bluuebunny/crossref_metadata_2025 huggingface dataset:
CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation
Authors: Kowarik Markus C , Cepok Sabine , Sellner Johann , Grummel Verena , Weber Martin S , Korn Thomas , Berthele Achim , Hemmer Bernhard
Published: May 2012

Background

The chemokines and cytokines CXCL13, CXCL12, CCL19, CCL21, BAFF and APRIL are believed to play a role in the recruitment of B cells to the central nervous system (CNS) compartment during neuroinflammation. To determine which chemokines/cytokines show the strongest association with a humoral immune response in the cerebrospinal fluid (CSF), we measured their concentrations in the CSF and correlated them with immune cell subsets and antibody levels.

Methods

Cytokine/chemokine concentrations were measured in CSF and serum by ELISA in patients with non-inflammatory neurological diseases (NIND, n = 20), clinically isolated syndrome (CIS, n = 30), multiple sclerosis (MS, n = 20), Lyme neuroborreliosis (LNB, n = 8) and patients with other inflammatory neurological diseases (OIND, n = 30). Albumin, IgG, IgA and IgM were measured by nephelometry. CSF immune cell subsets were determined by seven-color flow cytometry.

Results

CXCL13 was significantly elevated in the CSF of all patient groups with inflammatory diseases. BAFF levels were significantly increased in patients with LNB and OIND. CXCL12 was significantly elevated in patients with LNB. B cells and plasmablasts were significantly elevated in the CSF of all patients with inflammatory diseases. CXCL13 showed the most consistent correlation with CSF B cells, plasmablasts and intrathecal Ig synthesis.

Conclusions

CXCL13 seems to be the major determinant for B cell recruitment to the CNS compartment in different neuroinflammatory diseases. Thus, elevated CSF CXCL13 levels rather reflect a strong humoral immune response in the CNS compartment than being specific for a particular disease entity.
An ethnobotanical survey of medicinal plants used in Terai forest of western Nepal
Authors: Singh Anant Gopal , Kumar Akhilesh , Tewari Divya Darshan
Published: May 2012

Background

Nepal Himalayas have been known as a rich source for valuable medicinal plants since Vedic periods. Present work is the documentation of indigenous knowledge on plant utilization as natural remedy by the inhabitants of terai forest in Western Nepal.

Methods

Study was conducted during 2010–2011 following standard ethnobotanical methods. Data about medicinal uses of plants were collected by questionnaire, personal interview and group discussion with pre identified informants. Voucher specimens were collected with the help of informants, processed into herbarium following standard methods, identified with the help of pertinent floras and taxonomic experts, and submitted in Department of Botany, Butwal Multiple Campus, Tribhuvan University, Nepal for future references.

Results

During the present study 66 medicinal plant species belonging to 37 families and 60 genera has been documented. These plants were used to treat various diseases and ailments grouped under 11 disease categories, with the highest number of species (41) being used for gastro-intestinal disorders, followed by dermatological disorders (34). In the study area the informants’ consensus about usages of medicinal plants ranges from 0.93 to 0.97 with an average value of 0.94. Herbs (53%) were the primary source of medicine, followed by trees (23%). Curcuma longa (84%) and Azadirachta indica (76%) are the most frequently and popularly used medicinal plant species in the study area. Acacia catechu, Bacopa monnieri, Bombax ceiba, Drymaria diandra, Rauvolfia serpentina, and Tribulus terrestris are threatened species which needs to be conserved for future use.

Conclusions

The high degree of consensus among the informants suggests that current use and knowledge are still strong, and thus the preservation of today's knowledge shows good foresight in acting before much has been lost. The connections between plant use and conservation are also important ones, especially as the authors note that neither the local inhabitants nor the government is addressing the potential loss of valuable species in this region.
Prevalence of and factors associated with daily smoking among Inner Mongolia medical students in China: a cross-sectional questionnaire survey
Authors: Bian Jiang , Du Maolin , Liu Zhiyue , Fan Yancun , Eshita Yuki , Sun Juan
Published: May 2012

Background

To date, no study on smoking behavior of medical students in Inner Mongolia has been reported. The aim of the present study was to determine the 1-month prevalence of and factors associated with daily smoking among medical students in Inner Mongolia of China, to assist interventions designed to reduce the smoking behavior of medical college students in this region.

Methods

During December 2010 and January 2011 a cross-sectional survey was conducted among medical students at the Inner Mongolia Medical College using a self-administered questionnaire. The questionnaire consisted of three sections: students’ basic information, attitude on smoking behavior, and smoking status of the student daily smokers. Students who smoked every day in the last 30 days were regarded as daily smokers. Factors associated with smoking were identified using binary logistic regression analysis.

