bluuebunny/crossref_metadata_2025 huggingface dataset:
Difficulties in Caring for a Patient With Cancer at the End of Life at Home and Complicated Grief
Authors: Ando Michiyo , Ninosaka Yasuyoshi , Okamura Kazuhisa , Ishi Yoko
Published: December 2013

The present study aimed to investigate difficulties in caring for a patient with cancer at the end of life at home and to examine relationships between difficulties with care and complicated grief. The 45 bereaved family members completed the Family Difficulty Scale (FDS) and the Inventory of Complicated Grief (ICG). The FDS score for “ Patient’s pain and condition” was the highest, followed by “ Caregivers did not want home care” and “No support from others.” There was a significant relationship between FDS and ICG scores. These results suggest that the condition of the patient, the view of the caregiver on home care, and the absence of other support are important factors contributing to difficulties of family caregivers, and that these difficulties may lead to complicated grief.
Pure shear fracture study in a brittle graphite material containing a U-notch
Authors: Torabi AR , Fakoor M , Darbani MA
Published: December 2013

A disc-type specimen containing a central bean-shaped slit, called the U-notched Brazilian disc specimen, was utilized to measure experimentally the mode II notch fracture toughness of a type of commercial polycrystalline graphite. First, 24 U-notched Brazilian disc graphite specimens were fabricated for four different notch tip radii, and the monotonic fracture tests were performed under pure mode I and pure mode II loading conditions; 12 for each loading mode. The recorded fracture loads were converted to the corresponding notch fracture toughness values, and the ratio mode II notch fracture toughness/mode I notch fracture toughness was experimentally determined. Then, assuming that the experimental values of mode I notch fracture toughness are known, the mode II notch fracture toughnesses were theoretically predicted by means of two brittle fracture criteria, namely the existing U-notched maximum tangential stress and the newly developed U-notched mean stress. A very good agreement was found to exist between the theoretical and the experimental results. Also, found in this research was that both the criteria could predict well the experimentally measured fracture initiation angles.
Cardiac surgery in a Patient With Pemphigus Vulgaris
Authors: Takahashi Mitsuko , Rhee Amanda J. , Rakasi Raghuveer R. , Yildirim Asu , Silvay George , Reddy Ramachandra C.
Published: December 2013

Pemphigus vulgaris is an autoimmune disorder that causes blistering of the skin and mucous membranes. We present a patient with pemphigus vulgaris who required combined coronary artery bypass grafting and mitral valve repair. The challenges that we faced and modifications to the technique required in this situation are described and reviewed.
‘Cosmopolitanism’ and ‘Conviviality’? Some conceptual considerations concerning the late Ottoman Empire
Authors: Freitag Ulrike
Published: December 2013

In this article, I argue that the concept of ‘conviviality’, at least in a non-elitist understanding, allows us to pay closer attention to the conditions under which people of different ethnic, linguistic, religious and national backgrounds and of all social strata managed to live together peacefully in the late Ottoman Empire. This phenomenon, which can be observed in port cities in particular, has often been discussed under the term of ‘Ottoman cosmopolitanism’. The latter term, both in its wider usage and in the historiography linked to the Ottoman Empire, has become heavily laden with moral prescripts often originating in particular Western, liberal ideas. I will argue here that ‘cosmopolitanism’ and ‘conviviality’ can be seen as complementing each other, the former tendentially (albeit not exclusively) focussing more on elite interactions and emphasising the interactions of people of different ethnic and religious origin, the latter opening a window onto the quotidian practices of everyday interactions by people regardless of their origin. Evidently, there are large areas of overlap between both concepts; nevertheless, it might be useful to separate them heuristically.
Order of actions mitigates hypocrisy judgments for ingroup more than outgroup members
Authors: Barden Jamie , Rucker Derek D. , Petty Richard E. , Rios Kimberly
Published: December 2013

Compared to the conventional order of hypocritical actions—saying one thing and then doing another—merely reversing the order of these actions can mitigate whether an individual is judged to be a hypocrite (Barden, Rucker, & Petty, 2005). The present research examines how factors extraneous to a target’s own actions—specifically, group membership—influence hypocrisy judgments. Three experiments provided consistent evidence that reversing the order of statement and behavior mitigated hypocrisy judgments to a greater extent when observers judged ingroup targets compared to outgroup targets. This pattern was observed across two distinct groups (i.e., gender and political party). In addition, mediational evidence suggested that the greater mitigation for ingroup targets stemmed from the observer’s greater tendency to make attributions that ingroup targets had genuinely changed for the better.
Perceived stigma in persons with early-stage dementia: Longitudinal findings: Part 1
Authors: Burgener Sandy C , Buckwalter Kathleen , Perkhounkova Yelena , Liu Megan F , Riley Rebecca , Einhorn Carol J , Fitzsimmons Suzanne , Hahn-Swanson Carolyn
Published: December 2013

