bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence and consequences of early wound infection after internal fixation for trauma in HIV-positive patients
Authors: Bates J. , Mkandawire N. , Harrison W. J.
Published: August 2012

We report a prospective single-blind controlled study of the incidence of early wound infection after internal fixation for trauma in 609 patients, of whom 132 were HIV-positive. Wounds were assessed for healing using the ASEPSIS score. There was no significant difference in the rate of infection between HIV-positive and HIV-negative patients undergoing clean surgery (4.2% vs 6%, respectively; p = 0.65). HIV-positive patients did not receive additional antibiotic prophylaxis or antiretroviral therapy as part of their management. The difference in the rate of infection between HIV-positive and HIV-negative patients with an open fracture or other contamination was not significant (33% vs 15%, respectively; p = 0.064). There was no relationship between CD4 count and infection rate. HIV status did not significantly influence the number of secondary surgical procedures (p = 0.183) or the likelihood of developing chronic osteomyelitis (p = 0.131). Although previous contamination from the time of injury was a risk factor for infection in mal- and nonunions, it was not significantly increased in HIV-positive patients (p = 0.144).

We conclude that clean implant surgery in HIV-positive patients is safe, with no need for additional prophylaxis.
Medial patellofemoral ligament reconstruction
Authors: Howells N. R. , Barnett A. J. , Ahearn N. , Ansari A. , Eldridge J. D.
Published: August 2012

We report a prospective analysis of clinical outcome in patients treated with medial patellofemoral ligament (MPFL) reconstruction using an autologous semitendinosus graft. The technique includes superolateral portal arthroscopic assessment before and after graft placement to ensure correct graft tension and patellar tracking before fixation. Between October 2005 and October 2010, a total of 201 consecutive patients underwent 219 procedures. Follow-up is presented for 211 procedures in 193 patients with a mean age of 26 years (16 to 49), and mean follow-up of 16 months (6 to 42). Indications were atraumatic recurrent patellar dislocation in 141 patients, traumatic recurrent dislocation in 50, pain with subluxation in 14 and a single dislocation with persistent instability in six. There have been no recurrent dislocations/subluxations. There was a statistically significant improvement between available pre- and post-operative outcome scores for 193 patients (all p < 0.001). Female patients with a history of atraumatic recurrent dislocation and all patients with history of previous surgery had a significantly worse outcome (all p < 0.05). The indication for surgery, degree of dysplasia, associated patella alta, time from primary dislocation to surgery and evidence of associated cartilage damage at operation did not result in any significant difference in outcome.

This series adds considerably to existing evidence that MPFL reconstruction is an effective surgical procedure for selected patients with patellofemoral instability.
The effectiveness of injections of hyaluronic acid or corticosteroid in patients with subacromial impingement
Authors: Penning L. I. F. , de Bie R. A. , Walenkamp G. H. I. M.
Published: August 2012

A total of 159 patients (84 women and 75 men, mean age of 53 (20 to 87)) with subacromial impingement were randomised to treatment with subacromial injections using lidocaine with one of hyaluronic acid (51 patients), corticosteroid (53 patients) or placebo (55 patients). Patients were followed up for 26 weeks. The primary outcome was pain on a visual analogue score (VAS), and secondary outcomes included the Constant Murley score, shoulder pain score, functional mobility score, shoulder disability questionnaire and pain-specific disability score. The different outcome measures showed similar results. After three, six and 12 weeks corticosteroid injections were superior to hyaluronic acid injections and only at six weeks significantly better than placebo injections. The mean short-term reduction in pain on the VAS score at 12 weeks was 7% (sd 2.7; 97.5% confidence interval (CI) 0.207 to 1.55; p = 0.084) in the hyaluronic acid group, 28% (sd 2.8; 97.5% CI 1.86 to 3.65; p < 0.001) in the corticosteroid group and 23% (sd 3.23; 97.5% CI 1.25 to 3.26; p < 0.001) in the placebo group. At 26 weeks there was a reduction in pain in 63% (32 of 51) of patients in the hyaluronic acid group, 72% (38 of 53) of those in the corticosteroid group and 69% (38 of 55) of those in the placebo group.

We were not able to show a convincing benefit from hyaluronic acid injections compared with corticosteroid or placebo injections. Corticosteroid injections produced a significant reduction in pain in the short term (three to 12 weeks), but in the long term the placebo injection produced the best results.
Can T1-rho MRI detect acetabular cartilage degeneration in femoroacetabular impingement?
Authors: Rakhra K. S. , Lattanzio P-J. , Cárdenas-Blanco A. , Cameron I. G. , Beaulé P. E.
Published: August 2012

