bluuebunny/crossref_metadata_2025 huggingface dataset:
Supervised Spike-Timing-Dependent Plasticity: A Spatiotemporal Neuronal Learning Rule for Function Approximation and Decisions
Authors: Franosch Jan-Moritz P. , Urban Sebastian , van Hemmen J. Leo
Published: September 2013

How can an animal learn from experience? How can it train sensors, such as the auditory or tactile system, based on other sensory input such as the visual system? Supervised spike-timing-dependent plasticity (supervised STDP) is a possible answer. Supervised STDP trains one modality using input from another one as “supervisor.” Quite complex time-dependent relationships between the senses can be learned. Here we prove that under very general conditions, supervised STDP converges to a stable configuration of synaptic weights leading to a reconstruction of primary sensory input.
Speech Emotional Features Extraction Based on Electroglottograph
Authors: Chen Lijiang , Mao Xia , Wei Pengfei , Compare Angelo
Published: September 2013

This study proposes two classes of speech emotional features extracted from electroglottography (EGG) and speech signal. The power-law distribution coefficients (PLDC) of voiced segments duration, pitch rise duration, and pitch down duration are obtained to reflect the information of vocal folds excitation. The real discrete cosine transform coefficients of the normalized spectrum of EGG and speech signal are calculated to reflect the information of vocal tract modulation. Two experiments are carried out. One is of proposed features and traditional features based on sequential forward floating search and sequential backward floating search. The other is the comparative emotion recognition based on support vector machine. The results show that proposed features are better than those commonly used in the case of speaker-independent and content-independent speech emotion recognition.
Complete Classification of the Macroscopic Behavior of a Heterogeneous Network of Theta Neurons
Authors: Luke Tanushree B. , Barreto Ernest , So Paul
Published: September 2013

We design and analyze the dynamics of a large network of theta neurons, which are idealized type I neurons. The network is heterogeneous in that it includes both inherently spiking and excitable neurons. The coupling is global, via pulselike synapses of adjustable sharpness. Using recently developed analytical methods, we identify all possible asymptotic states that can be exhibited by a mean field variable that captures the network's macroscopic state. These consist of two equilibrium states that reflect partial synchronization in the network and a limit cycle state in which the degree of network synchronization oscillates in time. Our approach also permits a complete bifurcation analysis, which we carry out with respect to parameters that capture the degree of excitability of the neurons, the heterogeneity in the population, and the coupling strength (which can be excitatory or inhibitory). We find that the network typically tends toward the two macroscopic equilibrium states when the neuron's intrinsic dynamics and the network interactions reinforce one another. In contrast, the limit cycle state, bifurcations, and multistability tend to occur when there is competition among these network features. Finally, we show that our results are exhibited by finite network realizations of reasonable size.
Scutellaria yildirimlii (Lamiaceae), a new species from Turkey
Authors: Çiçek Mehmet , YAPRAK AHMET EMRE
Published: September 2013

A new species, Scutellaria yildirimlii, is described from gypseous slopes of inner Anatolia, Turkey, and illustrated. The new species resembles S. pectinata, but it differs in densely lanate hairs, its greyish dwarf prostrate and mat-forming habit, and strongly revolute leaves.
Annotated list and key to the stream fishes of Trinidad & Tobago
Authors: PHILLIP DAWN A.T. , TAPHORN DONALD C. , HOLM ERLING , GILLIAM JAMES F. , LAMPHERE BRADLEY A. , LÓPEZ-FERNÁNDEZ HERNÁN
Published: September 2013

Based on historical and museum records and recent extensive collecting we compiled a checklist of 77 fish species reported from the streams of Trinidad and Tobago. A key with photographs is provided to aid in identifications, as well as brief notes on habitat, diet, reproduction, maximum size, local common names and distribution.
Two New Genera of Jumping Spiders from Hainan Island, China (Araneae, Salticidae)
Authors: ZHOU YUANYE , LI SHUQIANG
Published: September 2013

Two new genera of the spider family Salticidae, Corusca gen. nov. and Insula gen. nov., are described. Nine new species of the genus Corusca gen. nov. and 11 new species of the genus Insula gen. nov. are reported from Hainan, Southern China: Corusca acris sp. nov. (male), C. bawangensis sp. nov. (male), C. falcata sp. nov. (male), C. gracilis sp. nov. (male and female), C. jianfengensis sp. nov. (male and female), C. sanyaensis sp. nov. (male and female), C. setifera sp. nov. (male and female), C. viriosa sp. nov. (male and female), C. wuzhishanensis sp. nov. (male and female), Insula curva sp. nov. (male and female), I. hebetata sp. nov. (male and female), I. limuensis sp. nov. (male and female), I. longa sp. nov. (male and female), I. minuta sp. nov. (male and female), I. nigricula sp. nov. (male and female), I. ramosa sp. nov. (male and female), I. scutata sp. nov. (male and female), I. squamata sp. nov. (male and female), I. tumida sp. nov. (male and female), I. uncinata sp. nov. (male and female). The males of two known species, Corusca liaoi (Peng & Li, 2006) and Insula maculata (Peng & Kim, 1997), which are transferred from Eupoa, are reported for the first time.
Revision and cladistic analysis of the Guineo-Congolian spider genus Smeringopina Kraus (Araneae, Pholcidae)
Authors: HUBER BERNHARD A.
Published: September 2013

