cones. Here, we report thatNrl−/−retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by 4 months of age, resulting in a thinner but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic electroretinogram. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of genes related to stress response and inflammation, implying their involvement in cone death. TheNrl−/−mouse illustrates the long-term viability of cones in the absence of rods and retinal pigment epithelium defects in a rodless retina. We propose thatNrl−/−retina may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula.
Neuronal Gap Junction Coupling Is Regulated by Glutamate and Plays Critical Role in Cell Death during Neuronal Injury
Authors: Wang Yongfu , Song Ji-Hoon , Denisova Janna V. , Park Won-Mee , Fontes Joseph D. , Belousov Andrei B.
Published: January 2012

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI), and epilepsy. The coupling of neurons by gap junctions (electrical synapses) increases during neuronal injury. We report here that the ischemic increase in neuronal gap junction coupling is regulated by glutamate via group II metabotropic glutamate receptors (mGluRs). Specifically, using electrotonic coupling, Western blots, and siRNA in the mouse somatosensory cortexin vivoandin vitro, we demonstrate that activation of group II mGluRs increases background levels of neuronal gap junction coupling and expression of connexin 36 (Cx36) (neuronal gap junction protein), and inactivation of group II mGluRs prevents the ischemia-mediated increases in the coupling and Cx36 expression. We also show that the regulation is via cAMP/PKA (cAMP-dependent protein kinase)-dependent signaling and posttranscriptional control of Cx36 expression and that other glutamate receptors are not involved in these regulatory mechanisms. Furthermore, using the analysis of neuronal death, we show that inactivation of group II mGluRs or genetic elimination of Cx36 both dramatically reduce ischemia-mediated neuronal deathin vitroandin vivo. Similar results are obtained usingin vitromodels of TBI and epilepsy. Our results indicate that neuronal gap junction coupling is a critical component of glutamate-dependent neuronal death. They also suggest that causal link among group II mGluR function, neuronal gap junction coupling, and neuronal death has a universal character and operates in different types of neuronal injuries.
Disruption of NMDA Receptors in Oligodendroglial Lineage Cells Does Not Alter Their Susceptibility to Experimental Autoimmune Encephalomyelitis or Their Normal Development
Authors: Guo Fuzheng , Maeda Yoshiko , Ko Emily Mills , Delgado Monica , Horiuchi Makoto , Soulika Athena , Miers Laird , Burns Travis , Itoh Takayuki , Shen Haitao , Lee Eunyoung , Sohn Jiho , Pleasure David
Published: January 2012

Pharmacological studies have suggested that oligodendroglial NMDA glutamate receptors (NMDARs) mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), a model of human MS, by timed conditional disruption of oligodendroglial NR1, an essential subunit of functional NMDARs, using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system. We found that selective ablation of oligodendroglial NR1 did not alter the clinical severity of EAE elicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35–55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1 KO and non-KO mice in numbers of axons lost in spinal cord dorsal funiculi or severity of spinal cord demyelination. Similarly, constitutive deletion of NR3A, a modulatory subunit of oligodendroglial NMDARs, did not alter the course of MOG-peptide EAE. Furthermore, conditional and constitutive ablation of NR1 in neonatal oligodendrocyte progenitor cells did not interrupt their normal maturation and differentiation. Collectively, our data suggest that oligodendroglial lineage NMDARs are neither required for timely postnatal development of the oligodendroglial lineage, nor significant participants in the pathophysiology of MOG-peptide EAE.
Intermittent Visual Feedback Can Boost Motor Learning of Rhythmic Movements: Evidence for Error Feedback Beyond Cycles
Authors: Ikegami Tsuyoshi , Hirashima Masaya , Osu Rieko , Nozaki Daichi
Published: January 2012