Advanced MRI cartilage imaging such as T1-rho (T1ρ) for the diagnosis of early cartilage degradation prior to morpholgic radiological changes may provide prognostic information in the management of joint disease. This study aimed first to determine the normal T1ρ profile of cartilage within the hip, and secondly to identify any differences in T1ρ profile between the normal and symptomatic femoroacetabular impingement (FAI) hip. Ten patients with cam-type FAI (seven male and three female, mean age 35.9 years (28 to 48)) and ten control patients (four male and six female, mean age 30.6 years (22 to 35)) underwent 1.5T T1ρ MRI of a single hip. Mean T1ρ relaxation times for full thickness and each of the three equal cartilage thickness layers were calculated and compared between the groups. The mean T1ρ relaxation times for full cartilage thickness of control and FAI hips were similar (37.17 ms (sd 9.95) and 36.71 ms (sd 6.72), respectively). The control group demonstrated a T1ρ value trend, increasing from deep to superficial cartilage layers, with the middle third having significantly greater T1ρ relaxation values than the deepest third (p = 0.008). The FAI group demonstrated loss of this trend. The deepest third in the FAI group demonstrated greater T1ρ relaxation values than controls (p = 0.028).

These results suggest that 1.5T T1ρ MRI can detect acetabular hyaline cartilage changes in patients with FAI.
Canadian Survey of Critical Care Pharmacists' Views and Involvement in Clinical Research
Authors: Perreault Marc M , Thiboutot Zoé , Burry Lisa D , Rose Louise , Kanji Salmaan , LeBlanc Jaclyn M , Carr Roxane R , Williamson David R
Published: August 2012

BACKGROUND:

The involvement of Canadian critical care pharmacists in clinical research is not well documented.

OBJECTIVE:

To describe the clinical research experience of Canadian critical care pharmacists, describe their views about clinical research, and identify factors that facilitate their involvement in clinical research.

METHODS:

A cross-sectional electronic survey of Canadian critical care pharmacists was developed through an iterative process and conducted from July to October 2010. We invited 325 pharmacists from 129 hospitals across Canada to participate. Surveys with more than 30% of questions unanswered were discarded.

RESULTS:

Analyzable response rate was 66.2%. Overall, 33 pharmacists (15.7%) were highly involved in research, 54 (25.7%) were moderately involved, and 123 (58.6%) were minimally involved. Most respondents (97.2%) believed that critical care pharmacist involvement in research was desirable, and many (80.4%) expressed interest to be more involved in research. Nearly all respondents (99.5%) agreed that more support should be provided to pharmacists interested in conducting research. Pharmacists currently involved in research have obtained higher academic degrees (adjusted OR 11.23; p < 0.001), express a strong interest in research (adjusted OR 7.44; p < 0.001), report a higher level of training for involvement in research (adjusted OR 2.23; p = 0.047), and practice more often in a university hospital (adjusted OR 3.68; p = 0.004) within an intensive care unit where involvement in research is valued (adjusted OR 5.61; p < 0.001). Support from pharmacy departments is not related to involvement in research (adjusted OR 1.22; p = 0.633).

CONCLUSIONS:

Canadian critical care pharmacists are involved to varying degrees in clinical research and are very interested in initiating and supporting research activities. Opportunities are present but significant barriers exist. The value of pharmacist-initiated research needs recognition as a priority within hospital pharmacy administration.
Gas Holdup and Frictional Pressure Drop In a Modified Slurry Bubble Column
Authors: Sivaiah Mekala , Majumder Subrata Kumar
Published: August 2012

This article presents the analysis of gas holdup, pressure drop and bubble size of gas-liquid-solid flow in a modified downflow slurry bubble column. The analysis is done based on the Lockhart-Martinelli principle. The Lockhart-Martinelli model is modified and incorporate to predict the frictional pressure drop and gas holdup of three-phase flow in the modified bubble column. The effects of operating variables such as slurry flow rate, gas flow rate, slurry concentration and particle diameter on frictional pressure drop and gas holdup are investigated. To predict the gas holdup, Sauter mean bubble diameter and pressure drop, correlations have also been developed as function of different dimensionless groups by introducing the operating variables and physical properties. The studies of the pressure drop in the downflow slurry bubble column may give insight into a further understanding and modeling of the three-phase flow characteristics in industrial applications.
Youth Unemployment, Terrorism and Political Violence, Evidence from the Israeli/Palestinian Conflict
Authors: Caruso Raul , Gavrilova Evelina
Published: August 2012

This paper analyzes the relationship between youth unemployment and Palestinian violence. First a qualitative explanation of the underlying mechanism is given. Eventually, empirical results suggest that there is a positive association between the growth rate of youth unemployment and the brutality and incidence of violence, proxied by the numbers of victims, and incidents. Results also show that: (i) there is a negative association between the added value in the agricultural sector and both measures of violence; (ii) there is a positive association between the share of employment in agriculture and violence; (iii) there is a negative association between manufacturing added value and brutality of incidents. Results also suggest that male youth unemployment rather than female unemployment helps to explain Palestinian violence.
The Impact of the Economic Costs of Conflict on Individuals' Political Attitudes
Authors: Ben Bassat Avi , Dahan Momi , Geys Benny , Klor Esteban F.
Published: August 2012