This longitudinal study examined perceived stigma in persons with dementia, with 50 persons with dementia, and 47 corresponding family caregivers. Data were collected at baseline and at 6, 12, and 18 months. Study results are reported in two parts, with findings regarding the stability of perceived stigma, measured using the modified Stigma Impact Scale, and relationship of stigma to person-centered variables being reported here. Findings included stability in perceived stigma, which did not show a downward trend until 18 months. Significant differences at baseline were found only for geographic location (rural vs. urban) with persons living in urban areas having higher levels of Stigma Impact Scale internalized shame compared to rural counterparts. Cognitive functioning was significantly, positively related to the Stigma Impact Scale social rejection and social isolation subscales. Findings support the enduring nature of perceived stigma over the early disease stages and the relationship of perceived stigma to some person-centered characteristics.
The assessment of breathlessness in pulmonary arterial hypertension: Reliability and validity of the Dyspnoea-12
Authors: Yorke Janelle , Armstrong Iain
Published: December 2013

Breathlessness is a cardinal symptom of pulmonary arterial hypertension (PAH); yet no breathlessness instrument has been previously tested for reliability and validity for this population. Using a cross-sectional design, we tested the psychometric properties of the Dyspnoea-12 (D-12), for the assessment of breathlessness in PAH. Pearson’s correlations with World Health Organization functional class (WHO FC), Minnesota Living with Heart failure – pulmonary hypertension modified version (MLHF-PH), Hospital Anxiety and Depression scale (HADS) and 6-minute walk distance test (6MWD) were conducted. Participants ( n = 176) were mostly female (70.5%), mean age 54.3±14 years; diagnosed with idiopathic PAH (48.9%), congenital heart disease (27.8%) and connective tissue disease (23.3%); and most were WHO FC II (32.4%) and III (52.3%). The D-12 showed excellent internal consistency for the total and two-component scores for physical and emotional (Cronbach’s α 0.95, 0.93 and 0.94, respectively). D-12 total score was significantly associated with MLHF-PH ( r = 0.70), HADS (anxiety r = 0.54 and depression r = 0.68), WHO FC ( r = 0.49), and 6MWD ( r = -0.26). In patients with PAH, the D-12 - a short patient reported measure of breathlessness severity that taps the physical and emotional components, is a reliable and valid instrument.
Management of adult obesity
Authors: Zemaryalai Tamana , Abas Mustafa
Published: December 2013

Over the past three decades the prevalence of obesity in the UK has more than doubled, making it one of our fastest growing health problems. This rise has become a serious public health concern, due to the association of obesity with serious chronic-disease-related morbidity, including type-2 diabetes, cardiovascular disease and several cancers, and the resulting healthcare costs. England has the highest rates of obesity in Europe, with more than 60% of adults and one-third of 10 and 11 year olds overweight or obese. Obesity is set to take over from cigarette smoking as the major preventable cause of disease and death in the UK. Objectives in the management and treatment of obesity should target not only weight loss, but also reducing the potential associated risks that may add to its detrimental impact on health. This article aims to outline a healthy diet, discuss the associated health risks and treatment options available in the management of adult obesity, from lifestyle modifications to bariatric surgery.
CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell–engaging antibody AMG 330
Authors: Krupka Christina , Kufer Peter , Kischel Roman , Zugmaier Gerhard , Bögeholz Jan , Köhnke Thomas , Lichtenegger Felix S. , Schneider Stephanie , Metzeler Klaus H. , Fiegl Michael , Spiekermann Karsten , Baeuerle Patrick A. , Hiddemann Wolfgang , Riethmüller Gert , Subklewe Marion
Published: December 2013

Key Points

CD33 expression levels in AML correlate with specific disease characteristics. Potent cytotoxicity against primary AML blasts is mediated by a CD33/CD3-bispecific antibody.
Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus
Authors: Bäck Jennie , Lood Christian , Bengtsson Anders A , Ekdahl Kristina Nilsson , Nilsson Bo
Published: December 2013

Introduction

Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.

Methods

Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters.

Results

Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT.

Conclusions

Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.
Azimuthal anisotropy in microseismic monitoring: A Bakken case study
Authors: Grechka Vladimir , Yaskevich Sergey
Published: December 2013

Hydraulic fracturing, routinely applied for enhancing the permeability of unconventional oil and gas reservoirs, is one of the possible causes for azimuthal anisotropy of the treated formations. Accounting for both naturally occurring and completion induced azimuthal anisotropy leads to marked improvements in the results of microseismic data processing. As illustrated on a data set acquired in the Bakken Field, North Dakota, USA, those improvements include the possibility of modeling the observed shear-wave splitting, reduction of misfit between the picked and modeled traveltimes of microseismic events, and relocation and tightening of the spatial distribution of the event hypocenters. In addition and perhaps most importantly for the development of microseismic technology, the feasibility of joint inversion of field microseismic data for the event locations and azimuthally anisotropic velocity model containing triclinic layers is demonstrated.
Activation of Angiotensin Type 2 Receptors Partially Ameliorates Streptozotocin-Induced Diabetes in Male Rats by Islet Protection
Authors: Shao Chunhong , Yu Li , Gao Lie
Published: December 2013