Movement error is a driving force behind motor learning. For motor learning with discrete movements, such as point-to-point reaching, it is believed that the brain uses error information of the immediately preceding movement only. However, in the case of continuous and repetitive movements (i.e., rhythmic movements), there is a ceaseless inflow of performance information. Thus, an accurate temporal association of the motor commands with the resultant movement errors is not necessarily guaranteed. We investigated how the brain overcomes this challenging situation. Human participants adapted rhythmic movements between two targets to visuomotor rotations, the amplitudes of which changed randomly from cycle to cycle (the duration of one cycle was ∼400 ms). A system identification technique revealed that the motor adaptation was affected not just by the preceding movement error, but also by a history of errors from the previous cycles. Error information obtained from more than one previous cycle tended to increase, rather than decrease, movement error. This result led to a counterintuitive prediction: providing visual error feedback for only a fraction of cycles should enhance visuomotor adaptation. As predicted, we observed that motor adaptation to a constant visual rotation (30°) was significantly enhanced by providing visual feedback once every fourth or fifth cycle rather than for every cycle. These results suggest that the brain requires a specific processing time to modify the motor command, based on the error information, and so is unable to deal appropriately with the overwhelming flow of error information generated during rhythmic movements.
Catenin-Dependent Cadherin Function Drives Divisional Segregation of Spinal Motor Neurons
Authors: Bello Sanusi M. , Millo Hadas , Rajebhosale Manisha , Price Stephen R.
Published: January 2012

Motor neurons that control limb movements are organized as a neuronal nucleus in the developing ventral horn of the spinal cord called the lateral motor column. Neuronal migration segregates motor neurons into distinct lateral and medial divisions within the lateral motor column that project axons to dorsal or ventral limb targets, respectively. This migratory phase is followed by an aggregation phase whereby motor neurons within a division that project to the same muscle cluster together. These later phases of motor neuron organization depend on limb-regulated differential cadherin expression within motor neurons. Initially, all motor neurons display the same cadherin expression profile, which coincides with the migratory phase of motor neuron segregation. Here, we show that this early, pan-motor neuron cadherin function drives the divisional segregation of spinal motor neurons in the chicken embryo by controlling motor neuron migration. We manipulated pan-motor neuron cadherin function through dissociation of cadherin binding to their intracellular partners. We found that of the major intracellular transducers of cadherin signaling, γ-catenin and α-catenin predominate in the lateral motor column.In vivomanipulations that uncouple cadherin–catenin binding disrupt divisional segregation via deficits in motor neuron migration. Additionally, reduction of the expression of cadherin-7, a cadherin predominantly expressed in motor neurons only during their migration, also perturbs divisional segregation. Our results show that γ-catenin-dependent cadherin function is required for spinal motor neuron migration and divisional segregation and suggest a prolonged role for cadherin expression in all phases of motor neuron organization.
Inner Hair Cells Are Not Required for Survival of Spiral Ganglion Neurons in the Adult Cochlea
Authors: Zilberstein Yael , Liberman M. Charles , Corfas Gabriel
Published: January 2012

Studies of sensorineural hearing loss have long suggested that survival of spiral ganglion neurons (SGNs) depends on trophic support provided by their peripheral targets, the inner hair cells (IHCs): following ototoxic drugs or acoustic overexposure, IHC death is rapid whereas SGN degeneration is always delayed. However, recent noise-trauma studies show that SGNs can die even when hair cells survive, and transgenic mouse models show that supporting cell dysfunction can cause SGN degeneration in the absence of IHC pathology. To reexamine this issue, we studied a model of IHC loss that does not involve noise or ototoxic drugs. Mice lacking the gene for the high-affinity thiamine transporter (Slc19a2) have normal cochlear structure and function when fed a regular (thiamine-rich) diet. However, dietary thiamine restriction causes widespread, rapid (within 10 d) loss of IHCs. Using this model, we show that SGNs can survive for months after IHC loss, indicating that (1) IHCs are not necessary for neuronal survival, (2) neuronal loss in the other hearing loss models is likely due to effects of the trauma on the sensory neurons or other inner ear cells, and (3) that other cells, most likely supporting cells of the organ of Corti, are the main source of SGN survival factors. These results overturn a long-standing dogma in the study of sensorineural hearing loss and highlight the importance of cochlear supporting cells in neuronal survival in the adult inner ear.
Prenatal Immune Activation Interacts with GeneticNurr1Deficiency in the Development of Attentional Impairments
Authors: Vuillermot Stéphanie , Joodmardi Eliza , Perlmann Thomas , Ove Ögren Sven , Feldon Joram , Meyer Urs
Published: January 2012

