bluuebunny/crossref_metadata_2025 huggingface dataset:
How bold is blood oxygenation level‐dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions
Authors: Niendorf T. , Pohlmann A. , Arakelyan K. , Flemming B. , Cantow K. , Hentschel J. , Grosenick D. , Ladwig M. , Reimann H. , Klix S. , Waiczies S. , Seeliger E.
Published: September 2014

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level‐dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD‐MRI is non‐invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre‐) clinical studies revived the question as to how bold renal BOLD‐MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD‐MRI are summarized. The link between tissue oxygenation and the oxygenation‐sensitive MR biomarker is outlined. The merits and limitations of renal BOLD‐MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal and renal tissue partial pressure of oxygen (pO2) are discussed with a focus on factors confounding the vs. tissue pO2 relation. Multi‐modality in vivo approaches suitable for detailing the role of the confounding factors that govern are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.
The role of adenylyl cyclase isoform 6 in β‐adrenoceptor signalling in murine airways
Authors: Birrell Mark A , Bonvini Sara J , Wortley Michael A , Buckley James , Yew‐Booth Liang , Maher Sarah A , Dale Nicole , Dubuis Eric D , Belvisi Maria G
Published: September 2014

Background and Purpose

Adenylyl cyclase (AC) is a key signalling enzyme for many GPCRs and catalyses the conversion of ATP to cAMP which, in turn, is a crucial determinant of many biological responses. β‐Adrenoceptor agonists are prescribed as bronchodilators for asthma and chronic obstructive pulmonary disease, and it is commonly assumed that they elicit their actions via AC‐dependent production of cAMP. However, empirical evidence in support of this is lacking and the exact mechanism by which these drugs acts remains elusive. This is partly due to the existence of at least 10 different isoforms of AC and the absence of any truly selective pharmacological inhibitors. Here, we have used genetically modified mice and model systems to establish the role of AC isoforms in the airway responses to β‐adrenoceptor agonists.

Experimental Approach

Receptors mediating responses to β‐adrenoceptor agonists in airway smooth muscle (ASM) and sensory nerve were identified in isolated tissue systems. Expression of mRNA for the AC isoforms in ASM and neurones was determined by qPCR. Functional responses were assessed in AC isoform KO mice and wild‐type controls.

Key Results

Airway and vagal tissue expressed mRNA for various isoforms of AC. AC6 was the most prominent isoform. Responses to β‐adrenoceptor agonists in tissues from AC6 KO mice were virtually abolished.

Conclusions and Implications

AC6 played a critical role in relaxation of ASM to β1‐adrenoceptor agonists and in modulation of sensory nerves by β1‐3‐adrenoceptor agonists. These results further unravel the signalling pathway of this extensively prescribed class of medicine.
Associations Between Family Structure Change and Child Behavior Problems: The Moderating Effect of Family Income
Authors: Ryan Rebecca M. , Claessens Amy , Markowitz Anna J.
Published: September 2014

This study investigated conditions under which family structure matters most for child well‐being. Using data from the Children of the National Longitudinal Survey of Youth (n = 3,936), a national sample of U.S. families, it was estimated how changes in family structure related to changes in children's behavior between age 3 and 12 separately by household income level to determine whether associations depended on families' resources. Early changes in family structure, particularly from a two‐biological‐parent to single‐parent family, predicted increases in behavior problems more than later changes, and movements into single and stepparent families mattered more for children of higher versus lower income parents. Results suggest that for children of higher income parents, moving into a stepfamily may improve, not undermine, behavior.
B7x/B7-H4 modulates the adaptive immune response and ameliorates renal injury in antibody-mediated nephritis
Authors: Pawar R D , Goilav B , Xia Y , Herlitz L , Doerner J , Chalmers S , Ghosh K , Zang X , Putterman C
Published: September 2014