Results

A total of 6044 valid surveys were returned. The overall prevalence of daily smoking was 9.8% while the prevalence of daily smoking among males and females were 29.4% and 1.7%, respectively. Males in the Faculty of Medicine Information Management had the highest daily smoking rate (48.9%). Logistic regression models found that the main factors associated with daily smoking among male medical students were highest year of study (OR = 3.62; CI: 1.18–11.05); attitude towards smoking behavior Do not care about people smoking around you (OR = 2.75; CI: 2.08–3.64); and Smoking is harmful to their health (OR = 4.40; CI: 2.21–8.75). The main factor associated with daily smoking among female medical students was attitude towards smoking behavior Eliminate smoking on campus (OR = 0.11; CI: 0.06–0.23). Both for male and female medical students, there was no association between ethnicity and cigarette daily smoking. In regard to smoking status, more than 60% of daily smokers began smoking in high school, 61.3% smoked less than 5 cigarettes per day, 62.9% of the daily smokers’ families opposed their smoking behavior, and after an hour of not smoking 74.6% daily smokers did not feel uncomfortable.

Conclusions

Antismoking education should be further promoted in Inner Mongolia medical students, with consideration given to the factors associated with daily smoking behavior found in the present study.
A selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits gastric cancer cell growth
Authors: Yin Xiao-Fei , Chen Jie , Mao Wei , Wang Yu-Hong , Chen Min-Hu
Published: May 2012

Background

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor associated with gastric carcinogenesis. 3,3'-Diindolylmethane (DIM) is a relatively non-toxic selective AhR modulator. This study was to detect the effects of DIM on gastric cancer cell growth.

Methods

Gastric cancer cell SGC7901 was treated with DIM at different concentrations (0,10,20,30,40,50 μmol/L) with or without an AhR antagonist, resveratrol. The expression of AhR and Cytochrome P4501A1 (CYP1A1), a classic target gene of AhR pathway, were detected by RT-PCR and Western blot; cell viability was measured by MTT assay, and the changes in cell cycle and apoptosis were analyzed by flow cytometry.

Results

RT-PCR and western-blot showed that with the increase of the concentration of DIM, AhR protein gradually decreased and CYP1A1 expression increased, suggesting that DIM activated the AhR pathway and caused the translocation of AhR from cytoplasm to nucleus. MTT assay indicated that the viability of SGC7901 cells was significantly decreased in a concentration- and time-dependent manner after DIM treatment and this could be partially reversed by resveratrol. Flow cytometry analysis showed that DIM arrested cell cycle in G1 phase and induced cell apoptosis.

Conclusion

Selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. AhR may be a potential therapeutic target for gastric cancer treatment.
Antipsychotic use and diagnosis of delirium in the intensive care unit
Authors: Swan Joshua T , Fitousis Kalliopi , Hall Jeffrey B , Todd S Rob , Turner Krista L
Published: May 2012

Introduction

Delirium is an independent risk factor for prolonged hospital length of stay (LOS) and increased mortality. Several antipsychotics have been studied for the treatment of intensive care unit (ICU) delirium that has led to a high variability in prescribing patterns for these medications. We hypothesize that in clinical practice the documentation of delirium is lower than the incidence of delirium reported in prospective clinical trials. The objective of this study was to document the incidence of delirium diagnosed in ICU patients and to describe the utilization of antipsychotics in the ICU.

Methods

This was a retrospective, observational, cohort study conducted at 71 United States academic medical centers that reported data to the University Health System Consortium Clinical Database/Resource Manager. It included all patients 18 years of age and older admitted to the hospital between 1 January 2010 and 30 June 2010 with at least one day in the ICU.

Results

Delirium was diagnosed in 6% (10,034 of 164,996) of hospitalizations with an ICU admission. Antipsychotics were administered to 11% (17,764 of 164,996) of patients. Of the antipsychotics studied, the most frequently used were haloperidol (62%; n = 10,958) and quetiapine (31%; n = 5,448). Delirium was associated with increased ICU LOS (5 vs. 3 days, P < 0.001) and hospital LOS (11 vs. 6 days, P < 0.001), but not in-hospital mortality (8% vs. 9%, P = 0.419). Antipsychotic exposure was associated with increased ICU LOS (8 vs. 3 days, P < 0.001), hospital LOS (14 vs. 5 days, P < 0.001) and mortality (12% vs. 8%, P < 0.001). Of patients with antipsychotic exposure in the ICU, absence of a documented mental disorder (32%, n = 5,760) was associated with increased ICU LOS (9 vs. 7 days, P < 0.001), hospital LOS (16 vs. 13 days, P < 0.001) and in-hospital mortality (19% vs. 9%, P < 0.001) compared to patients with a documented mental disorder (68%, n = 12,004).

Conclusions

The incidence of documented delirium in ICU patients is lower than that documented in previous prospective studies with active screening. Antipsychotics are administered to 1 in every 10 ICU patients. When administration occurs in the absence of a documented mental disorder, antipsychotic use is associated with an even higher ICU and hospital LOS, as well as in-hospital mortality.
Continuous venovenous hemofiltration in severely burned patients with acute kidney injury: a cohort study
Authors: Chung Kevin K , Lundy Jonathan B , Matson James R , Renz Evan M , White Christopher E , King Booker T , Barillo David J , Jones John A , Cancio Leopoldo C , Blackbourne Lorne H , Wolf Steven E
Published: May 2012

Introduction

Acute kidney injury (AKI) is a common and devastating complication in critically ill burn patients with mortality reported to be between 80 and 100%. We aimed to determine the effect on mortality of early application of continuous venovenous hemofiltration (CVVH) in severely burned patients with AKI admitted to our burn intensive care unit (BICU).