Prenatal exposure to infection has been linked to increased risk of neurodevelopmental brain disorders, and recent evidence implicates altered dopaminergic development in this association. However, since the relative risk size of prenatal infection appears relatively small with respect to long-term neuropsychiatric outcomes, it is likely that this prenatal insult interacts with other factors in shaping the risk of postnatal brain dysfunctions. In the present study, we show that the neuropathological consequences of prenatal viral-like immune activation are exacerbated in offspring with genetic predisposition to dopaminergic abnormalities induced by mutations inNurr1, a transcription factor highly essential for normal dopaminergic development. We combined a mouse model of heterozygous genetic deletion ofNurr1with a model of prenatal immune challenge by the viral mimetic poly(I:C) (polyriboinosinic polyribocytidilic acid). In our gene–environment interaction model, we demonstrate that the combination of the genetic and environmental factors not only exerts additive effects on locomotor hyperactivity and sensorimotor gating deficits, but further produces synergistic effects in the development of impaired attentional shifting and sustained attention. We further demonstrate that the combination of the two factors is necessary to trigger maldevelopment of prefrontal cortical and ventral striatal dopamine systems. Our findings provide evidence for specific gene–environment interactions in the emergence of enduring attentional impairments and neuronal abnormalities pertinent to dopamine-associated brain disorders such as schizophrenia and attention deficit/hyperactivity disorder, and further emphasize a critical role of abnormal dopaminergic development in these etiopathological processes.
Kinases SPAK and OSR1 Are Upregulated by Estradiol and Activate NKCC1 in the Developing Hypothalamus
Authors: Nugent Bridget M. , Valenzuela Carla V. , Simons Timothy J. , McCarthy Margaret M.
Published: January 2012

In immature neurons the amino acid neurotransmitter, GABA provides the dominant mode for neuronal excitation by inducing membrane depolarization due to Cl−efflux through GABAAreceptors (GABAARs). The driving force for Cl−is outward because the Na+-K+-2Cl−cotransporter (NKCC1) elevates the Cl−concentration in these cells. GABA-induced membrane depolarization and the resulting activation of voltage-gated Ca2+channels is fundamental to normal brain development, yet the mechanisms that regulate depolarizing GABA are not well understood. The neurosteroid estradiol potently augments depolarizing GABA action in the immature hypothalamus by enhancing the activity of the NKCC1 cotransporter. Understanding how estradiol controls NKCC1 activity will be essential for a complete understanding of brain development. We now report that estradiol treatment of newborn rat pups significantly increases protein levels of two kinases upstream of the NKCC1 cotransporter, SPAK (STE20/SPS1-related proline alanine rich kinase) and OSR1 (oxidative stress response kinase). The estradiol-induced increase is transcription dependent, and its time course parallels that of estradiol-enhanced phosphorylation of NKCC1. Antisense oligonucleotide-mediated knockdown of SPAK, and to a lesser degree of OSR1, precludes estradiol-mediated enhancement of NKCC1 phosphorylation. Functionally, knockdown of SPAK or OSR1 in embryonic hypothalamic cultures diminishes estradiol-enhanced Ca2+influx induced by GABAAR activation. Our data suggest that SPAK and OSR1 may be critical factors in the regulation of depolarizing GABA-mediated processes in the developing brain. It will be important to examine these kinases with respect to sex differences and developmental brain anomalies in future studies.
SPINK3 modulates mouse sperm physiology through the reduction of nitric oxide level independently of its trypsin inhibitory activity
Authors: Zalazar L , Saez Lancellotti T E , Clementi M , Lombardo C , Lamattina L , De Castro R , Fornés M W , Cesari A
Published: January 2012