A large number of studies show that war and terrorism have a significant effect on individuals’ political attitudes. Yet, this extensive literature does not inspect the mechanisms behind this effect. This paper concentrates on one possible mechanism, by differentiating between the human toll of terror and war and the economic costs they cause. For these purposes we focus on the Israeli-Palestinian conflict, and use variation in the level of violence across time and space together with localities’ different exposure to the tourism sector to estimate their respective effects on political attitudes. Our results suggest that whereas fatalities from the conflict make Israelis more willing to grant territorial concessions to the Palestinians, the associated economic costs of conflict do not have a consistent significant effect on individuals’ political attitudes.
Cost Benefit Analysis of Centralized Wastewater Reuse Systems
Authors: Liang Xiao , van Dijk Meine Pieter
Published: August 2012

The present paper carries out a cost benefit analysis of centralized wastewater reuse systems in Beijing. This study consists of two parts: financial analysis and economic analysis. The financial analysis is made from the point of view of plant manager, in which financial benefits and cost is calculated. The economic analysis is made from the point of view of society, in which the economic, environmental and social benefits and cost are determined. The results of financial analysis show that the financial benefits are larger than cost, which means the centralized wastewater reuse systems are financially feasible. It implies that the investment on centralized wastewater reuse systems is profitable. The results of economic analysis show that the ratio of benefit to cost is larger than 1, which means the centralized wastewater reuse systems are economically feasible. It implies that centralized wastewater reuse systems have positive effects on the society. From the point of view of plant manager, centralized wastewater reuse systems could operate in a long term, while from the point of view of government or society, the centralized wastewater reuse systems are worth to be promoted.
An Empirical Estimate of the Labor Response Function for Benefit-Cost Analysis
Authors: Vitaliano Donald F.
Published: August 2012

Since the seminal contribution of Haveman and Krutilla(1968), the subject of the potential drawdown from the pool of unemployed versus diversion of labor from existing employments consequent upon a public investment project has been largely neglected in the BCA literature. The advent of a new BLS series on job vacancies now permits direct estimation of the crucial unemployment-vacancies (U-V) relationship, as compared to the ad hoc sine function using the unemployment rate assumed by Haveman and Krutilla. The probability p of a worker being drawn from the pool of unemployed is recast as a function of the job vacancy rate (vacancies/labor force) and shows higher values than Haveman and Krutilla at comparable rates of unemployment. At the height of the 2008-09 Great Recession, about half of Stimulus induced jobs were drawn from the pool of unemployed.
Cyclin A2: a genuine cell cycle regulator?
Authors: Bendris Nawal , Loukil Abdelhalim , Cheung Caroline , Arsic Nikola , Rebouissou Cosette , Hipskind Robert , Peter Marion , Lemmers Bénédicte , Blanchard Jean Marie
Published: August 2012

Cyclin A2 belongs to the core cell cycle regulators and participates in the control of both S phase and mitosis. However, several observations suggest that it is also endowed with other functions, and our recent data shed light on its involvement in cytoskeleton dynamic and cell motility. From the transcription of its gene to its posttranslational modifications, cyclin A2 regulation reveals the complexity of the regulatory network shaping cell cycle progression. We summarize our current knowledge on this cell cycle regulator and discuss recent findings raising the possibility that cyclin A2 might play a much broader role in epithelial tissues homeostasis.
Physiomechanical properties of ultra-lightweight foam core particleboard: different core densities
Authors: Shalbafan Ali , Luedtke Jan , Welling Johannes , Fruehwald Arno
Published: August 2012

Ultra-lightweight foam core particleboards have been produced in a novel one-step process with resinated wood particles for the faces and expandable polystyrene (EPS) as core layer material. The mechanical and physical properties of panels were investigated in terms of the different foam core densities and press parameters (temperature, pressing and foaming time). The bending strength properties of the panels were not significantly changed with increasing foam core density from 80 to 120 kg m-3. Panels produced at a press temperature of 130°C (1-EPS) have an improved core-face interface and also a denser surface layer, which positively influences the internal bond and thickness swelling. The panels produced at a press temperature of 160°C (2-EPS) have smaller and more foam cells and an improved fusion of foam beads and properties, which have a positive influence on the edge screw withdrawal resistance and water absorption.
Auditory working memory and early reading skills in Hebrew-speaking preschool children
Authors: Banai Karen , Yifat Rachel
Published: August 2012

The hypothesis that different subcomponents of auditory working memory are differentially related to early reading skills was tested in 63 Hebrew speaking 4-year-old children, using a battery of early reading (phonological processing and familiarity with written language) and memory (simple and complex spans) tasks. Complex spans accounted for significant amounts of variance on both facets of early reading even after the contribution of simple spans was accounted for. These findings suggest that the unique contribution of complex working memory to early reading can be identified as early as preschool and that the structure of correlations between reading and memory is similar across ages.
Auditory sensation via moist contact of the bone vibrator with skin at soft tissue sites
Authors: Geal-Dor Miriam , Shore Aliza Frankel , Sohmer Haim
Published: August 2012

Background: Auditory sensation can be elicited not only by air conduction (AC) with an earphone and by bone conduction by applying a bone vibrator to bony sites on the head, but also by a newly described mode based on applying the bone vibrator to soft tissue sites on the head, neck, and thorax (soft tissue conduction – STC). This study was designed to assess whether it is necessary to compress the skin at the STC sites, which could induce vibrations of the underlying bone.