We have previously demonstrated that rat islets express a high density of angiotensin type 2 receptors and that activation of this receptor evokes insulinotropic effect. In this study, we evaluated the protective effects of Compound 21 (C21), a nonpeptide angiotensin type 2 receptor agonist, on islets in streptozotocin (STZ)-induced diabetes. Rats were assigned to five groups: normal, STZ, and STZ plus C21 (0.24, 0.48, and 0.96 mg/kg·d). C21 was continually infused by a sc implanted osmotic minipump for 14 days, and STZ was bolus injected on day 7. Body weight, water intake, urine excretion, and blood glucose were monitored daily. On the last day, the rats received an oral glucose tolerance test, and the pancreata were saved to examine islet morphology and biochemical parameters of oxidative stress and apoptosis. We found that, compared with control STZ rats, C21-treated STZ rats displayed less water intake and urine excretion, lower blood glucose, higher serum insulin concentration, and improved glucose tolerance. These rats had more islets, larger islet mass, and up-regulated insulin protein and proinsulin 2 mRNA expressions in the pancreas. Their islets displayed lower superoxide, decreased gp91 expression, and increased superoxide dismutase 1 expression as well as less apoptosis and down-regulated caspase-3 expression. In the epididymal adipose tissue of these rats, we found a decreased adipocyte size and up-regulated adipocyte protein 2 expression. The protective effects of C21 on β-cells against the toxic effects of STZ were also confirmed in cultured INS-1E cells. These data suggest that C21 ameliorates STZ-induced diabetes by protecting pancreatic islets via antioxidative and antiapoptotic effects.
Abba Lerner and the Political Economy of Bureaucracy and Organizations
Authors: Cuda Daniel L.
Published: December 2013

This article introduces a previously unpublished paper by Abba P. Lerner that offers one of the first examples of economic ideas interacting with issues of bureaucracy and public organization. Written in 1942, the paper is titled “Design for a Streamlined War Economy,” and it argues that for the wartime US economy to achieve maximum performance, Congress should maintain a price system in lieu of bureaucratic rationing. Although “Design for a Streamlined War Economy,” as well as Lerner’s well-known 1944 book The Economics of Control, addresses the macroeconomy, only the 1942 paper explicitly extends Lerner’s thinking into the internal organization of a bureaucratic defense establishment. This is new and noteworthy. I argue that Lerner’s paper represents one of the first examples of twentieth-century economic thinking applied to bureaucracy.
Using Differences in Knowledge Across Neighborhoods to Uncover the Impacts of the EITC on Earnings
Authors: Chetty Raj , Friedman John N , Saez Emmanuel
Published: December 2013

We estimate the impacts of the Earned Income Tax Credit on labor supply using local variation in knowledge about the EITC schedule. We proxy for EITC knowledge in a Zip code with the fraction of individuals who manipulate reported self-employment income to maximize their EITC refund. This measure varies significantly across areas. We exploit changes in EITC eligibility at the birth of a child to estimate labor supply effects. Individuals in high-knowledge areas change wage earnings sharply to obtain larger EITC refunds relative to those in low-knowledge areas. These responses come primarily from intensive-margin earnings increases in the phase-in region. (JEL H23, H24, H31, J22, J23, J31)
Vertical Integration and Exclusivity in Platform and Two-Sided Markets
Authors: Lee Robin S
Published: December 2013

This paper measures the impact of vertically integrated and exclusive software on industry structure and welfare in the sixth-generation of the US video game industry (2000–2005). I specify and estimate a dynamic model of both consumer demand for hardware and software products, and software demand for hardware platforms. I use estimates to simulate market outcomes had platforms been unable to own or contract exclusively with software. Driven by increased software compatibility, hardware and software sales would have increased by 7 percent and 58 percent and consumer welfare by $1.5 billion. Gains would be realized only by the incumbent, suggesting exclusivity favored the entrant platforms. (JEL D12, L13, L22, L63, L86)
Long term delivery of pulsed magnetic fields does not alter visual discrimination learning or dendritic spine density in the mouse CA1 pyramidal or dentate gyrus neurons
Authors: Sykes Matthew , Makowiecki Kalina , Rodger Jennifer
Published: December 2013

Repetitive transcranial magnetic stimulation (rTMS) is thought to facilitate brain plasticity. However, few studies address anatomical changes following rTMS in relation to behaviour. We delivered 5 weeks of daily pulsed rTMS stimulation to adult ephrin-A2-/- and wildtype (C57BI/6j) mice (n=10 per genotype) undergoing a visual learning task and analysed learning performance, as well as spine density, in the dentate gyrus molecular and CA1 pyramidal cell layers in Golgi-stained brain sections. We found that neither learning behaviour, nor hippocampal spine density was affected by long term rTMS. Our negative results highlight the lack of deleterious side effects in normal subjects and are consistent with previous studies suggesting that rTMS has a bigger effect on abnormal or injured brain substrates than on normal/control structures.
Amplicon pyrosequencing and ion torrent sequencing of wild duck eubacterial microbiome from fecal samples reveals numerous species linked to human and animal diseases
Authors: Strong Thomas , Dowd Scot , Gutierrez Alexander F. , Molnar David , Coffman Jonathan
Published: December 2013

