bluuebunny/crossref_metadata_2025 huggingface dataset:
RCY1-Mediated Resistance to Cucumber mosaic virus Is Regulated by LRR Domain-Mediated Interaction with CMV(Y) Following Degradation of RCY1
Authors: Takahashi Hideki , Shoji Hiromi , Ando Sugihiro , Kanayama Yoshinori , Kusano Tomonobu , Takeshita Minoru , Suzuki Masashi , Masuta Chikara
Published: August 2012

RCY1, which encodes a coiled coil nucleotide-binding site leucine-rich repeat (LRR) class R protein, confers the hypersensitive response (HR) to a yellow strain of Cucumber mosaic virus (CMV[Y]) in Arabidopsis thaliana. Nicotiana benthamiana transformed with hemagglutinin (HA) epitope-tagged RCY1 (RCY1-HA) also exhibited a defense response accompanied by HR cell death and induction of defense-related gene expression in response to CMV(Y). Following transient expression of RCY1-HA by agroinfiltration, the defense reaction was induced in N. benthamiana leaves infected with CMV(Y) but not in virulent CMV(B2)-infected N. benthamiana leaves transiently expressing RCY1-HA or CMV(Y)-infected N. benthamiana leaves transiently expressing HA-tagged RPP8 (RPP8-HA), which is allelic to RCY1. This result suggests that Arabidopsis RCY1-conferred resistance to CMV(Y) could be reproduced in N. benthamiana leaves in a gene-for-gene manner. Expression of a series of chimeric constructs between RCY1-HA and RPP8-HA in CMV(Y)-infected N. benthamiana indicated that induction of defense responses to CMV(Y) is regulated by the LRR domain of RCY1. Interestingly, in CMV(Y)-infected N. benthamiana manifesting the defense response, the levels of both RCY1 and chimeric proteins harboring the RCY1 LRR domain were significantly reduced. Taken together, these data indicate that the RCY1-conferred resistance response to CMV(Y) is regulated by an LRR domain-mediated interaction with CMV(Y) and seems to be tightly associated with the degradation of RCY1 in response to CMV(Y).
Conservation physiology of marine fishes: advancing the predictive capacity of models
Authors: Jørgensen Christian , Peck Myron A. , Antognarelli Fabio , Azzurro Ernesto , Burrows Michael T. , Cheung William W. L. , Cucco Andrea , Holt Rebecca E. , Huebert Klaus B. , Marras Stefano , McKenzie David , Metcalfe Julian , Perez-Ruzafa Angel , Sinerchia Matteo , Fleng Steffensen John , Teal Lorna R. , Domenici Paolo
Published: August 2012

At the end of May, 17 scientists involved in an EU COST Action on Conservation Physiology of Marine Fishes met in Oristano, Sardinia, to discuss how physiology can be better used in modelling tools to aid in management of marine ecosystems. Current modelling approaches incorporate physiology to different extents, ranging from no explicit consideration to detailed physiological mechanisms, and across scales from a single fish to global fishery resources. Biologists from different sub-disciplines are collaborating to rise to the challenge of projecting future changes in distribution and productivity, assessing risks for local populations, or predicting and mitigating the spread of invasive species.
Mathematical theory and analytical solutions for the wave catching-up phenomena in a nonlinearly elastic composite bar
Authors: Huang Shou-Jun , Dai Hui-Hui , Chen Zhen , Kong De-Xing
Published: August 2012

Cracking induced by tensile wave at the free surface of an impacted target is an important issue in impact-resistant design. Here, we explore the use of material nonlinearity to undermine the strength of the tensile wave. More specifically, we consider waves in a two-material composite bar subjected to impact loading at one end. Multiple reflections cause a tensile wave being transmitted into the second material. The attention is on analytically and numerically studying the phenomenon that the tensile wave catches the first transmitted compressive wave. It turns out that, depending on the interval of the initial impact, catching-up phenomena can happen in two wave patterns. A general mathematical theory is provided to show the existence of these patterns together with some qualitative information. To gain more insights into such phenomena, asymptotic solutions are also constructed, which provide both qualitative and quantitative results on the requirement of the constitutive relation, the time and place at which the catching takes place, and how the initial impact, material and geometric parameters influence the solutions. Numerical simulations are also performed, confirming the validity of the analytical results. The analysis and results presented here could be useful for designing a composite structure that has a good impact-protection performance.
High morphological variation of vestibular system accompanies slow and infrequent locomotion in three-toed sloths
Authors: Billet Guillaume , Hautier Lionel , Asher Robert J. , Schwarz Cathrin , Crumpton Nick , Martin Thomas , Ruf Irina
Published: August 2012

