bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator
Authors: Flegg Jennifer A , Guerin Philippe J , White Nicholas J , Stepniewska Kasia
Published: December 2011

Background

A significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (ACT), signaled emergent artemisinin resistance in Western Cambodia. Accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in Plasmodium falciparum. The slope of the log-parasitaemia versus time relationship is considered to be the most robust measure of anti-malarial effect. However, an initial lag phase of numerical instability often precedes a steady exponential decline in the parasite count after the start of anti-malarial treatment. This lag complicates the clearance estimation, introduces observer subjectivity, and may influence the accuracy and consistency of reported results.

Methods

To address this problem, a new approach to modelling clearance of malaria parasites from parasitaemia-time profiles has been explored and validated. The methodology detects when a lag phase is present, selects the most appropriate model (linear, quadratic or cubic) to fit log-transformed parasite data, and calculates estimates of parasite clearance adjusted for this lag phase. Departing from previous approaches, parasite counts below the level of detection are accounted for and not excluded from the calculation.

Results

Data from large clinical studies with frequent parasite counts were examined. The effect of a lag phase on parasite clearance rate estimates is discussed, using individual patient data examples. As part of the World Wide Antimalarial Resistance Network's (WWARN) efforts to make innovative approaches available to the malaria community, an automated informatics tool: the parasite clearance estimator has been developed.

Conclusions

The parasite clearance estimator provides a consistent, reliable and accurate method to estimate the lag phase and malaria parasite clearance rate. It could be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds which affect ring-stage clearance.
Cellular oxido-reductive proteins of Chlamydomonas reinhardtii control the biosynthesis of silver nanoparticles
Authors: Barwal Indu , Ranjan Peeyush , Kateriya Suneel , Yadav Subhash Chandra
Published: December 2011

Background

Elucidation of molecular mechanism of silver nanoparticles (SNPs) biosynthesis is important to control its size, shape and monodispersity. The evaluation of molecular mechanism of biosynthesis of SNPs is of prime importance for the commercialization and methodology development for controlling the shape and size (uniform distribution) of SNPs. The unicellular algae Chlamydomonas reinhardtii was exploited as a model system to elucidate the role of cellular proteins in SNPs biosynthesis.

Results

The C. reinhardtii cell free extract (in vitro) and in vivo cells mediated synthesis of silver nanoparticles reveals SNPs of size range 5 ± 1 to 15 ± 2 nm and 5 ± 1 to 35 ± 5 nm respectively. In vivo biosynthesized SNPs were localized in the peripheral cytoplasm and at one side of flagella root, the site of pathway of ATP transport and its synthesis related enzymes. This provides an evidence for the involvement of oxidoreductive proteins in biosynthesis and stabilization of SNPs. Alteration in size distribution and decrease of synthesis rate of SNPs in protein-depleted fractions confirmed the involvement of cellular proteins in SNPs biosynthesis. Spectroscopic and SDS-PAGE analysis indicate the association of various proteins on C. reinhardtii mediated in vivo and in vitro biosynthesized SNPs. We have identified various cellular proteins associated with biosynthesized (in vivo and in vitro) SNPs by using MALDI-MS-MS, like ATP synthase, superoxide dismutase, carbonic anhydrase, ferredoxin-NADP+ reductase, histone etc. However, these proteins were not associated on the incubation of pre-synthesized silver nanoparticles in vitro.

Conclusion

Present study provides the indication of involvement of molecular machinery and various cellular proteins in the biosynthesis of silver nanoparticles. In this report, the study is mainly focused towards understanding the role of diverse cellular protein in the synthesis and capping of silver nanoparticles using C. reinhardtii as a model system.
Photodynamic therapy and end-stage tongue base cancer: short communication
Authors: Jerjes Waseem , Upile Tahwinder , Radhi Hani , Hopper Colin
Published: December 2011

We previously reported on the outcome of 21 patients with stage IV advanced and/or recurrent tongue base carcinoma subjected to mTHPC-PDT. We continue to develop on the previous work by treating more patients with this unforgiving disease. PDT has shown to be a very successful minimally-invasive surgical tool in managing this pathology. Tumour-associated symptoms were reduced significantly. The overall morbidity and mortality following PDT, in this group of patients, were far less when compared with other conventional modalities.
Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome
Authors: Fava Roy A , Kennedy Susan M , Wood Sheryl G , Bolstad Anne I , Bienkowska Jadwiga , Papandile Adrian , Kelly John A , Mavragani Clio P , Gatumu Margaret , Skarstein Kathrine , Browning Jeffrey L
Published: December 2011

Introduction

In Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome.

Methods

Male NOD mice were treated for up to ten weeks with an antagonist, LTBR-Ig, or control mouse antibody MOPC-21. Extra-orbital lacrimal glands were analyzed by immunohistochemistry for high endothelial venules (HEV), by Affymetrix gene-array analysis and real-time PCR for differential gene expression, and by ELISA for CXCL13 protein. Leukocytes from lacrimal glands were analyzed by flow-cytometry. Tear-fluid secretion-rates were measured and the integrity of the ocular surface was scored using slit-lamp microscopy and fluorescein isothiocyanate (FITC) staining. The chemokine CXCL13 was measured by ELISA in sera from Sjögren's syndrome patients (n = 27) and healthy controls (n = 30). Statistical analysis was by the two-tailed, unpaired T-test, or the Mann-Whitney-test for ocular integrity scores.