Our investigation into the composition of the wild duck,Aythya americana, eubacterial microbiome from a fecal sample using amplicon pyrosequencing revealed that the representative bacterial species were quite distinct from a pond water sample, and we were able to classify the major operational taxonomic units withFusobacterium mortiferum,Streptobacillus moniliformis,Lactobacillus intermedius,Actinomyces suimastitidis,Campylobacter Canadensis,Enterococcus cecorum,Lactobacillus aviarus,Actimomyces spp.,Pseudobutyrivibrio spp.and Helicobacter brantaerepresenting the majority of the eubacterial fecal microbiome.  Bacterial species present in the analysis revealed numerous organisms linked to human and animal diseases including septicemia, rat bite fever, pig mastitis, endocarditis, malar masses, genital infections, skin lesions, peritonitis, wound infections, septic arthritis, urocystitis, gastroenteritis and drinking water diseases.  In addition, to being known carriers of viral pathogens wild ducks should also be recognized as a potential source of a range of bacterial diseases.
Families of Individuals With Intellectual and Developmental Disabilities: Policy, Funding, Services, and Experiences
Authors: Hewitt Amy , Agosta John , Heller Tamar , Williams Ann Cameron , Reinke Jennifer
Published: December 2013

Families are critical in the provision of lifelong support to individuals with intellectual and developmental disabilities (IDD). Today, more people with IDD receive long-term services and supports while living with their families. Thus, it is important that researchers, practitioners, and policy makers understand how to best support families who provide at-home support to children and adults with IDD. This article summarizes (a) the status of research regarding the support of families who provide support at home to individuals with IDD, (b) present points of concern regarding supports for these families, and (c) associated future research priorities related to supporting families.
Self-Determination and Choice
Authors: Wehmeyer Michael L. , Abery Brian H.
Published: December 2013

Promoting self-determination and choice opportunities for people with intellectual and developmental disabilities has become best practice in the field. This article reviews the research and development activities conducted by the authors over the past several decades and provides a synthesis of the knowledge in the field pertaining to efforts to promote self-determination and choice.
New Transnational Governance and the Changing Composition of Regulatory Pluralism in Southeast Asia
Authors: Gillespie John
Published: December 2013

Over the past three decades, Transnational Production Regimes (TPRs) have become the main source of technical and regulatory knowledge for Southeast Asia corporations. Typically TPRs transfer knowledge from lead firms located in the industrial North to supplier firms located in Southeast Asia. Regulatory knowledge transferred through TPRs largely bypasses Southeast Asian laws and legal institutions to directly influence the behavior of supplier firms. Although socio-economic studies show that TPRs are responsible for generating much wealth creation in the region, they hardly register in the socio-legal literature. Drawing on ethnographic studies conducted in Vietnam, this paper will attempt to explain why different types of TPRs produce different regulatory responses in Vietnamese firms. Preliminary findings suggest differences in the way that regulatory knowledge transmitted through Northeast Asian and Euro-American TPRs is absorbed and integrated into the organisational fabric of Vietnamese firms. They also shed light on two well-documented phenomena in Vietnam. In conclusion the paper will argue that TPRs displace state commercial laws and are partially responsible for the slow progress of conventional law and development projects in changing regulatory practices. It will contend that the different kinds of TPRs generate regulatory pluralism and the uneven application of state law in different business sectors.
Zur Verortung Öffentlicher Bibliotheken auf den Homepages ihrer Kommunen – eine empirisch-quantitative Beschreibung
Authors: Nikolaizig Andrea , Süßkraut Anne
Published: December 2013

Der Internet-Auftritt einer Kommune ist eine etablierte Informationsquelle für ihre BürgerInnen oder Gäste über die jeweiligen kommunalen Angebote, Leistungen und Services. Es ist zu erwarten, dort auch die Öffentliche Bibliothek zu finden. Doch wie: direkt oder unter welchen Begriffen? Diese Untersuchung interessiert sich für die begriffliche Verortung der Öffentlichen Bibliotheken auf den Homepages (Startseiten) kommunaler Internet-Auftritte. Dazu wurden 1.557 kommunale Homepages besucht. Wenige Bibliotheken sind auf der Homepage unter dem Begriff „Bibliothek“ verlinkt. In der Mehrzahl der Fälle muss der Seitenbesucher die Bibliothek unter übergeordneten Begriffen oder Begriffspaaren denken. Die begriffliche Zuordnung ist nicht unerheblich, weil sie der Bibliothek eine funktionale Dominanz wie Kultur, Bildung, Freizeit, Tourismus, Verwaltung usw. zuweist. Sie leistet damit einen Beitrag zur Kommunikation der Bibliotheks-Philosophie in der Öffentlichkeit und wird von dieser entsprechend wahrgenommen.
Memory Consolidation by Replay of Stimulus-Specific Neural Activity
Authors: Deuker Lorena , Olligs Jan , Fell Juergen , Kranz Thorsten A. , Mormann Florian , Montag Christian , Reuter Martin , Elger Christian E. , Axmacher Nikolai
Published: December 2013