The semicircular canals (SCs), part of the vestibular apparatus of the inner ear, are directly involved in the detection of angular motion of the head for maintaining balance, and exhibit adaptive patterns for locomotor behaviour. Consequently, they are generally believed to show low levels of intraspecific morphological variation, but few studies have investigated this assumption. On the basis of high-resolution computed tomography, we present here, to our knowledge, the first comprehensive study of the pattern of variation of the inner ear with a focus on Xenarthra. Our study demonstrates that extant three-toed sloths show a high level of morphological variation of the bony labyrinth of the inner ear. Especially, the variation in shape, relative size and angles of their SCs greatly differ from those of other, faster-moving taxa within Xenarthra and Placentalia in general. The unique pattern of variation in three-toed sloths suggests that a release of selection and/or constraints on their organ of balance is associated with the observed wide range of phenotypes. This release is coincident with their slow and infrequent locomotion and may be related, among other possible factors, to a reduced functional demand for a precise sensitivity to movement.
Plant-ants use symbiotic fungi as a food source: new insight into the nutritional ecology of ant–plant interactions
Authors: Blatrix Rumsaïs , Djiéto-Lordon Champlain , Mondolot Laurence , La Fisca Philippe , Voglmayr Hermann , McKey Doyle
Published: August 2012

Usually studied as pairwise interactions, mutualisms often involve networks of interacting species. Numerous tropical arboreal ants are specialist inhabitants of myrmecophytes (plants bearing domatia, i.e. hollow structures specialized to host ants) and are thought to rely almost exclusively on resources derived from the host plant. Recent studies, following up on century-old reports, have shown that fungi of the ascomycete order Chaetothyriales live in symbiosis with plant-ants within domatia. We tested the hypothesis that ants use domatia-inhabiting fungi as food in three ant–plant symbioses:
Petalomyrmex phylax
/
Leonardoxa africana
,
Tetraponera aethiops
/
Barteria fistulosa
and
Pseudomyrmex penetrator
/
Tachigali
sp. Labelling domatia fungal patches in the field with either a fluorescent dye or
15
N showed that larvae ingested domatia fungi. Furthermore, when the natural fungal patch was replaced with a piece of a
15
N-labelled pure culture of either of two Chaetothyriales strains isolated from
T. aethiops
colonies, these fungi were also consumed. These two fungi often co-occur in the same ant colony. Interestingly,
T. aethiops
workers and larvae ingested preferentially one of the two strains. Our results add a new piece in the puzzle of the nutritional ecology of plant-ants.
Functional and evolutionary trade-offs co-occur between two consolidated memory phases in
Drosophila melanogaster
Authors: Lagasse Fabrice , Moreno Celine , Preat Thomas , Mery Frederic
Published: August 2012

Memory is a complex and dynamic process that is composed of different phases. Its evolution under natural selection probably depends on a balance between fitness benefits and costs. In
Drosophila
, two separate forms of consolidated memory phases can be generated experimentally: anaesthesia-resistant memory (ARM) and long-term memory (LTM). In recent years, several studies have focused on the differences between these long-lasting memory types and have found that, at the functional level, ARM and LTM are antagonistic. How this functional relationship will affect their evolutionary dynamics remains unknown. We selected for flies with either improved ARM or improved LTM over several generations, and found that flies selected specifically for improvement of one consolidated memory phase show reduced performance in the other memory phase. We also found that improved LTM was linked to decreased longevity in male flies but not in females. Conversely, males with improved ARM had increased longevity. We found no correlation between either improved ARM or LTM and other phenotypic traits. This is, to our knowledge, the first evidence of a symmetrical evolutionary trade-off between two memory phases for the same learning task. Such trade-offs may have an important impact on the evolution of cognitive capacities. On a neural level, these results support the hypothesis that mechanisms underlying these forms of consolidated memory are, to some degree, antagonistic.
Methylene Blue-Aided In Vivo Staining of Central Airways during Flexible Bronchoscopy
Authors: Zirlik Sabine , Hildner Kai M. , Neurath Markus F. , Fuchs Florian S.
Published: August 2012

Background. The early diagnosis of malignant and premalignant changes of the bronchial mucosa remains a major challenge during bronchoscopy. Intravital staining techniques are not new. Previous small case series suggested that analysis of the bronchial mucosal surface using chromoendoscopy allows a prediction between neoplastic and nonneoplastic lesions.Objectives. The aim of the present study was to evaluate chromobronchoscopy as a method to identify malignant and premalignant lesions in the central airways in a prospective manner.Methods. In 26 patients we performed chromoendoscopy with 0.1% methylene blue during ongoing flexible white light bronchoscopy. Circumscribed lesions in central airways were further analyzed by biopsies and histopathologic examination.Results. In the majority of cases neither flat nor polypoid lesions in the central airways were stained by methylene blue. In particular, exophytic growth of lung cancer did not show any specific pattern in chromobronchoscopy. However, a specific dye staining was detected in one case where exophytic growth of metastatic colorectal cancer was present in the right upper lobe. In two other cases, a circumscribed staining was noted in unsuspicious mucosa. But histology revealed inflammation only.Conclusions. In contrast to previous studies, the present findings clearly indicate that chromobronchoscopy is not useful for early detection of malignant or premalignant lesions of the central airways.
Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management
Authors: Ballas Samir K. , Kesen Muge R. , Goldberg Morton F. , Lutty Gerard A. , Dampier Carlton , Osunkwo Ifeyinwa , Wang Winfred C. , Hoppe Carolyn , Hagar Ward , Darbari Deepika S. , Malik Punam
Published: August 2012