The genus Smeringopina Kraus, 1957 is revised, with redescriptions of the nine previously known species and descriptions of 35 new species. Smeringopina is largely restricted to the tropical forests of West and Central Africa. It includes both large species that build their domed sheet-webs in protected spaces near the ground, and small (probably derived) litter-dwelling species. With leg spans up to 18 cm the former group includes some of the largest pholcids known. A first cladistic analysis of Smeringopina, based on 68 morphological (including SEM) characters, suggests several well-defined species groups but also identifies some problematic species whose phylogenetic position needs further study. The ‘Dahomey-Gap’ separates two small western clades (the guineensis species group and two species of the ankasa group) from all other species. The following new species are described: S. ankasa; S. attuleh; S. bamenda; S. bayaka; S. belinga; S. bioko; S. bomfobiri; S. bwiti; S. chaillu; S. djidji; S. ebolowa; S. essotah; S. etome; S. fang; S. fon; S. ibadan; S. iboga; S. kala; S. kikongo; S. kinguele; S. kribi; S. lekoni; S. luki; S. mayebout; S. mbouda; S. mohoba; S. moudouma; S. ndjole; S. ngungu; S. nyasoso; S. ogooue; S. sahoue; S. simintang; S. tchimbele; S. tebe.
The Maritime Influence on Diurnal Temperature Range in the Chesapeake Bay Area
Authors: Scheitlin Kelsey
Published: September 2013

This study analyzes the influence of the Atlantic Ocean and Chesapeake Bay on the diurnal temperature range (DTR) reported by nearby weather stations. Coastal locations reported the smallest DTRs and DTR fluctuations, and DTR increased with distance from the ocean. Month of the year and airmass type also proved to be significant predictors of DTR. All locations showed a bimodal annual DTR pattern with peaks during the transitional seasons and experienced the greatest DTR during dry and/or warm air masses. Proximity to the ocean had the largest (smallest) influence on DTR during dry (moist) air masses with extreme (moderate) temperatures. Seasonally, the proximity to the ocean had the strongest impact on DTR during early–middle spring. A multiple regression model using distance from water, month, and airmass type explains over 30% of DTR variability in the area (p < 0.01). Airmass type has the largest influence on DTR, and changes in both air mass and month impacted the DTR of continental locations more than coastal locations. Land use, cloud cover, and wind speed/direction are additional variables that could account for differences not explained by the model.
Numerical Simulation of 2010 Pakistan Flood in the Kabul River Basin by Using Lagged Ensemble Rainfall Forecasting
Authors: Ushiyama Tomoki , Sayama Takahiro , Tatebe Yuya , Fujioka Susumu , Fukami Kazuhiko
Published: September 2013

Lagged ensemble forecasting of rainfall and rainfall–runoff–inundation (RRI) forecasting were applied to the devastating flood in the Kabul River basin, the first strike of the 2010 Pakistan flood. The forecasts were performed using the Global Forecast System of the National Centers for Environmental Prediction (NCEP-GFS) and were provided four times daily. Dynamical downscaling was also applied to the forecasts by the Weather Research and Forecasting Model (WRF), a regional model. The forecasts of the rainfall and inundation area were verified by comparing rain gauge–corrected Global Satellite Mapping of Precipitation (GSMaP) data and the observed indicator of an inundation map based on Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data. The GFS predicted a sign of heavy rainfall in northern Pakistan 4 days ahead of the onset. However, most of the forecasts predicted it in wrong places, and only those performed after the rainfall onset predicted it in the accurate location. Downscaling corrected the locations of the misplaced GFS forecasts and also underestimated or overestimated rainfall amount derived from GFS. Finally, downscaled forecasts predicted a reliable amount of rainfall in the Kabul River basin 1 day ahead of the rainfall onset and predicted a high probability of heavy rainfall 3 days ahead. Lagged ensemble forecasts of discharge and inundation distribution based on GFS rainfall predicted the probability of the actual discharge and inundation distribution, but in low reliability. The reliability substantially improved when downscaled rainfall was used. The reliability of the flood alert system combining NCEP-GFS, dynamical downscaling by WRF, and the RRI model was at an acceptable level in this study.
Nonisothermal crystallization kinetics of biodegradable poly(lactic acid)/zinc phenylphosphonate composites
Authors: Han Qian , Wang Yaming , Shao Chunguang , Zheng Guoqiang , Li Qian , Shen Changyu
Published: September 2013