Kidney disease is one of the leading causes of death in patients with lupus and other autoimmune diseases affecting the kidney, and is associated with deposition of antibodies as well as infiltration of T lymphocytes and macrophages, which are responsible for initiation and/or exacerbation of inflammation and tissue injury. Current treatment options have relatively limited efficacy; therefore, novel targets need to be explored. The co-inhibitory molecule, B7x, a new member of the B7 family expressed predominantly by non-lymphoid tissues, has been shown to inhibit the proliferation, activation and functional responses of CD4 and CD8 T cells. In this study, we found that B7x was expressed by intrinsic renal cells, and was up-regulated upon stimulation with inflammatory triggers. After passive administration of antibodies against glomerular antigens, B7x−/− mice developed severe renal injury accompanied by a robust adaptive immune response and kidney up-regulation of inflammatory mediators, as well as local infiltration of T cells and macrophages. Furthermore, macrophages in the spleen of B7x−/− mice were polarized to an inflammatory phenotype. Finally, treatment with B7x-immunoglobulin (Ig) in this nephritis model decreased kidney damage and reduced local inflammation. We propose that B7x can modulate kidney damage in autoimmune diseases including lupus nephritis and anti-glomerular basement membrane disease. Thus, B7x mimetics may be a novel therapeutic option for treatment of immune-mediated kidney disease.
Optimizing the selection of patients with low rectal cancer for intersphincteric resection by evaluating vertical invasion to the levator and external sphincter
Authors: Narui K. , Ichikawa Y. , Ike H. , Ota M. , Saito S. , Fujii S. , Sasaki T. , Nozawa A. , Shimada H. , Endo I.
Published: September 2014

Aim

The indications for intersphincteric (ISR) anterior resection are not clearly defined. The aim of this study was to evaluate vertical extension of T2 or T3 low rectal cancer treated by rectal amputation to optimize patient selection for ISR.

Method

The abdominoperineal excision specimens of T2 or T3 low rectal cancer from 53 patients treated between 1992 and 2004 were retrospectively reviewed. Vertical invasion was quantified by measuring the shortest distance between the tumour and the striated muscle (T‐SM), assuming that this represented the surgical margin that would have be achieved had an ISR been performed.

Results

Involvement of the dentate line (DL) and intramural distal spread were independent risk factors for T‐SM ≤ 2 mm. The T‐SM was less when the inferior border of the tumour was on the distal side of the DL (r = 0.572, P < 0.001). The probability of involvement of the DL, intramural distal spread or either one of these being associated with T‐SM ≤ 2 mm was 43, 46 and 43%, respectively. All patients without both intramural distal spread and involvement of the DL had T‐SM > 2.

Conclusion

We recommend that ISR should only be performed for patients with T2 or T3 low rectal cancer in whom the lowest edge of the tumour is above the DL and there is no intramural distal spread. Such patients are relatively unlikely to have a T‐SM ≤ 2 mm.
Transvaginal repair of recurrent pouch–vaginal fistula
Authors: Sagar R. C. , Thornton M. , Herd A. , Brayshaw I. , Sagar P. M.
Published: September 2014

Aim

Pouch–vaginal fistula is an uncommon but unpleasant complication. The chance of successful repair with various surgical procedures is around 50% and the early promise of collagen button plugs was not followed by good long‐term results. We report a series of patients who underwent transvaginal repair of pouch–vaginal fistula after failed collagen plugs accompanied by a video to show the operative technique.

Method

Patients were identified from a prospectively maintained database. Patient demographics, operation notes, complications and ultimate outcome were recorded.

Results

Eleven patients, each of whom had previously undergone an attempt to close the fistula with a collagen button plug, underwent transvaginal repair. Nine (81%) were successful at a median follow‐up of 14 (6–56) months. The remaining two patients reported symptomatic improvement.

Conclusion

Pouch–vaginal fistula can be successfully closed by the transvaginal technique after a failed button plug procedure.
Diastolic function improves after resolution of takotsubo cardiomyopathy
Authors: Kumar Sanjay , Waldenborg Micael , Bhumireddy Priya , Ramkissoon Keshwar , Loiske Karin , Innasimuthu Antony L. , Grodman Richard S. , Heitner John F. , Emilsson Kent , Lazar Jason M.
Published: September 2014

Background

Takotsubo cardiomyopathy (TTC) is a condition of reversible left ventricular (LV) systolic dysfunction. However, the diastolic function (DF) manifestations of TTC have not been widely investigated. We performed a bicentric study with retrospective analysis of DF in patients with TTC, during onset and at follow‐up.