Serine protease inhibitor Kazal-type (SPINK3)/P12/PSTI-II is a small secretory protein from mouse seminal vesicle which contains a KAZAL domain and shows calcium (Ca2+)-transport inhibitory (caltrin) activity. This molecule was obtained as a recombinant protein and its effect on capacitated sperm cells was examined. SPINK3 inhibited trypsin activityin vitrowhile the fusion protein GST-SPINK3 had no effect on this enzyme activity. The inactive GST-SPINK3 significantly reduced the percentage of spermatozoa positively stained for nitric oxide (NO) with the specific probe DAF-FM DA and NO concentration measured by Griess method in capacitated mouse sperm; the same effect was observed when sperm were capacitated under low Ca2+concentration, using either intracellular (BAPTA-AM) or extracellular Ca2+(EDTA) chelators. The percentage of sperm showing spontaneous and progesterone-induced acrosomal reaction was significantly lower in the presence of GST-SPINK3 compared to untreated capacitated spermatozoa. Interestingly, this decrease was overcome by the exogenous addition of the NO donors, sodium nitroprusside (SNP), andS-nitrosoglutathione (GSNO). Phosphorylation of sperm proteins in tyrosine residues was partially affected by GST-SPINK3, however, only GSNO was able to reverse this effect. Sperm progressive motility was not significantly diminished by GST-SPINK3 or BAPTA-AM but enhanced by the addition of SNP. This is the first report that demonstrates that SPINK3 modulates sperm physiology through a downstream reduction of endogenous NO concentration and independently of SPINK3 trypsin inhibitory activity.
“Point” Centromeres of Saccharomyces Harbor Single Centromere-Specific Nucleosomes
Authors: Henikoff Steven , Henikoff Jorja G
Published: January 2012

The “point” centromere of budding yeast is genetically defined by an ∼125-bp sequence. Recent fluorescence measurements of kinetochore clusters have suggested that this sequence specifies multiple centromere histone 3 (CenH3) nucleosomes. However, high-resolution mapping demonstrates that there is only one CenH3 nucleosome per centromere, providing biochemical confirmation of the point centromere model.
Field Emission Mechanism of H-Terminated N-Type Diamond NEA Surface
Authors: Yamada Takatoshi , Hasegawa Masataka , Yamaguchi Hisato , Kudo Yuki , Okano Ken , Nebel Christoph E.
Published: January 2012

Field electron emission model of hydrogen-terminated n-type diamond was discussed. Ultra-violet photoelectron spectroscopy characterizations indicated that the electron affinity was -0.7 eV and an internal barrier of about 3.5 eV existed on the surface. Field electron emission properties depended on anode-diamond distances. Schottky barrier lowering model suggested that this internal barrier was lowered by the electric field (5.4x106 V/cm) applied onto the negative electron affinity surface of the H-terminated n-type diamond.
Fabrication of Organic Small Molecular Thin Films based on Ultrasonic Spray-Assisted Vapor-Deposition Method
Authors: Piao Jinchun , Katori Shigetaka , Ikenoue Takumi , Fujita Shizuo
Published: January 2012

Small molecular thin films using solution-based method is a challengeable subject in organic optical and electronic devices. In our previous research, we successfully deposited aluminum tris(8-hydroxyquinoline) (Alq3) films on glass substrate. In this paper, aiming at future exploration of electroluminescent devices, we deposited N, N ’-Bis(3-methylphenyl)-N,N’- diphenylbenzidine) (TPD) films on indium-tin-oxide (ITO) substrates using the vapor-deposition method. Photoluminescence characteristics evidenced the actual formation of TPD thin films. Together with the good surface morphology and low leakage current of the films, the results are promising for actual device fabrication at low cost and low material loss.
Initiation and Decomposition of Tetrazole Containing Green Energetic Materials
Authors: Piekiel Nicholas W. , Cavicchi Richard E. , Zachariah Michael R.
Published: January 2012