The effect of zinc phenylphosphonate on the crystallization of poly(lactic acid) using differential scanning calorimetry operating in dynamical mode at various cooling rates is reported. Experimental data were analyzed using the Avrami, Tobin, and Ozawa models. It is concluded that the addition of zinc phenylphosphonate modifies the crystallization process of poly(lactic acid) (changing the value of the Avrami exponent). Various parameters such as the crystallization half-time and crystallization rate constant reflect that zinc phenylphosphonate significantly accelerates the crystallization process. The activation energy value of the crystallization of poly(lactic acid), determined by the Kissinger method, increases with the addition of zinc phenylphosphonate.
Karl Barth and the Question of Atheism
Authors: Bender Kimlyn J.
Published: September 2013

In light of the contemporary growth of atheism in the West, this article examines Karl Barth’s response to the atheism of the modern period with an eye towards understanding how Barth’s idiosyncratic engagement with modern atheism might prove to be a helpful resource for the church of today in providing its own response. Barth’s engagement with atheism is discussed in light of his understanding of christology, election, sin, and ecclesiology, as well as with an appreciation for the significance of his conducting this engagement from within the realm of dogmatic theology rather than in the area of philosophical theology or the philosophy of religion where atheism is most often addressed.
CT Measured Normative Cartilage Growth in Children Requiring Costochondral Grafting
Authors: Andreoli Steven M. , Mills Jared C. , Kilpatrick Lauren A. , White David R. , Patel Krishna G.
Published: September 2013

Objective

Careful operative timing is required for children undergoing microtia repair using autologous costochondral grafting. This operation is performed as early as age 6 in efforts to treat children before school matriculation while allowing for sufficient rib growth. There remains a paucity of data regarding cartilaginous growth of the ribs and synchondrosis routinely harvested during microtia repair. This study employs CT imaging to generate normative costochondral growth characteristics in children.

Study Design

A population‐based study was performed.

Setting

Tertiary care children's hospital.

Subjects and Methods

Chest CTs were reviewed in 360 children ages 3 to 20 years. Measurements included: length of ribs 6, 7, and 8 and the height and width of the synchondrosis between ribs 6 and 7. Growth charts are presented for gender and laterality.

Results

At age 6: ribs 6, 7, and 8 measure 5.96 ± 0.69, 7.79 ± 0.84, and 6.33 ± 1.01 cm, respectively. In adulthood the mean length of ribs 6, 7, and 8 are 8.29 ± 1.00, 11.10 ± 1.19, and 8.95 ± 1.99 cm, respectively. The vertical height of the synchondrosis at years 6 and 20 are 2.42 ± 0.39 and 3.59 ± 0.53 cm, respectively. Ribs 6, 7, and 8 as well as the synchondrosis grow in a nearly linear fashion.

Conclusions

Cartilaginous growth of ribs 6 to 8 during early childhood is nearly linear. Synchondrosis height approaches adult auricle width at 8 years. Rib size is consistently larger in males and on the left side. These data are useful for the pediatric otolaryngologist and facial plastics and reconstructive surgeon performing microtia surgery.
Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways
Authors: Monte Aline Santos , de Souza Greicy Coelho , McIntyre Roger S , Soczynska Joanna K , dos Santos Júnia Vieira , Cordeiro Rafaela Carneiro , Ribeiro Bruna Mara Machado , de Lucena David Freitas , Vasconcelos Silvânia Maria Mendes , de Sousa Francisca Cléa Florenço , Carvalho André Férrer , Macêdo Danielle S
Published: September 2013

It has been hypothesized that oxidative imbalance and alterations in nitrergic signaling play a role in the neurobiology of schizophrenia. Preliminary evidence suggests that adjunctive minocycline treatment is efficacious for cognitive and negative symptoms of schizophrenia. This study investigated the effects of minocycline in the prevention and reversal of ketamine-induced schizophrenia-like behaviors in mice. In the reversal protocol, animals received ketamine (20 mg/kg per day intraperitoneally or saline for 14 days, and minocycline (25 or 50 mg/kg daily), risperidone or vehicle treatment from days 8 to 14. In the prevention protocol, mice were pretreated with minocycline, risperidone or vehicle prior to ketamine. Behaviors related to positive (locomotor activity and prepulse inhibition of startle), negative (social interaction) and cognitive (Y maze) symptoms of schizophrenia were also assessed. Glutathione (GSH), thiobarbituric acid-reactive substances (TBARS) and nitrite levels were measured in the prefrontal cortex, hippocampus and striatum. Minocycline and risperidone prevented and reversed ketamine-induced alterations in behavioral paradigms, oxidative markers (i.e. ketamine-induced decrease and increase in GSH levels and TBARS content, respectively) as well as nitrite levels in the striatum. These data provide a rationale for evaluating minocycline as a novel psychotropic agent and suggest that its mechanism of action includes antioxidant and nitrergic systems.
Sturge-Weber syndrome with late onset hemiplegic migraine-like attacks and progressive unilateral cerebral atrophy
Authors: Planche Vincent , Chassin Olivier , Leduc Louise , Regnier Wendy , Kelly Antony , Colamarino Renato
Published: September 2013