Methods: In 15 normal-hearing subjects, thresholds were assessed with the bone vibrator in air (control for possible AC), direct contact of the bone vibrator with the mastoid and regions around the lip, and indirect contact (via a cotton wool wick, dry or wet) of the bone vibrator with sites around the lip.

Results: Even though the best (lowest) thresholds were obtained with direct contact, the subjects clearly heard the sound stimulation when presented only by the gentle contact of the wick with the skin, especially when the contact site was moist.

Conclusions: STC stimulation does not require vibrations of the skull bone and seems to involve the transmission of auditory frequency vibrations, through a series of soft tissues, to the inner ear.
The identification problem for the functional equation with a parameter
Authors: Anikonov Yurii E.
Published: August 2012

In this paper we consider a nonlinear problem
of simultaneous search of
functions , of functional equations

with variable parameter p. We formulate and prove existence of formulas for functions
, which belong to special classes.
Placental transfer of clarithromycin in human pregnancies with preterm premature rupture of membranes
Authors: Park Hyun Soo , Ahn Byung-Jin , Jun Jong Kwan
Published: August 2012

Aim: The aim of this study was to evaluate the transplacental transfer of clarithromycin, which was used in the treatment of preterm premature rupture of membranes (PPROM) in human pregnancies, by comparing umbilical cord and maternal serum clarithromycin concentrations.

Methods: Singleton pregnant women with PPROM (<34 weeks) were prospectively enrolled between April 2009 and January 2011. The diagnosis of PPROM was made with vaginal pooling, leakage, nitrazine, and Amnisure tests. The women were managed expectantly with bed rest, corticosteroids, and a triple antibiotic combination including ceftriaxone, clindamycin, and clarithromycin. Amniocentesis was offered, and culture for aerobe/anaerobe and mycoplasma was performed. After delivery, blood was drawn from the mother’s antecubital and umbilical cord veins. Clarithromycin concentrations were measured using liquid chromatography-tandem mass spectrometry. The percentage and correlation between cord and maternal serum clarithromycin concentrations were calculated. Logistic regression analysis was performed to investigate the factors related to the cord and maternal serum clarithromycin concentration percentage.

Results: A total of 34 cord-maternal serum pairs were included in the final analysis. The mean cord-maternal serum clarithromycin concentration percentage was 7.93±0.9%. There was a good correlation between cord serum and maternal serum clarithromycin concentration (r=0.795, P<0.001). The cord-maternal serum clarithromycin concentration percentage significantly increased according to advancing gestation (P<0.001).

Conclusions: Our data showed that the mean placental transfer of clarithromycin is approximately 8% and dependent on gestational age.
Polymorphism 1936A>G in the AKAP10 gene (encoding A-kinase-anchoring protein 10) is associated with higher cholesterol cord blood concentration in Polish full-term newborns
Authors: Łoniewska Beata , Kaczmarczyk Mariusz , Clark Jeremy Simon , Kordek Agnieszka , Ciechanowicz Andrzej
Published: August 2012

Aims: A-Kinase anchoring proteins (AKAPs) coordinate the specificity of protein kinase A signaling by localizing the kinase to subcellular sites. The 1936G (V646) AKAP10 allele has been associated with adults with low cholinergic/vagus nerve sensitivity and with newborns with increased blood pressure. Decreased activity of the parasympathetic system is associated with risk of metabolic syndrome. The aim of this study was to answer the question of whether 1936A>G AKAP10 polymorphism is associated with metabolic changes in full-term newborns that are predictive factors for the metabolic phenotype in adulthood.

Methods: The study included 114 consecutive healthy Polish newborns born after the end of the 37th week of gestation to healthy women with uncomplicated pregnancies. At birth, cord blood of neonates was obtained for isolation of genomic DNA and cholesterol as well as triglyceride concentration.

Results: The cholesterol level in homozygotes GG was significantly higher than that in 1936A variant carriers (AG+AA, recessive mode of inheritance).

Conclusions: Our results demonstrate a possible association between the 1936G AKAP10 variant and the total cholesterol level in the cord blood of the Polish newborn population.
Navigating the Auditory Scene: An Expert Role for the Hippocampus
Authors: Teki Sundeep , Kumar Sukhbinder , von Kriegstein Katharina , Stewart Lauren , Lyness C. Rebecca , Moore Brian C. J. , Capleton Brian , Griffiths Timothy D.
Published: August 2012