Results

LTBR blockade for eight weeks reduced B-cell accumulation (approximately 5-fold), eliminated HEV in lacrimal glands, and reduced the entry rate of lymphocytes into lacrimal glands. Affymetrix-chip analysis revealed numerous changes in mRNA expression due to LTBR blockade, including reduction of homeostatic chemokine expression. The reduction of CXCL13, CCL21, CCL19 mRNA and the HEV-associated gene GLYCAM-1 was confirmed by PCR analysis. CXCL13 protein increased with disease progression in lacrimal-gland homogenates, but after LTBR blockade for 8 weeks, CXCL13 was reduced approximately 6-fold to 8.4 pg/mg (+/- 2.7) from 51 pg/mg (+/-5.3) in lacrimal glands of 16 week old control mice. Mice given LTBR blockade exhibited an approximately two-fold greater tear-fluid secretion than control mice (P = 0.001), and had a significantly improved ocular surface integrity score (P = 0.005). The mean CXCL13 concentration in sera from Sjögren's patients (n = 27) was 170 pg/ml, compared to 92.0 pg/ml for sera from (n = 30) healthy controls (P = 0.01).

Conclusions

Blockade of LTBR pathways may have therapeutic potential for treatment of Sjögren's syndrome.
Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration
Authors: Riera Katherine M , Rothfusz Nicole E , Wilusz Rebecca E , Weinberg JB , Guilak Farshid , L McNulty Amy
Published: December 2011

Introduction

Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair.

Methods

A micro-wound assay was used to assess meniscal cell migration and proliferation in response to the following treatments for 0, 24, or 48 hours: 0 to 10 ng/mL IL-1, TNF-α, or TGF-β1, in the presence or absence of 10% serum. Proliferated and total cells were fluorescently labeled and imaged using confocal laser scanning microscopy and the number of proliferated, migrated, and total cells was determined in the micro-wound and edges of each image. Meniscal cell proliferation was also assessed throughout meniscal repair model explants treated with 0 or 10 ng/mL IL-1, TNF-α, or TGF-β1 for 14 days. At the end of the culture period, biomechanical testing and histological analyses were also performed. Statistical differences were assessed using an ANOVA and Newman-Keuls post hoc test.

Results

IL-1 and TNF-α decreased cell proliferation in both cell and tissue models of meniscal repair. In the presence of serum, TGF-β1 increased outer zone cell proliferation in the micro-wound and in the cross section of meniscal repair model explants. Both IL-1 and TNF-α decreased the integrative shear strength of repair and extracellular matrix deposition in the meniscal repair model system, while TGF-β1 had no effect on either measure.

Conclusions

Meniscal cell proliferation in vivo may be diminished following joint injury due to the up-regulation of inflammatory cytokines, thereby limiting native cellular repair of meniscal lesions. Therefore, therapies that can promote meniscal cell proliferation have promise to enhance meniscal repair and improve tissue engineering strategies.
Glucagon-Like Peptide-1 Enhances Glucokinase Activity in Pancreatic β-Cells through the Association of Epac2 with Rim2 and Rab3A
Authors: Park Jae-Hyung , Kim Sun-Joo , Park Sung-Hee , Son Dae-Gu , Bae Jae-Hoon , Kim Hyoung Kyu , Han Jin , Song Dae-Kyu
Published: December 2011

Glucokinase (GK), which phosphorylates d-glucose, is a major glucose sensor in β-cells for glucose-stimulated insulin secretion (GSIS) and is a promising new drug target for type 2 diabetes (T2D). In T2D, pancreatic β-cells exhibit defective glucose sensitivity, which leads to impaired GSIS. Although glucagon-like peptide-1-(7–36)-amide (GLP-1) is known to enhance β-cell glucose sensitivity, the effect of GLP-1 on GK activity is still unknown. The present study demonstrated that GLP-1 pretreatment for 30 min significantly enhanced GK activity in a glucose-dependent manner, with a lower Michaelis-Menten constant (Km) but unchanged maximal velocity (Vmax). Thus, GLP-1 acutely enhanced cellular glucose uptake, mitochondrial membrane potential, and cellular ATP levels in response to glucose in rat INS-1 and native β-cells. This effect of GLP-1 occurred via its G protein-coupled receptor pathway in a cAMP-dependent but protein kinase A-independent manner with evidence of exchange protein activated by cAMP (Epac) involvement. Silencing Epac2, interacting molecule of the small G protein Rab3 (Rim2), or Ras-associated protein Rab3A (Rab3A) significantly blocked the effect of GLP-1. These results suggested that GLP-1 can further potentiate GSIS by enhancing GK activity through the signaling of Epac2 to Rim2 and Rab3A, which is the similar pathway for GLP-1 to potentiate Ca2+-dependent insulin granule exocytosis. The present finding may also be an important mechanism of GLP-1 for recovery of GSIS in T2D.
Circadian Feeding Drive of Metabolic Activity in Adipose Tissue and not Hyperphagia Triggers Overweight in Mice: Is There a Role of the Pentose-Phosphate Pathway?
Authors: Stucchi Paula , Gil-Ortega Marta , Merino Beatriz , Guzmán-Ruiz Rocío , Cano Victoria , Valladolid-Acebes Ismael , Somoza Beatriz , Le Gonidec Sophie , Argente Jesús , Valet Philippe , Chowen Julie Ann , Fernández-Alfonso Marisol , Ruiz-Gayo Mariano
Published: December 2011