Methods

We performed a retrospective cohort study comparing a population of patients managed with early and aggressive CVVH compared with historical controls managed conservatively before the availability of CVVH. Patients with total body surface area (TBSA) burns of more than 40% and AKI were treated with early CVVH and their outcomes compared with a group of historical controls.

Results

Overall, the 28-day mortality was significantly lower in the CVVH arm (n = 29) compared with controls (n = 28) (38% vs. 71%, P = 0.011) as was the in-hospital mortality (62% vs. 86%, P = 0.04). In a subgroup of patients in shock, a dramatic reduction in the pressor requirement was seen after 24 and 48 hours of treatment. Compared with controls (n = 19), significantly fewer patients in the CVVH group (n = 21) required vasopressors at 24 hours (100% vs 43%, P < 0.0001) and at 48 hours (94% vs 24%, P < 0.0001). In those with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), there was a significant increase from baseline in the partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio at 24 hours in the CVVH group (n = 16, 174 ± 78 to 327 ± 122, P = 0.003) but not the control group (n = 20, 186 ± 64 to 207 ± 131, P = 0.98).

Conclusions

The application of CVVH in adult patients with severe burns and AKI was associated with a decrease in 28-day and hospital mortality when compared with a historical control group, which largely did not receive any form of renal replacement. Clinical improvements were realized in the subgroups of patients with shock and ALI/ARDS. A randomized controlled trial comparing early CVVH to standard care in this high-risk population is planned.
Reforming the Carceral Past
Authors: Bruggeman Seth C.
Published: May 2012

New research concerning unprecedented growth in the US penal system during the twentieth century creates rich opportunities for prison museums to engage broad audiences in a conversation about the problems of mass incarceration. The case of Eastern State Penitentiary, however, suggests that public historians' ability to call the law into question may be limited by the founding vision of their host intuitions. Specifically at issue are the priorities of historic preservationists whose architectural commitments risk obscuring important histories of race, power, and community. If they do, we stand to forget that many of the same social forces underlying the United States' carceral turn account too for the gentrification of its urban spaces during the late twentieth century. Eastern State's complicity in both may explain why it still struggles to fulfill its mission to “place current issues of corrections and justice in an historical framework.”
Can we interpret serum thyroglobulin results?
Authors: Clark Penny , Franklyn Jayne
Published: May 2012

Thyroglobulin (Tg) is a tumour marker for differentiated thyroid cancer. Interpretation requires a knowledge of the current thyrotropin (TSH) concentration as secretion is TSH-dependent. While a raised serum Tg may be indicative of residual or recurrent thyroid cancer, trauma to the thyroid (e.g. surgical, biopsy or due to radioiodine treatment) also causes an increase. Tg may be measured when TSH is suppressed and also following recombinant TSH (rhTSH) stimulation. Interpretation of results in pregnancy and in children is discussed. Assay bias and interference by endogenous Tg antibodies (Abs) are the main confounders in the interpretation of results. Although there is an international standard for Tg, there are large differences in results and yet there are few assay-specific clinical decision limits. Patients should therefore be monitored with the same assay. Endogenous TgAbs may cause false-negative interference in immunometric assays and may cause false-positive results in radioimmunoassay. Although the measurement of TgAbs has been advocated for predicting interference, it is now clear that interference can still occur when TgAbs have not been detected, the effect being TgAb-assay-specific. Approaches to identifying those samples where there may be interference are discussed. The laboratory should have a protocol for the investigation of possible interferences and data on the bias of the Tg assay that they use. An appreciation of the clinical uses of the service is required as an understanding by endocrinologists, oncologists and endocrine surgeons of the analytical limitations of the service.
Staffing Call Centers with Impatient Customers: Refinements to Many-Server Asymptotics
Authors: Zhang Bo , van Leeuwaarden Johan S. H. , Zwart Bert
Published: May 2012

In call centers it is crucial to staff the right number of agents so that the targeted service levels are met. These staffing problems typically lead to constraint satisfaction problems that are hard to solve. During the last decade, a beautiful many-server asymptotic theory has been developed to solve such problems for large call centers, and optimal staffing rules are known to obey the square-root staffing principle. This paper presents refinements to many-server asymptotics and this staffing principle for a Markovian queueing model with impatient customers.
Cargo Capacity Management with Allotments and Spot Market Demand
Authors: Levin Yuri , Nediak Mikhail , Topaloglu Huseyin
Published: May 2012

We consider a problem faced by an airline that operates a number of parallel flights to transport cargo between a particular origin to destination pair. The airline can sell its cargo capacity either through allotment contracts or on the spot market, where customers exhibit choice behavior between different flights. The goal is to simultaneously select allotment contracts among available bids and find a booking control policy for the spot market to maximize the sum of the profit from the allotments and the total expected profit from the spot market. We formulate the booking control problem on the spot market as a dynamic program and construct approximations to its value functions, which can be used to estimate the total expected profit from the spot market. We show that our value function approximations provide upper bounds on the optimal total expected profit from the spot market, and they allow us to solve the allotment selection problem through a sequence of linear mixed-integer programs with a special structure. Furthermore, the value function approximations are useful for constructing a booking control policy for the spot market with desirable monotonic properties. Computational experiments show that the proposed approach can be scaled to realistic problems and provides well-performing allotment allocation and booking control decisions.
Technology Adoption with Uncertain Future Costs and Quality
Authors: Smith James E. , Ulu Canan
Published: May 2012