Methods

Twenty‐eight patients with TTC (64 ± 10 years, F 24) were included. All underwent echocardiograms acutely and at the recovery phase (average three months later). Diastolic and systolic function parameters were recorded, including E‐wave velocity (E), A‐wave velocity, E/A ratio, relaxation (e′) and contractility (S′) based on tissue Doppler velocities of the mitral annuli, ejection fraction (EF), left atrial (LA) size and DF stages.

Results

Recovery, including the mean difference with 95% confidence interval, was associated with tending improvement (i.e. uncorrected significance) in E [13 cm s−1 (−24, −2·3), P = 0·02] and in E/A ratio [0·2 (−0·41, −0·02), P = 0·04], as well as significant improvement (after multiple comparison correction) in mean e′ [2·0 cm s−1 (−3·3, −1·2), P<0·001] and in A‐wave duration [29 ms (−46·7, −12·7), P = 0·002]. LA area tended to decrease during recovery [−2 cm² (0·33, 2·4), P = 0·01]. Improvement in DF stages was significant between the phases (21% versus 58% defined as normal DF, P = 0·016). Improvement in LVEF correlated with improvement in mean e′ (r = 0·52, P = 0·02).

Conclusions

TTC is associated with an acute impairment of conventional DF variables, which improves during recovery. DF recovery seems to occur in parallel with systolic recovery in patients with TTC.
The View from Way Below: Inter‐Species Encounter, Membranes, and the Reality of Christ
Authors: Dahill Lisa E.
Published: September 2014

Viewing modern life from the perspective and world of those whose lives are treated as expendable commodities in our current economic systems—humans and creatures of every other species—creates, Bonhoeffer asserts, the most reliable hermeneutical standpoint for seeing and living in reality. This essay attempts to fashion in broad strokes a Christian theology of creaturely re‐engagement: learning to live again “way below,” in literal and metaphoric touch with reality. I assert that Bonhoeffer's theology of I/Thou encounter as the means of humans’ ethical formation has the potential to ground a broader theology of inter‐species encounter as well.
Increased stroke risk among adult asthmatic patients
Authors: Chung Wei‐Sheng , Lin Cheng‐Li , Chen Yung‐Fu , Ho Feng‐Ming , Hsu Wu‐Huei , Kao Chia‐Hung
Published: September 2014

Background

We conducted a nationwide population‐based cohort study to investigate the effects of asthma on the risk of stroke development in an Asian population.

Materials and methods

Newly diagnosed asthmatic patients aged ≥ 18 years were identified, and asthma‐free controls were randomly selected from the general population and frequency matched according to age, sex and index year using records obtained from the National Health Insurance Research Database between 2000 and 2010. Both cohorts were followed up until the end of 2011 to measure the incidence of stroke. The risk of stroke was analysed using Cox proportional hazard regression models, including factors such as sex, age and comorbidities.

Results

We followed the asthmatic patients for 104 697 person‐years and followed the nonasthmatic people for 426 729 person‐years. The incidence density rate of stroke increased in all of the groups of asthmatic patients compared with that of the controls when stratified according to sex, age and comorbidities. The hazard ratio (HR) of stroke was 1·37‐fold greater for the asthmatic cohort, compared with that for the nonasthmatic cohort, after adjusting for sex, age and comorbidities. The adjusted HR of developing stroke substantially increased with older age and the increased frequency of asthmatic exacerbation and hospitalization. The patients receiving beta‐2 agonists as a treatment exhibited a significantly greater risk of stroke compared with the patients receiving only inhaled corticosteroids, after adjusting for covariates.

Conclusion

Asthma may be an independent risk factor for stroke, and its severity exhibits a dose response of stroke development.
Models for transition clinics
Authors: Carrizosa Jaime , An Isabelle , Appleton Richard , Camfield Peter , Von Moers Arpad
Published: September 2014

Transition is a purposeful, planned process that addresses the medical, psychosocial, educational, and vocational needs of adolescents and young adults with chronic medical conditions, as they advance from a pediatric and family‐centered to an adult, individual focused health care provider. This article describes some of the models for transition clinics or services for epilepsy in five countries (Canada, France, Colombia, Germany, and the United Kingdom). These models include joint adult and pediatric clinics, algorithm‐driven service, and a check list system in the context of pediatric care. Evaluation of these models is limited, and it is not possible to choose an optimal program. The attitude and motivation of health care providers may be the most important elements.
Ecosystem properties of semiarid savanna grassland in West Africa and its relationship with environmental variability
Authors: Tagesson Torbern , Fensholt Rasmus , Guiro Idrissa , Rasmussen Mads Olander , Huber Silvia , Mbow Cheikh , Garcia Monica , Horion Stéphanie , Sandholt Inge , Holm‐Rasmussen Bo , Göttsche Frank M. , Ridler Marc‐Etienne , Olén Niklas , Lundegard Olsen Jørgen , Ehammer Andrea , Madsen Mathias , Olesen Folke S. , Ardö Jonas
Published: September 2014

