bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on the strategies in multicomponent activity monitoring within the phytopharmaceutical field
Authors: Gostner Johanna M , Wrulich Oliver A , Jenny Marcel , Fuchs Dietmar , Ueberall Florian
Published: March 2012

Background

To-date modern drug research has focused on the discovery and synthesis of single active substances. However, multicomponent preparations are gaining increasing importance in the phytopharmaceutical field by demonstrating beneficial properties with respect to efficacy and toxicity.

Discussion

In contrast to single drug combinations, a botanical multicomponent therapeutic possesses a complex repertoire of chemicals that belong to a variety of substance classes. This may explain the frequently observed pleiotropic bioactivity spectra of these compounds, which may also suggest that they possess novel therapeutic opportunities. Interestingly, considerable bioactivity properties are exhibited not only by remedies that contain high doses of phytochemicals with prominent pharmaceutical efficacy, but also preparations that lack a sole active principle component. Despite that each individual substance within these multicomponents has a low molar fraction, the therapeutic activity of these substances is established via a potentialization of their effects through combined and simultaneous attacks on multiple molecular targets. Although beneficial properties may emerge from such a broad range of perturbations on cellular machinery, validation and/or prediction of their activity profiles is accompanied with a variety of difficulties in generic risk-benefit assessments. Thus, it is recommended that a comprehensive strategy is implemented to cover the entirety of multicomponent-multitarget effects, so as to address the limitations of conventional approaches.

An integration of standard toxicological methods with selected pathway-focused bioassays and unbiased data acquisition strategies (such as gene expression analysis) would be advantageous in building an interaction network model to consider all of the effects, whether they were intended or adverse reactions.
Formulas for the Reidemeister, Lefschetz and Nielsen coincidence number of maps between infra-nilmanifolds
Authors: Ha Ku Yong , Lee Jong Bum , Penninckx Pieter
Published: March 2012

We prove practical formulas for the Reidemeister coincidence number, the Lefschetz coincidence number and the Nielsen coincidence number of continuous maps between oriented infra-nilmanifolds of equal dimension. In order to obtain these formulas, we use the averaging formulas for the Lefschetz coincidence number and for the Nielsen coincidence number and we develop an averaging formula for the Reidemeister coincidence number. We also give a simple proof of the averaging formula for the Lefschetz coincidence number.

Mathematics Subject Classification 2000: 55M20; 57S30.
Gastrocnemius muscle herniation as a rare differential diagnosis of ankle sprain: case report and review of the literature
Authors: Bergmann Greta , Ciritsis Bernhard D , Wanner Guido A , Simmen Hans-Peter , Werner Clément ML , Osterhoff Georg
Published: March 2012

Background

Muscle herniation of the leg is a rare clinical entity. Yet, knowing this condition is necessary to avoid misdiagnosis and delayed treatment. In the extremities, muscle herniation most commonly occurs as a result of an acquired fascial defect, often due to trauma. Different treatment options for symptomatic extremity muscle herniation in the extremities, including conservative treatment, fasciotomy and mesh repair have been described.

Case presentation

We present the case of a patient who presented with prolonged symptoms after an ankle sprain. The clinical picture showed a fascial insufficiency with muscle bulging under tension. Ultrasound and MRI imaging confirmed the diagnosis of muscle hernia of the medial gastrocnemius on the right leg. Conservative treatment did not lead to success. Therefore, the fascial defect was treated surgically by repairing the muscle herniation using a synthetic vicryl propylene patch.

Conclusions

Muscle hernias should be taken into consideration as a rare differential diagnosis whenever patients present with persisting pain or soft tissue swelling after ankle sprain. Diagnosis is mainly based on clinical aspect and physical examination, but can be confirmed by radiologic imaging techniques, including (dynamic) ultrasound and MRI. If conservative treatment fails, we recommend the closure with mesh patches for large fascial defects.
Effect of pregnancy on serum cytokines in SLE patients
Authors: Doria Andrea , Cutolo Maurizio , Ghirardello Anna , Zen Margherita , Villalta Danilo , Tincani Angela , Punzi Leonardo , Iaccarino Luca , Petri Michelle
Published: March 2012

Introduction

The aim of this study was to evaluate an extensive panel of cytokines involved in immune regulation during pregnancy in patients with systemic lupus erythematosus (SLE) and in healthy women.

Methods

A total of 47 consecutive successful pregnancies in 46 SLE patients and 56 pregnancies in 56 matched healthy subjects, as controls, were prospectively studied. Serum interleukin (IL)-1-α, IL-1-β, IL-2, IL-6, IL-8, IL-10, IL-12p70, interferon (INF)-γ and tumor necrosis factor (TNF)-α were detected in sera obtained at the first and third trimester of pregnancy by a highly sensitive, multiplexed sandwich ELISA.