In this paper we study the impact of uncertainty about future innovations in quality and costs on consumers' technology adoption decisions. We model the uncertainty in the technology's quality and costs as a Markov process and consider three models of the adoption decision. The first model assumes that consumers do a simple net present value (NPV) analysis that compares the NPV of adopting to that of not adopting, without considering the possibility of waiting. The second model is a stochastic dynamic program that considers the possibility of waiting and views the adoption decision as a one-time event, i.e., the consumer will only make a single purchase, the only question is when. The third model allows repeat purchases so the consumer may “upgrade” by purchasing new versions of the technology whenever it suits her.

We study structural properties of these models, e.g., the following: What changes in qualities and costs will make the consumer better off? What changes will encourage adoption? We will see that the simple NPV and single-purchase model have many intuitive properties: with the right notion of improvements and reasonable assumptions about the technology changes, we find that improvements in the technology make the consumer better off and encourage adoption. Here improvements are defined using a partial order on quality and cost pairs. The results are more complicated in the repeat-purchase model. Under the same conditions on technology changes, technology improvements will make the consumer better off. However, except for special cases of transitions, these improvements may make the consumer better off and discourage adoption.
A Conic Integer Programming Approach to Stochastic Joint Location-Inventory Problems
Authors: Atamtürk Alper , Berenguer Gemma , Shen Zuo-Jun (Max)
Published: May 2012

We study several joint facility location and inventory management problems with stochastic retailer demand. In particular, we consider cases with uncapacitated facilities, capacitated facilities, correlated retailer demand, stochastic lead times, and multicommodities. We show how to formulate these problems as conic quadratic mixed-integer problems. Valid inequalities, including extended polymatroid and extended cover cuts, are added to strengthen the formulations and improve the computational results. Compared to the existing modeling and solution methods, the new conic integer programming approach not only provides a more general modeling framework but also leads to fast solution times in general.
Gastroenteropancreatic Neuroendocrine Tumors: Update on Therapeutics
Authors: Ganetsky Alex , Bhatt Valkal
Published: May 2012

OBJECTIVE:

To review the available literature addressing the treatment of pancreatic neuroendocrine tumors (PNETs) and carcinoid tumors.

DATA SOURCES:

Relevant literature was identified by a PubMed search (January 1977-December 2011) of English-language literature using the terms gastroenteropancreatic neuroendocrine tumor, pancreatic neuroendocrine, carcinoid, and pancreatic islet cell tumor.

STUDY SELECTION AND DATA EXTRACTION:

All published studies and abstracts, as well as relevant consensus guidelines, evaluating the current literature about PNETs and carcinoid tumors were included.

DATA SYNTHESIS:

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a genetically diverse group of complex malignancies with varying biological and clinical courses. Historically believed to be rare, recent epidemiologic data suggest their incidence is rising. Two of the most commonly diagnosed GEP-NETs are PNETs and carcinoid tumors. Both subtypes are well-differentiated tumors and present as low or intermediate grade. The systemic manifestations of PNETs and carcinoid tumors are diverse and are related to the secretion of affected hormones and biogenic amines. Surgical resection of localized disease remains the only curative option. However, the utility of this approach is limited because most patients are diagnosed with advanced disease. Recent advances have led to an improvement in outcomes in patients with PNETs and carcinoid tumors. This review describes traditional therapies as well as emerging strategies being investigated to help manage these cancers. Treatment of poorly differentiated GEP-NETs is beyond the scope of this review.

CONCLUSIONS:

The advent of new therapies for PNETs and carcinoid tumors has introduced a paradigm shift in the management of this heterogeneous malignancy.
Temperature-Tolerant COLD-PCR Reduces Temperature Stringency and Enables Robust Mutation Enrichment
Authors: Castellanos-Rizaldos E , Liu Pingfang , Milbury Coren A , Guha Minakshi , Brisci Angela , Cremonesi Laura , Ferrari Maurizio , Mamon Harvey , Makrigiorgos G Mike
Published: May 2012

BACKGROUND

Low-level mutations in clinical tumor samples often reside below mutation detection limits, thus leading to false negatives that may impact clinical diagnosis and patient management. COLD-PCR (coamplification at lower denaturation temperature PCR) is a technology that magnifies unknown mutations during PCR, thus enabling downstream mutation detection. However, a practical difficulty in applying COLD-PCR has been the requirement for strict control of the denaturation temperature for a given sequence, to within ±0.3 °C. This requirement precludes simultaneous mutation enrichment in sequences of substantially different melting temperature (Tm) and limits the technique to a single sequence at a time. We present a temperature-tolerant (TT) approach (TT-COLD-PCR) that reduces this obstacle.