Memory consolidation transforms initially labile memory traces into more stable representations. One putative mechanism for consolidation is the reactivation of memory traces after their initial encoding during subsequent sleep or waking state. However, it is still unknown whether consolidation of individual memory contents relies on reactivation of stimulus-specific neural representations in humans. Investigating stimulus-specific representations in humans is particularly difficult, but potentially feasible using multivariate pattern classification analysis (MVPA). Here, we show in healthy human participants that stimulus-specific activation patterns can indeed be identified with MVPA, that these patterns reoccur spontaneously during postlearning resting periods and sleep, and that the frequency of reactivation predicts subsequent memory for individual items. We conducted a paired-associate learning task with items and spatial positions and extracted stimulus-specific activity patterns by MVPA in a simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) study. As a first step, we investigated the amount of fMRI volumes during rest that resembled either one of the items shown before or one of the items shown as a control after the resting period. Reactivations during both awake resting state and sleep predicted subsequent memory. These data are first evidence that spontaneous reactivation of stimulus-specific activity patterns during resting state can be investigated using MVPA. They show that reactivation occurs in humans and is behaviorally relevant for stabilizing memory traces against interference. They move beyond previous studies because replay was investigated on the level of individual stimuli and because reactivations were not evoked by sensory cues but occurred spontaneously.
Atp6ap2/(Pro)renin Receptor Interacts with Par3 as a Cell Polarity Determinant Required for Laminar Formation during Retinal Development in Mice
Authors: Kanda Atsuhiro , Noda Kousuke , Yuki Kenya , Ozawa Yoko , Furukawa Takahisa , Ichihara Atsuhiro , Ishida Susumu
Published: December 2013

(Pro)renin receptor [(P)RR], also known as Atp6ap2, has attracted growing attention as a key molecule for tissue renin-angiotensin system (RAS). In addition to its role in tissue RAS activation, Atp6ap2/(P)RR was originally identified as an accessory subunit for vacuolar H+-ATPase (v-ATPase), which is a multisubunit proton pump involved in diverse and fundamental cellular physiology. In this study, to elucidate the physiological function of Atp6ap2/(P)RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P)RR in photoreceptor development. Deletion of photoreceptorAtp6ap2/(P)RRdid not affect retinal cell differentiation, but led to laminar disorganization around the outer nuclear layer together with severe dysfunction of photoreceptor cells. In the CKO mice, cell adhesion and polarity molecules, some of which were colocalized with Atp6ap2/(P)RR at the apical edge of the wild-type developing retina, were substantially dispersed together with mislocalization of retinal progenitor cells apart from the apical surface. Among theses molecules, coimmunoprecipitation using retinal homogenates andATP6AP2/(P)RR-transfected cells showed that Atp6ap2/(P)RR interacted with partitioning defective 3 homolog (PAR3) protein, which is known to function in the Par-atypical protein kinase C (aPKC) system. Furthermore, yeast two-hybrid assays demonstrated direct molecular interaction between ATP6AP2/(P)RR and PAR3. Our present data revealed the novel function of Atp6ap2/(P)RR required for laminar formation during retinal development. We propose that this cellular activity associated with the Par-aPKC system, in addition to the v-ATPase function and tissue RAS activation, is the third biological role of Atp6ap2/(P)RR.
Distinct Determinants of Sparse Activation during Granule Cell Maturation
Authors: Dieni Cristina V. , Nietz Angela K. , Panichi Roberto , Wadiche Jacques I. , Overstreet-Wadiche Linda
Published: December 2013

Adult neurogenesis continually produces a small population of immature granule cells (GCs) within the dentate gyrus. The physiological properties of immature GCs distinguish them from the more numerous mature GCs and potentially enables distinct network functions. To test how the changing properties of developing GCs affect spiking behavior, we examined synaptic responses of mature and immature GCs in hippocampal slices from adult mice. Whereas synaptic inhibition restricted GC spiking at most stages of maturation, the relative influence of inhibition, excitatory synaptic drive, and intrinsic excitability shifted over the course of maturation. Mature GCs received profuse afferent innervation such that spiking was suppressed primarily by inhibition, whereas immature GC spiking was also limited by the strength of excitatory drive. Although the input resistance was a reliable indicator of maturation, it did not determine spiking probability at immature stages. Our results confirm the existence of a transient period during GC maturation when perforant path stimulation can generate a high probability of spiking, but also reveal that immature GC excitability is tempered by functional synaptic inhibition and reduced excitatory innervation, likely maintaining the sparse population activity observedin vivo.
Consecutive TMS-fMRI Reveals an Inverse Relationship in BOLD Signal between Object and Scene Processing
Authors: Mullin Caitlin R. , Steeves Jennifer K. E.
Published: December 2013

The human visual system is capable of recognizing an infinite number of scenes containing an abundance of rich visual information. There are several cortical regions associated with the representation of a scene, including those specialized for object processing (the lateral occipital area [LO]) and for the spatial layout of scenes (the parahippocampal place area). Although behavioral studies have demonstrated that these image categories (scenes and objects) exert an influence on each other such that scene context can facilitate object identification or that scene categorization can be impaired by the presence of a salient object, little is known about the apparent cortical interactions involved in building the conscious representation of a complete scene. It has been shown that transcranial magnetic stimulation (TMS) to the left LO disrupts object categorization but facilitates scene categorization. Here, we show that this effect is also reflected by changes in the BOLD signal such that TMS to the left LO decreases BOLD signal at the stimulation site (LO) while viewing objects and increases BOLD signal in the left PPA when viewing scenes. This suggests that these regions, although likely not on a strict hierarchy of bottom-up coding, share functional communication likely in the form of inhibitory connections.
Membrane-Anchored Aβ Accelerates Amyloid Formation and Exacerbates Amyloid-Associated Toxicity in Mice
Authors: Nagarathinam Amudha , Höflinger Philip , Bühler Anika , Schäfer Claudia , McGovern Gillian , Jeffrey Martin , Staufenbiel Matthias , Jucker Mathias , Baumann Frank
Published: December 2013