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of theβglobin gene resulting in the substitution of glutamic acid by valine at position 6 of theβglobin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.
Condensins: universal organizers of chromosomes with diverse functions
Authors: Hirano Tatsuya
Published: August 2012

Condensins are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. Most eukaryotic species have two different types of condensin complexes, known as condensins I and II, that fulfill nonoverlapping functions and are subjected to differential regulation during mitosis and meiosis. Recent studies revealed that the two complexes contribute to a wide variety of interphase chromosome functions, such as gene regulation, recombination, and repair. Also emerging are their cell type- and tissue-specific functions and relevance to human disease. Biochemical and structural analyses of eukaryotic and bacterial condensins steadily uncover the mechanisms of action of this class of highly sophisticated molecular machines. Future studies on condensins will not only enhance our understanding of chromosome architecture and dynamics, but also help address a previously underappreciated yet profound set of questions in chromosome biology.
Biased transcription and selective degradation of small RNAs shape the pattern of DNA elimination in Tetrahymena
Authors: Schoeberl Ursula E. , Kurth Henriette M. , Noto Tomoko , Mochizuki Kazufumi
Published: August 2012

The ciliated protozoan Tetrahymena undergoes extensive programmed DNA elimination when the germline micronucleus produces the new macronucleus during sexual reproduction. DNA elimination is epigenetically controlled by DNA sequences of the parental macronuclear genome, and this epigenetic regulation is mediated by small RNAs (scan RNAs [scnRNAs]) of ∼28–30 nucleotides that are produced and function by an RNAi-related mechanism. Here, we examine scnRNA production and turnover by deep sequencing. scnRNAs are produced exclusively from the micronucleus and nonhomogeneously from a variety of chromosomal locations. scnRNAs are preferentially derived from the eliminated sequences, and this preference is mainly determined at the level of transcription. Despite this bias, a significant fraction of scnRNAs is also derived from the macronuclear-destined sequences, and these scnRNAs are degraded during the course of sexual reproduction. These results indicate that the pattern of DNA elimination in the new macronucleus is shaped by the biased transcription in the micronucleus and the selective degradation of scnRNAs in the parental macronucleus.
Context-specific roles for paracrine IL-6 in lymphomagenesis
Authors: Gilbert Luke A. , Hemann Michael T.
Published: August 2012

A basic requirement for the development of complex organ systems is that the cellular response to identical environmental cues can vary significantly between distinct cell types and developmental stages. While it is well established that paracrine signaling can similarly elicit diverse responses in distinct tumor types, the relevance of developmental stage-specific signaling responses to tumor development remains unclear. Here, we show that the same microenvironmental factor, IL-6, can both promote and prevent lymphoma development by acting on cells at distinct stages of hematopoietic development. Specifically, paracrine IL-6 signaling promotes the survival of transplanted hematopoietic stem cells following lethal irradiation, allowing for the persistence and expansion of progenitor cells bearing a cancer-promoting alteration. Conversely, IL-6 signaling also initiates a paracrine secretory program in the bone marrow that promotes B-cell differentiation and inhibits the development of B-cell malignancies. Thus, stage-specific responses to cytokines may promote progenitor cell expansion while also inhibiting neoplastic development within a single developmental lineage. Once transformed, the resulting B-cell lymphomas again use paracrine IL-6 signaling as a survival signal, highlighting the ability of tumor cells to co-opt pathways used for stem cell protection. These data not only suggest a complex regulation of tumor development by the preneoplastic microenvironment, but also that this regulation can decisively impact the outcome of well-established tumor modeling approaches.
Regulation of dendritic branching by Cdc42 GAPs: Figure 1.
Authors: Simó Sergi , Cooper Jonathan A.
Published: August 2012

Nerve cells form elaborate, highly branched dendritic trees that are optimized for the receipt of synaptic signals. Recent work published in this issue ofGenes & Developmentby Rosario and colleagues (pp. 1743–1757) shows that a Cdc42-specific GTPase-activating protein (NOMA-GAP) regulates the branching of dendrites by neurons in the top layers of the mouse cortex. The results raise interesting questions regarding the specification of arbors in different cortical layers and the mechanisms of dendrite branching.
Formaldehyde Fixation of Drosophila Testes
Authors: Bonaccorsi Silvia , Giansanti Maria G. , Cenci Giovanni , Gatti Maurizio
Published: August 2012

This protocol describes formaldehyde fixation of Drosophila testes. The procedure preserves chromosome morphology very well, allowing a clear visualization of the chromosome condensation–decondensation cycle. It also results in excellent preservation of microtubules for immunostaining. The main disadvantage of this fixation technique is its poor preservation of cell morphology, as viewed by phase-contrast optics. In addition, because it involves a rather hard squashing of formaldehyde-fixed testes, it results in meiotic figures which are flatter and larger than those obtained using methanol-acetone or paraformaldehyde fixation protocols.
Analysis of Drosophila Larval Feeding Response to Quinine-Adulterated Food
Authors: Shen Ping
Published: August 2012

