bluuebunny/crossref_metadata_2025 huggingface dataset:
Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes
Authors: Robison Patrick , Caporizzo Matthew A. , Ahmadzadeh Hossein , Bogush Alexey I. , Chen Christina Yingxian , Margulies Kenneth B. , Shenoy Vivek B. , Prosser Benjamin L.
Published: April 2016

A close-up view of cardiac cell mechanics

Heart cells contain a very well-organized array of cytoskeletal elements, including actin and microtubules that help them to perform their mechanical functions. Robison
et al.
used an advanced imaging approach to study the inner workings of mouse cardiac myocytes in real time. They observed microtubule “buckling” under contractile force in beating cardiomyocytes. This buckling was regulated by interaction with desmin and by the tubulin tyrosination state. The findings suggest a role for stable detyrosinated microtubules whose buckling under tension contributes to cardiac muscle strength.

Science
, this issue p.
10.1126/science.aaf0659
Precocity in a tiny titanosaur from the Cretaceous of Madagascar
Authors: Curry Rogers Kristina , Whitney Megan , D’Emic Michael , Bagley Brian
Published: April 2016

Tiny giant

Titanosaurs were the largest land vertebrates to have evolved, but even they had to start small. Curry Rogers
et al.
describe a baby
Rapetosaurus
only 35 cm at the hip at death. Histological and limb analysis suggest that this tiny giant had a much greater range of movement than it would have had as an adult. Furthermore, the work confirms hypotheses that these largest of dinosaurs were precocial, being able to move independently immediately after birth. This pattern differs from that seen in many contemporary dinosaur groups, such as theropods and ornithischians, for which increasing evidence suggests that parental care was important.

Science
, this issue p.
450
Mineral clues to past volcanism
Authors: Kump Lee
Published: April 2016

A study of zircon minerals from around the world shows that volcanism is a key driver of long-term climate change

[Also see Report by

McKenzie
et al.

]
Development and Validation of a Quantitative, One-Step, Multiplex, Real-Time Reverse Transcriptase PCR Assay for Detection of Dengue and Chikungunya Viruses
Authors: Simmons Monika , Myers Todd , Guevara Carolina , Jungkind Donald , Williams Maya , Houng Huo-Shu
Published: April 2016

Dengue virus (DENV) and chikungunya virus (CHIKV) are important human pathogens with common transmission vectors and similar clinical presentations. Patient care may be impacted by the misdiagnosis of DENV and CHIKV in areas where both viruses cocirculate. In this study, we have developed and validated a one-step multiplex reverse transcriptase PCR (RT-PCR) to simultaneously detect, quantify, and differentiate between four DENV serotypes (pan-DENV) and chikungunya virus. The assay uses TaqMan technology, employing two forward primers, three reverse primers, and four fluorophore-labeled probes in a single-reaction format. Coextracted and coamplified RNA was used as an internal control (IC), and
in vitro
-transcribed DENV and CHIKV RNAs were used to generate standard curves for absolute quantification. The diagnostic 95% limits of detection (LOD) within the linear range were 50 and 60 RNA copies/reaction for DENV (serotypes 1 to 4) and CHIKV, respectively. Our assay was able to detect 53 different strains of DENV, representing four serotypes, and six strains of CHIKV. No cross-reactivity was observed with related flaviviruses and alphaviruses, To evaluate diagnostic sensitivity and specificity, 89 clinical samples positive or negative for DENV (serotypes 1 to 4) and CHIKV by the standard virus isolation method were tested in our assay. The multiplex RT-PCR assay showed 95% sensitivity and 100% specificity for DENV and 100% sensitivity and specificity for CHIKV. With an assay turnaround time of less than 2 h, including extraction of RNA, the multiplex quantitative RT-PCR assay provides rapid diagnosis for the differential detection of two clinically indistinguishable diseases, whose geographical occurrence is increasingly overlapping.
Epidemiology of Invasive Group B Streptococcal Disease in Alberta, Canada, from 2003 to 2013
Authors: Alhhazmi Areej , Hurteau Donna , Tyrrell Gregory J.
Published: April 2016