Results

Medians (pg/ml) of serum levels of most helper T (Th)1-type cytokines were significantly lower in the third trimester compared with those observed in the first trimester of pregnancy in healthy women: INF-γ 2.0 vs 3.4, TNF-α 10.2 vs 11.5, IL-1-α 0.9 vs 1.1, IL-1-β 0.6 vs 1.0, IL-2 3.0 vs 3.5, and IL-12p70 4.9 vs 5.6 (P-values < 0.02 for all). By contrast, only the IL-1-α serum levels were lower in the third trimester compared with the first trimester in SLE patients (P = 0.006). IFN-γ/IL-6 and IFN-γ/IL-10 ratios were higher in controls than in SLE (P = 0.002, and P = 0.001, respectively); moreover, they were significantly reduced in the third compared to the first trimester of pregnancy in healthy women, but not in SLE.

Conclusions

In SLE patients, Th1/Th2 cytokine serum level ratio does not decrease during pregnancy progression as much as in healthy pregnant women. This could account for the observation of a low frequency of disease flares in the third trimester of gestation.
Proteomic analysis of acquired tamoxifen resistance in MCF-7 cells reveals expression signatures associated with enhanced migration
Authors: Zhou Changhua , Zhong Qiu , Rhodes Lyndsay V , Townley Ian , Bratton Melyssa R , Zhang Qiang , Martin Elizabeth C , Elliott Steven , Collins-Burow Bridgette M , Burow Matthew E , Wang Guangdi
Published: March 2012

Introduction

Acquired tamoxifen resistance involves complex signaling events that are not yet fully understood. Successful therapeutic intervention to delay the onset of hormone resistance depends critically on mechanistic elucidation of viable molecular targets associated with hormone resistance. This study was undertaken to investigate the global proteomic alterations in a tamoxifen resistant MCF-7 breast cancer cell line obtained by long term treatment of the wild type MCF-7 cell line with 4-hydroxytamoxifen (4-OH Tam).

Methods

We cultured MCF-7 cells with 4-OH Tam over a period of 12 months to obtain the resistant cell line. A gel-free, quantitative proteomic method was used to identify and quantify the proteome of the resistant cell line. Nano-flow high-performance liquid chromatography coupled to high resolution Fourier transform mass spectrometry was used to analyze fractionated peptide mixtures that were isobarically labeled from the resistant and control cell lysates. Real time quantitative PCR and Western blots were used to verify selected proteomic changes. Lentiviral vector transduction was used to generate MCF-7 cells stably expressing S100P. Online pathway analysis was performed to assess proteomic signatures in tamoxifen resistance. Survival analysis was done to evaluate clinical relevance of altered proteomic expressions.

Results

Quantitative proteomic analysis revealed a wide breadth of signaling events during transition to acquired tamoxifen resistance. A total of 629 proteins were found significantly changed with 364 up-regulated and 265 down-regulated. Collectively, these changes demonstrated the suppressed state of estrogen receptor (ER) and ER-regulated genes, activated survival signaling and increased migratory capacity of the resistant cell line. The protein S100P was found to play a critical role in conferring tamoxifen resistance and enhanced cell motility.

Conclusions

Our data demonstrate that the adaptive changes in the proteome of tamoxifen resistant breast cancer cells are characterized by down-regulated ER signaling, activation of alternative survival pathways, and enhanced cell motility through regulation of the actin cytoskeleton dynamics. Evidence also emerged that S100P mediates acquired tamoxifen resistance and migration capacity.
Risk factors for the development of acute lung injury in patients with infectious pneumonia
Authors: Kojicic Marija , Li Guangxi , Hanson Andrew C , Lee Kun-Moo , Thakur Lokendra , Vedre Jayanth , Ahmed Adil , Baddour Larry M , Ryu Jay H , Gajic Ognjen
Published: March 2012

Introduction

Although pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others. The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia.

Methods

A retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007. In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner.

Results

The s tudy included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to 75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development.

Conclusions

The development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality. Inappropriate initial antimicrobial treatment and transfusion predict the development of ALI independent of pathogen.
Pivotal Advance: Arginase-1-independent polyamine production stimulates the expression of IL-4-induced alternatively activated macrophage markers while inhibiting LPS-induced expression of inflammatory genes
Authors: Van den Bossche Jan , Lamers Wouter H , Koehler Eleonore S , Geuns Jan M C , Alhonen Leena , Uimari Anne , Pirnes-Karhu Sini , Van Overmeire Eva , Morias Yannick , Brys Lea , Vereecke Lars , De Baetselier Patrick , Van Ginderachter Jo A
Published: March 2012

In macrophages, basal polyamine (putrescine, spermidine, and spermine) levels are relatively low but are increased upon IL-4 stimulation. This Th2 cytokine induces Arg1 activity, which converts arginine into ornithine, and ornithine can be decarboxylated by ODC to produce putrescine, which is further converted into spermidine and spermine. Recently, we proposed polyamines as novel agents in IL-4-dependent E-cadherin regulation in AAMs. Here, we demonstrate for the first time that several, but not all, AAM markers depend on polyamines for their IL-4-induced gene and protein expression and that polyamine dependency of genes relies on the macrophage type. Remarkably, Arg1-deficient macrophages display rather enhanced IL-4-induced polyamine production, suggesting that an Arg1-independent polyamine synthesis pathway may operate in macrophages. On the other side of the macrophage activation spectrum, LPS-induced expression of several proinflammatory genes was increased significantly in polyamine-depleted CAMs. Overall, we propose Arg1 independently produced polyamines as novel regulators of the inflammatory status of the macrophage. Indeed, whereas polyamines are needed for IL-4-induced expression of several AAM mediators, they inhibit the LPS-mediated expression of proinflammatory genes in CAMs.
IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease
Authors: Jurado Javier O , Pasquinelli Virginia , Alvarez Ivana B , Peña Delfina , Rovetta Ana I , Tateosian Nancy L , Romeo Horacio E , Musella Rosa M , Palmero Domingo , Chuluyán H Eduardo , García Verónica E
Published: March 2012

Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-γ alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M. tuberculosis infection, but the role of IL-17-producing cells in human TB remains to be understood. Therefore, we investigated the induction and regulation of IFN-γ and IL-17 during the active disease. TB patients were classified as High and Low Responder individuals according to their T cell responses against the antigen, and cytokine expression upon M. tuberculosis stimulation was investigated in peripheral blood and pleural fluid. Afterwards, the potential correlation among the proportions of cytokine-producing cells and clinical parameters was analyzed. In TB patients, M. tuberculosis induced IFN-γ and IL-17, but in comparison with BCG-vaccinated healthy donors, IFN-γ results were reduced significantly, and IL-17 was markedly augmented. Moreover, the main source of IL-17 was represented by CD4+IFN-γ+IL-17+ lymphocytes, a Th1/Th17 subset regulated by IFN-γ. Interestingly, the ratio of antigen-expanded CD4+IFN-γ+IL-17+ lymphocytes, in peripheral blood and pleural fluid from TB patients, was correlated directly with clinical parameters associated with disease severity. Indeed, the highest proportion of CD4+IFN-γ+IL-17+ cells was detected in Low Responder TB patients, individuals displaying severe pulmonary lesions, and longest length of disease evolution. Taken together, the present findings suggest that analysis of the expansion of CD4+IFN-γ+IL-17+ T lymphocytes in peripheral blood of TB patients might be used as an indicator of the clinical outcome in active TB.
Loss of Neuronal Potassium/Chloride Cotransporter 3 (KCC3) Is Responsible for the Degenerative Phenotype in a Conditional Mouse Model of Hereditary Motor and Sensory Neuropathy Associated with Agenesis of the Corpus Callosum
Authors: Shekarabi Masoud , Moldrich Randal X. , Rasheed Sarah , Salin-Cantegrel Adéle , Laganière Janet , Rochefort Daniel , Hince Pascale , Huot Karine , Gaudet Rébecca , Kurniawan Nyoman , Sotocinal Susana G. , Ritchie Jennifer , Dion Patrick A. , Mogil Jeffrey S. , Richards Linda J. , Rouleau Guy A.
Published: March 2012

Disruption of the potassium/chloride cotransporter 3 (KCC3), encoded by theSLC12A6gene, causes hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder affecting both the peripheral nervous system and CNS. However, the precise role of KCC3 in the maintenance of ion homeostasis in the nervous system and the pathogenic mechanisms leading to HMSN/ACC remain unclear. We established twoSlc12a6Cre/LoxP transgenic mouse lines expressing C-terminal truncated KCC3 in either a neuron-specific or ubiquitous fashion. Our results suggest that neuronal KCC3 expression is crucial for axon volume control. We also demonstrate that the neuropathic features of HMSN/ACC are predominantly due to a neuronal KCC3 deficit, while the auditory impairment is due to loss of non-neuronal KCC3 expression. Furthermore, we demonstrate that KCC3 plays an essential role in inflammatory pain pathways. Finally, we observed hypoplasia of the corpus callosum in both mouse mutants and a marked decrease in axonal tracts serving the auditory cortex in only the general deletion mutant. Together, these results establish KCC3 as an important player in both central and peripheral nervous system maintenance.
Local Visual Energy Mechanisms Revealed by Detection of Global Patterns
Authors: Morgenstern Yaniv , Elder James H.
Published: March 2012

A central goal of visual neuroscience is to relate the selectivity of individual neurons to perceptual judgments, such as detection of a visual pattern at low contrast or in noise. Since neurons in early areas of visual cortex carry information only about a local patch of the image, detection of global patterns must entail spatial pooling over many such neurons. Physiological methods provide access to local detection mechanisms at the single-neuron level but do not reveal how neural responses are combined to determine the perceptual decision. Behavioral methods provide access to perceptual judgments of a global stimulus but typically do not reveal the selectivity of the individual neurons underlying detection. Here we show how the existence of a nonlinearity in spatial pooling does allow properties of these early mechanisms to be estimated from behavioral responses to global stimuli. As an example, we consider detection of large-field sinusoidal gratings in noise. Based on human behavioral data, we estimate the length and width tuning of the local detection mechanisms and show that it is roughly consistent with the tuning of individual neurons in primary visual cortex of primate. We also show that a local energy model of pooling based on these estimated receptive fields is much more predictive of human judgments than competing models, such as probability summation. In addition to revealing underlying properties of early detection and spatial integration mechanisms in human cortex, our findings open a window on new methods for relating system-level perceptual judgments to neuron-level processing.
Activation of NMDA Receptors Upregulates A Disintegrin and Metalloproteinase 10 via a Wnt/MAPK Signaling Pathway
Authors: Wan Xian-Zi , Li Bei , Li Yi-Chen , Yang Xiang-Ling , Zhang Wei , Zhong Ling , Tang Shao-Jun
Published: March 2012