High-fat (HF) diets trigger an increase in adipose tissue and body weight (BW) and disordered eating behavior. Our study deals with the hypothesis that circadian distribution of energy intake is more relevant for BW dynamics than diet composition. Four-week-old mice were exposed for 8 wk to a HF diet and compared with animals receiving control chow. HF mice progressively increased BW, decreased the amount of nocturnal (1800–0900 h) calories (energy or food intake) (30%) and increased diurnal (0900–1800 h) caloric intake (energy or food intake), although total daily intake was identical between groups. Animals were killed at 3-h intervals and plasma insulin, leptin, corticosterone, glucose, and fatty acid levels quantified. Adipose tissue was weighed, and enzymatic activities integral to the pentose phosphate pathway (PPP) assayed in lumbar adipose tissue. Phosphorylated AMP-dependent protein kinase and fatty acid synthase were quantified by Western blotting. In HF mice, there was a shift in the circadian oscillations of plasma parameters together with an inhibition of PPP activity and a decrease in phosphorylated AMP-dependent protein kinase and fatty acid synthase. In a second experiment, HF mice were forced to adhere to a circadian pattern of food intake similar to that in control animals. In this case, BW, adipose tissue, morning plasma parameters and PPP activity appeared to be normal. These data indicate that disordered feeding behavior can trigger BW gain independently of food composition and daily energy intake. Because PPP is the main source of reduced nicotinamide adenine dinucleotide phosphate, we suggest that PPP inhibition might be an early marker of adipose dysfunction in diet-induced obesity.
Somatostatin Inhibition of GnRH Neuronal Activity and the Morphological Relationship between GnRH and Somatostatin Neurons in Rats
Authors: Koyama Makiko , Yin Chengzhu , Ishii Hirotaka , Sakuma Yasuo , Kato Masakatsu
Published: December 2011

In rodents, GnRH neurons are diffusely distributed from the medial septum through to the medial preoptic area and control gonadal functions through the pituitary. The activity of GnRH neurons is regulated by a variety of bioactive substances, including the inhibitory peptide somatostatin. In the present study, we focused on somatostatin because intracerebroventricular injection of somatostatin inhibits the LH surge in rats and reduces LH secretion in ewes. Somatostatin also decreases GnRH release from rat hypothalamic slices. In mice, somatostatin is also thought to suppress GnRH neuronal activity through contact on the soma of GnRH neurons. However, similar data are missing in rats. Moreover, rat GnRH neurons receive only a few synaptic inputs. In this study, we assessed the morphological relationship between GnRH and somatostatin neurons. Confocal microscopy on the sections from the medial septum through medial preoptic area revealed about 35 close contacts per rat between the GnRH and somatostatin neuronal fibers in the organum vasculosum of the lamina terminalis region. No contact of somatostatin fibers on the GnRH neuronal somata was observed. Multicell RT-PCR for somatostatin receptor mRNA in rat GnRH neurons was also performed, which revealed moderate expression of somatostatin receptor subtypes 1–5. In addition, patch clamp experiments were carried out in acute slice preparations. Somatostatin suppressed neuronal firing in cells recorded in a cell-attached configuration and also induced whole-cell outward currents in GnRH neurons. These findings suggest that somatostatin directly inhibits the activity of rat GnRH neurons through volume transmission in the organum vasculosum of the lamina terminalis region.
Hepatic Suppression of Foxo1 and Foxo3 Causes Hypoglycemia and Hyperlipidemia in Mice
Authors: Zhang Kebin , Li Ling , Qi Yajuan , Zhu Xiaoping , Gan Boyi , DePinho Ronald A. , Averitt Travis , Guo Shaodong
Published: December 2011

Dysregulation of blood glucose and triglycerides are the major characteristics of type 2 diabetes mellitus. We sought to identify the mechanisms regulating blood glucose and lipid homeostasis. Cell-based studies established that the Foxo forkhead transcription factors Forkhead box O (Foxo)-1, Foxo3, and Foxo4 are inactivated by insulin via a phosphatidylinositol 3-kinase/Akt-dependent pathway, but the role of Foxo transcription factors in the liver in regulating nutrient metabolism is incompletely understood. In this study, we used the Cre/LoxP genetic approach to delete the Foxo1, Foxo3, and Foxo4 genes individually or a combination of two or all in the liver of lean or db/db mice and assessed the role of Foxo inactivation in regulating glucose and lipid homeostasis in vivo. In the lean mice or db/db mice, hepatic deletion of Foxo1, rather than Foxo3 or Foxo4, caused a modest reduction in blood glucose concentrations and barely affected lipid homeostasis. Combined deletion of Foxo1 and Foxo3 decreased blood glucose levels, elevated serum triglyceride and cholesterol concentrations, and increased hepatic lipid secretion and caused hepatosteatosis. Analysis of the liver transcripts established a prominent role of Foxo1 in regulating gene expression of gluconeogenic enzymes and Foxo3 in the expression of lipogenic enzymes. Our findings indicate that Foxo1 and Foxo3 inactivation serves as a potential mechanism by which insulin reduces hepatic glucose production and increases hepatic lipid synthesis and secretion in healthy and diabetic states.
Zinc Depletion Causes Multiple Defects in Ovarian Function during the Periovulatory Period in Mice
Authors: Tian X. , Diaz F. J.
Published: December 2011