METHODS

We describe thermocycling programs featuring a gradual increase of the denaturation temperature during COLD-PCR. This approach enabled enrichment of mutations when the cycling achieves the appropriate critical denaturation temperature of each DNA amplicon that is being amplified. Validation was provided for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) and TP53 (tumor protein p53) exons 6–9 by use of dilutions of mutated DNA, clinical cancer samples, and plasma-circulating DNA.

RESULTS

A single thermocycling program with a denaturation-temperature window of 2.5–3.0 °C enriches mutations in all DNA amplicons simultaneously, despite their different Tms. Mutation enrichments of 6–9-fold were obtained with TT-full-COLD-PCR. Higher mutation enrichments were obtained for the other 2 forms of COLD-PCR, fast-COLD-PCR, and ice-COLD-PCR.

CONCLUSIONS

Low-level mutations in diverse amplicons with different Tms can be mutation enriched via TT-COLD-PCR provided that their Tms fall within the denaturation-temperature window applied during amplification. This approach enables simultaneous enrichment of mutations in several amplicons and increases significantly the versatility of COLD-PCR.
S-SCAM/MAGI-2 Is an Essential Synaptic Scaffolding Molecule for the GluA2-Containing Maintenance Pool of AMPA Receptors
Authors: Danielson Eric , Zhang Nanyan , Metallo Jacob , Kaleka Kanwardeep , Shin Seung Min , Gerges Nashaat , Lee Sang H.
Published: May 2012

Synaptic plasticity, the cellular basis of learning and memory, involves the dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses. One of the remaining key unanswered aspects of AMPAR trafficking is the mechanism by which synaptic strength is preserved despite protein turnover. In particular, the identity of AMPAR scaffolding molecule(s) involved in the maintenance of GluA2-containing AMPARs is completely unknown. Here we report that the synaptic scaffolding molecule (S-SCAM; also called membrane-associated guanylate kinase inverted-2 and atrophin interacting protein-1) plays the critical role of maintaining synaptic strength. Increasing S-SCAM levels in rat hippocampal neurons led to specific increases in the surface AMPAR levels, enhanced AMPAR-mediated synaptic transmission, and enlargement of dendritic spines, without significantly effecting GluN levels or NMDA receptor (NMDAR) EPSC. Conversely, decreasing S-SCAM levels by RNA interference-mediated knockdown caused the loss of synaptic AMPARs, which was followed by a severe reduction in the dendritic spine density. Importantly, S-SCAM regulated synaptic AMPAR levels in a manner, dependent on GluA2 not GluA1, sensitive toN-ethylmaleimide-sensitive fusion protein interaction, and independent of activity. Further, S-SCAM increased surface AMPAR levels in the absence of PSD-95, while PSD-95 was dependent on S-SCAM to increase surface AMPAR levels. Finally, S-SCAM overexpression hampered NMDA-induced internalization of AMPARs and prevented the induction of long term-depression, while S-SCAM knockdown did not. Together, these results suggest that S-SCAM is an essential AMPAR scaffolding molecule for the GluA2-containing pool of AMPARs, which are involved in the constitutive pathway of maintaining synaptic strength.
Approach–Avoidance Processes Contribute to Dissociable Impacts of Risk and Loss on Choice
Authors: Wright Nicholas D. , Symmonds Mkael , Hodgson Karen , Fitzgerald Thomas H. B. , Crawford Bonni , Dolan Raymond J.
Published: May 2012

Value-based choices are influenced both by risk in potential outcomes and by whether outcomes reflect potential gains or losses. These variables are held to be related in a specific fashion, manifest in risk aversion for gains and risk seeking for losses. Instead, we hypothesized that there are independent impacts of risk and loss on choice such that, depending on context, subjects can show either risk aversion for gains and risk seeking for losses or the exact opposite. We demonstrate this independence in a gambling task, by selectively reversing a loss-induced effect (causing more gambling for gains than losses and the reverse) while leaving risk aversion unaffected. Consistent with these dissociable behavioral impacts of risk and loss, fMRI data revealed dissociable neural correlates of these variables, with parietal cortex tracking risk and orbitofrontal cortex and striatum tracking loss. Based on our neural data, we hypothesized that risk and loss influence action selection through approach–avoidance mechanisms, a hypothesis supported in an experiment in which we show valence and risk-dependent reaction time effects in line with this putative mechanism. We suggest that in the choice process risk and loss can independently engage approach–avoidance mechanisms. This can provide a novel explanation for how risk influences action selection and explains both classically described choice behavior as well as behavioral patterns not predicted by existing theory.
Guidance-Cue Control of Horizontal Cell Morphology, Lamination, and Synapse Formation in the Mammalian Outer Retina
Authors: Matsuoka Ryota L. , Jiang Zheng , Samuels Ivy S. , Nguyen-Ba-Charvet Kim T. , Sun Lu O. , Peachey Neal S. , Chédotal Alain , Yau King-Wai , Kolodkin Alex L.
Published: May 2012