Background

Sturge-Weber syndrome (SWS) is an uncommon etiology of hemiplegic migraine-like (HM-like) attacks, associated with epilepsy and mental retardation.

Case

We report the case of a 40-year-old woman with SWS who has been suffering from HM-like episodes since she was 24, with no history of seizure or mental retardation. Susceptibility weighted imaging (SWI)-MRI and CT scans have shown bilateral calcifications of the choroidal plexuses, a developmental venous anomaly with dilated transmedullary veins and a left parieto-occipital leptomeningeal angioma. 18F-Fluorodeoxyglucose (FDG)-PET/CT revealed a diffuse left-hemisphere hypometabolism. The comparison between the MRI performed at the age of 24 and the one performed at the age of 40 highlighted a progressive unilateral fronto-temporo-parietal atrophy. Surprisingly, even now, cognitive functions of this patient are relatively preserved. Lamotrigine permitted an improvement of HM-like attacks.

Discussion

Explanations for this minimally symptomatic form of SWS may be the absence of seizure, the importance of her deep venous drainage, the absence of cortical calcification and white matter impairment in the affected hemisphere, and, paradoxically, the severely asymmetric cortical metabolism. Furthermore, this case reinforces the hypothesis that alteration of cerebral hemodynamics could precipitate the cortical spreading depression giving rise to migraine with aura.

Conclusion

We propose to consider SWS as a cause of apparently isolated hemiplegic migraine and lamotrigine as a preventive medication in HM-like attacks.
The Impact of Caregiving
Authors: Drummond J. D. , Brotman Shari , Silverman Marjorie , Sussman Tamara , Orzeck Pam , Barylak Lucy , Wallach Isabelle
Published: September 2013

Using an adapted phenomenological approach, the current study explores older women’s stories about the ways in which providing care to their spouse or partner has affected their sexual and intimate lives. Findings suggest that older women’s sexual identities and experiences of sexuality are marked by both ageist constructions of “older woman as asexual” and loss of self associated with taking on the role of caregiver. Findings also suggest that women resist these constructions of self through the development of other forms of intimacy in their lives. Suggestions for increasing opportunities to address women’s realities in service provision are highlighted.
Importance of Spiritual Care for Cardiac Patients Admitted to Coronary Care Units in the Gaza Strip
Authors: Abu-El-Noor Mysoon Khalil , Abu-El-Noor Nasser Ibrahim
Published: September 2013

Purpose: This study aimed to assess the perception of hospitalized cardiac patients in coronary care units (CCUs) in the Gaza Strip about the importance of assessing and providing spiritual care to them. Design: This was a cross-sectional study. Methods: A valid and reliable instrument previously developed by Musa was used to assess patients’ perception about the importance of assessing spiritual needs and providing spiritual care to cardiac patients admitted to CCUs. Findings: Out of 279 cardiac patients, 275 (response rate of 98.6%) agreed to be involved in this study. Results revealed that both assessing spiritual needs (69.69%) and providing spiritual care (76.97%) were very important to cardiac patients with rating spiritual care intervention as more important than spiritual assessment. Conclusions: Assessing and providing spiritual care is crucial to cardiac patients. Therefore, health policy makers need to pay more attention to this group of vulnerable patients and need to adopt a spiritual care policy into the Palestinian health care system, which might help to decrease their stress, length of hospitalization, and the cost of treatment.
Health Education 2.0
Authors: Fielding Jonathan E.
Published: September 2013

Social, physical, and economic environments are the greatest determinants of our individual and collective health. Inadequate or substandard environments of all types present barriers to health. Addressing these broader determinants will be the quintessential core in the next era of public health practice. The framework for health improvement is shifting to a robust and comprehensive ecological model, wherein the broader constructs of health determinants will be central issues in population health improvement practice requiring expanded partnerships, increased application of scientific evidence, and healthy policy development within and outside of the traditional health sector. Health educators are uniquely positioned to effectively engage essential partners, shape information for policy makers, leverage the evidence base to implement effective interventions and maximize beneficial health outcomes, and add to the evidence base with thorough and systematic evaluation and reporting.
Noongar Dandjoo
Authors: Johnston Michelle , Bishop Russell
Published: September 2013