Shortly before ovulation, the oocyte acquires developmental competence and granulosa cells undergo tremendous changes including cumulus expansion and luteinization. Zinc is emerging as a key regulator of meiosis in vitro, but a complete understanding of zinc-mediated effects during the periovulatory period is lacking. The present study uncovers the previously unknown role of zinc in maintaining meiotic arrest before ovulation. A zinc chelator [N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN)] caused premature germinal vesicle breakdown and associated spindle defects in denuded oocytes even in the presence of a phosphodiesterase 3A inhibitor (milrinone). TPEN also potently blocked cumulus expansion by blocking induction of expansion-related transcripts Has2, Ptx3, Ptgs2, and Tnfaip6 mRNA. Both meiotic arrest and cumulus expansion were rescued by exogenous zinc. Lack of cumulus expansion is due to an almost complete suppression of phospho-Sma- and Mad-related protein 2/3 signaling. Consistent with a decrease in phospho-Sma- and Mad-related protein 2/3 signaling, TPEN also decreased cumulus transcripts (Ar and Slc38a3) and caused a surprising increase in mural transcripts (Lhcgr and Cyp11a1) in cumulus cells. In vivo, feeding a zinc-deficient diet for 10 d completely blocked ovulation and compromised cumulus expansion. However, 42.5% of oocytes had prematurely resumed meiosis before human chorionic gonadotropin injection, underscoring the importance of zinc before ovulation. A more acute 3-d treatment with a zinc-deficient diet did not block ovulation but did increase the number of oocytes trapped in luteinizing follicles. Moreover, 23% of ovulated oocytes did not reach metaphase II due to severe spindle defects. Thus, acute zinc deficiency causes profound defects during the periovulatory period with consequences for oocyte maturation, cumulus expansion, and ovulation.
Chronic Disease and the Shifting Focus of Public Health: Is Prevention Still a Political Lightweight?
Authors: Mayes Rick , Oliver Thomas R.
Published: December 2011

Why is it so politically difficult to obtain government investment in public health initiatives that are aimed at addressing chronic disease? This article examines the structural disadvantage faced by those who advocate for public health policies and practices to reduce chronic disease related to people's unhealthy lifestyles and physical environments. It identifies common features that make it difficult to establish and maintain initiatives to prevent or reduce costly illness and physical suffering: (1) public health benefits are generally dispersed and delayed; (2) benefactors of public health are generally unknown and taken for granted; (3) the costs of many public health initiatives are concentrated and generate opposition from those who would pay them; and (4) public health often clashes with moral values or social norms. The article concludes by discussing the importance of a new paradigm, “health in all policies,” that targets the enormous health and economic burdens associated with chronic conditions and asserts a need for new policies, practices, and participation beyond the confines of traditional public health agencies and services.
Regulation of behaviorally associated gene networks in worker honey bee ovaries
Authors: Wang Ying , Kocher Sarah D. , Linksvayer Timothy A. , Grozinger Christina M. , Page Robert E. , Amdam Gro V.
Published: December 2011

Several lines of evidence support genetic links between ovary size and division of labor in worker honey bees. However, it is largely unknown how ovaries influence behavior. To address this question, we first performed transcriptional profiling on worker ovaries from two genotypes that differ in social behavior and ovary size. Then, we contrasted the differentially expressed ovarian genes with six sets of available brain transcriptomes. Finally, we probed behavior-related candidate gene networks in wild-type ovaries of different sizes. We found differential expression in 2151 ovarian transcripts in these artificially selected honey bee strains, corresponding to approximately 20.3% of the predicted gene set of honey bees. Differences in gene expression overlapped significantly with changes in the brain transcriptomes. Differentially expressed genes were associated with neural signal transmission (tyramine receptor, TYR) and ecdysteroid signaling; two independently tested nuclear hormone receptors (HR46 and ftz-f1) were also significantly correlated with ovary size in wild-type bees. We suggest that the correspondence between ovary and brain transcriptomes identified here indicates systemic regulatory networks among hormones (juvenile hormone and ecdysteroids), pheromones (queen mandibular pheromone), reproductive organs and nervous tissues in worker honey bees. Furthermore, robust correlations between ovary size and neuraland endocrine response genes are consistent with the hypothesized roles of the ovaries in honey bee behavioral regulation.
Contextual chemosensory urine signaling in an African cichlid fish
Authors: Maruska Karen P. , Fernald Russell D.
Published: December 2011