The Dahra field site in Senegal, West Africa, was established in 2002 to monitor ecosystem properties of semiarid savanna grassland and their responses to climatic and environmental change. This article describes the environment and the ecosystem properties of the site using a unique set of in situ data. The studied variables include hydroclimatic variables, species composition, albedo, normalized difference vegetation index (NDVI), hyperspectral characteristics (350–1800 nm), surface reflectance anisotropy, brightness temperature, fraction of absorbed photosynthetic active radiation (FAPAR), biomass, vegetation water content, and land‐atmosphere exchanges of carbon (NEE) and energy. The Dahra field site experiences a typical Sahelian climate and is covered by coexisting trees (~3% canopy cover) and grass species, characterizing large parts of the Sahel. This makes the site suitable for investigating relationships between ecosystem properties and hydroclimatic variables for semiarid savanna ecosystems of the region. There were strong interannual, seasonal and diurnal dynamics in NEE, with high values of ~−7.5 g C m−2 day−1 during the peak of the growing season. We found neither browning nor greening NDVI trends from 2002 to 2012. Interannual variation in species composition was strongly related to rainfall distribution. NDVI and FAPAR were strongly related to species composition, especially for years dominated by the species Zornia glochidiata. This influence was not observed in interannual variation in biomass and vegetation productivity, thus challenging dryland productivity models based on remote sensing. Surface reflectance anisotropy (350–1800 nm) at the peak of the growing season varied strongly depending on wavelength and viewing angle thereby having implications for the design of remotely sensed spectral vegetation indices covering different wavelength regions. The presented time series of in situ data have great potential for dryland dynamics studies, global climate change related research and evaluation and parameterization of remote sensing products and dynamic vegetation models.
SUMO‐targeted ubiquitin ligase RNF4 plays a critical role in preventing chromosome loss
Authors: Hirota Kouji , Tsuda Masataka , Murai Junko , Takagi Tokiyo , Keka Islam Shamima , Narita Takeo , Fujita Mari , Sasanuma Hiroyuki , Kobayashi Junya , Takeda Shunichi
Published: September 2014

RING finger protein 4 (RNF4) represents a subclass of ubiquitin ligases that target proteins modified by the small ubiquitin‐like modifier (SUMO) for ubiquitin‐mediated degradation. We disrupted the RNF4 gene in chicken DT40 cells and found that the resulting RNF4−/− cells gradually lost proliferation capability. Strikingly, this compromised proliferation was associated with an unprecedented cellular effect: the gradual decrease in the number of intact chromosomes. In the 6 weeks after gene targeting, there was a 25% reduction in the DNA content of the RNF4−/− cells. Regarding trisomic chromosome 2, 60% of the RNF4−/− cells lost one homologue, suggesting that DNA loss was mediated by whole chromosome loss. To determine the cause of this chromosome loss, we examined cell‐cycle checkpoint pathways. RNF4−/− cells showed a partial defect in the spindle assembly checkpoint, premature dissociation of sister chromatids, and a marked increase in the number of lagging chromosomes at anaphase. Thus, combined defects in SAC and sister chromatid cohesion may result in increased lagging chromosomes, leading to chromosome loss without accompanying chromosome gain in RNF4−/− cells. We therefore propose that RNF4 plays a novel role in preventing the loss of intact chromosomes and ensures the maintenance of chromosome integrity.
Reciprocal Relations Between Emotional Self‐Efficacy Beliefs and Ego‐Resiliency Across Time
Authors: Milioni Michela , Alessandri Guido , Eisenberg Nancy , Castellani Valeria , Zuffianò Antonio , Vecchione Michele , Caprara Gian Vittorio
Published: September 2014