As media employers increasingly shift the burden for the provision of skills training from themselves to universities, academics must develop innovative ways to ensure their graduates are truly job ready, beyond merely simulating industry practice and offering conventional work experience opportunities. Under the umbrella term Work Integrated Learning (WIL), universities have adopted a range of educational approaches that combine theory with practice to enhance learning experiences for students. But not all WIL initiatives are the same and nor do they always achieve their objectives. However, three series of the award-winning student TV production Noongar Dandjoo, produced by Curtin University, offer a new model for teaching substantive journalism, program production as well as cultural awareness and cultural sensitivity under an offshoot of WIL called service-learning. As this article seeks to demonstrate, Noongar Dandjoo is making a lasting and positive impression on students who are applying their experiences working with indigenous people beyond university.
Reporting the Environment
Authors: Anuar Mustafa K.
Published: September 2013

Environmental degradation is not only a product of human neglect of the physical environment, but is often the result of conflict between competing interests over scarce resources. Minority communities and the poor, who are affected by the conflict, are pushed to the margins. This commentary reflects on how the people affected by the rare earth project in Pahang, an eastern state in Peninsula Malaysia, are marginalised by the mainstream press.
IFNL3 mediates interaction between innate immune cells: Implications for hepatitis C virus pathogenesis
Authors: O’Connor Kate S , Ahlenstiel Golo , Suppiah Vijayaprakash , Schibeci Stephen , Ong Adrian , Leung Reynold , van der Poorten David , Douglas Mark W , Weltman Martin D , Stewart Graeme J , Liddle Christopher , George Jacob , Booth David R
Published: September 2013

Common IFN lambda 3 ( IFNL3) variants have been demonstrated to affect spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. The functional basis of these genetic variants has yet to be determined. Data examining the effect of IFNL3, specifically, in innate immune cells is lacking. Here, we determined the expression of IFNL3 and its receptor IFNLR1 in blood immune cell subsets and in HCV-infected livers. Next we assessed their sensitivity to IFNL3. All participants were genotyped for the IFNL3 SNPs rs8099917 and rs12979860. Importantly, unstimulated blood immune cells express significantly higher levels of IFNL3 than HCV liver biopsies. Plasmacytoid dendritic cells (pDCs) are the predominant producers of IFNLR1, especially in response to IFN-α. PBMCs, monocytes and pDCs all respond to IFNL3 based on MxA up-regulation. No differences in IFNL3 expression levels between rs8099917 or rs12979860 genotypes were detected. This is the first study to show peripheral blood pDCs to be the main producers of IFNL3, especially compared with HCV-infected livers. This makes innate immune cells the key players in determining the functional significance of INFL3 polymorphisms in patients with HCV.
The contested terrain of sport diplomacy in a globalizing world
Authors: Jackson Steven J.
Published: September 2013

Sport continues to occupy a rather ambiguous position within the context of politics, foreign policy and diplomatic relations. While one can identify a long list of cases where sport has been credited with diverting conflict, contributing to peace negotiations and helping develop better cultural understanding, there are also many cases where sport has not only fueled conflict but also served as its source. This paper seeks to: (1) highlight the unique features of sport as a cultural site and practice in relation to diplomacy; (2) briefly overview some key dimensions and limitations of sport as an instrument of diplomacy; and (3) offer a preliminary examination of contemporary sport organizations and events in order to understand the implications of the transformational shift occurring between state diplomacy and what might be termed “corporate diplomacy” within an increasingly global context.
Sport as a catalyst for cooperation: Why sport dialogue between the two Koreas succeeds in some cases but not in others
Authors: Jung Giwoong
Published: September 2013

There is a wide belief that sport has a positive utility in the diplomatic arena and can be used as a catalyst for cooperation. The very instrumental effectiveness of sport gave a birth to the idea that sport can be used effectively to promote contact between or among hostile countries. This idea was adopted by the governments of the two Koreas and a sport agenda was used as a pretext for initiating official dialogues between the two countries. Throughout the history of South–North dialogues, we can find some cases of success and other cases of failure. Some successful dialogues brought concrete results of cooperation, while other unsuccessful dialogues ended only as pre-steps that did not develop into cooperation or negotiation. Thus our attention should go to two directions. One is “what is the main force which drove the two Koreas to open a sport dialogue?” The other is to find out “why sport dialogues between the two Koreas succeed in some cases but not others”. This article aims to review the role of sport as an instrument or a catalyst for cooperation. The author divides the whole period of dialogues into several phases and examines the role of sport. After reviewing the success and failure of dialogues, the author argues for sport to be used as a tool for dialogue, the strategic choice of the actors being the prerequisite. The author emphasizes that strategic choices made by the governments of the two Koreas play an important role when casting sport as an instrument to develop relations, which is explained with the framework of simple 2 × 2 games. In line with this, this article explores the strategic thoughts of the two Koreas by reviewing the political intentions, situations of the time, contextual connectivity and strategic thinkings of two Koreas.
Soft power at home and abroad: Sport diplomacy, politics and peace-building
Authors: Nygård Håvard Mokleiv , Gates Scott
Published: September 2013