Chemosensory signaling is crucial for communication in many fish species, but little is known about how signalers modulate chemical output in response to sensory information and social context. Here, we tested the hypothesis that dominant male African cichlid fish (Astatotilapia burtoni) use urine signals during social interactions, and demonstrate that this signaling depends on social context (reproductive; territorial) and on available sensory information (visual cues; full interaction). We injected males with dye to visualize urine pulses and exposed them to full sensory information or visual cues alone of four types: (1) dominant male; (2) gravid (reproductively receptive) females; (3) mouth-brooding (non-receptive) females; or (4) control (no fish). We found that males released urine sooner and increased their urination frequency when visually exposed to gravid females as compared with mouth-brooding females and or no-fish controls. While males could distinguish female reproductive states using visual cues alone, courtship behavior rates were ∼10-fold higher when they fully interacted with gravid females compared with receiving visual cues alone. Males also increased their urination and territorial behaviors when exposed to another male, suggesting that chemical signals may convey information on dominance status. These data support the hypothesis that dominant males use urine as a chemical signal and adjust the frequency of their urine output based on contextual information.
High levels of dietary fat impair glucose homeostasis in rainbow trout
Authors: Figueiredo-Silva A. Cláudia , Panserat Stéphane , Kaushik Sadasivam , Geurden Inge , Polakof Sergio
Published: December 2011

This study was designed to assess the effects of dietary fat levels on glucose homeostasis in rainbow trout under prolonged hyperglycaemia induced by high carbohydrate intake. Trout were fed identical amounts of one of two iso-energetic diets containing either a low (LFD, 3%) or a high fat level (HFD, 20%) and similar amounts of digestible carbohydrates (26–30%) for 14 days. While a single high fat meal reduced glycaemia compared with a low fat meal, the consumption of a high fat diet for 14 days resulted in prolonged hypergylcaemia and reduced plasma glucose clearance in response to an exogenous glucose or insulin challenge. The hyperglycaemic phenotype in trout was characterised by a reduction of the activities of lipogenic and glucose phosphorylating enzymes with a concomitant stimulation of enzymes involved in glucose production in the liver and reduced glycogen levels in the white muscle. Impaired glucose tolerance (IGT) was further associated with a significant reduction of insulin receptor substrate 1 (IRS1) protein content in muscle, and with a poor response of HFD fed fish to an exogenous insulin load, suggestive of impaired insulin signalling in trout fed with a HFD. To our knowledge, this is the first study showing that a teleost can also develop a high fat-induced IGT, characterised by persistent hyperglycaemia and reduced insulin sensitivity, established symptoms of IGT and the prediabetic insulin-resistant state in mammals. Our results also provide evidence that persistent hyperglycaemia after a high carbohydrate meal stems from a metabolic interaction between dietary macronutrients rather than from high carbohydrate intake alone.
Local acoustic particle motion guides sound-source localization behavior in the plainfin midshipman fish,Porichthys notatus
Authors: Zeddies David G. , Fay Richard R. , Gray Michael D. , Alderks Peter W. , Acob Andrew , Sisneros Joseph A.
Published: December 2011

Sound-source localization behavior was studied in the plainfin midshipman fish (Porichthys notatus) by making use of the naturally occurring phonotaxis response of gravid females to playback of the male's advertisement call. The observations took place outdoors in a circular concrete tank. A dipole sound projector was placed at the center of the tank and an 80–90 Hz tone (the approximate fundamental frequency to the male's advertisement call) was broadcast to gravid females that were released from alternative sites approximately 100 cm from the source. The phonotaxic responses of females to the source were recorded, analyzed and compared with the sound field. One release site was approximately along the vibratory axis of the dipole source, and the other was approximately orthogonal to the vibratory axis. The sound field in the tank was fully characterized through measurements of the sound pressure field using hydrophones and acoustic particle motion using an accelerometer. These measurements confirmed that the sound field was a nearly ideal dipole. When released along the dipole vibratory axis, the responding female fish took essentially straight paths to the source. However, when released approximately 90 deg to the source's vibratory axis, the responding females took highly curved paths to the source that were approximately in line with the local particle motion axes. These results indicate that the acoustic cues used by fish during sound-source localization include the axes of particle motion of the local sound field.
Impaired Endogenously Evoked Automated Reaching in Parkinson's Disease
Authors: Torres Elizabeth B. , Heilman Kenneth M. , Poizner Howard
Published: December 2011