Over a typical career piano tuners spend tens of thousands of hours exploring a specialized acoustic environment. Tuning requires accurate perception and adjustment of beats in two-note chords that serve as a navigational device to move between points in previously learned acoustic scenes. It is a two-stage process that depends on the following: first, selective listening to beats within frequency windows, and, second, the subsequent use of those beats to navigate through a complex soundscape. The neuroanatomical substrates underlying brain specialization for such fundamental organization of sound scenes are unknown. Here, we demonstrate that professional piano tuners are significantly better than controls matched for age and musical ability on a psychophysical task simulating active listening to beats within frequency windows that is based on amplitude modulation rate discrimination. Tuners show a categorical increase in gray matter volume in the right frontal operculum and right superior temporal lobe. Tuners also show a striking enhancement of gray matter volume in the anterior hippocampus, parahippocampal gyrus, and superior temporal gyrus, and an increase in white matter volume in the posterior hippocampus as a function of years of tuning experience. The relationship with gray matter volume is sensitive to years of tuning experience and starting age but not actual age or level of musicality. Our findings support a role for a core set of regions in the hippocampus and superior temporal cortex in skilled exploration of complex sound scenes in which precise sound “templates” are encoded and consolidated into memory over time in an experience-dependent manner.
Age-Related Changes in the Neurophysiology of Language in Adults: Relationship to Regional Cortical Thinning and White Matter Microstructure
Authors: Kemmotsu Nobuko , Girard Holly M. , Kucukboyaci N. Erkut , McEvoy Linda K. , Hagler Donald J. , Dale Anders M. , Halgren Eric , McDonald Carrie R.
Published: August 2012

Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18–33 years) and 10 middle-aged (42–64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250 to 350 ms and in left inferior prefrontal cortex from 350 to 450 ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250 and 350 ms, and were associated with left temporal thinning and frontotemporal FA reductions. N400 reductions were not associated with poorer task performance. Rather, increasing age was associated with reduction in the left prefrontal N400, which in turn was also associated with slower response time. These results reveal that changes in the neurophysiology of language occur by middle age and appear to be partially mediated by structural brain loss. These neurophysiological changes may reflect an adaptive process that ensues as communication between left perisylvian regions declines.
Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice
Authors: Benani Alexandre , Hryhorczuk Cécile , Gouazé Alexandra , Fioramonti Xavier , Brenachot Xavier , Guissard Christophe , Krezymon Alice , Duparc Thibaut , Colom André , Nédélec Emmanuelle , Rigault Caroline , Lemoine Aleth , Gascuel Jean , Gerardy-Schahn Rita , Valet Philippe , Knauf Claude , Lorsignol Anne , Pénicaud Luc
Published: August 2012

Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticity-driven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.
PEDF Is a Novel Oligodendrogenic Morphogen Acting on the Adult SVZ and Corpus Callosum
Authors: Sohn Jiho , Selvaraj Vimal , Wakayama Kouji , Orosco Lori , Lee Eunyoung , Crawford Susan E. , Guo Fuzheng , Lang Jordan , Horiuchi Makoto , Zarbalis Konstantinos , Itoh Takayuki , Deng Wenbin , Pleasure David
Published: August 2012

Pigment epithelium-derived factor (PEDF) is a serine protease inhibitor (serpin) protein with well established neuroprotective and anti-angiogenic properties. Recent studies have also shown that PEDF enhances renewal of adult subventricular zone (SVZ) neural precursors. In neurosphere cultures prepared from the SVZ of adult mice, we found that addition of recombinant PEDF to the medium enhanced expressions of oligodendroglial lineage markers (NG2 and PDGFrα) and transcription factors (Olig1, Olig2, and Sox10). Similarly, continuous PEDF administration into the lateral ventricles of adult glial fibrillary acidic protein:green fluorescent protein (GFAP:GFP) transgenic mice increased the proportions of GFAP:GFP+ and GFAP:GFP− SVZ neural precursors coexpressing oligodendroglial lineage markers and transcription factors. Notably, PEDF infusion also resulted in an induction of doublecortin- and Sox10 double-positive cells in the adult SVZ. Immunoreactive PEDF receptor was detectable in multiple cell types in both adult SVZ and corpus callosum. Furthermore, PEDF intracerebral infusion enhanced survival and maturation of newly born oligodendroglial progenitor cells in the normal corpus callosum, and accelerated oligodendroglial regeneration in lysolecithin-induced corpus callosum demyelinative lesions. Western blot analysis showed a robust upregulation of endogenous PEDF in the corpus callosum upon lysolecithin-induced demyelination. Our results document previously unrecognized oligodendrotrophic effects of recombinant PEDF on the adult SVZ and corpus callosum, demonstrate induction of endogenous CNS PEDF production following demyelination, and make PEDF a strong candidate for pharmacological intervention in demyelinative diseases.
Suppressive Surrounds of Receptive Fields In Monkey Frontal Eye Field
Authors: Cavanaugh James , Joiner Wilsaan M. , Wurtz Robert H.
Published: August 2012