Pathological, genetic, and biochemical hallmarks of Alzheimer's disease (AD) are linked to amyloid-β (Aβ) peptide aggregation. Especially misfolded Aβ42peptide is sufficient to promote amyloid plaque formation. However, the cellular compartment facilitating the conversion of monomeric Aβ to aggregated toxic Aβ species remains unknown.In vitromodels suggest lipid membranes to be the driving force of Aβ conversion. To this end, we generated two novel mouse models, expressing either membrane-anchored or nonanchored versions of the human Aβ42peptide. Strikingly, membrane-anchored Aβ42robustly accelerated Aβ deposition and exacerbated amyloid-associated toxicity upon crossing with Aβ precursor protein transgenic mice. Thesein vivofindings support the hypothesis that Aβ–membrane interactions play a pivotal role in early-onset AD as well as neuronal damage and provide evidence to study Aβ–membrane interactions as therapeutic targets.
Secretagogue Stimulation of Neurosecretory Cells Elicits Filopodial Extensions Uncovering New Functional Release Sites
Authors: Papadopulos Andreas , Martin Sally , Tomatis Vanesa M. , Gormal Rachel S. , Meunier Frederic A.
Published: December 2013

Regulated exocytosis in neurosecretory cells relies on the timely fusion of secretory granules (SGs) with the plasma membrane. Secretagogue stimulation leads to an enlargement of the cell footprint (surface area in contact with the coverslip), an effect previously attributed to exocytic fusion of SGs with the plasma membrane. Using total internal reflection fluorescence microscopy, we reveal the formation of filopodia-like structures in bovine chromaffin and PC12 cells driving the footprint expansion, suggesting the involvement of cortical actin network remodeling in this process. Using exocytosis-incompetent PC12 cells, we demonstrate that footprint enlargement is largely independent of SG fusion, suggesting that vesicular exocytic fusion plays a relatively minor role in filopodial expansion. The footprint periphery, including filopodia, undergoes extensive F-actin remodeling, an effect abolished by the actomyosin inhibitors cytochalasin D and blebbistatin. Imaging of both Lifeact-GFP and the SG marker protein neuropeptide Y-mCherry reveals that SGs actively translocate along newly forming actin tracks before undergoing fusion. Together, these data demonstrate that neurosecretory cells regulate the number of SGs undergoing exocytosis during sustained stimulation by controlling vesicular mobilization and translocation to the plasma membrane through actin remodeling. Such remodeling facilitates thede novoformation of fusion sites.
Simultaneous EEG-fMRI Reveals Temporal Evolution of Coupling between Supramodal Cortical Attention Networks and the Brainstem
Authors: Walz Jennifer M. , Goldman Robin I. , Carapezza Michael , Muraskin Jordan , Brown Truman R. , Sajda Paul
Published: December 2013

Cortical and subcortical networks have been identified that are commonly associated with attention and task engagement, along with theories regarding their functional interaction. However, a link between these systems has not yet been demonstrated in healthy humans, primarily because of data acquisition and analysis limitations. We recorded simultaneous EEG–fMRI while subjects performed auditory and visual oddball tasks and used these data to investigate the BOLD correlates of single-trial EEG variability at latencies spanning the trial. We focused on variability along task-relevant dimensions in the EEG for identical stimuli and then combined auditory and visual data at the subject level to spatially and temporally localize brain regions involved in endogenous attentional modulations. Specifically, we found that anterior cingulate cortex (ACC) correlates strongly with both early and late EEG components, whereas brainstem, right middle frontal gyrus (rMFG), and right orbitofrontal cortex (rOFC) correlate significantly only with late components. By orthogonalizing with respect to event-related activity, we found that variability in insula and temporoparietal junction is reflected in reaction time variability, rOFC and brainstem correlate with residual EEG variability, and ACC and rMFG are significantly correlated with both. To investigate interactions between these correlates of temporally specific EEG variability, we performed dynamic causal modeling (DCM) on the fMRI data. We found strong evidence for reciprocal effective connections between the brainstem and cortical regions. Our results support the adaptive gain theory of locus ceruleus–norepinephrine (LC–NE) function and the proposed functional relationship between the LC–NE system, right-hemisphere ventral attention network, and P300 EEG response.
Antagonistic Functions of Dishevelleds Regulate Frizzled3 Endocytosis via Filopodia Tips in Wnt-Mediated Growth Cone Guidance
Authors: Onishi Keisuke , Shafer Beth , Lo Charles , Tissir Fadel , Goffinet Andre M. , Zou Yimin
Published: December 2013