In the vertebrate retina, neuronal circuitry required for visual perception is organized within specific laminae. Photoreceptors convey external visual information to bipolar and horizontal cells at triad ribbon synapses established within the outer plexiform layer (OPL), initiating retinal visual processing. However, the molecular mechanisms that organize these three classes of neuronal processes within the OPL, thereby ensuring appropriate ribbon synapse formation, remain largely unknown. Here we show that mice with null mutations inSema6AorPlexinA4(PlexA4) exhibit a pronounced defect in OPL stratification of horizontal cell axons without any apparent deficits in bipolar cell dendrite or photoreceptor axon targeting. Furthermore, these mutant horizontal cells exhibit aberrant dendritic arborization and reduced dendritic self-avoidance within the OPL. Ultrastructural analysis shows that the horizontal cell contribution to rod ribbon synapse formation inPlexA4−/−retinas is disrupted. These findings define molecular components required for outer retina lamination and ribbon synapse formation.
Connectivity Changes Underlying Spectral EEG Changes during Propofol-Induced Loss of Consciousness
Authors: Boly Mélanie , Moran Rosalyn , Murphy Michael , Boveroux Pierre , Bruno Marie-Aurélie , Noirhomme Quentin , Ledoux Didier , Bonhomme Vincent , Brichant Jean-François , Tononi Giulio , Laureys Steven , Friston Karl
Published: May 2012

The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.
Nonsynaptic NMDA Receptors Mediate Activity-Dependent Plasticity of Gap Junctional Coupling in the AII Amacrine Cell Network
Authors: Kothmann W. Wade , Trexler E. Brady , Whitaker Christopher M. , Li Wei , Massey Stephen C. , O'Brien John
Published: May 2012

Many neurons are coupled by electrical synapses into networks that have emergent properties. In the retina, coupling in these networks is dynamically regulated by changes in background illumination, optimizing signal integration for the visual environment. However, the mechanisms that control this plasticity are poorly understood. We have investigated these mechanisms in the rabbit AII amacrine cell, a multifunctional retinal neuron that forms an electrically coupled network via connexin 36 (Cx36) gap junctions. We find that presynaptic activity of glutamatergic ON bipolar cells drives increased phosphorylation of Cx36, indicative of increased coupling in the AII network. The phosphorylation is dependent on activation of nonsynaptic NMDA receptors that colocalize with Cx36 on AII amacrine cells, and is mediated by CaMKII. This activity-dependent increase in Cx36 phosphorylation works in opposition to dopamine-driven reduction of phosphorylation, establishing a local dynamic regulatory mechanism, and accounting for the nonlinear control of AII coupling by background illumination.
Genetic Analysis of Ecdysis Behavior inDrosophilaReveals Partially Overlapping Functions of Two Unrelated Neuropeptides
Authors: Lahr Eleanor C. , Dean Derek , Ewer John
Published: May 2012

Ecdysis behavior allows insects to shed their old exoskeleton at the end of every molt. It is controlled by a suite of interacting hormones and neuropeptides, and has served as a useful behavior for understanding how bioactive peptides regulate CNS function. Previous findings suggest that crustacean cardioactive peptide (CCAP) activates the ecdysis motor program; the hormone bursicon is believed to then act downstream of CCAP to inflate, pigment, and harden the exoskeleton of the next stage. However, the exact roles of these signaling molecules in regulating ecdysis remain unclear. Here we use a genetic approach to investigate the functions of CCAP and bursicon inDrosophilaecdysis. We show that null mutants in CCAP express no apparent defects in ecdysis and postecdysis, producing normal adults. By contrast, a substantial fraction of flies genetically null for one of the two subunits of bursicon [encoded by thepartner of bursicongene (pburs)] show severe defects in ecdysis, with escaper adults exhibiting the expected failures in wing expansion and exoskeleton pigmentation and hardening. Furthermore, flies lacking both CCAP and bursicon show much more severe defects at ecdysis than do animals null for either neuropeptide alone. Our results show that the functions thought to be subserved by CCAP are partially effected by bursicon, and that bursicon plays an important and heretofore undescribed role in ecdysis behavior itself. These findings have important implications for understanding the regulation of this vital insect behavior and the mechanisms by which hormones and neuropeptides control the physiology and behavior of animals.
Subregional, Dendritic Compartment, and Spine Subtype Specificity in Cocaine Regulation of Dendritic Spines in the Nucleus Accumbens
Authors: Dumitriu Dani , LaPlant Quincey , Grossman Yael S. , Dias Caroline , Janssen William G. , Russo Scott J. , Morrison John H. , Nestler Eric J.
Published: May 2012

Numerous studies have found that chronic cocaine increases dendritic spine density of medium spiny neurons in the nucleus accumbens (NAc). Here, we used single-cell microinjections and advanced 3D imaging and analysis techniques to extend these findings in several important ways: by assessing cocaine regulation of dendritic spines in the core versus shell subregions of NAc in the mouse, over a broad time course (4 h, 24 h, or 28 d) of withdrawal from chronic cocaine, and with a particular focus on proximal versus distal dendrites. Our data demonstrate subregion-specific, and in some cases opposite, regulation of spines by cocaine on proximal but not distal dendrites. Notably, all observed density changes were attributable to selective regulation of thin spines. At 4 h after injection, the proximal spine density is unchanged in the core but significantly increased in the shell. At 24 h, the density of proximal dendritic spines is reduced in the core but increased in the shell. Such downregulation of thin spines in the core persists through 28 d of withdrawal, whereas the spine density in the shell returns to baseline levels. Consistent with previous results, dendritic tips exhibited upregulation of dendritic spines after 24 h of withdrawal, an effect localized to the shell. The divergence in regulation of proximal spine density in NAc core versus shell by cocaine correlates with recently reported electrophysiological data from a similar drug administration regimen and might represent a key mediator of changes in the reward circuit that drive aspects of addiction.
NMDA Receptors with Incomplete Mg2+Block Enable Low-Frequency Transmission through the Cerebellar Cortex
Authors: Schwartz Eric J. , Rothman Jason S. , Dugué Guillaume P. , Diana Marco , Rousseau Charly , Silver R. Angus , Dieudonné Stéphane
Published: May 2012