A critical step in determining how a neuron contributes to visual processing is determining its visual receptive field (RF). While recording from neurons in frontal eye field (FEF) of awake monkeys (Macaca mulatta), we probed the visual field with small spots of light and found excitatory RFs that decreased in strength from RF center to periphery. However, presenting stimuli with different diameters centered on the RF revealed suppressive surrounds that overlapped the previously determined excitatory RF and reduced responses by 84%, on average. Consequently, in that overlap area, stimulation produced excitation or suppression, depending on the stimulus. Strong stimulation of the RF periphery with annular stimuli allowed us to quantify this effect. A modified difference of Gaussians model that independently varied center and surround activation accounted for the nonlinear activity in the overlap area. Our results suggest that (1) the suppressive surrounds found in FEF are fundamentally the same as those in V1 except for the size and strength of excitatory and suppressive mechanisms, (2) methodically assaying suppressive surrounds in FEF is essential for correctly interpreting responses to large and/or peripheral stimuli and therefore understanding the effects of stimulus context, and (3) regulating the relative strength of the surround clearly changes neuronal responses and may therefore play a significant part in the neuronal changes resulting from visual attention and stimulus salience.
Selective Functional Interactions between Excitatory and Inhibitory Cortical Neurons and Differential Contribution to Persistent Activity of the Slow Oscillation
Authors: Tahvildari Babak , Wölfel Markus , Duque Alvaro , McCormick David A.
Published: August 2012

The neocortex depends upon a relative balance of recurrent excitation and inhibition for its operation. During spontaneous Up states, cortical pyramidal cells receive proportional barrages of excitatory and inhibitory synaptic potentials. Many of these synaptic potentials arise from the activity of nearby neurons, although the identity of these cells is relatively unknown, especially for those underlying the generation of inhibitory synaptic events. To address these fundamental questions, we developed anin vitrosubmerged slice preparation of the mouse entorhinal cortex that generates robust and regular spontaneous recurrent network activity in the form of the slow oscillation. By performing whole-cell recordings from multiple cell types identified with green fluorescent protein expression and electrophysiological and/or morphological properties, we show that distinct functional subpopulations of neurons exist in the entorhinal cortex, with large variations in contribution to the generation of balanced excitation and inhibition during the slow oscillation. The most active neurons during the slow oscillation are excitatory pyramidal and inhibitory fast spiking interneurons, receiving robust barrages of both excitatory and inhibitory synaptic potentials. Weak action potential activity was observed in stellate excitatory neurons and somatostatin-containing interneurons. In contrast, interneurons containing neuropeptide Y, vasoactive intestinal peptide, or the 5-hydroxytryptamine (serotonin) 3a receptor, were silent. Our data demonstrate remarkable functional specificity in the interactions between different excitatory and inhibitory cortical neuronal subtypes, and suggest that it is the large recurrent interaction between pyramidal neurons and fast spiking interneurons that is responsible for the generation of persistent activity that characterizes the depolarized states of the cortex.
T-Type Calcium Channels Consolidate Tonic Action Potential Output of Thalamic Neurons to Neocortex
Authors: Deleuze Charlotte , David François , Béhuret Sébastien , Sadoc Gérard , Shin Hee-Sup , Uebele Victor N. , Renger John J. , Lambert Régis C. , Leresche Nathalie , Bal Thierry
Published: August 2012

The thalamic output during different behavioral states is strictly controlled by the firing modes of thalamocortical neurons. During sleep, their hyperpolarized membrane potential allows activation of the T-type calcium channels, promoting rhythmic high-frequency burst firing that reduces sensory information transfer. In contrast, in the waking state thalamic neurons mostly exhibit action potentials at low frequency (i.e., tonic firing), enabling the reliable transfer of incoming sensory inputs to cortex. Because of their nearly complete inactivation at the depolarized potentials that are experienced during the wake state, T-channels are not believed to modulate tonic action potential discharges. Here, we demonstrate using mice brain slices that activation of T-channels in thalamocortical neurons maintained in the depolarized/wake-like state is critical for the reliable expression of tonic firing, securing their excitability over changes in membrane potential that occur in the depolarized state. Our results establish a novel mechanism for the integration of sensory information by thalamocortical neurons and point to an unexpected role for T-channels in the early stage of information processing.
NMDA Antagonist Ketamine Reduces Task Selectivity in Macaque Dorsolateral Prefrontal Neurons and Impairs Performance of Randomly Interleaved Prosaccades and Antisaccades
Authors: Skoblenick Kevin , Everling Stefan
Published: August 2012

Ketamine, an NMDA receptor antagonist, has been shown to induce behavioral abnormalities in humans that mimic the positive, negative, and most importantly cognitive deficits observed in schizophrenia. Similar cognitive deficits have been observed in nonhuman primates after a subanesthetic dose of ketamine, including an impairment in their ability to perform the antisaccade task, which requires the suppression of a prosaccade toward a flashed stimulus and the generation of a saccade in the opposite direction. The neural basis underlying these cognitive impairments remains unknown. Here, we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine during the performance of randomly interleaved prosaccade and antisaccade trials. Ketamine impeded the monkeys' ability to maintain and apply the correct task rule and increased reaction times of prosaccades and antisaccades. These behavioral changes were associated with an overall increase in activity of PFC neurons and a reduction in their task selectivity. Our results suggest that the mechanism underlying ketamine-induced cognitive abnormalities may be the nonspecific increase in PFC activity and the associated reduction of task selectivity.
Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner
Authors: Fornasiero Eugenio F. , Raimondi Andrea , Guarnieri Fabrizia C. , Orlando Marta , Fesce Riccardo , Benfenati Fabio , Valtorta Flavia
Published: August 2012