Intended reaches triggered by exogenous targets often coexist with spontaneous, automated movements that are endogenously activated. It has been posited that Parkinson's disease (PD) primarily impairs automated movements, but it is unknown to what extent this may affect multijoint/limb control, particularly when patients are off their dopaminergic medications. Here we tested nine human patients with PD while off dopaminergic medication versus nine age-matched normal controls (NCs). Participants performed intentional reaches forward to a target in a dark room and then transitioned back to their initial posture. Upon target flash, three forms of guidance were used: (1) memory with eyes closed, (2) continuous target vision only, and (3) vision of their moving finger only. The trajectories of their arm joints were measured and their joint velocities decomposed into the (intended) task-relevant and the (spontaneous) task-incidental degrees of freedom (DOF). We also measured the balance between these two subsets of DOF as these movements unfolded. In PD patients we found that the incidental DOF values were abnormally variable during the retracting movements and prevailed over the task-relevant DOF values. By contrast, their forward intentional motions were abnormally dominated by the task-relevant components. Moreover, the patients abruptly transitioned between voluntary and automated modes of joint control, and, unlike NCs, the type of visual guidance differentially affected their postural trajectories. These findings lend support to an emerging view that there is a loss of automated control in PD patients that contributes to impairments in voluntary control, and that basal ganglia–cortical circuits are critical for the maintenance and balance of multijoint control.
Cholinergic Control in Developing Prefrontal–Hippocampal Networks
Authors: Janiesch P. Christoph , Krüger Hanna-Sophie , Pöschel Beatrice , Hanganu-Opatz Ileana L.
Published: December 2011

The cholinergic drive enhances input processing in attentional and mnemonic context by interacting with the activity of prefrontal–hippocampal networks. During development, acetylcholine modulates neuronal proliferation, differentiation, and synaptic plasticity, yet its contribution to the maturation of cognitive processing resulting from early entrainment of neuronal networks in oscillatory rhythms remains widely unknown. Here we show that cholinergic projections growing into the rat prefrontal cortex (PFC) toward the end of the first postnatal week boost the generation of nested gamma oscillations superimposed on discontinuous spindle bursts by acting on functional muscarinic but not nicotinic receptors. Although electrical stimulation of cholinergic nuclei increased the occurrence of nested gamma spindle bursts by 41%, diminishment of the cholinergic input by either blockade of the receptors or chronic immunotoxic lesion had the opposite effect. This activation of locally generated gamma episodes by direct cholinergic projections to the PFC was accompanied by indirect modulation of underlying spindle bursts via cholinergic control of hippocampal theta activity. With ongoing maturation and switch of network activity from discontinuous bursts to continuous theta–gamma rhythms, accumulating cholinergic projections acting on both muscarinic and nicotinic receptors mediated the transition from high-amplitude slow to low-amplitude fast rhythms in the PFC. By exerting multiple actions on the oscillatory entrainment of developing prefrontal–hippocampal networks, the cholinergic input may refine them for later gating processing in executive and mnemonic tasks.
Terminal Field and Firing Selectivity of Cholecystokinin-Expressing Interneurons in the Hippocampal CA3 Area
Authors: Lasztóczi Bálint , Tukker John J. , Somogyi Peter , Klausberger Thomas
Published: December 2011

Hippocampal oscillations reflect coordinated neuronal activity on many timescales. Distinct types of GABAergic interneuron participate in the coordination of pyramidal cells over different oscillatory cycle phases. In the CA3 area, which generates sharp waves and gamma oscillations, the contribution of identified GABAergic neurons remains to be defined. We have examined the firing of a family of cholecystokinin-expressing interneurons during network oscillations in urethane-anesthetized rats and compared them with firing of CA3 pyramidal cells. The position of the terminals of individual visualized interneurons was highly diverse, selective, and often spatially coaligned with either the entorhinal or the associational inputs to area CA3. The spike timing in relation to theta and gamma oscillations and sharp waves was correlated with the innervated pyramidal cell domain. Basket and dendritic-layer-innervating interneurons receive entorhinal and associational inputs and preferentially fire on the ascending theta phase, when pyramidal cell assemblies emerge. Perforant-path-associated cells, driven by recurrent collaterals of pyramidal cells fire on theta troughs, when established pyramidal cell assemblies are most active. In the CA3 area, slow and fast gamma oscillations occurred on opposite theta oscillation phases. Perforant-path-associated and some COUP-TFII-positive interneurons are strongly coupled to both fast and slow gamma oscillations, but basket and dendritic-layer-innervating cells are weakly coupled to fast gamma oscillations only. During sharp waves, different interneuron types are activated, inhibited, or remain unaffected. We suggest that specialization in pyramidal cell domain and glutamatergic input-specific operations, reflected in the position of GABAergic terminals, is the evolutionary drive underlying the diversity of cholecystokinin-expressing interneurons.
Involvement of NOX1/NADPH Oxidase in Morphine-Induced Analgesia and Tolerance
Authors: Ibi Masakazu , Matsuno Kuniharu , Matsumoto Misaki , Sasaki Mika , Nakagawa Takayuki , Katsuyama Masato , Iwata Kazumi , Zhang Jia , Kaneko Shuji , Yabe-Nishimura Chihiro
Published: December 2011