How growth cones detect small concentration differences of guidance cues for correct steering remains a long-standing puzzle. Commissural axons engage planar cell polarity (PCP) signaling components to turn anteriorly in a Wnt gradient after midline crossing. We found here that Frizzled3, a Wnt receptor, undergoes endocytosis via filopodia tips. Wnt5a increases Frizzled3 endocytosis, which correlates with filopodia elongation. We discovered an unexpected antagonism between Dishevelleds, which may function as a signal amplification mechanism in filopodia where PCP signaling is activated: Dishevelled2 blocks Dishevelled1-induced Frizzled3 hyperphosphorylation and membrane accumulation. A key component of apical-basal polarity (A-BP) signaling, aPKC, also inhibits Dishevelled1-induced Frizzled3 hyperphosphorylation.Celsr3, another PCP component, is required in commissural neurons for anterior turning. Frizzled3 hyperphosphorylation is increased inCelsr3mutant mice, where PCP signaling is impaired, suggesting Frizzled3 hyperphosphorylation does correlate with loss of PCP signalingin vivo. Furthermore, we found that the small GTPase, Arf6, which is required for Frizzled3 endocytosis, is essential for Wnt-promoted outgrowth, highlighting the importance of Frizzled3 recycling in PCP signaling in growth cone guidance. In a Wnt5a gradient, more Frizzled3 endocytosis and activation of atypical protein kinase C was observed on the side of growth cones facing higher Wnt5a concentration, suggesting that spatially controlled Frizzled3 endocytosis is part of the key mechanism for growth cone steering.
Neuronal Clearance of Amyloid-β by Endocytic Receptor LRP1
Authors: Kanekiyo Takahisa , Cirrito John R. , Liu Chia-Chen , Shinohara Mitsuru , Li Jie , Schuler Dorothy R. , Shinohara Motoko , Holtzman David M. , Bu Guojun
Published: December 2013

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population. Accumulation, aggregation, and deposition of amyloid-β (Aβ) peptides generated through proteolytic cleavage of amyloid precursor protein (APP) are likely initiating events in the pathogenesis of AD. While Aβ production is accelerated in familial AD, increasing evidence indicates that impaired clearance of Aβ is responsible for late-onset AD. Because Aβ is mainly generated in neurons, these cells are predicted to have the highest risk of encountering Aβ among all cell types in the brain. However, it is still unclear whether they are also involved in Aβ clearance. Here we show that receptor-mediated endocytosis in neurons by the low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in brain Aβ clearance. LRP1 is known to be an endocytic receptor for multiple ligands including Aβ. Conditional knock-out ofLrp1in mouse forebrain neurons leads to increased brain Aβ levels and exacerbated amyloid plaque deposition selectively in the cortex of amyloid model APP/PS1 mice without affecting Aβ production.In vivomicrodialysis studies demonstrated that Aβ clearance in brain interstitial fluid is impaired in neuronalLrp1knock-out mice. Because the neuronal LRP1-deletion did not affect the mRNA levels of major Aβ degrading enzymes, neprilysin and insulin-degrading enzyme, the disturbed Aβ clearance is likely due to the suppression of LRP1-mediated neuronal Aβ uptake and degradation. Together, our results demonstrate that LRP1 plays an important role in receptor-mediated clearance of Aβ and indicate that neurons not only produce but also clear Aβ.
Peripheral TGF-β1 Signaling Is a Critical Event in Bone Cancer-Induced Hyperalgesia in Rodents
Authors: Xu Qian , Zhang Xiao-Meng , Duan Kai-Zheng , Gu Xi-Yao , Han Mei , Liu Ben-Long , Zhao Zhi-Qi , Zhang Yu-Qiu
Published: December 2013

Pain is the most common symptom of bone cancer. TGF-β, a major bone-derived growth factor, is largely released by osteoclast bone resorption during the progression of bone cancer and contributes to proliferation, angiogenesis, immunosuppression, invasion, and metastasis. Here, we further show that TGF-β1 is critical for bone cancer-induced pain sensitization. We found that, after the progression of bone cancer, TGF-β1 was highly expressed in tumor-bearing bone, and the expression of its receptors, TGFβRI and TGFβRII, was significantly increased in the DRG in a rat model of bone cancer pain that is based on intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade of TGF-β receptors by the TGFβRI antagonist SD-208 robustly suppressed bone cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral injection of TGF-β1 directly induced thermal hyperalgesia in intact rats and wide-type mice, but not inTrpv1−/−mice. Whole-cell patch-clamp recordings from DRG neurons showed that transient receptor potential vanilloid (TRPV1) sensitivity was significantly enhanced on PTD 14. Extracellular application of TGF-β1 significantly potentiated TRPV1 currents and increased [Ca2+]iin DRG neurons. Pharmacological studies revealed that the TGF-β1 sensitization of TRPV1 and the induction of thermal hyperalgesia required the TGF-βR-mediated Smad-independent PKCε and TGF-β activating kinase 1-p38 pathways. These findings suggest that TGF-β1 signaling contributes to bone cancer pain via the upregulation and sensitization of TRPV1 in primary sensory neurons and that therapeutic targeting of TGF-β1 may ameliorate the bone cancer pain in advanced cancer.
Factors affecting Cyperus difformis seed germination and seedling emergence
Authors: Derakhshan A. , Gherekhloo J.
Published: December 2013