The precise subcellular organization of synaptic vesicles (SVs) at presynaptic sites allows for rapid and spatially restricted exocytotic release of neurotransmitter. The synapsins (Syns) are a family of presynaptic proteins that control the availability of SVs for exocytosis by reversibly tethering them to each other and to the actin cytoskeleton in a phosphorylation-dependent manner. Syn ablation leads to reduction in the density of SV proteins in nerve terminals and increased synaptic fatigue under high-frequency stimulation, accompanied by the development of an epileptic phenotype. We analyzed cultured neurons from wild-type andSyn I,II,III−/−triple knock-out (TKO) mice and found that SVs were severely dispersed in the absence of Syns. Vesicle dispersion did not affect the readily releasable pool of SVs, whereas the total number of SVs was considerably reduced at synapses of TKO mice. Interestingly, dispersion apparently involved exocytosis-competent SVs as well; it was not affected by stimulation but was reversed by chronic neuronal activity blockade. Altogether, these findings indicate that Syns are essential to maintain the dynamic structural organization of synapses and the size of the reserve pool of SVs during intense SV recycling, whereas an additional Syn-independent mechanism, whose molecular substrate remains to be clarified, targets SVs to synaptic boutons at rest and might be outpaced by activity.
A Precluding But Not Ensuring Role of Entrained Low-Frequency Oscillations for Auditory Perception
Authors: Ng Benedict Shien Wei , Schroeder Tim , Kayser Christoph
Published: August 2012

Oscillatory activity in sensory cortices reflects changes in local excitation–inhibition balance, and recent work suggests that phase signatures of ongoing oscillations predict the perceptual detection of subsequent stimuli. Low-frequency oscillations are also entrained by dynamic natural scenes, suggesting that the chance of detecting a brief target depends on the relative timing of this to the entrained rhythm. We tested this hypothesis in humans by implementing a cocktail-party-like scenario requiring subjects to detect a target embedded in a cacophony of background sounds. Using EEG to measure auditory cortical oscillations, we find that the chance of target detection systematically depends on both power and phase of theta-band (2–6 Hz) but not alpha-band (8–12 Hz) oscillations before target. Detection rates were higher and responses faster when oscillatory power was low and both detection rate and response speed were modulated by phase. Intriguingly, the phase dependency was stronger for miss than for hit trials, suggesting that phase has a inhibiting but not ensuring role for detection. Entrainment of theta range oscillations prominently occurs during the processing of attended complex stimuli, such as vocalizations and speech. Our results demonstrate that this entrainment to attended sensory environments may have negative effects on the detection of individual tokens within the environment, and they support the notion that specific phase ranges of cortical oscillations act as gatekeepers for perception.
Identification of Functional Circuitry between Retrosplenial and Postrhinal Cortices during Fear Conditioning
Authors: Robinson Siobhan , Poorman Caroline E. , Marder Thomas J. , Bucci David J.
Published: August 2012

The retrosplenial cortex (RSP) and postrhinal cortex (POR) are heavily interconnected with medial temporal lobe structures involved in learning and memory. Previous studies indicate that RSP and POR are necessary for contextual fear conditioning, but it remains unclear whether these regions contribute individually or instead work together as a functional circuit to modulate learning and/or memory. In Experiment 1, learning-related neuronal activity was assessed in RSP from home cage, shock-only, context-only, or fear-conditioned rats using real-time PCR and immunohistochemical methods to quantify immediate-early gene expression. A significant increase in activity-regulated cytoskeleton-associated protein (Arc) mRNA and Arc and c-Fos protein expression was detected in RSP from fear-conditioned rats compared with all other groups. In Experiment 2, retrograde tracing combined with immunohistochemistry revealed that, compared with controls, a significant proportion of cells projecting from RSP to POR were immunopositive for c-Fos in fear-conditioned rats. These results demonstrate that neurons projecting from RSP to POR are indeed active during fear conditioning. In Experiment 3, a functional disconnection paradigm was used to further examine the interaction between RSP and POR during fear conditioning. Compared with controls, rats with unilateral lesions of RSP and POR on opposite sides of the brain exhibited impaired contextual fear memory, whereas rats with unilateral lesions in the same hemisphere displayed intermediate levels of freezing compared with controls and rats with contralateral lesions. Collectively, these results are the first to show that RSP and POR function as a cortical network necessary for contextual fear learning and memory.
Adaptor Protein APPL1 Couples Synaptic NMDA Receptor with Neuronal Prosurvival Phosphatidylinositol 3-Kinase/Akt Pathway
Authors: Wang Yu-bin , Wang Jie-jie , Wang Shao-hua , Liu Shuang-Shuang , Cao Jing-yuan , Li Xiao-ming , Qiu Shuang , Luo Jian-hong
Published: August 2012