The present study examined the longitudinal relations of adolescents' self‐reported ego‐resiliency to their emotional self‐efficacy beliefs in expressing positive emotions and in managing negative emotions as they moved into early adulthood. Participants were 239 females and 211 males with a mean age of 17 years (SD = .80) at T1, 19 years (SD = .80) at T2, 21 years (SD = .82) at T3, and 25 years (SD = .80) at T4. A four‐wave cross‐lagged regression model and mediational analyses were used. In a panel structural equation model controlling for the stability of the constructs, reciprocal relationships across time were found between ego‐resiliency and emotional self‐efficacy beliefs related to the expression of positive emotions and to the management of negative emotions. Moreover, the relation between ego‐resiliency assessed at T1 and T3, and ego‐resiliency assessed at T2 and T4, was mediated through emotional self‐efficacy beliefs (at T2 and T3, respectively), and vice versa. The posited conceptual model accounted for a significant portion of variance in ego‐resiliency and has implications for understanding the development of ego‐resiliency.
Interview with Noam Chomsky, 1984
Authors: Joyce Anne
Published: September 2014

Dr. Chomsky is [emeritus] Institute Professor in the Department of Linguistics and Philosophy at the Massachusetts Institute of Technology. He is the author of The Fateful Triangle: The United States, Israel and the Palestinians (1983). The following interview was conducted by Anne Joyce, editor of Middle East Policy, on October 18, 1984 (when the title of this publication was American‐Arab Affairs).
Semiautomatic Extraction of Road Horizontal Alignment from a Mobile LiDAR System
Authors: Holgado‐Barco Alberto , González‐Aguilera Diego , Arias‐Sanchez Pedro , Martinez‐Sanchez Joaquin
Published: September 2014

This article proposes a method to semiautomatically extract the road axis through a mobile LiDAR system, a recent popular technology for transportation‐related applications, road estimation and even to enhance driver safety. In particular, the approach developed has two components: (1) the feature extraction from LiDAR data to model the road axis, and (2) the estimation of the horizontal alignment that meets the requirements and practice for a transportation authority. Given the massive and complex character of the data captured by the system, a hierarchical (coarse‐to‐fine) and robust strategy based on segmentation, parameterization and filtering, which determine the road centerline together with the geometric elements that compose its horizontal alignment, such as straight lines, circular arcs, and clothoids, has been developed and implemented. Test results using a simulated and a real data are discussed and validated. The experimental results obtained with real cases guarantying relative accuracies under 2%, being a useful approach to produce accurate estimations of the horizontal geometric features of the road alignment.
Relationships and genetic consequences of contrasting modes of speciation among endemic species of Robinsonia (Asteraceae, Senecioneae) of the Juan Fernández Archipelago, Chile, based on AFLPs and SSRs
Authors: Takayama Koji , López‐Sepúlveda Patricio , Greimler Josef , Crawford Daniel J. , Peñailillo Patricio , Baeza Marcelo , Ruiz Eduardo , Kohl Gudrun , Tremetsberger Karin , Gatica Alejandro , Letelier Luis , Novoa Patricio , Novak Johannes , Stuessy Tod F.
Published: September 2014

This study analyses and compares the genetic signatures of anagenetic and cladogenetic speciation in six species of the genus Robinsonia (Asteraceae, Senecioneae), endemic to the Juan Fernández Islands, Chile.

Population genetic structure was analyzed by amplified fragment length polymorphism (AFLP) and microsatellite (simple sequence repeat, SSR) markers from 286 and 320 individuals, respectively, in 28 populations. Each species is genetically distinct. Previous hypotheses of classification among these species into subgenera and sections, via morphological, phytochemical, isozymic and internal transcribed spacer (ITS) data, have been confirmed, except that R. saxatilis appears to be related to R. gayana rather than R. evenia.

Analysis of phylogenetic results and biogeographic context suggests that five of these species have originated by cladogenesis and adaptive radiation on the older Robinson Crusoe Island. The sixth species, R. masafuerae, restricted to the younger Alejandro Selkirk Island, is closely related to and an anagenetic derivative of R. evenia from Robinson Crusoe.