Group B streptococci (GBS) cause severe invasive disease in both neonates and adults. Understanding the epidemiology of GBS provides information that can include determining disease prevalence rates in defined populations and geographic regions, documenting the success of GBS screening programs, and understanding antimicrobial susceptibility patterns. In Alberta, only neonatal invasive GBS (iGBS) disease is notifiable to health authorities. We performed a surveillance study of iGBS in Alberta, Canada, from 2003 to 2013. Over the 11-year period, the disease incidence rate increased from a low of 3.92 cases/100,000 population to a high of 5.99 cases/100,000 population. The capsular polysaccharide serotypes (CPSs) found were CPS III (20.3%), CPS V (19.1%), CPS Ia (18.9%), CPS Ib (12.7%), CPS II (11.1%), CPS IV (6.3%), and nontypeable GBS (9.4%). Rates of early-onset disease (0 to 7 days) increased from 0.15 cases/1,000 live births (in 2003) to 0.34 cases/1,000 live births (in 2013). Rates of late-onset disease (>7 to 90 days) also rose, from 0.15 cases/1,000 live births (in 2003) to 0.39 cases/1,000 live births (in 2013). Alberta also experienced an increase in CPS IV isolates, from 2 cases (in 2003) to 24 cases (in 2013), of which the majority were
hvgA
positive (86.6%). The predominant sequence type (ST) in 2013 was ST459. Erythromycin resistance rose from 23.6% to 43.9% (in 2013). Clindamycin resistance also increased, from 12.2% to 32.5%. In summary, Alberta, Canada, has experienced an increase in GBS disease; the increase includes both neonatal and adult disease. CPS IV cases also notably increased during the surveillance period, as did resistance to erythromycin and clindamycin.
Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters
Authors: Hammerbeck Christopher D. , Brocato Rebecca L. , Bell Todd M. , Schellhase Christopher W. , Mraz Steven R. , Queen Laurie A. , Hooper Jay W.
Published: April 2016

Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS.

IMPORTANCEHantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are poised to defend against hantavirus infection, but those antiviral responses may also contribute to hantavirus disease. Here, we demonstrate that, like in our prior T and B cell studies, alveolar macrophages neither prevent hantavirus infection nor cause hantavirus disease. While these studies reflect pathogenesis in the hamster model, they should help us rule out specific cell types and prompt us to consider other potential mechanisms of disease in an effort to improve the outcome of human HPS.
Influenza Virus Hemagglutinin Glycoproteins with Different N-Glycan Patterns Activate Dendritic Cells
In Vitro
Authors: Liu Wen-Chun , Lin Yu-Li , Spearman Maureen , Cheng Pei-Yun , Butler Michael , Wu Suh-Chin
Published: April 2016

Influenza virus hemagglutinin (HA) N-glycans play important regulatory roles in the control of virus virulence, antigenicity, receptor-binding specificity, and viral escape from the immune response. Considered essential for controlling innate and adaptive immune responses against influenza virus infections, dendritic cells (DCs) trigger proinflammatory and adaptive immune responses in hosts. In this study, we engineered Chinese hamster ovary (CHO) cell lines expressing recombinant HA from pandemic H1, H5, and H7 influenza viruses. rH1HA, rH5HA, and rH7HA were obtained as wild-type proteins or in the presence of kifunensine (KIF) or further with endo-β-
N
-acetylglucosaminidase-treated KIF (KIF+E) to generate single-
N
-acetylglucosamine (GlcNAc) N-glycans consisting of (i) terminally sialylated complex-type N-glycans, (ii) high-mannose-type N-glycans, and (iii) single-GlcNAc-type N-glycans. Our results show that high-mannose-type and single-GlcNAc-type N-glycans, but not complex-type N-glycans, are capable of inducing more active hIL12 p40, hIL12 p70, and hIL-10 production in human DCs. Significantly higher HLA-DR, CD40, CD83, and CD86 expression levels, as well reduced endocytotic capacity in human DCs, were noted in the high-mannose-type rH1HA and single-GlcNAc-type rH1HA groups than in the complex-type N-glycan rH1HA group. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). The high-mannose-type or single-GlcNAc-type N-glycans of both avian and human HA types are more stimulatory than the complex-type N-glycans. HA-stimulated DC activation was accomplished partially through a mannose receptor(s). These results provide more understanding of the contribution of glycosylation of viral proteins to the immune responses and may have implications for vaccine development.