Soft power is the power to persuade whereby one actor in a non-coercive manner convinces another to want the same things he/she wants. Sport can be used as tool of soft power both internationally and domestically. Peace-building and nation-building can be achieved through four mechanisms of sport diplomacy and politics: image-building; building a platform for dialogue; trust-building; and reconciliation, integration and anti-racism. These mechanisms are not deterministically controllable and can have unintended consequences. On the one hand, sporting events can be used as a means of building trust between adversaries. On the other, the hostilities between peoples can be mirrored on playing fields. This article examines the intended and unintended consequences of each mechanism. It also examines the role of confounding economic factors. Each article comprising this Special Issue explores a different mechanism of sport politics and public diplomacy.
High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis
Authors: Fürst Daniel , Müller Carlheinz , Vucinic Vladan , Bunjes Donald , Herr Wolfgang , Gramatzki Martin , Schwerdtfeger Rainer , Arnold Renate , Einsele Hermann , Wulf Gerald , Pfreundschuh Michael , Glass Bertram , Schrezenmeier Hubert , Schwarz Klaus , Mytilineos Joannis
Published: September 2013

Key Points

HLA mismatches at the allele and antigen level (possibly with the exception of HLA-DQB1) should be treated equally in donor selection. HLA mismatches at >1 locus (including HLA-DQB1) have additive detrimental effects.
Effector T cells require fatty acid metabolism during murine graft-versus-host disease
Authors: Byersdorfer Craig A. , Tkachev Victor , Opipari Anthony W. , Goodell Stefanie , Swanson Jacob , Sandquist Stacy , Glick Gary D. , Ferrara James L. M.
Published: September 2013

Key Points

T cells activated during GVHD increase their dependence upon fatty acid oxidation. This dependence is not observed following acute activation or during normal immune reconstitution, suggesting novel therapeutic targets.
Redox signaling in pathophysiology of hypertension
Authors: Majzunova Miroslava , Dovinova Ima , Barancik Miroslav , Chan Julie YH
Published: September 2013

Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.
Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats
Authors: Smeding Lonneke , Kuiper Jan Willem , Plötz Frans B , Kneyber Martin CJ , Groeneveld AB Johan
Published: September 2013

Background

Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.

Materials and methods

N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.

Results

Instillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.

Conclusions

Injurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.
Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses
Authors: Pitta Denise da Rocha , Sarian Luis Otávio , Barreta Amilcar , Campos Elisabete Aparecida , de Angelo Andrade Liliana Lucci , Fachini Ana Maria Dias , Campbell Leonardo Martins , Derchain Sophie
Published: September 2013

Background

This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound.

Methods

This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae.

Results

Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI.

Conclusion

Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.
Molecular dynamics simulations on the Tre1 G protein-coupled receptor: exploring the role of the arginine of the NRY motif in Tre1 structure
Authors: Pruitt Margaret M , Lamm Monica H , Coffman Clark R
Published: September 2013

Background

The arginine of the D/E/NRY motif in Rhodopsin family G protein-coupled receptors (GPCRs) is conserved in 96% of these proteins. In some GPCRs, this arginine in transmembrane 3 can form a salt bridge with an aspartic acid or glutamic acid in transmembrane 6. The Drosophila melanogaster GPCR Trapped in endoderm-1 (Tre1) is required for normal primordial germ cell migration. In a mutant form of the protein, Tre1sctt, eight amino acids RYILIACH are missing, resulting in a severe disruption of primordial germ cell development. The impact of the loss of these amino acids on Tre1 structure is unknown. Since the missing amino acids in Tre1sctt include the arginine that is part of the D/E/NRY motif in Tre1, molecular dynamics simulations were performed to explore the hypothesis that these amino acids are involved in salt bridge formation and help maintain Tre1 structure.

Results

Structural predictions of wild type Tre1 (Tre1+) and Tre1sctt were subjected to over 250 ns of molecular dynamics simulations. The ability of the model systems to form a salt bridge between the arginine of the D/E/NRY motif and an aspartic acid residue in transmembrane 6 was analyzed. The results indicate that a stable salt bridge can form in the Tre1+ systems and a weak salt bridge or no salt bridge, using an alternative arginine, is likely in the Tre1sctt systems.