The food responses of Drosophila larvae offer an excellent opportunity to study the genetic and neural regulation of feeding behavior. Compared with fed larvae, hungry larvae are more likely to display aggressive foraging, rapid food intake, compensatory feeding, and stress-resistant food procurement. Omnivores, including humans, tend to avoid noxious or unfamiliar food. Fly larvae avoid bitter substances such as quinine. As an increasing amount of quinine is added to an otherwise palatable liquid medium containing sugar and inactivated yeast, larvae become less likely to consume the tainted food. Larval feeding activity is assayed by scoring the percentage of larvae containing dyed food in a large portion of the midgut. Defensive foraging behavior can be modulated by physiological need and food deprivation significantly increases larval tolerance to quinine. Therefore, the larval response to quinine food and its regulation by hunger provides a useful paradigm for elucidating the genetic and neural regulation of food choice that favors short-term survival. The test described here is designed for quantitative assessment of the motivation of individual larvae to ingest quinine-adulterated food under different energy states. The test is applicable to routine functional testing and larger-scale screening of genetic mutations and biologics that might affect food consumption.
Whole-Mount Fluorescence In Situ Hybridization and Antibody Staining of Drosophila Embryos
Authors: Broihier Heather
Published: August 2012

Whole-mount RNA in situ hybridizations with digoxigenin-conjugated probes and alkaline phosphatase biochemistry have been used widely for many years to map expression pattern domains in the Drosophila embryo. To capitalize on the number of molecular markers in the central nervous system (CNS) and to enable expression analysis at the single-cell level, fluorescence in situ hybridization procedures are becoming standard. This protocol describes methods for the simultaneous detection of RNA and protein using fluorescence in Drosophila embryos. It uses the tyramide signal amplication (TSA) system from PerkinElmer to amplify a horseradish peroxidase (HRP) signal. By combining this technology with an HRP-conjugated antidigoxigenin antibody, we can detect standard antidigoxigenin RNA probes fluorescently.
Cellular Bioluminescence Imaging
Authors: Welsh David K. , Noguchi Takako
Published: August 2012

Bioluminescence imaging of live cells has recently been recognized as an important alternative to fluorescence imaging. Fluorescent probes are much brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide much better spatial and temporal resolution and much better contrast for delineating cell structure. However, with bioluminescence imaging there is virtually no background or toxicity. As a result, bioluminescence can be superior to fluorescence for detecting and quantifying molecules and their interactions in living cells, particularly in long-term studies. Structurally diverse luciferases from beetle and marine species have been used for a wide variety of applications, including tracking cells in vivo, detecting protein–protein interactions, measuring levels of calcium and other signaling molecules, detecting protease activity, and reporting circadian clock gene expression. Such applications can be optimized by the use of brighter and variously colored luciferases, brighter microscope optics, and ultrasensitive, low-noise cameras. This article presents a review of how bioluminescence differs from fluorescence, its applications to cellular imaging, and available probes, optics, and detectors. It also gives practical suggestions for optimal bioluminescence imaging of single cells.
The effects of early‐age thermal manipulation and daily short‐term fasting on performance and body temperatures in broiler exposed to heat stress
Authors: Günal M.
Published: August 2012

This study was conducted to investigate the effects of thermal manipulation at 5 days of age and short‐term fasting during the warmest part of the day on responses to prolonged heat stress of broilers. A total of 240‐day‐old Ross 308 female broiler chicks were divided into three groups: control, thermal manipulation (chicks were exposed to 36 °C for 24 h at 5 days of age) and short‐term fasting during the warmest part of the day (10.00–17.00 h). Prolonged heat stress was induced daily from 28 to 42 days by heating until the ambient temperature reached 32–35 °C between 10.00 and 17.00 h. Both thermal manipulation and short‐term fasting resulted in a decrease in rectal temperatures and haematocrit values at 35 and 41 days of age. Thermal manipulation improved body weight, feed consumption and feed conversion. However, short‐term fasting caused a reduction in body weight and a deterioration in feed conversion. Short‐term fasting lowered the percentages of carcass, whereas thermal manipulation highered breast yield. Both thermal manipulation and short‐term fasting decreased heart mass and abdominal fat.
Folic acid supplementation prevents the changes in hepatic promoter methylation status and gene expression in intrauterine growth‐retarded piglets during early weaning period
Authors: Jing‐bo L. , Ying Y. , Bing Y. , Xiang‐bing M. , Zhi‐qing H. , Guo‐quan H. , Hong C. , Dai‐wen C.
Published: August 2012