IMPORTANCE
Influenza viruses trigger seasonal epidemics or pandemics with mild-to-severe consequences for human and poultry populations. DCs are the most potent professional antigen-presenting cells, which play a crucial role in the link between innate and adaptive immunity. In this study, we obtained stable-expression CHO cells to produce rH1HA, rH5HA, and rH7HA proteins containing distinct N-glycan patterns. These rHA proteins, each with a distinct N-glycan pattern, were used to investigate interactions with mouse and human DCs. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). High-mannose-type and single-GlcNAc-type N-glycans were more effective than complex-type N-glycans in triggering mouse and human DC activation and maturation. We believe these results provide some useful information for influenza vaccine development regarding how influenza virus HA proteins with different types of N-glycans activate DCs.
Cancer-associated myositis associated with oesophageal adenocarcinoma arising in Barrett's oesophagus without serum myogenic enzymes elevation: an example suggesting the importance of MRI
Authors: Sasaki Yosuke , Shimizu Hiroshige , Nemoto Tetsuo , Urita Yoshihisa
Published: April 2016

The strong association between myositis and malignancy has been well recognised. Cancer-associated myositis (CAM) is thought to be a cross-reaction to regenerating muscle tissue similar to tumour antigen. We report a case of CAM due to oesophageal adenocarcinoma arising in Barrett's oesophagus without elevation of myogenic enzymes, diagnosed by MRI and repeated endoscopy. Elderly onset, prominent symptoms, lack of interstitial pneumonia, poorer response to immunosuppressive therapies, and the combination of negative conventional myositis-related antibodies and positive anti-p155/140 antibody may help to distinguish CAM from idiopathic inflammatory myopathy. As the prognosis of patients with CAM depends on the malignancy, aggressive diagnosis of CAM and the causative malignancy is required. Our experience underscores the importance of avoiding the over-reliance on serum myogenic enzymes for excluding CAM and recognising MRI as a useful diagnostic tool of myositis.
Epidemiology of neurological manifestations in Sjögren's syndrome: data from the French ASSESS Cohort
Authors: Carvajal Alegria Guillermo , Guellec Dewi , Mariette Xavier , Gottenberg Jacques-Eric , Dernis Emmanuelle , Dubost Jean-Jacques , Trouvin Anne-Priscille , Hachulla Eric , Larroche Claire , Le Guern Veronique , Cornec Divi , Devauchelle-Pensec Valérie , Saraux Alain
Published: April 2016

Objectives

Neurological manifestations seem common in primary Sjögren's syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort of patients with pSS, the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort.

Methods

The ASSESS cohort, established in 2006, includes 395 patients fulfilling American–European Consensus Group criteria for pSS. Demographic and clinical data were compared between patient groups with and without neurological manifestations, and across patient groups with peripheral nervous system (PNS) manifestations, central nervous system (CNS) manifestations and no neurological manifestations.

Results

Data at inclusion were available for 392 patients, whose mean age was 58±12 years. Mean follow-up was 33.9 months. Neurological manifestations were present in 74/392 (18.9%) patients, including 63 (16%) with PNS manifestations and 14 (3.6%) with CNS manifestations. Prevalences were 9.2% for pure sensory neuropathy, 5.3% for sensorimotor neuropathy, 1.3% for cerebral vasculitis and 1.0% for myelitis. Neurological manifestations were associated with greater pSS activity as assessed using the ESSDAI (9.4±6.8 vs 4.3±4.8; p<0.001) and proportion of patients taking immunomodulatory/immunosuppressive drugs (32.4% (24/74) versus 13.8% (44/318), p=0003). New neurological symptoms were more common in patients with than without prior neurological manifestations (RR=3.918 (95% CI 1.91 to 8.05); p<0.001).