A disintegrin and metalloproteinase 10 (ADAM10) is the constitutive α-secretase that governs the nonamyloidogenic pathway of β-amyloid precursor protein processing and is an attractive drug target for treating Alzheimer's disease. To date, little is known about the mechanism by which ADAM10 is regulated in neurons. Using mouse primary cortical neurons, we show here that NMDA receptor (NMDAR) activation led to upregulation of the genes encoding ADAM10 and β-catenin proteins. Interestingly, the ADAM10 upregulation was abolished by inhibitors of Wnt/β-catenin signaling. Conversely, activation of the Wnt/β-catenin signaling pathway by recombinant Wnt3a stimulated ADAM10 expression. We further showed that both the NMDAR- and Wnt3a-induced ADAM10 upregulation was blocked by ERK inhibitors. We suggest that the NMDARs control ADAM10 expression via a Wnt/MAPK signaling pathway.
Does the Human Dorsal Stream Really Process a Category for Tools?
Authors: Sakuraba Satoshi , Sakai Shinya , Yamanaka Masanori , Yokosawa Koichi , Hirayama Kazumi
Published: March 2012

Previously, Almeida et al. (2008) used a technique called Continuous Flash Suppression to show that human dorsal stream cortical areas specifically responded to a “tool category.” Here, we used the same technique to clarify what attributes of tools are processed in the dorsal stream. We examined surface attributes and shape. A significant priming effect was found when we removed surface attributes by using line drawings instead of photographs. In a second experiment, we manipulated shape and we found that there were no significant priming effects when we used nonelongated tool pictures as tool prime stimuli. To better clarify the effect of shape attributes on priming effects, we conducted a further experiment using elongated stick-like rectangles as prime stimuli and found that elongated shapes significantly shortened the reaction time to the tool pictures as target stimuli. Additionally, when elongated vegetables were used as prime stimuli, the reaction time to the tool pictures as target stimuli was also significantly shortened, but there was no effect when stubby vegetables were used. Finally, when we controlled for orientation by presenting rotated elongated stick-like rectangles, diamond shapes, and cut circles as prime stimuli, we found that rectangles replicated the same significant priming effect as previous experiments, but the others did not. These results suggest that the dorsal stream processes elongated shapes but does not process the tool category specifically.
The Cost of Accumulating Evidence in Perceptual Decision Making
Authors: Drugowitsch Jan , Moreno-Bote Rubén , Churchland Anne K. , Shadlen Michael N. , Pouget Alexandre
Published: March 2012

Decision making often involves the accumulation of information over time, but acquiring information typically comes at a cost. Little is known about the cost incurred by animals and humans for acquiring additional information from sensory variables due, for instance, to attentional efforts. Through a novel integration of diffusion models and dynamic programming, we were able to estimate the cost of making additional observations per unit of time from two monkeys and six humans in a reaction time (RT) random-dot motion discrimination task. Surprisingly, we find that the cost is neither zero nor constant over time, but for the animals and humans features a brief period in which it is constant but increases thereafter. In addition, we show that our theory accurately matches the observed reaction time distributions for each stimulus condition, the time-dependent choice accuracy both conditional on stimulus strength and independent of it, and choice accuracy and mean reaction times as a function of stimulus strength. The theory also correctly predicts that urgency signals in the brain should be independent of the difficulty, or stimulus strength, at each trial.
Agrin-Signaling Is Necessary for the Integration of Newly Generated Neurons in the Adult Olfactory Bulb
Authors: Burk Katja , Desoeuvre Angelique , Boutin Camille , Smith Martin A. , Kröger Stephan , Bosio Andreas , Tiveron Marie-Catherine , Cremer Harold
Published: March 2012

In the adult forebrain, new interneurons are continuously generated and integrated into the existing circuitry of the olfactory bulb (OB). In an attempt to identify signals that regulate this synaptic integration process, we found strong expression of agrin in adult generated neuronal precursors that arrive in the olfactory bulb after their generation in the subventricular zone. While the agrin receptor components MuSK and Lrp4 were below detection level in neuron populations that represent synaptic targets for the new interneurons, the alternative receptor α3-Na+K+-ATPase was strongly expressed in mitral cells. Using a transplantation approach, we demonstrate that agrin-deficient interneuron precursors migrate correctly into the OB. However, in contrast to wild-type neurons, which form synapses and survive for prolonged periods, mutant neurons do not mature and are rapidly eliminated. Usingin vivobrain electroporation of the olfactory system, we show that the transmembrane form of agrin alone is sufficient to mediate integration and demonstrate that excess transmembrane agrin increases the number of dendritic spines. Last, we providein vivoevidence that an interaction between agrin and α3-Na+K+-ATPase is of functional importance in this system.
Multisensory Decision-Making in Rats and Humans
Authors: Raposo David , Sheppard John P. , Schrater Paul R. , Churchland Anne K.
Published: March 2012