During intrauterine life, genome interacts with maternal signals to influence the mRNA expression levels of specific genes persistently by regulating DNA methylation status. The objective of this study was to examine the responses of glucocorticoid receptor (GR), peroxisome proliferator‐activated receptor alpha and gamma (PPARα and PPARγ) promoter methylation, mRNA expression of genes involved in energy metabolism and metabolite concentrations of intrauterine growth‐retarded (IUGR) piglets to dietary folic acid supplementation. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal birth weight (NBW) piglets were fed a basal diet or a basal diet supplemented with 5 mg/kg of folic acid from weaning (day 14) to day 35 of age. Triglycerides in hepatic tissue and plasma were significantly elevated in control diets‐fed IUGR piglets compared with NBW piglets but were decreased by dietary folic acid supplementation. Hepatic mRNA expression levels of GR, PPARα, PPARγ, fatty acid synthase and phosphoenolpyruvate carboxykinase (PEPCK) in IUGR piglets fed a control diet were significantly higher than that in NBW piglets, and promoter methylation status of GR, PPARα and PPARγ in IUGR piglets was reduced significantly compared with NBW piglets. However, the changes in gene expression and DNA methylation status of IUGR piglets were reversed by dietary folic acid supplementation. Hepatic DNA methyltransferase activity was greater with dietary folic acid supplementation regardless of birth weight. Taken together, these results demonstrated that folic acid supplementation during early period of life could prevent the changes of promoter methylation status and gene expressions in the liver of IUGR piglets.
Possible antistenotic effect of tranilast in a patient with small bowel tuberculosis to prevent intestinal obstruction due to stenosis progression by antituberculous chemotherapy
Authors: Oshitani Nobuhide , Takeda Shogo , Matsumoto Hiroko , Minamino Hiroaki , Hayakawa Tsuyoshi , Aomatsu Kazuki
Published: August 2012

Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.
A topical aqueous calcineurin inhibitor for the treatment of naturally occurring keratoconjunctivitis sicca in dogs
Authors: Gilger Brian C. , Wilkie David A. , Salmon Jacklyn H. , Peel Michael R.
Published: August 2012

Purpose The purpose of this study was to evaluate the efficacy of an aqueous calcineurin inhibitor, SCY‐641, in the treatment of naturally occurring canine immune‐mediated keratoconjunctivitis sicca (KCS).

Methods A randomized, double‐masked, placebo‐controlled clinical study of 56‐day duration was performed in dogs with naturally occurring immune‐mediated KCS assigned to treatment with either topical twice‐daily aqueous calcineurin inhibitor solution (SCY‐641) or artificial tears (placebo) by the study administrator. Clinical examination and Schirmer tear tests (STT) were performed prior to therapy and at days 7, 14, 28, and 56 after initiation of treatment.

Results Twenty dogs were enrolled in the study with ten receiving placebo and 10 receiving SCY‐641 in one or both eyes. No adverse effects were noted with any treatment. There were no significant differences in mean STT values in dogs in group either at day 0 (prior to therapy) or after 7 days of treatment. At 14, 28, and 56 days after initiation of treatment, mean STT and increase in STT over baseline in dogs treated with SCY‐641 were significantly higher than in dogs treated with placebo (P < 0.04).

Conclusions SCY‐641 was well tolerated by dogs with naturally occurring KCS, and by 14 days after initiating therapy, dogs treated with SCY‐641 had significantly higher STT than placebo‐treated dogs. These preliminary results indicate that topical SCY‐641, in a stable clear aqueous solution, is efficacious in a spontaneous model of KCS and warrants further evaluation as a treatment of immune‐mediated KCS.
Neuron‐specific non‐classical release of prothymosin alpha: a novel neuroprotective damage‐associated molecular patterns
Authors: Halder Sebok Kumar , Matsunaga Hayato , Ueda Hiroshi
Published: August 2012

Prothymosin alpha (ProTα), a nuclear protein devoid of signal sequence, has been shown to possess a number of cellular functions including cell survival. Most recently, we demonstrated that ProTα is localized in the nuclei of neurons, while it is found in both nuclei and cytoplasm in the astrocytes and microglia of adult brain. However, the cell type‐specific non‐classical release of ProTα under cerebral ischemia is yet unknown. In this study, we report that ProTα is non‐classically released along with S100A13 from neurons in the hippocampus, striatum and somatosensory cortex at 3 h after cerebral ischemia, but amlexanox (an anti‐allergic compound) reversibly blocks this neuronal ProTα release. We found that none of ProTα is released from astrocytes and microglia under ischemic stress. Indeed, ProTα intensity is increased gradually in astrocytes and microglia through 24 h after the cerebral ischemia. Interestingly, Z‐Val‐Ala‐Asp fluoromethyl ketone, a caspase 3 inhibitor, pre‐treatment induces ProTα release from astrocytes in the ischemic brain, but this release is reversibly blocked by amlexanox. However, Z‐Val‐Ala‐Asp fluoromethyl ketone as well as amlexanox has no effect on ProTα distribution in microglia upon cerebral ischemia. Taken together, these results suggest that only neurons have machineries to release ProTα upon cerebral ischemic stress in vivo.
Activation of platelet protein kinase C by ultraviolet light B mediates platelet transfusion–related acute lung injury in a two‐event animal model
Authors: Zhi Li , Chi Xuan , Gelderman Monique P. , Vostal Jaroslav G.
Published: August 2012

BACKGROUND: We recently reported that infusion of ultraviolet light B (UVB)‐exposed human platelets (HPs) can be the second event that mediates acute lung injury (ALI) in a two‐event mouse model of transfusion‐related acute lung injury (mTRALI). We have now identified changes in HPs induced by UVB light and responses of the recipient animal that mediate the mTRALI.