Conclusions

Prevalences of peripheral and central neurological manifestations in pSS are about 15% and 5%, respectively. Neurological manifestations are associated with greater pSS activity. New neurological manifestations are more common in patients with prior neurological involvement.
Divergent evolution for diverse substrate recognition by family 31 glycoside hydrolases
Authors: Chaudet M.M. , Rose D.R.
Published: April 2016

Carbohydrates make up an important component of our diet, contributing a significant portion to our total caloric intake. The ability to harvest these molecules for energy is reliant on the activity of carbohydrate-active enzymes. Family 31 α-glucosidases are a group of glycoside hydrolases that has been shown to play a key role in the metabolic process of hydrolyzing dietary starch into monomers of glucose. The purpose of the research presented here is to explore evolutionary changes that occurred within this family of glycoside hydrolases, and to relate these divergences to observed structural differences in relation to predicted substrate preferences. Here we report specific single amino acid changes that are believed to have arisen through evolution, and are directly related to the ability of these enzymes to bind different starch-based glycans. Through phylogenetic analysis we observed a number of evolutionary adaptions that we believe resulted in duplicated genes that allow for the efficient utilization of dietary starch.
Equation to predict maximum pipe stress incorporating internal and external loadings on buried pipes
Authors: Robert D.J. , Rajeev P. , Kodikara J. , Rajani B.
Published: April 2016

Pipelines used for water and other services are very important lifelines in modern society. Commonly, these buried pipes are subjected to significant stresses due to external (traffic and earth) and internal (water pressure) loads. As many of these pipelines were laid sometime in the last century or earlier, in most cases their condition has deteriorated primarily by electrochemical and (or) microbiological corrosion. Corrosion activity (internal and external) can manifest in various forms, but in many cases will lead to reduced pipe thickness, which in turn leads to an increase in pipe stresses induced by the external and internal loads. Currently available analytical procedures to estimate pipe stresses are based on oversimplifications such as the two-dimensional (2-D) analysis based on Winkler springs, limiting their application to general pipe burial conditions. This paper describes the application of a three-dimensional (3-D) finite element method to analyse a buried pipe subjected to external and internal loads. Firstly, the finite element model is validated against the data from field tests conducted on the basis of a cast iron pipe that was laid in 1930 at Strathfield, Sydney, Australia. The results of these 3-D finite element analyses are then used to develop a closed-form expression to predict maximum stresses in pipes of different sizes buried in different soil types. Having obtained a good agreement between the proposed model outcomes and the 3-D finite element analysis results, the proposed model has been validated against the field test data under different internal and external loadings. The verified outcomes of the model reveal that it can be used to predict maximum stresses without conducting a full-scale finite element analysis, which often requires specific computational resources and computational skills. Furthermore, the proposed model can be used in probabilistic analyses, where a large number of calculations need to be carried out to account for the uncertainty of the input variables. The applications of the model are also discussed in relation to the assessment of pipe performance and remaining safe life.
A NEW ERA FOR MONETARY POLICY: CHALLENGES FOR THE EUROPEAN CENTRAL BANK
Authors: RIET AD VAN
Published: April 2016

Since the start of the global financial crisis, the European Central Bank (ECB) has faced exceptional challenges in fulfilling its price stability mandate, marking the start of a new era of monetary policy-making for the eurozone. This paper reviews the ECB’s evolving response from mid-2007 to early-2015, showing how it combined the standard tool of adjusting its policy interest rates with non-standard passive and active balance-sheet measures, accompanied by a forward guidance of its intended monetary stance. Altogether, the ECB stayed focused on price stability while fulfilling the two classical roles of lender of last resort to resolve money market tensions and market maker of last resort to repair monetary transmission. Addressing the many challenges was complicated by the nexus between fragile banks and vulnerable governments, the ensuing financial fragmentation and the complex institutional and political structure of the eurozone. Looking ahead, the new reinforced European financial architecture could make the ECB’s monetary policy task of maintaining price stability for the eurozone easier to accomplish.
Neutrino mass matrices with two vanishing cofactors and Fritzsch texture for charged lepton mass matrix
Authors: Wang Weijian , Guo Shu-Yuan , Wang Zhi-Gang
Published: April 2016