We report a novel multisensory decision task designed to encourage subjects to combine information across both time and sensory modalities. We presented subjects, humans and rats, with multisensory event streams, consisting of a series of brief auditory and/or visual events. Subjects made judgments about whether the event rate of these streams was high or low. We have three main findings. First, we report that subjects can combine multisensory information over time to improve judgments about whether a fluctuating rate is high or low. Importantly, the improvement we observed was frequently close to, or better than, the statistically optimal prediction. Second, we found that subjects showed a clear multisensory enhancement both when the inputs in each modality were redundant and when they provided independent evidence about the rate. This latter finding suggests a model where event rates are estimated separately for each modality and fused at a later stage. Finally, because a similar multisensory enhancement was observed in both humans and rats, we conclude that the ability to optimally exploit sequentially presented multisensory information is not restricted to a particular species.
Microstimulation of the Monkey Superior Colliculus Induces Pupil Dilation Without Evoking Saccades
Authors: Wang Chin-An , Boehnke Susan E. , White Brian J. , Munoz Douglas P.
Published: March 2012

The orienting reflex is initiated by a salient stimulus and facilitates quick, appropriate action. It involves a rapid shift of the eyes, head, and attention and other physiological responses such as changes in heart rate and transient pupil dilation. The SC is a critical structure in the midbrain that selects incoming stimuli based on saliency and relevance to coordinate orienting behaviors, particularly gaze shifts, but its causal role in pupil dilation remains poorly understood in mammals. Here, we examined the role of the primate SC in the control of pupil dynamics. While requiring monkeys to keep their gaze fixed, we delivered weak electrical microstimulation to the SC, so that saccadic eye movements were not evoked. Pupil size increased transiently after microstimulation of the intermediate SC layers (SCi) and the size of evoked pupil dilation was larger on a dim versus bright background. In contrast, microstimulation of the superficial SC layers did not cause pupil dilation. Thus, the SCi is directly involved not only in shifts of gaze and attention, but also in pupil dilation as part of the orienting reflex, and the function of pupil dilation may be related to increasing visual sensitivity. The shared neural mechanisms suggest that pupil dilation may be associated with covert attention.
Deletion of Ecto-5′-Nucleotidase (CD73) Reveals Direct Action Potential-Dependent Adenosine Release
Authors: Klyuch Boris P. , Dale Nicholas , Wall Mark J.
Published: March 2012

Purinergic signaling is a highly complex system of extracellular communication involved in many physiological and pathological functions in the mammalian brain. Its complexity stems from the multitude of purine receptor subtypes and endogenous purine receptor ligands (including ATP, ADP, UTP, UDP, and adenosine). Potentially all of these ligands could be directly released, and some could also arise from extracellular metabolism. A widely held consensus is that, except under pathological conditions, extracellular adenosine arises only from ectoATPase-mediated metabolism of previously released ATP. Here, we have used mice that lack theCD73gene (encoding ecto-5′-nucleotidase that converts AMP to adenosine) to test whether action potential-dependent adenosine release in the cerebellum depends on prior ATP release. Surprisingly, we have uncovered two parallel pathways of adenosine release: one that is indirect via glutamate receptor-dependent release of ATP and a second of equal amplitude that has no dependence on prior release of ATP and thus represents the direct release of adenosine. This component of adenosine release is blocked by bafilomycin and modulated by mGlu4 receptor activation, strongly supporting adenosine release by exocytosis from parallel fibers. Our findings are a major step in understanding the mechanisms of adenosine release and are likely to have implications for all aspects of physiology where adenosine plays a key modulatory role.
The Interaction between Cell Adhesion Molecule L1, Matrix Metalloproteinase 14, and Adenine Nucleotide Translocator at the Plasma Membrane Regulates L1-Mediated Neurite Outgrowth of Murine Cerebellar Neurons
Authors: Loers Gabriele , Makhina Tatjana , Bork Ute , Dörner Andrea , Schachner Melitta , Kleene Ralf
Published: March 2012

We have identified the adenine nucleotide translocator (ANT) isoforms ANT1 and ANT2 that are present in the plasma membrane of mouse cerebellar neurons as novel binding partners of the cell adhesion molecule L1. The direct interaction between ANT and L1 is mediated by sites within the fibronectin type III domains of L1 and the first and third extracellular loops of the ANT proteins. We also show that L1 interacts with the ANT binding partner matrix metalloprotease 14 (MMP14) and that the ANT proteins bind directly to the L1 interaction partner glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Moreover, we provide evidence that the functional interplay between L1, ANT proteins, MMP14, and GAPDH at the plasma membrane mediates L1-induced neurite outgrowth of cerebellar neurons. Disruption of this interplay by ANT inhibitors, ANT-derived synthetic peptides, and/or function-blocking MMP14 and ANT antibodies leads to alterations in L1-dependent neurite outgrowth. Stimulation of L1-mediated signaling in cerebellar neurons triggers transient ATP secretion via ANT proteins and leads to transient src family-dependent tyrosine phosphorylation of L1, ANT1, ANT2, and MMP14. Thus, our results indicate that plasma membrane-localized ANT1 and ANT2 regulate L1-mediated neurite outgrowth in conjunction with MMP14.
Geführte akustische Wellen zur Flüssigkeitscharakterisierung
Authors: Rautenberg Jens , Bause Fabian , Henning Bernd
Published: March 2012