Conclusions

The weak salt bridge or lack of a salt bridge in the Tre1sctt systems could be one possible explanation for the disrupted function of Tre1sctt in primordial germ cell migration. These results provide a framework for studying the importance of the arginine of the D/E/NRY motif in the structure and function of other GPCRs that are involved in cell migration, such as CXCR4 in the mouse, zebrafish, and chicken.
Cytostatic versus cytocidal profiling of quinoline drug combinations via modified fixed-ratio isobologram analysis
Authors: Gorka Alexander P , Jacobs Lauren M , Roepe Paul D
Published: September 2013

Background

Drug combination therapy is the frontline of malaria treatment. There is an ever-accelerating need for new, efficacious combination therapies active against drug resistant malaria. Proven drugs already in the treatment pipeline, such as the quinolines, are important components of current combination therapy and also present an attractive test bank for rapid development of new concepts.

Methods

The efficacy of several drug combinations versus chloroquine-sensitive and chloroquine-resistant strains was measured using both cytostatic and cytocidal potency assays.

Conclusions

These screens identify quinoline and non-quinoline pairs that exhibit synergy, additivity, or antagonism using the fixed-ratio isobologram method and find tafenoquine – methylene blue combination to be the most synergistic. Also, interestingly, for selected pairs, additivity, synergy, or antagonism defined by quantifying IC50 (cytostatic potency) does not necessarily predict similar behaviour when potency is defined by LD50 (cytocidal potency). These data further support an evolving new model for quinoline anti-malarials, wherein haem and haemozoin are the principle target for cytostatic activity, but may not be the only target relevant for cytocidal activity.
Organization of Plasmodium falciparum spliceosomal core complex and role of arginine methylation in its assembly
Authors: Hossain Manzar , Sharma Shweta , Korde Reshma , Kanodia Shivani , Chugh Monika , Rawat Khushboo , Malhotra Pawan
Published: September 2013

Background

Splicing and alternate splicing are the two key biological processes that result in the generation of diverse transcript and protein isoforms in Plasmodium falciparum as well as in other eukaryotic organisms. Not much is known about the organization of splicing machinery and mechanisms in human malaria parasite. Present study reports the organization and assembly of Plasmodium spliceosome Sm core complex.

Methods

Presence of all the seven Plasmodium Sm-like proteins in the intra-erythrocytic stages was assessed based on the protein(s) expression analysis using immuno-localization and western blotting. Localization/co-localization studies were performed by immunofluorescence analysis on thin parasite smear using laser scanning confocal microscope. Interaction studies were carried out using yeast two-hybrid analysis and validated by in vitro pull-down assays. PfPRMT5 (arginine methyl transferase) and PfSmD1 interaction analysis was performed by pull-down assays and the interacting proteins were identified by MALDI-TOF spectrometry.

Results

PfSm proteins are expressed at asexual blood stages of the parasite and show nucleo-cytoplasmic localization. Protein-protein interaction studies showed that PfSm proteins form a heptameric complex, typical of spliceosome core complex as shown in humans. Interaction of PfSMN (survival of motor neuron, tudor domain containing protein) or PfTu-TSN (Tudor domain of Tudor Staphylococcal nuclease) with PfSmD1 proteins was found to be methylation dependent. Co-localization by immunofluorescence and co-immunoprecipitation studies suggested an association between PfPRMT5 and PfSmD1, indicating the role of arginine methylation in assembly of Plasmodium spliceosome complex.

Conclusions

Plasmodium Sm-like proteins form a heptameric ring-like structure, although the arrangement of PfSm proteins slightly differs from human splicing machinery. The data shows the interaction of PfSMN with PfSmD1 and this interaction is found to be methylation dependent. PfPRMT5 probably exists as a part of methylosome complex that may function in the cytoplasmic assembly of Sm proteins at asexual blood stages of P. falciparum.
YB-1 dependent oncolytic adenovirus efficiently inhibits tumor growth of glioma cancer stem like cells
Authors: Mantwill Klaus , Naumann Ulrike , Seznec Janina , Girbinger Vroni , Lage Hermann , Surowiak Pawel , Beier Dagmar , Mittelbronn Michel , Schlegel Jürgen , Holm Per Sonne
Published: September 2013

Background

The brain cancer stem cell (CSC) model describes a small subset of glioma cells as being responsible for tumor initiation, conferring therapy resistance and tumor recurrence. In brain CSC, the PI3-K/AKT and the RAS/mitogen activated protein kinase (MAPK) pathways are found to be activated. In consequence, the human transcription factor YB-1, knowing to be responsible for the emergence of drug resistance and driving adenoviral replication, is phosphorylated and activated. With this knowledge, YB-1 was established in the past as a biomarker for disease progression and prognosis. This study determines the expression of YB-1 in glioblastoma (GBM) specimen in vivo and in brain CSC lines. In addition, the capacity of Ad-Delo3-RGD, an YB-1 dependent oncolytic adenovirus, to eradicate CSC was evaluated both in vitro and in vivo.