It is well known that NMDA receptors (NMDARs) can both induce neurotoxicity and promote neuronal survival under different circumstances. Recent studies show that such paradoxical responses are related to the receptor location: the former to the extrasynaptic and the latter to the synaptic. The phosphoinositide 3-kinase (PI3K)/Akt kinase cascade is a key pathway responsible for the synaptic NMDAR-dependent neuroprotection. However, it is still unknown how synaptic NMDARs are coupled with the PI3K/Akt pathway. Here, we explored the role of an adaptor protein—adaptor protein containing pH domain, PTB domain, and leucine zipper motif (APPL1)—in this signal coupling using rat cortical neurons. We found that APPL1 existed in postsynaptic densities and associated with the NMDAR complex through binding to PSD95 at its C-terminal PDZ-binding motif. NMDARs, APPL1, and the PI3K/Akt cascade formed a complex in rat cortical neurons. Synaptic NMDAR activity increased the association of this complex, induced activation of the PI3K/Akt pathway, and consequently protected neurons against starvation-induced apoptosis. Perturbing APPL1 interaction with PSD95 by a peptide comprising the APPL1 C-terminal PDZ-binding motif dissociated the PI3K/Akt pathway from NMDARs. Either the peptide or lentiviral knockdown of APPL1 blocked synaptic NMDAR-dependent recruitment and activation of PI3K/Akt pathway, and consequently blocked synaptic NMDAR-dependent neuroprotection. These results suggest that APPL1 contributes to connecting synaptic NMDARs with the intracellular PI3K/Akt cascade and the downstream prosurvival signaling pathway in rat cortical neurons.
Dynamics of Cortical Neuronal Ensembles Transit from Decision Making to Storage for Later Report
Authors: Ponce-Alvarez Adrián , Nácher Verónica , Luna Rogelio , Riehle Alexa , Romo Ranulfo
Published: August 2012

Decisions based on sensory evaluation during single trials may depend on the collective activity of neurons distributed across brain circuits. Previous studies have deepened our understanding of how the activity of individual neurons relates to the formation of a decision and its storage for later report. However, little is known about how decision-making and decision maintenance processes evolve in single trials. We addressed this problem by studying the activity of simultaneously recorded neurons from different somatosensory and frontal lobe cortices of monkeys performing a vibrotactile discrimination task. We used the hidden Markov model to describe the spatiotemporal pattern of activity in single trials as a sequence of firing rate states. We show that the animal's decision was reliably maintained in frontal lobe activity through a selective state sequence, initiated by an abrupt state transition, during which many neurons changed their activity in a concomitant way, and for which both latency and variability depended on task difficulty. Indeed, transitions were more delayed and more variable for difficult trials compared with easy trials. In contrast, state sequences in somatosensory cortices were weakly decision related, had less variable transitions, and were not affected by the difficulty of the task. In summary, our results suggest that the decision process and its subsequent maintenance are dynamically linked by a cascade of transient events in frontal lobe cortices.
Kainic Acid-Induced Neuronal Degeneration in Hippocampal Pyramidal Neurons Is Driven by Both Intrinsic and Extrinsic Factors: Analysis of FVB/N↔C57BL/6 Chimeras
Authors: Liu Li , Hamre Kristin M. , Goldowitz Dan
Published: August 2012

The excitotoxic effects of kainic acid (KA) in the mouse hippocampus is strain dependent. Following KA administration, the large majority of hippocampal pyramidal cells die in the FVB/N (FVB) mouse, while the pyramidal cells of the C57BL/6 (B6) strain are largely spared. We generated aggregation chimeras between the sensitive FVB and the resistant B6 strains to investigate whether intrinsic or extrinsic features of a neuron confer cell vulnerability or resistance to KA. The constitutive expression of transgenic green fluorescence protein (GFP) or β-galactosidase expressed from the ROSA26 locus was used to mark cells in FVB or B6 mice, respectively. These makers enable the identification of cells from each parental genotype while TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling)-staining labeled dying cells. The analysis of the percentage of dying cells in FVB-GFP ↔ B6-ROSA chimeras yielded an intriguing mix of both intrinsic and extrinsic factors in the readout of cell phenotype. Thus, normally resistant B6-ROSA pyramidal neurons demonstrated an increasing sensitivity to KA, in a linear fashion, when the percentage of FVB-GFP cells was increased, either across chimeras or in different regions of the same chimera. However, the death of B6-ROSA pyramidal cells never exceeded ∼70% of the total amount of B6 neurons regardless of the amount of FVB cells in the chimeric hippocampus. In a similar manner, FVB-GFP cells show lower amounts of cell death in chimeras that are colonized by B6-ROSA cells, but again, are never fully rescued. These data indicate that both intrinsic and extrinsic factors modulate the sensitivity of hippocampal pyramidal cells to kainic acid.