Das Spektrum akustischer Wellenleiter zur Flüssigkeitscharakterisierung reicht von der Seismologie und Geophysik mit Wellenleiterdimensionen von einigen km bis hin zur Prozessmesstechnik mit Sensordimensionen von wenigen mm. In diesem Beitrag wird ein phänomenologischer Weg zur Klassifizierung der Wellenleiter entwickelt, wobei stets die Oberflächenauslenkungen an der Wellenleitergrenze und die Anzahl der an der Wellenausbreitung beteiligten Moden Berücksichtigung finden. Im weiteren Verlauf werden Möglichkeiten zur Modellierung, Simulation und Messung multimodaler Wellenausbreitung im akustischen Wellenleiter gezeigt.
Anwendung von pyroelektrischen PZT-Dünnschichten für die winkelauflösende Flammendetektion
Authors: Neumann Norbert , Ebermann Martin , Hoppe Silke
Published: March 2012

Das bei einer Verbrennung entstehende CO2 emittiert ein spezifisches Strahlungsspektrum bei etwa 4,3 μm Wellenlänge, das mit einem IR-Flammendetektor erfasst werden kann. Die marktüblichen Sensoren detektieren eine Flamme in einem festgelegten Gebiet (Field-of-View), ihre genaue Position kann jedoch nicht ermittelt werden. Der vorgestellte 3×3-Matrixsensor generiert zusätzliche Richtungsinformationen für eine räumliche Ortung der Flamme mit einer Winkelauflösung von bis zu 5°.
Oxidation of a Anticholinergic Drug Atropine Sulfate Monohydrate by Alkaline Copper(III) Periodate Complex: A Kinetic and Mechanistic Study
Authors: Byadagi Kirthi S. , Hosahalli Rajeshwari V. , Nandibewoor Sharanappa T. , Chimatadar Shivamurti A.
Published: March 2012

The oxidation of a anticholinergic drug, Atropine sulfate monohydrate (ASM) by diperiodatocuprate(III) (DPC) has been investigated spectrophotometrically in aqueous alkaline medium at a constant ionic strength of 0.50 mol dm-3. The reaction between diperiodatocuprate(III) and atropine sulfate exhibits1:2stoichiometry (atropine sulfate: diperiodatocuprate(III)). The main oxidation products were identified and confirmed by spectral studies including IR,1H NMR and GC-MS. A suitable mechanism is proposed. The order with respect to diperiodatocuprate(III) concentration was unity, while the order with respect to atropine sulfate concentration was less than unity over the concentration range studied. The rates increased with an increase in alkali concentration and decreased with an increase in periodate concentration. The activation parameters with respect to slow step of the mechanism were calculated and the thermodynamic quantities we are also determined. Kinetic experiments suggest that [Cu(OH)2(H3IO6)]-is the reactive species of copper(III).
Pakistan in 2011
Authors: Fair C. Christine
Published: March 2012

Pakistan came into sharp conflict with the U.S. and the international community in 2011 over its long-standing support of Islamist militants. The killing of Osama bin Laden left many speculating whether Pakistan's intelligence agencies were either complicit in harboring him or incompetent. Pakistan's various conflicts, as well as Pakistan Taliban violence, continue to claim thousands of lives. Economic growth remains inadequate to provide jobs for its ever-growing population, and both the civilian and military leaderships appear unwilling to make structural economic changes to attract vital international developmental aid.
Sri Lanka in 2011
Authors: Goodhand Jonathan
Published: March 2012

Local elections consolidated the Mahinda Rajapaksa administration's grip on power. State-led efforts to stimulate economic growth continued with major infrastructure projects in the northeastern and southern parts of Sri Lanka. No significant progress was made toward a political settlement and reconciliation with the Tamil community, and the government came under increasing international pressure about its conduct in the last months of the civil war after the release of the United Nations Advisory Panel report.
Nepal and Bhutan in 2011
Authors: Shneiderman Sara , Turin Mark
Published: March 2012

Nepal's political transition to a democratic federal republic remains incomplete. A November 2011 agreement on post-conflict integration and rehabilitation offers reason for hope. Continued disagreements over the structure of the federal state and its form of government have delayed the constitution-making process. Corruption, impunity, and weak infrastructure combine to erode Nepali confidence in effective governance. Bhutan's democratic exercise continues to be carefully controlled by entrenched elites, but the country held its first-ever local elections successfully and economic growth stabilized.
Japan in 2011
Authors: Rosenbluth Frances Mccall
Published: March 2012

Japan's government under the Democratic Party of Japan has limped along for another year, hampered by a divided legislature and an aging population reluctant to pay for the pensions and services it requires. The natural disasters of March 2011 were a tragic sideshow to the deep political problems that continue to plague Japan.
Brunei in 2011
Authors: Case William
Published: March 2012