The cerebellar cortex coordinates movements and maintains balance by modifying motor commands as a function of sensory-motor context, which is encoded by mossy fiber (MF) activity. MFs exhibit a wide range of activity, from brief precisely timed high-frequency bursts, which encode discrete variables such as whisker stimulation, to low-frequency sustained rate-coded modulation, which encodes continuous variables such as head velocity. While high-frequency MF inputs have been shown to activate granule cells (GCs) effectively, much less is known about sustained low-frequency signaling through the GC layer, which is impeded by a hyperpolarized resting potential and strong GABAA-mediated tonic inhibition of GCs. Here we have exploited the intrinsic MF network of unipolar brush cells to activate GCs with sustained low-frequency asynchronous MF inputs in rat cerebellar slices. We find that low-frequency MF input modulates the intrinsic firing of Purkinje cells, and that this signal transmission through the GC layer requires synaptic activation of Mg2+-block-resistant NMDA receptors (NMDARs) that are likely to contain the GluN2C subunit. Slow NMDAR conductances sum temporally to contribute approximately half the MF-GC synaptic charge at hyperpolarized potentials. Simulations of synaptic integration in GCs show that the NMDAR and slow spillover-activated AMPA receptor (AMPAR) components depolarize GCs to a similar extent. Moreover, their combined depolarizing effect enables the fast quantal AMPAR component to trigger action potentials at low MF input frequencies. Our results suggest that the weak Mg2+block of GluN2C-containing NMDARs enables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.
κ-Opioid Receptors within the Nucleus Accumbens Shell Mediate Pair Bond Maintenance
Authors: Resendez Shanna L. , Kuhnmuench Morgan , Krzywosinski Tarin , Aragona Brandon J.
Published: May 2012

The prairie vole is a socially monogamous species in which breeder pairs typically show strong and selective pair bonds. The establishment of a pair bond is associated with a behavioral transition from general affiliation to aggressive rejection of novel conspecifics. This “selective aggression” is indicative of mate guarding that is necessary to maintain the initial pair bond. In the laboratory, the neurobiology of this behavior is studied using resident-intruder testing. Although it is well established that social behaviors in other species are mediated by endogenous opioid systems, opiate regulation of pair bond maintenance has never been studied. Here, we used resident-intruder testing to determine whether endogenous opioids within brain motivational circuitry mediate selective aggression in prairie voles. We first show that peripheral blockade of κ-opioid receptors with the antagonist norbinaltorphimine (nor-BNI; 100 mg/kg), but not with the preferential μ-opioid receptor antagonist naloxone (1, 10, or 30 mg/kg), decreased selective aggression in males. We then provide the first comprehensive characterization of κ- and μ-opioid receptors in the prairie vole brain. Finally, we demonstrate that blockade of κ-opioid receptors (500 ng nor-BNI) within the nucleus accumbens (NAc) shell abolishes selective aggression in both sexes, but blockade of these receptors within the NAc core enhances this behavior specifically in females. Blockade of κ-opioid receptors within the ventral pallidum or μ-opioid receptors with the specific μ-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-PenThr-NH2 (1 ng CTAP) within the NAc shell had no effect in either sex. Thus, κ-opioid receptors within the NAc shell mediate aversive social motivation that is critical for pair bond maintenance.
Spatiotemporal Changes to the Subventricular Zone Stem Cell Pool through Aging
Authors: Shook Brett A. , Manz David H. , Peters John J. , Kang Sangwook , Conover Joanne C.
Published: May 2012

Through adulthood, the rodent subventricular zone (SVZ) stem cell niche generates new olfactory bulb interneurons. We had previously reported that the number of new neurons produced in the SVZ declines through aging; however, age-related changes attributable specifically to the SVZ neural stem cell (NSC) population have not been fully characterized. Here, we conducted a spatiotemporal evaluation of adult SVZ NSCs. We assessed ventricle-contacting NSCs, which together with ependymal cells form regenerative units (pinwheels) along the lateral wall of the lateral ventricle. Based on their apical GFAP-expressing process, individual NSCs were identified across the ventricle surface using serial reconstruction of the SVZ. We observed an 86% decline in total NSCs/mm2of intact ependyma in 2-year old versus 3-month-old mice, with fewer NSC processes within each aged pinwheel. This resulted in an associated 78% decline in total pinwheel units/mm2. Regional analysis along the lateral ventricle surface revealed that the age-dependent decline of NSCs and pinwheels is spatially uniform and ultimately maintains the conserved ratio of olfactory bulb interneuron subtypes generated in young mice. However, the overall neurogenic output of the aged SVZ is reduced. Surprisingly, we found no significant change in the number of actively proliferating NSCs per mm2of ventricle surface. Instead, our data reveal that, although the total NSC number, pinwheel units and NSCs per pinwheel decline with age, the percentage of actively, mitotic NSCs increases, indicating that age-related declines in SVZ-mediated olfactory bulb neurogenesis occur downstream of NSC proliferation.
Segregated Pathways Carrying Frontally Derived Top-Down Signals to Visual Areas MT and V4 in Macaques
Authors: Ninomiya Taihei , Sawamura Hiromasa , Inoue Ken-ichi , Takada Masahiko
Published: May 2012