A T-Jump/Time-of-Flight Mass Spectrometer (T-Jump/TOFMS) is used to probe the decomposition of several aminotetrazole containing energetic materials under very high heating rates of 105-106 K/s. Subtle differences between materials in functional group placement and anion composition allow for further understanding of the decomposition pathway of the tetrazole structure and various anions. Two decomposition pathways for the tetrazole ring are observed, which result in the primary formation of HN3 or N2. Further analysis is performed using a rapid-heating μ-DSC device, which revealed lower activation energies than previously reported.
Characterization of Un-stabilized Orthorhombic Zirconia Synthesized at Ambient Temperature and Pressure
Authors: Trubelja Miriam P. , Potter Donald , Rawn Claudia , More Karren , Helble Joseph J.
Published: January 2012

Bulk structures of un-stabilized ZrO2-x with x in the 0 ≤ x ≤ 0.44 range under ambient pressure exist in three different structures (monoclinic, tetragonal and cubic). At ambient temperature and elevated pressures above 3.5 GPa, zirconia, at these compositions, a fourth phase is found, the orthorhombic structure. A dilute sol-gel method was used to produce nanoscale zirconia particles containing the unstabilized orthorhombic cotunnite structure for use in this project. Extensive characterization of this material indicates that the critical factor in determining the synthesized structures appears to be the number and placement of oxygen vacancies. These results also indicate that surface energy alone is not the controlling factor in determining the crystal structure synthesized.
Reusable hybride CoFe2O4-ZnO hollow nanosphere photocatalysts
Authors: Wilson A. , Mishra S. R. , Rai B. K. , Gupta R.K. , Ghosh K.
Published: January 2012

Magnetically separable and reusable core-shell CoFe2O4-ZnO photocatalyst nanospheres were prepared via hydrothermal synthesis technique using glucose derived carbon nanospheres as template. The morphology and phase of core-shell hybrid structure of CoFe2O4-ZnO was assessed via TEM, and XRD. The UV-vis photocatalytic activity of the composite was assessed via measuring the degradation rate of modeled pollutant methylene blue in water. The magnetic composite showed high UV photocatalytic activity for the degradation of methylene blue. The photocatalytic activity was found to be ZnO shell thickness dependent. Thicker ZnO shells lead to higher rate of photocatalytic activity. Hybrid nanospheres recovered using external magnetic field demonstrated good repeatability of photocatalytic activity. These results promise the reusability of hybrid nanospheres for photocatalytic activity.
Hydrothermally Grown Nanostructured Tungsten Trioxide (hydrate) Films and their Photocatalytic Properties
Authors: Jiao Z. H. , Sun X.W.
Published: January 2012

We report the growth of sheet-like nanostructured tungsten trioxide hydrate (3WO3·H2O) film on fluorine doped tin oxide (FTO) substrate via a facile crystal-seed-assisted hydrothermal method by using CH3COONH4 as capping agent. Dense thin film composed of irregular blocks with smaller surface area was obtained without the addition of CH3COONH4. X-ray diffraction (XRD) studies indicated that both films were of orthorhombic structure. The nanosheet film grown with CH3COONH4 after dehydration showed highly improved photocatalytic activities than the nanoblock one. The maximum anodic photocurrents of 1.16 mA/cm2 for oxidization of methanol and 0.5 mA/cm2 for water splitting were obtained for the nanosheet film with a highest photoconversion efficiency of about 0.3% under simulated solar illumination.
SiGe Nanowires Grown by LPCVD using Ga-Au Catalysts
Authors: Monasterio M. , Rodríguez A. , Rodríguez T. , Ballesteros C.
Published: January 2012

The use of Ga-Au alloys as metal catalysts for the growth of SiGe nanowires has been investigated. The grown nanowires are cylindrical and straight, with a defect-free crystalline structure, sharp nanowire-droplet interfaces and an almost constant Ge atomic fraction throughout all their length. These features represent significant improvements over the results obtained using pure Au.
Preparation of Al2O3 and AlN Nanotubes by Atomic Layer Deposition
Authors: Ozgit Cagla , Kayaci Fatma , Donmez Inci , Cagatay Engin , Uyar Tamer , Biyikli Necmi
Published: January 2012