The involvement of reactive oxygen species (ROS) in morphine-induced analgesia and tolerance has been suggested, yet how and where ROS take part in these processes remains largely unknown. Here, we report a novel role for the superoxide-generating enzyme NOX1/NADPH oxidase in the regulation of analgesia and acute analgesic tolerance. In mice lackingNox1(Nox1−/Y), the magnitude of the analgesia induced by morphine was significantly augmented. More importantly, analgesic tolerance induced by repeated administration of morphine was significantly suppressed compared with that in the littermates, wild-typeNox1+/Y. In a membrane fraction obtained from the dorsal spinal cord, no difference was observed in morphine-induced [35S]GTPγS-binding between the genotypes, whereas morphine-stimulated GTPase activity was significantly attenuated inNox1−/Y. At 2 h after morphine administration, a significant decline in [35S]GTPγS-binding was observed inNox1+/Ybut not inNox1−/Y. No difference in the maximal binding and affinity of [3H]DAMGO was observed between the genotypes, but the translocation of protein kinase C isoforms to the membrane fraction following morphine administration was almost completely abolished inNox1−/Y. Finally, the phosphorylation of RGS9-2 and formation of a complex by Gαi2/RGS9-2 with 14-3-3 found in morphine-treatedNox1+/Ywere significantly suppressed inNox1−/Y. Together, these results suggest that NOX1/NADPH oxidase attenuates the pharmacological effects of opioids by regulating GTPase activity and the phosphorylation of RGS9-2 by protein kinase C. NOX1/NADPH oxidase may thus be a novel target for the development of adjuvant therapy to retain the beneficial effects of morphine.
Synapsin I Senses Membrane Curvature by an Amphipathic Lipid Packing Sensor Motif
Authors: Krabben Ludwig , Fassio Anna , Bhatia Vikram Kjøller , Pechstein Arndt , Onofri Franco , Fadda Manuela , Messa Mirko , Rao Yijian , Shupliakov Oleg , Stamou Dimitrios , Benfenati Fabio , Haucke Volker
Published: December 2011

Sustained neurotransmitter release at synapses during high-frequency synaptic activity involves the mobilization of synaptic vesicles (SVs) from the tightly clustered reserve pool (RP). Synapsin I (Syn I), a brain-specific peripheral membrane protein that undergoes activity-dependent cycles of SV association and dissociation, is implicated in RP organization via its ability to cluster SVs. Although Syn I has affinity for phospholipids, the mechanism for the reversible association of synapsin with SV membranes remains enigmatic. Here, we show that rat Syn I is able to sense membrane curvature via an evolutionary conserved amphipathic lipid packing sensor motif (ALPS). Deletion or mutational inactivation of the ALPS impairs the ability of Syn I to associate with highly curved membranes and with SVs. Furthermore, a Syn I mutant lacking ALPS displays defects in its ability to undergo activity-induced cycles of dispersion and reclustering in neurons and fails to induce vesicle clusteringin vitro. Our data suggest a crucial role for ALPS-mediated sensing of membrane curvature in regulating synapsin function.
Atuações delinquentes, passagens ao ato suicida na adolescência
Authors: Benhaim Michèle
Published: December 2011

Como articular a passagem ao ato delinquente e a passagem ao ato suicida na adolescência? Pretende-se mostrar o quanto e como uma e outra esclarecem a relação com a transgressão no que esta tem de exploração, de verificação, de teste dos limites corporais, familiais e sociais.
Efetividade de um programa de aprimoramento vocal para professores
Authors: Luchesi Karen Fontes , Mourão Lucia Figueiredo , Kitamura Satoshi
Published: December 2011

OBJETIVO: analisar parâmetros fonoarticulatórios de professores, pré e pós-programa de aprimoramento vocal. MÉTODO: um programa de aprimoramento vocal foi oferecido numa escola estadual do município de Campinas, São Paulo, Brasil. Treze professores aceitaram participar do programa. Devido ao critério de exclusão, apenas cinco foram selecionados para as análises. Os sujeitos foram previamente submetidos à avaliação laringológica. Foram realizados 12 encontros semanais de 1 hora e 30 minutos na própria escola. No primeiro e no último encontro os sujeitos gravaram três "frases-veículo". As gravações foram submetidas à análise perceptivo-auditiva (para avaliação do pitch, da modulação e da articulação) e acústica (para avaliação da freqüência fundamental, da extensão de freqüência e dos dois primeiros formantes). Os dados foram submetidos à análise estatística. RESULTADOS: mesmo com o pequeno número de sujeitos, os resultados do presente estudo, revelaram ampliação significante da extensão de freqüência, indicando maior uso deste recurso expressivo pós-aprimoramento, além do aumento estatisticamente significante de F1 nas vogais /i/ e /u/ pós-intervenção, sugerindo melhora no ajuste articulatório. CONCLUSÕES: não foram observadas modificações no pitch, modulação e articulação avaliados por meio da análise perceptivo-auditiva, bem como da freqüência fundamental pós-intervenção.
Profissão e corporação: limites éticos da atuação do advogado
Authors: Mello Marcelo Pereira de , Barroso Márcia Regina C.
Published: December 2011

Este trabalho faz uma análise da atuação do Tribunal de Ética e Disciplina da OAB-RJ a partir de dois eixos: o primeiro acompanha uma análise qualitativa das infrações mais frequentes cometidas pelos advogados decorrentes de suas atividades profissionais e perpassa uma análise da administração das punições pelos membros do Tribunal. O segundo eixo persegue a avaliação deste Tribunal na estrutura organizacional interna da OAB e seu papel na legitimação da participação política da entidade. Sendo assim, analisamos a difícil tarefa de equilibrar-se entre as suas atividades de entidade de representação classista e o seu papel político.
Triple-Negative Subtype Predicts Poor Overall Survival and High Locoregional Relapse in Inflammatory Breast Cancer
Authors: Li Jing , Gonzalez-Angulo Ana M. , Allen Pamela K. , Yu Tse K. , Woodward Wendy A. , Ueno Naoto T. , Lucci Anthony , Krishnamurthy Savitri , Gong Yun , Bondy Melissa L. , Yang Wei , Willey Jie S. , Cristofanilli Massimo , Valero Vicente , Buchholz Thomas A.
Published: December 2011

Background.

Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC.

Methods.

We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors.

Results.

The median age was 50 years (range, 24–83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER=2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001–.03).

Conclusions.

TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.
Experimental tree removal in tallgrass prairie: variable responses of flora and fauna along a woody cover gradient
Authors: Alford Aaron L. , Hellgren Eric C. , Limb Ryan , Engle David M.
Published: December 2011

Woody plant encroachment is a worldwide phenomenon in grassland and savanna systems whose consequence is often the development of an alternate woodland state. Theoretically, an alternate state may be associated with changes in system state variables (e.g., species composition) or abiotic parameter shifts (e.g., nutrient availability). When state‐variable changes are cumulative, such as in woody plant encroachment, the probability of parameter shifts increases as system feedbacks intensify over time. Using a Before–After Control–Impact (BACI) design, we studied eight pairs of grassland sites undergoing various levels of eastern redcedar (Juniperus virginiana) encroachment to determine whether responses of flora and fauna to experimental redcedar removal differed according to the level of pretreatment redcedar cover. In the first year after removal, herbaceous plant species diversity and evenness, woody plant evenness, and invertebrate family richness increased linearly with pretreatment redcedar cover, whereas increases in small‐mammal diversity and evenness were described by logarithmic trends. In contrast, increases in woody plant diversity and total biomass of terrestrial invertebrates were accentuated at levels of higher pretreatment cover. Tree removal also shifted small‐mammal species composition toward a more grassland‐associated assemblage. During the second year postremoval, increases in herbaceous plant diversity followed a polynomial trend, but increases in most other metrics did not vary along the pretreatment cover gradient. These changes were accompanied by extremely high growing‐season precipitation, which may have homogenized floral and faunal responses to removal. Our results demonstrate that tree removal increases important community metrics among grassland flora and fauna within two years, with some responses to removal being strongly influenced by the stage of initial encroachment and modulated by climatic variability. Our results underscore the importance of decisive management for reversing the effects of woody plant encroachment in imperiled grassland ecosystems.
Do predators control prey species abundance? An experimental test with brown treesnakes on Guam
Authors: III Earl W. Campbell , Adams Amy A. Yackel , Converse Sarah J. , Fritts Thomas H. , Rodda Gordon H.
Published: December 2011

The effect of predators on the abundance of prey species is a topic of ongoing debate in ecology; the effect of snake predators on their prey has been less debated, as there exists a general consensus that snakes do not negatively influence the abundance of their prey. However, this viewpoint has not been adequately tested. We quantified the effect of brown treesnake (Boiga irregularis) predation on the abundance and size of lizards on Guam by contrasting lizards in two 1‐ha treatment plots of secondary forest from which snakes had been removed and excluded vs. two 1‐ha control plots in which snakes were monitored but not removed or excluded. We removed resident snakes from the treatment plots with snake traps and hand capture, and snake immigration into these plots was precluded by electrified snake barriers. Lizards were sampled in all plots quarterly for a year following snake elimination in the treatment plots. Following the completion of this experiment, we used total removal sampling to census lizards on a 100‐m2 subsample of each plot. Results of systematic lizard population monitoring before and after snake removal suggest that the abundance of the skink, Carlia ailanpalai, increased substantially and the abundance of two species of gekkonids, Lepidodactylus lugubris and Hemidactylus frenatus, also increased on snake‐free plots. No treatment effect was observed for the skink Emoia caeruleocauda. Mean snout–vent length of all lizard species only increased following snake removal in the treatment plots. The general increase in prey density and mean size was unexpected in light of the literature consensus that snakes do not control the abundance of their prey species. Our findings show that, at least where alternate predators are lacking, snakes may indeed affect prey populations.
Cognitive Load Theory: What It Is, Why It's Important for Accounting Instruction and Research
Authors: Mostyn Gregory R.
Published: December 2011

The purpose of this paper is to increase the awareness of accounting instructors, particularly those teaching introductory courses, of an important and relatively new development in cognitive psychology. This development, called cognitive load theory (CLT), both identifies the cognitive constraints of novice learners when learning complex tasks and also provides specific methods for improving learning efficiency. Despite extensive CLT research and its widespread application in the instructional design applications for many other fields, very little discussion has appeared in accounting education literature. This suggests not just an oversight, but also a great opportunity. This paper will present: (1) an overview of CLT and its use, (2) a brief history of recent learning theory and its effect on accounting education and the development of CLT, (3) a discussion of the key elements of CLT and its prescriptive research results for the classroom, and (4) suggestions for how CLT might benefit accounting research.