Microsatellite and AFLP data reveal considerable genetic variation among the cladogenetically derived species of Robinsonia, but within each the genetic variation is lower, highlighting presumptive genetic isolation and rapid radiation. The anagenetically derived R. masafuerae harbors a level of genetic variation similar to that of its progenitor, R. evenia. This is the first direct comparison of the genetic consequences of anagenetic and cladogenetic speciation in plants of an oceanic archipelago.
Differential Expression of Suppressor of Cytokine Signalling Proteins in Behçet's Disease
Authors: Hamedi M. , Bergmeier L. A. , Hagi‐Pavli E. , Vartoukian S. R. , Fortune F.
Published: September 2014

Behçet's disease (BD) is a chronic, multisystemic, recurrent vasculitis disease of unknown aetiology. Proinflammatory cytokines are a key feature of the disease, but the triggers for their induction are not well understood and/or controversial. Suppressor of cytokine signalling (SOCS) proteins which negatively regulate the JAK–STAT signalling pathway of cytokine induction may be dysregulated in BD. The expression of SOCS1 and 3 mRNA and protein was studied in peripheral blood mononuclear cells (PBMCs) and neutrophils of patients with BD and compared with healthy controls (HCs) and patients with recurrent aphthous stomatitis (RAS) using RT‐PCR, Western blot and immunohistochemistry. SOCS1 and 3 mRNA was also measured in buccal mucosal cells (BMC) of patients with BD and HCs. SOCS1 and 3 mRNA was significantly upregulated in PBMCs of patients with BD compared with HCs (P = 0.0149; P = 0.0007). In addition, there were subtle differences between expression in active and symptom‐free BD (quiescent BD). SOCS1 and SOCS 3 were also significantly upregulated in BMC from oral ulcers of BD compared with HCs (both at P = 0.0001). A differential expression of both SOCS1 and 3 was observed between PBMCs and neutrophils in patients with BD. Immunohistochemical analysis revealed differential expression of SOCS proteins in the buccal mucosa with an increased expression at the ulcer surface of ulcers than in the non‐ulcerated tissue. These observations suggest a dysregulation of the expression of these important regulators not only between patients with BD and healthy controls but also between mucosal and systemic tissues, which may reflect the nature of the aetiopathology of the disease.
Brain responses to food and weight loss
Authors: Behary Preeshila , Miras Alexander D.
Published: September 2014

New Findings

What is the topic of this review?

This report provides an overview of how functional neuroimaging technology has accelerated our understanding of human eating behaviour.

What advances does it highlight?

The human brain responds not only to hunger and satiation, but also to the rewarding value of food. The latter is encoded in the brain reward system, which promotes the consumption of energy‐dense food and is dysregulated in the context of obesity. In the majority of obese patients, dieting‐induced weight loss is resisted by compensatory activation of the homeostatic and hedonic brain systems, whereas pharmacological and bariatric surgery interventions might be more effective in overcoming this brain response.

In this symposium report, we examine how functional neuroimaging has revolutionized the study of human eating behaviour. In the last 20 years, functional magnetic resonance and positron emission tomography techniques have enabled researchers to understand how the human brain regions that control homeostatic and hedonic eating respond to food in physiological and pathological states. Hypothalamic, brainstem, limbic and cortical brain areas form part of a well‐co‐ordinated brain system that responds to central and peripheral neuronal, hormonal and nutrient signals. Even in physiological conditions, it promotes the consumption of energy‐dense food, because this is advantageous in evolutionary terms. Its function is dysregulated in the context of obesity so as to promote weight gain and resist weight loss. Pharmacological and bariatric surgical interventions might be more successful than lifestyle interventions in inducing weight loss and maintenance because, unlike dieting, they reduce not only hunger but also the reward value of food through their actions in homeostatic and hedonic brain regions. Functional neuroimaging is a research tool that cannot be used in isolation; its findings become meaningful and useful only when combined with data from direct measures of eating behaviour. The neuroimaging technology is continuously improving and is expected to contribute further to the in‐depth understanding of the obesity phenotype and accelerate the development of more effective and safer treatments for the condition.
Low-temperature plasma-enhanced atomic layer deposition of HfO2/Al2O3 nanolaminate structure on Si
Authors: Cao Duo , Cheng Xinhong , Zheng Li , Xu Dawei , Wang Zhongjian , Xia Chao , Shen Lingyan , Yu Yuehui , Shen DaShen
Published: September 2014