In this paper, we study the cofactor 2 zero neutrino mass matrices with the Fritzsch-type structure in charged lepton mass matrix (CLMM). In the numerical analysis, we perform a scan over the parameter space of all the 15 possible patterns to get a large sample of viable scattering points. Among the 15 possible patterns, three of them can accommodate the latest lepton mixing and neutrino mass data. We compare the predictions of the allowed patterns with their counterparts with diagonal CLMM. In this case, the severe cosmology bound on the neutrino mass set a strong constraint on the parameter space, rendering two patterns only marginally allowed. The Fritzsch-type CLMM will have impact on the viable parameter space and give rise to different phenomenological predictions. Each allowed pattern predicts the strong correlations between physical variables, which is essential for model selection and can be probed in future experiments. It is found that under the no-diagonal CLMM, the cofactor zeros structure in neutrino mass matrix is unstable as the running of renormalization group (RG) from seesaw scale to the electroweak scale. A way out of the problem is to propose the flavor symmetry under the models with a TeV seesaw scale. The inverse seesaw model and a loop-induced model are given as two examples.
Block-Based High Capacity Multilevel Image Steganography
Authors: Kasana Geeta , Singh Kulbir , Bhatia Satvinder Singh
Published: April 2016

This paper proposes a block-based high capacity steganography technique for digital images. The cover image is decomposed into blocks of equal size and the largest pixel of each block is found to embed the secret data bits and also the smallest pixel of each block is used for embedding to enhance the capacity. Embedding of secret data is performed using the concept that the pixel of a cover image has only two states — even and odd. Multilevel approach is also combined in the proposed technique to achieve high embedding capacity. In order to make the proposed technique more secure, a key is generated using embedding levels, block size, pixel embedding way, encryption parameters, and starting blocks of each embedding levels. Embedding capacity and visual quality of stego images generated by the proposed steganography technique are higher than the existing techniques. Steganalysis tests have been performed to show the un-detectability and imperceptibility of the proposed technique.
Hardware Design of Seizure Detection Based on Wavelet Transform and Sample Entropy
Authors: Wang Yuanfa , Li Zunchao , Feng Lichen , Wang Chuang , Jing Wen , Zhang Yefei
Published: April 2016

Detecting epileptic seizure is a very time consuming and costly task if a support vector machine (SVM) hardware processor is used. In this paper, an automated seizure detection scheme is developed by combining discrete wavelet transform (DWT), sample entropy (SampEn) and a novel classification algorithm based on each wavelet coefficient and voting strategy. In order to save circuit area, a Daubechies order 4 (db4) filter of lattice structure is introduced in DWT, only half elements of the symmetric distance matrix in the SampEn are stored and module reusing strategy is used. To speed up the detection, intermediate results are reused by reasonably organizing the SampEn calculation procedures. The seizure detection scheme is implemented in a field-programmable gate array (FPGA) and its classification performance is tested with publicly available epilepsy dataset.
Framework for Automatic Semantic Annotation of Arabic Websites
Authors: Helmy Tarek , Al-Bukhitan Saeed
Published: April 2016

In order to achieve the vision of the semantic Web, it is important to have enough amount of semantic content on the Web sources. To produce the semantic content on the existing Web, semantic annotation of the Web sources is required. Semantic annotation adds machine-readable content to the Web sources. Because the Web is growing at an exponential rate, semantic annotation by hand is not possible. In this paper, we present an Automatic Semantic Annotation Framework (ASAF) for semantic annotation of Arabic Web sources based on the domain ontologies. We present a learning approach that utilizes public Arabic resources, such as Wikipedia and WordNet for building Arabic ontologies. Moreover, we present different approaches for extracting name entities and relationships from Arabic Web sources. As a case study, we have developed and expanded a set of Arabic ontologies related to food, health, and nutrition through a set of processes. We have also developed the ASAF prototype, and showed how it can utilize these ontologies for extracting health, food related name entities, and relationships from the Web sources in order to annotate and store them in the knowledge-base. We conducted several experiments to test the capability of ASAF in recognizing the name entities and relationships using different approaches. Empirical evaluations of ASAF show promising performance results in terms of precision, recall, and [Formula: see text]-measure. The outcome of the presented framework could be utilized by semantic Web searching applications to retrieve precise answers to the end user smarter queries. An important feature of ASAF is that it could be ported to other domains with minimal extension. ASAF also contributes to the vision of the semantic Web in the target domains in Arabic Web sources.
Zn-complex of a natural yellow chlorophyll catabolite
Authors: Li Chengjie , Kräutler Bernhard
Published: April 2016