Brunei Darussalam remained untroubled throughout 2011. The government experimented with greater political openness and social reforms. It organized an election for at least part of its Legislative Council. It continued to make advances on women's and environmental issues. Meanwhile, the oil-based economy mostly remained steady. Foreign relations were benign.
China in 2011
Authors: Zheng Yongnian
Published: March 2012

This paper identifies major trends in China in 2011 and analyzes their implications. The past year has witnessed a continuous rise of anger among social groups, as demonstrated in various forms of social protests. Chinese intellectuals are becoming increasingly politically conscious and calling for political reform. However, the leadership is trapped in the politics of power succession; uncertainty is widespread.
Russia and the CIS in 2011
Authors: Tsygankov Andrei P.
Published: March 2012

During 2011, Russia made progress in recovering from the global financial crisis and moved toward further political centralization. Moscow also continued to prepare for an uncertain new world by pursuing pragmatic relations with Western and non-Western powers and by seeking to increase its influence among the states of the Commonwealth of Independent States.1
Afghanistan in 2011
Authors: Maley William
Published: March 2012

Afghanistan confronted further turbulence in 2011, involving the assassinations of prominent figures, tense regional relations, and uncertainty about where the draw down of foreign forces in Afghanistan might lead. Popular confidence in Afghanistan's future direction remains weak, and President Hamid Karzai has had little success in boosting his government's standing.
Rhetoric of Counsel in Thomas Elyot's Pasquil the Playne
Authors: Walzer Arthur
Published: March 2012

Pasquil the Playne, a dialogue written by the English Humanist Thomas Elyot (1490–1546), was inspired by Elyot's unsuccessful experience as a counselor to Henry VIII. Seizing on this biographical context, historians have read the dialogue as a product of Elyot's disillusionment, identifying Elyot with the blunt, truth-telling Pasquil. In contrast this paper reads Pasquil the Playne as a multi-voiced Lucianic dialogue, which gives expression to several perspectives on the rhetoric of counsel. This reading problematizes questions of appropriateness (prepon) and right timing (kairos) in giving advice to a prince. Moreover, Elyot exploits the open-ended spirit of the Lucianic dialogue to attempt to develop in the reader the prudential reasoning (phronesis) essential to wise counsel.
A High-Density Simple Sequence Repeat-Based Genetic Linkage Map of Switchgrass
Authors: Liu Linglong , Wu Yanqi , Wang Yunwen , Samuels Tim
Published: March 2012

Switchgrass (Panicum virgatum) has been identified as a promising cellulosic biofuel crop in the United States. Construction of a genetic linkage map is fundamental for switchgrass molecular breeding and the elucidation of its genetic mechanisms for economically important traits. In this study, a novel population consisting of 139 selfed progeny of a northern lowland genotype, NL 94 LYE 16X13, was used to construct a linkage map. A total of 2493 simple sequence repeat markers were screened for polymorphism. Of 506 polymorphic loci, 80.8% showed a goodness-of-fit of 1:2:1 segregation ratio. Among 469 linked loci on the framework map, 241 coupling vs. 228 repulsion phase linkages were detected that conformed to a 1:1 ratio, confirming disomic inheritance. A total of 499 loci were mapped to 18 linkage groups (LG), of which the cumulative length was 2085.2 cM, with an average marker interval of 4.2 cM. Nine homeologous LG pairs were identified based on multi-allele markers and comparative genomic analysis. Two clusters of segregation-distorted loci were identified on LG 5b and 9b, respectively. Comparative analysis indicated a one-to-one relationship between nine switchgrass homeologous groups and nine foxtail millet (Setaria italica) chromosomes, suggesting strong homology between the two species. The linkage map derived from selfing a heterozygous parent, instead of two separate maps usually constructed for a cross-fertilized species, provides a new genetic framework to facilitate genomics research, quantitative trait locus (QTL) mapping, and marker-assisted breeding.
Loss-of-Function Screen Reveals Novel Regulators Required forDrosophilaGermline Stem Cell Self-Renewal
Authors: Xing Yalan , Kurtz Irina , Thuparani Manisha , Legard Jillian , Ruohola-Baker Hannele
Published: March 2012

The germline stem cells (GSCs) of Drosophila melanogaster ovary provide an excellent model system to study the molecular mechanisms of stem cell self-renewal. To reveal novel factors required for Drosophila female GSC maintenance and/or division, we performed a loss-of-function screen in GSCs by using a collection of P-element–induced alleles of essential genes. Mutations in genes of various functional groups were identified to cause defects in GSC self-renewal. Here we report that a group of mutations affecting various ubiquitin-conjugating enzymes cause significant GSCs loss, including Plenty of SH3s (POSH), Ubiquitin-conjugating enzyme 10 (UbcD10), and pineapple eye (pie). Ubiquitin-mediated protein degradation plays a variety of roles in the regulation of many developmental processes, including mediating stem cell division through degradation of cell cycle regulators. We demonstrated that pie, sharing highly conserved RING domains with human E3 ubiquitin ligase G2E3 that are critical for early embryonic development, is specifically required for GSC maintenance, possibly through regulation of bone morphogenetic protein signaling pathway. Despite the previously reported role in imaginal disc cell survival, pie loss-of-function induced GSC loss is not to the result of caspase-involved cell death. Further efforts are needed to elucidate the functions of ubiquitin ligases in GSC maintenance, which will ultimately contribute to a better understanding of how the ubiquitin-conjugating enzymes regulate stem cell biology in mammalian systems.
Coding Gene Single Nucleotide Polymorphism Mapping and Quantitative Trait Loci Detection for Physiological Reproductive Traits in Brook Charr,Salvelinus fontinalis
Authors: Sauvage Christopher , Vagner Marie , Derôme Nicolas , Audet Céline , Bernatchez Louis
Published: March 2012