Specific knowledge about the dormancy, germination, and emergence patterns of weed species aids the development of integrated management strategies. Laboratory studies were conducted to determine the effect of several environmental factors on seed germination and seedling emergence of Cyperus difformis. Germination of freshly harvested seeds was inhibited by darkness; however, when seeds were subsequently transferred to complete light they germinated readily. Our results showed that 2 wk of cold stratification overcome the light requirement for germination. Seeds of C. difformis were able to germinate over a broad range of temperatures (25/15, 30/20, 35/25, and 40/30 ºC day/night). The response of germination rate to temperature was described as a non-linear function. Based on model outputs, the base, the optimum and the ceiling temperatures were estimated as 14.81, 37.72 and 45 ºC, respectively. A temperature of 120 ºC for a 5 min was required to inhibit 50% of maximum germination. The osmotic potential and salinity required for 50% inhibition of maximum germination were -0.47 MPa and 135.57 mM, respectively. High percentage of seed germination (89%) was observed at pH=6 and decreased to 12% at alkaline medium (pH 9) pH. Seeds sown on the soil surface gave the greatest percentage of seedling emergence, and no seedlings emerged from seeds buried in soil at depths of 1 cm.
Eficiência e residual no solo de herbicidas na cultura do feijão
Authors: Silva V.P. , Ferreira L.R. , D'Antonino L. , Carneiro J.E. , Silva G.R. , Fontes D.R.
Published: December 2013

Avaliou-se a eficiência de herbicidas na cultura do feijão e a possível ação residual desses produtos sobre as culturas de sorgo e de milho cultivadas em sucessão. O experimento foi realizado em campo e em casa de vegetação, avaliando-se os seguintes tratamentos: fomesafen (250 g L-1) e a mistura comercial de bentazon e imazamox (600 g L‑1 + 28 g L-1) nas doses de 25, 50, 75 e 100% da dose recomendada dos respectivos produtos comerciais, bem como a mistura em tanque desses herbicidas nas proporções de 75 + 25, 50 + 50 e 25 + 0,75%, além de duas testemunhas: uma capinada e outra sem capina. O fomesafen na dose de 250 g ha-1 proporcionou boa produtividade de feijão, porém prejudicou o crescimento de plantas de sorgo nas amostras de solo coletadas até 183 dias após a aplicação (DAA), indicando grande persistência do herbicida. No solo coletado aos 153 DAA, observou-se intoxicação nas plantas de milho, mas não houve influência no acúmulo de matéria seca da parte aérea nem na produção de grãos. A mistura pronta de bentazon e imazamox não foi eficiente no controle de plantas daninhas até a colheita do feijão. Contudo, quando a essa mistura adicionou-se o fomesafen, houve redução da dose do fomesafen em 75%, com ótimo controle de plantas daninhas e fácil condição de colheita do feijão, além de menor risco de carryover em plantas de sorgo e de milho. A persistência do fomesafen no solo não foi alterada com a mistura em tanque de bentazon e imazamox.
Selectivity of clomazone and S-metolachlor applied after cassava pruning
Authors: Costa N.V. , Andrade D.C. , Sontag D.A. , Scariot C.A. , Tsuzuki L.H.
Published: December 2013

The objective of this work was to evaluate the selectivity of clomazone in two formulations and S-metolachlor applied on shoots of different sizes after pruning of 'Baianinha' cassava. The experiment was arranged in a randomized block design in a factorial 5 x 2 (5 treatments x 2 sizes of shoots after pruning - 10 and 33 cm) with four replications. The herbicides evaluated were: clomazone (encapsulated suspension - 900 g h-1), clomazone (encapsulated suspension - 1,080 g ha-1), clomazone (emulsifiable concentrate 900 g ha-1), S-metolachlor (1,920 g ha-1) and an untreated control. During the experiment, all plots were kept free of weed interference by hand weeding. It was concluded that both the formulations of clomazone and S-metolachlor were selective when applied on both the shoot sizes evaluated. However, the application of S-metolachlor on 33 cm shoots gave higher selectivity to 'Baianinha' cassava plants.
A Sociologia Política Internacional distante da grande síntese: como articular relações entre as disciplinas de Relações Internacionais, Sociologia e Teoria Política
Authors: Bigo Didier
Published: December 2013

Este artigo analisa uma abordagem de Sociologia Política Internacional (SPI) inspirada em uma metodologia relacional e processual que questiona as premissas das RI quanto às fronteiras do internacional, a visão de que a política está no centro das ciências políticas e o nacionalismo metodológico no que diz respeito à sociedade. A fim de evitar dualismos, a SPI discute as diferentes epistemes em jogo e analisa a sociogênese das práticas dos atores em seus distintos universos profissionais e culturais, com atenção especial para as disputas por poder entre esses atores e para os processos de politização e (in)securitização. A SPI é, portanto, construtivista na medida em que seus autores são reflexivos e desconstroem reivindicações de conhecimento essencialistas. A SPI é também empiricista na medida em que seus autores são sensíveis às práticas dos seres humanos e a suas relações com objetos. Nessa abordagem, as teorias partem dessas relações sociológicas e históricas, sempre incrustadas em locais e tempos específicos. Logicamente, o empiricismo não significa positivismo, e o construtivismo não significa uma perspectiva idealista em que normas, ideias e crenças lideram o mundo. Dessa forma, a SPI também constitui um esforço de descolonizar o estudo das práticas das "sociedades transnacionais de indivíduos" dos chamados "grandes debates" das visões anglo-americanas, reproduzidos transversalmente em suas filosofias e abordagens de ciências sociais.