STUDY DESIGN AND METHODS: Effects of UVB on HPs were monitored by flow cytometry and aggregation. HPs exposed to UVB, with or without inhibitors to specific biochemical pathways, were infused into lipopolysaccharide (LPS)‐primed severe combined immunodeficient (SCID) mice. ALI was monitored by protein elevations in bronchoalveolar lavage fluid (BALF).

RESULTS: UVB increased fibrinogen binding and potentiated HP aggregation. Infusion of UVB HPs into LPS‐primed SCID mice led to macrophage inflammatory protein 2 (MIP‐2) elevations in plasma and BALF and resulted in ALI. Protein kinase C (PKC) inhibitors prevented UVB‐induced HP changes in vitro and reduced MIP‐2 elevation and mTRALI in vivo. Blocking of fibrinogen binding to HP αIIbβ3 with c7E3 monoclonal antibody prevented mTRALI. MIP‐2 elevation in vivo in response to UVB HPs was essential for ALI since blocking of MIP‐2 receptor in vivo prevented mTRALI.

CONCLUSION: PKC signaling mediates UVB‐induced HP fibrinogen binding and aggregation in vitro. The host animal responds to an infusion of UVB HPs by MIP‐2 elevation that mediates downstream mTRALI. Elucidation of molecular mechanisms in UVB HP–mediated mTRALI may provide insight into pulmonary adverse events reported with UV‐irradiated pathogen‐reduced platelets.
Electroanatomic Characterization and Ablation Outcome of Nonlesion Related Left Atrial Macroreentrant Tachycardia in Patients Without Obvious Structural Heart Disease
Authors: ZHANG JINLIN , TANG CHENG , ZHANG YONGHUA , HAN HONGWEI , LI ZHEN , SU XI
Published: August 2012

Nonlesion Related Left Atrial Macroreentrant Tachycardia. Introduction: Descriptions for left atrial macroreentry tachycardia (LAMRT) in patients without obvious structural heart disease or previous surgery or catheter radiofrequency (RF) ablation have been sparse.

Methods and Results:
Ten of 226 patients (7 women, mean age 57 ± 14) with LAMRT underwent electroanatomic mapping and catheter ablation. None of the 10 patients had structural heart disease or history of previous surgery or catheter ablation. In all patients, the reentry circuits were located within a large low‐voltage (bipolar voltage ≤ 0.5 mV) area in left atrium (LA), which contained 2.6 ± 1.2 electrically silent areas (ESAs) and/or lines of double potentials (LDPs). The tachycardia circuit propagated through a narrow isthmus (<5 mm width) bounded by ESAs/LDPs and adjacent anatomical barriers (e.g., mitral annulus). In these isthmus, low amplitude (0.21 ± 0.05 mV), long‐duration (123 ± 14 milliseconds) fractionated electrograms were found in 8 tachycardias, accounting for 43 ± 5% of the tachycardia cycle length. In 2 other tachycardias without fractionated electrograms, the electrogram amplitude in the isthmus was extremely low (<0.1 mV). RF energy was delivered at the isthmuses and terminated all 10 tachycardias. After ablation, the original LAMRT was not inducible in all patients. During follow‐up (mean14 ± 10 months), 2 patients developed recurrence of ATs and were successfully ablated.

Conclusion:
Extensive scarring of the LA formed arrhythmogenic substrates of LAMRT in this group of patients. Ablation targeting these narrow, slow conduction zones eliminated atrial tachycardia in all patients. (J Cardiovasc Electrophysiol, Vol. 24, pp. 53‐59, January 2013)
Short‐term intermittent hypoxia reduces the severity of acute mountain sickness
Authors: Wille M. , Gatterer H. , Mairer K. , Philippe M. , Schwarzenbacher H. , Faulhaber M. , Burtscher M.
Published: August 2012

Intermittent hypoxia (IH) is a promising approach to induce acclimatization and hence lower the risk of developing acute mountain sickness (AMS). We hypothesized that a short‐term IH protocol in normobaric hypoxia (7 × 1 h to 4500 m) effectively increases the hypoxic ventilatory response (HVR) and reduces the incidence and severity of AMS. Therefore, 26 men (25.5 ± 4.4 years), assigned in a double‐blinded fashion to the hypoxia group (HG) or placebo group (PG), spent 8 h at 5300 m before (PRE) and 2 days after cessation of the IH protocol (POST). Measurements included the evaluation of the Lake Louise Score (LLS) and the HVR. The severity of AMS decreased from PRE to POST in the HG (from 6.0 ± 2.7 at PRE to 4.1 ± 2.1 at POST), whereas the LLS in the PG stayed high (from 5.7 ± 2.9 to 5.5 ± 2.8, respectively). The HVR in the HG increased from 0.73 ± 0.4 L/min/% at PRE to 1.10 ± 0.5 L/min/% at POST and did not increase in the PG. The reduction of the LLS was inversely related to the changes in the HVR (r = −0.434), but the AMS incidence was not different between the HG and the PG at POST. In conclusion, short‐term IH reduced the severity of AMS development during a subsequent 8‐h exposure to normobaric hypoxia.
The soy isoflavone genistein inhibits the reduction inAchilles tendon collagen content induced by ovariectomy in rats
Authors: Ramos J. E. , Al‐Nakkash L. , Peterson A. , Gump B. S. , Janjulia T. , Moore M. S. , Broderick T. L. , Carroll C. C.
Published: August 2012