Al2O3 and AlN nanotubes were fabricated by depositing conformal thin films via atomic layer deposition (ALD) on electrospun nylon 66 (PA66) nanofiber templates. Depositions were carried out at 200°C, using trimethylaluminum (TMAl), water (H2O), and ammonia (NH3) as the aluminum, oxygen, and nitrogen precursors, respectively. Deposition rates of Al2O3 and AlN at this temperature were ∼1.05 and 0.86 Å/cycle. After the depositions, Al2O3- and AlN-coated nanofibers were calcinated at 500°C for 2 h in order to remove organic components. Nanotubes were characterized by using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). AlN nanotubes were polycrystalline as determined by high resolution TEM (HR-TEM) and selected area electron diffraction (SAED). TEM images of all the samples reported in this study indicated uniform wall thicknesses.
The role of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 in diabetic nephropathy
Authors: Sortica Denise Alves , Crispim Daisy , Zaffari Guilherme Pozueco , Friedman Rogério , Canani Luis Henrique
Published: January 2012

The increased prevalence of diabetes mellitus has caused a rise in the occurrence of its chronic complications, such as diabetic nephropathy (DN), which is associated with elevated morbidity and mortality. Familial aggregation studies have demonstrated that besides the known environmental risk factors, DN has a major genetic component. Therefore, it is necessary to identify genes associated with risk for or protection against DN. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is expressed in several tissues, including the kidneys. Increased levels of ENPP1 expression inhibit tyrosine-kinase activity of the insulin receptor in several cell types, leading to insulin resistance. K121Q polymorphism of the ENPP1 gene seems to be associated with insulin resistance and DN development. The elucidation of genetic factors and their associations will provide better understanding of the pathogenesis of DN and, may consequently, lead to a more effective approach to prevention and treatment.
Economic evaluation of outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service
Authors: Borges Anna Paula de Sá , Guidoni Camilo Molino , Freitas Osvaldo de , Pereira Leonardo Régis Leira
Published: January 2012

OBJECTIVE: To analyze the costs related to visits and drug prescription in outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service. SUBJECTS AND METHODS: A prospective and experimental study was carried out. Seventy one patients were divided into two groups: control and pharmaceutical care. Patients in the pharmaceutical care group were followed up monthly by a single clinical pharmacist. RESULTS: The pharmaceutical care group had a statistically significant reduction in costs of metformin and emergency department visits, and increased costs with their family physicians. On the other hand, the control group had a statistically significant increase of 21.3% in the general costs of treatment and visits. CONCLUSION: The pharmaceutical care group maintained the same costs related to drugs and visits, while the control group showed a significant increase in general costs.
Quantification of HIV-1 viral RNA in the blood in needles used for venous puncture in HIV-infected individuals
Authors: Rossin Iris Ricardo , Machado Alcyone Artioli , Junqueira Érica Maria , Martinez Roberto
Published: January 2012

INTRODUCTION: Occupational HIV infection among healthcare workers is an important issue in exposures involving blood and body fluids. There are few data in the literature regarding the potential and the duration of infectivity of HIV type 1 (HIV-1) in contaminated material under adverse conditions. METHODS: We quantified HIV-1 viral RNA in 25×8mm calibre hollow-bore needles, after punctures, in 25 HIV-1-infected patients selected during the sample collection. All of the patients selected were between the ages of 18 and 55. Five samples were collected from 16 patients: one sample for the immediate quantification of HIV-1 RNA in the plasma and blood samples from the interior of 4 needles to be analyzed at 0h, 6h, 24h, and 72h after collection. In nine patients, another test was carried out in the blood from one additional needle, in which HIV-1 RNA was assessed 168h after blood collection. The method used to assess HIV-1 RNA was nucleic acid sequence-based amplification. RESULTS: Up to 7 days after collection, HIV-1 RNA was detected in all of the needles. The viral RNA remained stable up to 168h, and there were no statistically significant differences among the needle samples. CONCLUSIONS: Although the infectivity of the viral material in the needles is unknown, the data indicate the need to re-evaluate the practices in cases of occupational accidents in which the source is not identified.