Methods

YB-1 expression was investigated by immunoblot and immuno-histochemistry. In vitro, viral replication as well as the capacity of Ad-Delo3-RGD to replicate in and, in consequence, to kill CSC was determined by real-time PCR and clonogenic dilution assays. In vivo, Ad-Delo3-RGD-mediated tumor growth inhibition was evaluated in an orthotopic mouse GBM model. Safety and specificity of Ad-Delo3-RGD were investigated in immortalized human astrocytes and by siRNA-mediated downregulation of YB-1.

Results

YB-1 is highly expressed in brain CSC lines and in GBM specimen. Efficient viral replication in and virus-mediated lysis of CSC was observed in vitro. Experiments addressing safety aspects of Ad-Delo3-RGD showed that (i) virus production in human astrocytes was significantly reduced compared to wild type adenovirus (Ad-WT) and (ii) knockdown of YB-1 significantly reduced virus replication. Mice harboring othotopic GBM developed from a temozolomide (TMZ)-resistant GBM derived CSC line which was intratumorally injected with Ad-Delo3-RGD survived significantly longer than mice receiving PBS-injections or TMZ treatment.

Conclusion

The results of this study supported YB-1 based virotherapy as an attractive therapeutic strategy for GBM treatment which will be exploited further in multimodal treatment concepts.
Identical effects of VEGF and serum-deprivation on phenotype and function of adipose-derived stromal cells from healthy donors and patients with ischemic heart disease
Authors: Follin Bjarke , Tratwal Josefine , Haack-Sørensen Mandana , Elberg Jens Jørgen , Kastrup Jens , Ekblond Annette
Published: September 2013

Background

Adipose-derived stromal cells (ASCs) stimulated with vascular endothelial growth factor (VEGF) and serum-deprived, are applied in the first in-man double-blind placebo-controlled MyStromalCell Trial, as a novel therapeutic option for treatment of ischemic heart disease (IHD). This in vitro study explored the effect of VEGF and serum deprivation on endothelial differentiation capacity of ASCs from healthy donors and IHD patients.

Methods

ASCs stimulated with rhVEGFA165 in serum-deprived medium for one to three weeks were compared with ASCs in serum-deprived (2% fetal bovine serum) or complete medium (10% fetal bovine serum). Expression of VEGF receptors, endothelial and stem cell markers was measured using qPCR, flow cytometry and immunocytochemistry. In vitro tube formation and proliferation was also measured.

Results

ASCs from VEGF-stimulated and serum-deprived medium significantly increased transcription of transcription factor FOXF1, endothelial marker vWF and receptor VEGFR1 compared with ASCs from complete medium. ASCs maintained stem cell characteristics in all conditions. Tube formation of ASCs occurred in VEGF-stimulated and serum-deprived medium. The only difference between healthy and patient ASCs was a variation in proliferation rate.

Conclusions

ASCs from IHD patients and healthy donors proved equally inclined to differentiate in endothelial direction by serum-deprivation, however with no visible additive effect of VEGF stimulation. The treatment did not result in complete endothelial differentiation, but priming towards endothelial lineage.
Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors
Authors: Wei Bin , Han Lei , Abbink Truus E M , Groppelli Elisabetta , Lim Daina , Thaker Youg Raj , Gao Wei , Zhai Rongrong , Wang Jianhua , Lever Andrew , Jolly Clare , Wang Hongyan , Rudd Christopher E
Published: September 2013

Background

Immune cell adaptor protein ADAP (adhesion and degranulation-promoting adaptor protein) mediates aspects of T-cell adhesion and proliferation. Despite this, a connection between ADAP and infection by the HIV-1 (human immunodeficiency virus-1) has not been explored.

Results

In this paper, we show for the first time that ADAP and its binding to SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) regulate HIV-1 infection via two distinct mechanisms and co-receptors. siRNA down-regulation of ADAP, or expression of a mutant that is defective in associating to its binding partner SLP-76 (termed M12), inhibited the propagation of HIV-1 in T-cell lines and primary human T-cells. In one step, ADAP and its binding to SLP-76 were needed for the activation of NF-κB and its transcription of the HIV-1 long terminal repeat (LTR) in cooperation with ligation of co-receptor CD28, but not LFA-1. In a second step, the ADAP-SLP-76 module cooperated with LFA-1 to regulate conjugate formation between T-cells and dendritic cells or other T-cells as well as the development of the virological synapse (VS) and viral spread between immune cells.

Conclusions

These findings indicate that ADAP regulates two steps of HIV-1 infection cooperatively with two distinct receptors, and as such, serves as a new potential target in the blockade of HIV-1 infection.