The objective of this study was to evaluate the effects of genistein and moderate intensity exercise onAchilles tendon collagen and cross‐linking in intact and ovariectomized (OVX) femaleSprague–Dawley rats. Rats were separated into eight groups (n = 9/group): intact orOVX, treadmill exercised or sedentary, genistein‐treated (300 mg/kg/day) or vehicle. After 6 weeks, tendons were assayed for the collagen‐specific amino acid hydroxyproline and hydroxylyslpyridinoline (HP). Collagen content was not influenced by exercise (P = 0.40) but was lower (P < 0.001) inOVX‐vehicle rats compared with intact vehicle rats (OVX: 894 ± 35 μg collagen/mg dry weight; intact: 1185 ± 72 μg collagen/mg dry weight). In contrast, collagen content inOVXrats treated with genistein was greater (P = 0.010, 1198 ± 121 μg collagen/mg dry weight) when compared with untreated rats and was not different from intact rats (P = 0.89).HPcontent was lower inOVXgenistein‐treated rats when compared with intact genistein‐treated rats, but only within the sedentary animals (P = 0.05, intact‐treated: 232 ± 39 mmol/mol collagen;OVX‐treated: 144 ± 21 mmol/mol collagen). Our findings suggest that ovariectomy leads to a reduction in tendon collagen, which is prevented by genistein.HPcontent, however, may not have increased in proportion to the addition of collagen. Genistein may be useful for improving tendon collagen content in conditions of estrogen deficiency.
Theories of Human Nature: Key Issues
Authors: Stenmark Mikael
Published: August 2012

Issues about human nature are at the core of philosophy, but theories of human nature can be found in many academic disciplines and all humans have opinions and sometimes fairly strong opinions about who we are. We sometimes talk more specifically about, for instance, a Christian view of human nature and distinguish it from say the Blank Slate theory or a Darwinian understanding of human nature. But what is more exactly a theory of human nature? In this essay I survey a number of key issues which philosophers and other scholars have maintained that a theory of human nature, which pretends to be adequate and comprehensive, needs to address.
Development and Validation of QuEChERS Method for Estimation of Chlorantraniliprole Residue in Vegetables
Authors: Singh Balwinder , Kar Abhijit , Mandal Kousik , Kumar Rajinder , Sahoo Sanjay Kumar
Published: August 2012

Abstract:  An easy, simple and efficient analytical method was standardized and validated for the estimation of residues of chlorantraniliprole in different vegetables comprising brinjal, cabbage, capsicum, cauliflower, okra, and tomato. QuEChERS method was used for the extraction and cleanup of chlorantraniliprole residues on these vegetables. Final clear extracts of ethyl acetate were concentrated under vacuum and reconstituted into high performance liquid chromatograph (HPLC) grade acetonitrile, and residues were estimated using HPLC equipped with PDA detector system, C18 column and confirmed by liquid chromatograph mass spectrometer (LC‐MS/MS), and high performance thin layer chromatograph (HPTLC). HPLC grade acetonitrile:water (80:20, v/v) was used as mobile phase @ 0.4 mL/min. Chlorantraniliprole presented distinct peak at retention time of 9.82 min. Consistent recoveries ranging from 85% to 96% for chlorantraniliprole were observed when samples were spiked at 0.10, 0.25, 0.50, and 1.00 mg/kg levels. The limit of quantification of this method was worked out to be 0.10 mg/kg.

Practical Application:  The QuEChERS sample preparation is suitable for determination of chlorantraniliprole in brinjal, cabbage, capsicum, cauliflower, okra and tomato and thus demonstrating the great versatility of this method. The proposed analytical method using liquid chromatography techniques for the determination of chlorantraniliprole in different vegetable matrices has been demonstrated to be sensitive, fast, precise, accurate, and robust and can be used to monitor chlorantraniliprole residues in different vegetables.
Do the Investment and Return‐on‐Equity Factors Proxy for Economic Risks?
Authors: Wang Zijun
Published: August 2012

We study the information content of two new return factors, the investment factor (IA) and the return‐on‐equity factor (ROE), as proposed by Chen, Novy‐Marx, and Zhang in 2011. First, IA is a strong predictor for future gross domestic product (GDP) growth despite the presence of other financial and economic variables. IA subsumes the pricing power of the GDP factor for the cross section of asset returns. Second, ROE is closely related to innovations in dividend yield and term spread. When modeled together with innovations in state variables that forecast future investment opportunities, IA and ROE lose their explanatory power.
Plasma neurofilament pNF‐H concentration is not increased in acute equine grass sickness
Authors: STRATFORD C. H. , PEMBERTON A. , CAMERON L. , McGORUM B. C.
Published: August 2012