The bottom-up processing of visual information is strongly influenced by top-down signals, at least part of which is thought to be conveyed from the frontal cortex through the frontal eye field (FEF) and the lateral intraparietal area (LIP). Here we investigated the architecture of multisynaptic pathways from the frontal cortex to the middle temporal area (MT) of the dorsal visual stream and visual area 4 (V4) of the ventral visual stream in macaques. In the first series of experiments, the retrograde trans-synaptic tracer, rabies virus, was injected into MT or V4. Three days after rabies injections, the second-order (disynaptically connected) neuron labeling appeared in the ventral part of area 46 (area 46v), along with the first-order (monosynaptically connected) neuron labeling in FEF and LIP. In the MT-injection case, second-order neurons were also observed in the supplementary eye field (SEF). In the next series of experiments, double injections of two fluorescent dyes, fast blue and diamidino yellow, were made into MT and V4 to examine whether the frontal inputs are mediated by distinct or common neuronal populations. Virtually no double-labeled neurons were observed in FEF or LIP, indicating that separate neuronal populations mediate the frontal inputs to MT and V4. The present results define that the multisynaptic frontal input to V4 arises primarily from area 46v, whereas the input to MT arises from not only area 46v but also SEF, through distinct FEF and LIP neurons. Segregated pathways from the frontal cortex possibly carry the functionally diverse top-down signals to each visual stream.
Colonizing Taiwan
Authors: Ching Leo T. S.
Published: May 2012

Taiwan was the first acquired country to be placed on the Japanese overseas empire after the resounding victories of the Sino-Japanese War in 1895. This acquisition was not a primary objective of the Japanese imperial power, but it was a desire to undermine and to unseat Chinese influence over the strategic positions of Korea and southern Manchuria that encouraged Japanese aggression. The incorporation of Taiwan into the Japanese Empire reveals the particular historical relationship of Japanese colonialism in the geopolitics of global colonialism. The author emphasizes two issues in this chapter: (1) the particularization of Japanese imperialism and colonialism are different and unique, highlighting the interrelationship and interdependency of the Japanese case with the generality of global capitalist colonialism; and (2) the lack of the decolonization process in the separation of the Japanese Empire has prevented both Japan and Taiwan from addressing and confronting their colonial relationship and the overall Japanese colonial legacy.
Entangled Oppositions
Authors: Ching Leo T. S.
Published: May 2012

The historical and political nature of Taiwanese neo-nationalist thought was shortened and complicated not only by its colonial relationship to Japanese colonial power, but also by that to semi-colonized mainland China. The issue that the author addresses in this chapter is the enclosed discursive space of Taiwanese political movements in a chaotic period which ironically enabled the proliferation of political and neo-nationalist identity formations and associations. The Taiwanese identity which emerged at that time was necessarily a relation on a plurality of identifications which do not necessarily form relationships with one another, with the exception of the liberal and Marxist opposition. The primacy given to ethno-nationalism in identifying the various beliefs of Taiwanese political movements serves to deny and obscure the fundamental and contradictory class antagonism within the development of capitalism in colonial Taiwan.
Between Assimilation and Imperialization
Authors: Ching Leo T. S.
Published: May 2012

“Imperialization” or kôminka is not the only “conviction” in becoming Japanese through “faith” in the Emperor, but the externalization of colonial ideology was remarkably demonstrated by the opening epigraphs. The author argues with the interrogation into the ideology kôminka necessarily exposing the colonial myth of dôka or “assimilation” that allegedly preceded and made possible the arrival of kôminka. In the study of Japanese colonialism, kôminka was an extension of dôka on a linear and consistent trajectory of Japanese colonial policy. The author also argues that dôka, as a colonial ideology, represented a generalized field of the colonial project which defined a coherent philosophy or systematic policy.
Introduction
Authors: Ching Leo T. S.
Published: May 2012

On the unseasonably warm morning of February 24, 1979, seven Taiwanese aborigines slowly but steadily made their way to the office at the Yasuguni jinja, a shrine that consecrates the spirits of Japanese soldiers killed during the Second World War.1 The members of the entourage, five men and two women, had exhausted their savings and money borrowed from people in their villages to come to Japan. They were representatives from several aboriginal territories. More precisely, they were representing the descendants of the hundreds of aboriginal soldiers who fought and died during the war in the name of the Japanese Emperor. Many nonaboriginal Taiwanese ex-soldiers have made similar pilgrimages....