A linkage map of 40 linkage groups (LGs) was developed for brook charr, Salvelinus fontinalis, using an F2 interstrain hybrid progeny (n = 171) and 256 coding gene SNP developed specifically for brook charr and validated from a large (>1000) subset of putative SNP, as well as 81 microsatellite markers. To identify quantitative trait loci (QTL) related to reproduction functions, these fish were also phenotyped at six physiological traits, including spermatozoid head diameter, sperm concentration, plasma testosterone, plasma 11-keto-testosterone, egg diameter, and plasma 17β-estradiol. Five significant QTL were detected over four LGs for egg diameter and plasma 17β-estradiol concentration in females, and sperm concentration as well as spermatozoid head diameter in males. In females, two different QTLs located on LG 11 and LG 34 were associated with the egg number, whereas one QTL was associated with plasma 17β-estradiol concentration (LG 8). Their total percent variance explained (PVE) was 26.7% and 27.6%, respectively. In males, two QTL were also detected for the sperm concentration, and their PVE were estimated at 18.58% and 14.95%, respectively. The low QTL number, associated with the high PVE, suggests that the variance in these reproductive physiological traits was either under the control of one major gene or a small number of genes. The QTL associated with sperm concentration, plasma 17β-estradiol, and egg diameter appeared to be under a dominance effect, whereas the two others were under a negative additive effect. These results show that genes underlying the phenotypic variance of these traits are under different modes of action (additive vs. dominance) and may be used to predict an increase or a decrease in their phenotypic values in subsequent generations of selective breeding. Moreover, this newly developed panel of mapped SNP located in coding gene regions will be useful for screening wild populations, especially in the context of investigating the genetic impact of massive stocking of domestic brook charr to support the angling industry throughout eastern North America.
Ancestry Informative Marker Set for Han Chinese Population
Authors: Qu Hui-Qi , Li Quan , Xu Shuhua , McCormick Joseph B , Fisher-Hoch Susan P , Xiong Momiao , Qian Ji , Jin Li
Published: March 2012

The population of Han Chinese is ∼1.226 billion people. Genetic heterogeneity between northern Han Chinese (N-Han) and southern Han Chinese (S-Han) has been demonstrated by recent genome-wide studies. As an initial step toward health disparities and personalized medicine in Chinese population, this study developed a set of ancestry informative markers (AIM) for Han Chinese population.
The Yeast Nuclear Pore Complex and Transport Through It
Authors: Aitchison John D , Rout Michael P
Published: March 2012

Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cell’s genome. This exchange requires a dedicated transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear envelope and composed of proteins termed nucleoporins (or “Nups”), and (2) nuclear transport factors that recognize the cargoes to be transported and ferry them across the NPCs. This transport is regulated at multiple levels, and the NPC itself also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Here we summarize how the yeast Saccharomyces has been used extensively as a model system to understand the fundamental and highly conserved features of this transport system, revealing the structure and function of the NPC; the NPC’s role in the regulation of gene expression; and the interactions of transport factors with their cargoes, regulatory factors, and specific nucleoporins.
Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae
Authors: Ljungdahl Per O , Daignan-Fornier Bertrand
Published: March 2012

Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.
Validação do conteúdo de instrumento para caracterizar pessoas maiores de 50 anos portadoras do Vírus da Imunodeficiência Humana/Síndrome da Imunodeficiência Adquirida
Authors: Lima Tiago Cristiano de , Gallani Maria Cecília Bueno Jayme , Freitas Maria Isabel Pedreira de
Published: March 2012

OBJETIVO: Apresentar o desenvolvimento e a validação de um instrumento para caracterização de pessoas, com 50 anos ou mais, portadoras do Vírus da Imunodeficiência Humana/Síndrome da Imunodeficiência Adquirida. MÉTODOS: O conteúdo do instrumento, elaborado com base na literatura consultada e experiência profissional dos pesquisadores, foi validado por sete peritos. A validação foi feita em dois momentos de avaliação, utilizando-se o coeficiente de concordância de Kendall para avaliar no primeiro momento a concordância entre os juízes quanto à pertinência, clareza e abrangência do conteúdo e, no segundo, a pertinência e abrangência. O teste de Cochran foi utilizado para avaliar a concordância quanto à clareza, na segunda avaliação. RESULTADOS: Observou-se discordância entre os peritos na primeira avaliação e após a reformulação do instrumento, obteve-se concordância na segunda avaliação. CONCLUSÃO: O instrumento para caracterização dessa população foi validado em relação ao conteúdo, sendo aplicado pelos pesquisadores e encontra-se disponível para utilização.