“Non-fluorescent” chlorophyll catabolites (NCCs) were named “rusty pigments” originally, as they easily oxidized to yellow chlorophyll catabolites (YCCs) and other colored natural “phyllobilins.” In the present work, binding of Zn(II)-ions by YCC and its methyl ester YCC-Me, and structural investigations of the resulting Zn(II)-complexes are reported. Binding of Zn-ions to the weakly luminescent YCC or YCC-Me in DMSO produces orange-yellow complexes that exhibit strong green emission. The Zn-complex of YCC-Me was isolated and characterized by UV-vis-, fluorescence-, mass- and NMR-spectra. The data revealed a 2:1 complex, Zn(YCC-Me)[Formula: see text], in which YCC-Me serves as bidentate ligand. The Zn(II)-center in Zn(YCC-Me)[Formula: see text] is, thereby, deduced to be coordinated in a pseudo tetrahedral fashion. Formation of Zn(YCC-Me)[Formula: see text] (and of Zn(YCC)[Formula: see text] is compatible with an isomerization of the lactam form of ring D to the corresponding lactim tautomer in these neutral Zn(II)-complexes.
Cross-Sectional Determinants of Information Quality Proxies and Cost of Capital Measures
Authors: Liu Michelle , Wysocki Peter
Published: April 2016

This paper examines the source of the documented empirical link between measures of “accruals quality” and a firm’s cost of capital. First, we argue that when regressions include accruals quality and operating volatility as determinants, these highly correlated measures capture different underlying constructs. Second, we find that in such regressions, the accruals quality measure displays inconsistent associations, while operating volatility variables display robust associations, with various cost of capital measures. Third, we provide research design suggestions to disentangle the effect of accruals quality from operating volatility, and we show how this method leads to less noisy coefficient estimates. These findings should be useful in designing empirical tests of the hypothesized associations involving accruals quality, operating volatility, and cost of capital.
FOXSI-2: Upgrades of the Focusing Optics X-ray Solar Imager for its Second Flight
Authors: Christe Steven , Glesener Lindsay , Buitrago-Casas Camilo , Ishikawa Shin-Nosuke , Ramsey Brian , Gubarev Mikhail , Kilaru Kiranmayee , Kolodziejczak Jeffery J. , Watanabe Shin , Takahashi Tadayuki , Tajima Hiroyasu , Turin Paul , Shourt Van , Foster Natalie , Krucker Sam
Published: April 2016

The Focusing Optics X-ray Solar Imager (FOXSI) sounding rocket payload flew for the second time on 2014 December 11. To enable direct Hard X-Ray (HXR) imaging spectroscopy, FOXSI makes use of grazing-incidence replicated focusing optics combined with fine-pitch solid-state detectors. FOXSI’s first flight provided the first HXR focused images of the Sun. For FOXSI’s second flight several updates were made to the instrument including updating the optics and detectors as well as adding a new Solar Aspect and Alignment System (SAAS). This paper provides an overview of these updates as well as a discussion of their measured performance.
Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure
Authors: Rautava Samuli , Walker W. Allan , Lu Lei
Published: April 2016

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment.
Brown adipose tissue: The heat is on the heart
Authors: Thoonen Robrecht , Hindle Allyson G. , Scherrer-Crosbie Marielle
Published: April 2016

The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart.
Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study
Authors: Nyúl-Tóth Ádám , Suciu Maria , Molnár Judit , Fazakas Csilla , Haskó János , Herman Hildegard , Farkas Attila E. , Kaszaki József , Hermenean Anca , Wilhelm Imola , Krizbai István A.
Published: April 2016

The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.
Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in coronary artery soluble guanylate cyclase depletion by angiotensin II
Authors: Patel Dhara , Alhawaj Raed , Kelly Melissa R. , Accarino John J. O. , Lakhkar Anand , Gupte Sachin A. , Sun Dong , Wolin Michael S.
Published: April 2016