Although a presumptive diagnosis of acute grass sickness (AGS) can be made on the basis of clinical signs, a definitive ante mortem diagnosis currently requires histological examination of enteric ganglia. Development of an accurate noninvasive ante mortem diagnostic test is therefore warranted. The objective of this study was to determine whether quantification of the plasma concentrations of the heavily phosphorylated form of major neurofilament subunit NF‐H (pNF‐H), which mirror the degree of axonal degeneration in some human and animal neurodegenerative disorders, could distinguish AGS‐affected and control horses. The pNF‐H was quantified in plasma from 20 AGS cases and 20 control horses using a commercial enzyme‐linked immunosorbent assay kit. Five AGS and 4 control samples had detectable pNF‐H concentrations (>0.0759 ng/ml). There was no significant intergroup difference in pNF‐H concentrations. It was concluded that plasma pNF‐H is not a useful biomarker for the diagnosis of AGS.
Effects of a constant‐rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies
Authors: GOZALO‐MARCILLA M. , HOPSTER K. , GASTHUYS F. , HATZ L. , KRAJEWSKI A. E. , SCHAUVLIEGE S.
Published: August 2012

Reasons for performing study:Dexmedetomidine has been administered in the equine as a constant‐rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses.

Objectives:To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies.

Methods:Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10–T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant‐current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05).

Results:An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%).

Conclusions and potential relevance:A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane.
In vivo targeted delivery of large payloads with an ultrasound clinical scanner
Authors: Couture Olivier , Urban Alan , Bretagne Alice , Martinez Lucie , Tanter Mickael , Tabeling Patrick
Published: August 2012

Purpose:

Performing drug‐delivery with an ultrasonic imaging scannerin situ could drastically simplify treatment and improve its specificity. Our objective is to deliver large amounts of an encapsulated agent in vivo using a clinical ultrasound scanner with a millimetric resolution. This study describes the encapsulation of fluorescein within ultrasound‐inducible composite droplets and its targeted release in predefined zones in the liver of rats.

Methods:

An aqueous solution of fluorescein was encapsulated within perfluorocarbon liquid in 4μm monodisperse droplets using a microfluidic system. The agent was then injected within the femoral vein of 12 rats. After exploratory ultrasound imaging, the sonographer defined five zones in the liver and a release sequence was initiated on the same apparatus. The surface of the liver was observed under fluorescence macroscopy and intraoperative fluorescence camera in vivo, before liver samples were sliced for pathology.

Results:

Following the conversion of the droplets, a 25 dB increase in contrast was observed in the zones selected by the sonographer. These hyperechoic regions were colocalized with the bright fluorescent spots observed on the surface of the liver. A minimum peak‐negative pressure of 2.6 MPa, which is within regulations for imaging pulses, was required for the delivery of the content of the droplets. The tissue and cellular structures were not affected by the exposure to the release sequence.

Conclusions:

Since composite droplets can carry various therapeutic and imaging agents, they could deliver such agents specifically in any organ accessible to ultrasound.
Uncertainty incorporated beam angle optimization for IMPT treatment planning
Authors: Cao Wenhua , Lim Gino J. , Lee Andrew , Li Yupeng , Liu Wei , Ronald Zhu X. , Zhang Xiaodong
Published: August 2012

Purpose:

Beam angle optimization (BAO) by far remains an important and challenging problem in external beam radiation therapy treatment planning. Conventional BAO algorithms discussed in previous studies all focused on photon‐based therapies. Impact of BAO on proton therapy is important while proton therapy increasingly receives great interests. This study focuses on potential benefits of BAO on intensity‐modulated proton therapy (IMPT) that recently began available to clinical cancer treatment.

Methods:

The authors have developed a novel uncertainty incorporated BAO algorithm for IMPT treatment planning in that IMPT plan quality is highly sensitive to uncertainties such as proton range and setup errors. A linear programming was used to optimize robust intensity maps to scenario‐based uncertainties for an incident beam angle configuration. Unlike conventional intensity‐modulated radiation therapy with photons (IMXT), the search space for IMPT treatment beam angles may be relatively small but optimizing an IMPT plan may require higher computational costs due to larger data size. Therefore, a deterministic local neighborhood search algorithm that only needs a very limited number of plan objective evaluations was used to optimize beam angles in IMPT treatment planning.

Results:

Three prostate cancer cases and two skull base chordoma cases were studied to demonstrate the dosimetric advantages and robustness of optimized beam angles from the proposed BAO algorithm. Two‐ to four‐beam plans were optimized for prostate cases, and two‐ and three‐beam plans were optimized for skull base cases. By comparing plans with conventional two parallel‐opposed angles, all plans with optimized angles consistently improved sparing at organs at risks, i.e., rectum and femoral heads for prostate, brainstem for skull base, in either nominal dose distribution or uncertainty‐based dose distributions. The efficiency of the BAO algorithm was demonstrated by comparing it with alternative methods including simulated annealing and genetic algorithm. The numbers of IMPT plan objective evaluations required were reduced by up to a factor of 5 while the same optimal angle plans were converged in selected comparisons.

Conclusions:

Uncertainty incorporated BAO may introduce pronounced improvement of IMPT plan quality including dosimetric benefits and robustness over uncertainties, based on the five clinical studies in this paper. In addition, local search algorithms may be more efficient in finding optimal beam angles than global optimization approaches for IMPT BAO.