Oxidation of the soluble guanylate cyclase (sGC) heme promotes loss of regulation by nitric oxide (NO) and depletion of sGC. We hypothesized that angiotensin II (ANG II) stimulation of mitochondrial superoxide by its type 1 receptor could function as a potential inhibitor of heme biosynthesis by ferrochelatase, and this could decrease vascular responsiveness to NO by depleting sGC. These processes were investigated in a 24-h organoid culture model of bovine coronary arteries (BCA) with 0.1 μM ANG II. Treatment of BCA with ANG II increased mitochondrial superoxide, depleted mitochondrial superoxide dismutase (SOD2), ferrochelatase, and cytochrome oxidase subunit 4, and sGC, associated with impairment of relaxation to NO. These processes were attenuated by organoid culture with 8-bromo-cGMP and/or δ-aminolevulinic acid (a stimulator of sGC by protoporphyrin IX generation and heme biosynthesis). Organoid culture with Mito-TEMPOL, a scavenger of mitochondrial matrix superoxide, also attenuated ANG II-elicited ferrochelatase depletion and loss of relaxation to NO, whereas organoid culture with Tempol, an extramitochondrial scavenger of superoxide, attenuated the loss of relaxation to NO by ANG II, but not ferrochelatase depletion, suggesting cytosolic superoxide could be an initiating factor in the loss of sGC regulation by NO. The depletion of cytochrome oxidase subunit 4 and sGC (but not catalase) suggests that sGC expression may be very sensitive to depletion of heme caused by ANG II disrupting ferrochelatase activity by increasing mitochondrial superoxide. In addition, cGMP-dependent activation of protein kinase G appears to attenuate these ANG II-stimulated processes through both preventing SOD2 depletion and increases in mitochondrial and extramitochondrial superoxide.
The effect of elevations in internal temperature on event-related potentials during a simple cognitive task in humans
Authors: Shibasaki Manabu , Namba Mari , Oshiro Misaki , Crandall Craig G. , Nakata Hiroki
Published: April 2016

The effect of hyperthermia on cognitive function remains equivocal, perhaps because of methodological discrepancy. Using electroencephalographic event-related potentials (ERPs), we tested the hypothesis that a passive heat stress impairs cognitive processing. Thirteen volunteers performed repeated auditory oddball paradigms under two thermal conditions, normothermic time control and heat stress, on different days. For the heat stress trial, these paradigms were performed at preheat stress (i.e., normothermic) baseline, when esophageal temperature had increased by ∼0.8°C, when esophageal temperature had increased by ∼2.0°C, and during cooling following the heat stress. The reaction time and ERPs were recorded in each session. For the time control trial, subjects performed the auditory oddball paradigms at approximately the same time interval as they did in the heat stress trial. The peak latency and amplitude of an indicator of auditory processing (N100) were not altered regardless of thermal conditions. An indicator of stimulus classification/evaluation time (latency of P300) and the reaction time were shortened during heat stress; moreover an indicator of cognitive processing (the amplitude of P300) was significantly reduced during severe heat stress (8.3 ± 1.3 μV) relative to the baseline (12.2 ± 1.0 μV, P < 0.01). No changes in these indexes occurred during the time control trial. During subsequent whole body cooling, the amplitude of P300 remained reduced, and the reaction time and latency of P300 remained shortened. These results suggest that excessive elevations in internal temperature reduce cognitive processing but promote classification time.
Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy
Authors: Avoli Massimo , de Curtis Marco , Gnatkovsky Vadym , Gotman Jean , Köhling Rüdiger , Lévesque Maxime , Manseau Frédéric , Shiri Zahra , Williams Sylvain
Published: April 2016

Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80–200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250–500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF- or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well.
Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays
Authors: Johnen Sandra , Meißner Frank , Krug Mario , Baltz Thomas , Endler Ingolf , Mokwa Wilfried , Walter Peter
Published: April 2016

Background.To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells.Methods.MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact.Results.Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genesCCNC,MYC, andTP53was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes.Conclusions.All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue.
Ecotoxicity and Preliminary Risk Assessment of Nonivamide as a Promising Marine Antifoulant
Authors: Liu Sujing , Zhou Jun , Ma Xuanxuan , Liu Ying , Ma Xing , Xia Chuanhai
Published: April 2016

The unclear environmental performance of nonivamide limits its application as a marine antifoulant. In this study, the natural degradation of nonivamide was studied in seawater and tap water. The half-life was 5.8 d, 8.8 d, 12.2 d, and 14.7 d in seawater and tap water in photolysis and biolysis, respectively. Furthermore, the ecotoxicity of nonivamide was assessed using marine microalgae,Chlorella vulgarisandPlatymonassp.;EC50,  6 dvalues on the growth ofChlorella vulgarisandPlatymonassp. were 16.9 mg L−1and 19.21 mg L−1, respectively. The toxicity and environmental risk of nonivamide on microalgae were significantly decreased due to the natural degradation in seawater.
Circulating Permeability Factors in Primary Focal Segmental Glomerulosclerosis: A Review of Proposed Candidates
Authors: Königshausen Eva , Sellin Lorenz
Published: April 2016

Primary focal segmental glomerulosclerosis (FSGS) is a major cause of the nephrotic syndrome and often leads to end-stage renal disease. This review focuses on circulating permeability factors in primary FSGS that have been implicated in the pathogenesis for a long time, partly due to the potential recurrence in renal allografts within hours after transplantation. Recently, three molecules have been proposed as a potential permeability factor by different groups: the soluble urokinase plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), and CD40 antibodies. Both CLCF-1 and CD40 antibodies have not been validated by independent research groups yet. Since the identification of suPAR, different studies have questioned the validity of suPAR as a biomarker to distinguish primary FSGS from other proteinuric kidney diseases as well as suPAR’s pathogenic role in podocyte damage. Researchers have suggested that cleaved molecules of suPAR have a pathogenic role in FSGS but further studies are needed to determine this role. In future studies, proposed standards for the research of the permeability factor should be carefully followed. The identification of the permeability factor in primary FSGS would be of great clinical relevance as it could influence potential individual treatment regimen.
Greenhouse Gases Emissions from Wastewater Treatment Plants: Minimization, Treatment, and Prevention
Authors: Campos J. L. , Valenzuela-Heredia D. , Pedrouso A. , Val del Río A. , Belmonte M. , Mosquera-Corral A.
Published: April 2016

The operation of wastewater treatment plants results in direct emissions, from the biological processes, of greenhouse gases (GHG) such as carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O), as well as indirect emissions resulting from energy generation. In this study, three possible ways to reduce these emissions are discussed and analyzed:(1)minimization through the change of operational conditions,(2)treatment of the gaseous streams, and(3)prevention by applying new configurations and processes to remove both organic matter and pollutants. In current WWTPs, to modify the operational conditions of existing units reveals itself as possibly the most economical way to decrease N2O and CO2emissions without deterioration of effluent quality. Nowadays the treatment of the gaseous streams containing the GHG seems to be a not suitable option due to the high capital costs of systems involved to capture and clean them. The change of WWTP configuration by using microalgae or partial nitritation-Anammox processes to remove ammonia from wastewater, instead of conventional nitrification-denitrification processes, can significantly reduce the GHG emissions and the energy consumed. However, the area required in the case of microalgae systems and the current lack of information about stability of partial nitritation-Anammox processes operating in the main stream of the WWTP are factors to be considered.
Shengmai San Ameliorates Myocardial Dysfunction and Fibrosis in Diabetic db/db Mice
Authors: Zhao Juan , Cao Tong-Tong , Tian Jing , Chen Hui-hua , Zhang Chen , Wei Hong-Chang , Guo Wei , Lu Rong
Published: April 2016

In this study, we mainly investigated the effects of Shengmai San (SMS) on diabetic cardiomyopathy (DCM) in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24‐week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF‐β dependent pathway.
Shrinking Regions in a Shrinking Country: The Geography of Population Decline in Lithuania 2001–2011
Authors: Ubarevičienė Rūta , van Ham Maarten , Burneika Donatas
Published: April 2016

Shrinking populations have been gaining increasing attention, especially in postsocialist Eastern and Central European countries. While most studies focus on specific cities and regions, much less is known about the spatial dimension of population decline on the national level and the local factors determining spatially uneven population change. This study uses Lithuanian census data from the years 2001 to 2011 to get insight into the geography of population change for the whole country. Lithuania has experienced one of the highest rates of population decline in the world in the last decades. The predictive models show that regional factors have a strong effect on the variation in population change throughout the country but also reveal that sociodemographic and economic area characteristics play a role in the process of decline. Our results give little hope to those who would like to reverse the ongoing trends of population change and emphasize the need for spatial planning to cope with the changes. This is an approach which currently does not exist in practice in Lithuania.