HfO2/Al2O3 nanolaminate was deposited on a Si substrate by plasma-enhanced atomic layer deposition at 150 °C with in situ plasma treatment. Unilayer HfO2 and Al2O3 films were prepared for comparison. Films were treated by rapid thermal annealing at 870 °C in a nitrogen atmosphere for 30 s. Al atoms in the HfO2/Al2O3 nanolaminate diffuse into HfO2 layers during rapid thermal annealing, facilitating the formation of tetragonal HfO2. The HfO2/Al2O3 nanolaminate has an effective dielectric constant of 20.7, a breakdown electric field of 7.4 MV/cm, and leakage current of 2.3 × 10−5 mA/cm2 at a gate bias of Vg = −1 V. The valence band offset, conduction band offset, and the band gap of the film are 2.75, 1.96, and 5.83 eV, respectively.
A Role for Science Investments in Advancing Newborn Health
Authors: Bhutta Zulfiqar A. , Darmstadt Gary L.
Published: September 2014

Advances in neonatal health require funding and appropriate allocation of resources.
Contemporary Vaccine Challenges: Improving Global Health One Shot at a Time
Authors: Orenstein Walter A. , Seib Katherine , Graham-Rowe Duncan , Berkley Seth
Published: September 2014

Developing new vaccines for additional diseases as well as improving their supply and delivery is crucial for global health.
Two Paths Diverged in a Schwann Cell
Authors: Tesar Paul J.
Published: September 2014

Balanced activation of both Mek-Erk and PI3K-Akt pathways in Schwann cells enhances myelination and enables functional recovery in a rodent model of Charcot-Marie-Tooth disease.
Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
Authors: Biondo Carmelo , Mancuso Giuseppe , Midiri Angelina , Signorino Giacomo , Domina Maria , Lanza Cariccio Veronica , Venza Mario , Venza Isabella , Teti Giuseppe , Beninati Concetta
Published: September 2014

Signal transduction via MyD88, an adaptor protein engaged by the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family receptors, has a crucial role in host defenses against group B streptococcus (GBS). To examine the contribution of IL-1R signaling to MyD88-dependent host defenses, we analyzed GBS infection in type I IL-1R (IL-1RI)-deficient mice. Most of these animals displayed clinical signs of sepsis and neurological disease and died after a challenge with a bacterial dose that did not cause illness or death in any of the wild-type animals. Moreover, bacterial numbers in the blood and brains of the immunodefective mice were considerably increased. The ability of blood leukocytes or bone marrow-derived macrophages to kill GBSin vitrowas not affected by a lack of IL-1RI. However, it was found in a newly developed model of GBS-induced peritoneal inflammation that IL-1 signaling selectively promoted the production of the chemokines KC and MIP-1α and neutrophil recruitment. Moreover, the secretion of KC and MIP-1α, but not tumor necrosis factor alpha, by peritoneal macrophages stimulated with GBS was significantly decreased in the absence of IL-1RI. Accordingly, the number of neutrophils in the blood and the concentration of myeloperoxidase, a neutrophil marker, in infected organs were severely reduced in the immunodefective mice during GBS disease, concomitantly with a reduction in tissue KC and MIP-1α levels. In conclusion, IL-1RI plays a crucial role in host defenses against GBS by inducing the high-level production of chemokines and the subsequent recruitment of neutrophilic polymorphonuclear leukocytes to infection sites.

IMPORTANCEGroup B streptococcus (GBS) is a serious and frequent human pathogen. Experimental infection with this bacterium has been widely used to understand the mechanism whereby the body’s first line of defense, represented by cells and molecules of the innate immune system, fights infections. In both humans and mice, defective function of the adaptor molecule MyD88 has been associated with extreme susceptibility to infection by GBS and other extracellular bacteria. We show here that lack of signaling by interleukin-1 (IL-1) cytokines can largely, although not completely, explain the increased susceptibility to infection observed in the absence of MyD88 function. We show, in particular, that IL-1 signaling through the IL-1 receptor promotes the production of the leukocyte attractant chemokines KC and MIP-1α and recruitment of neutrophils to GBS infection sites, thereby enabling these leukocytes to clear the infection. Our findings indicate that stimulation of IL-1 signaling may be useful as an alternative therapeutic strategy to treat GBS infections.
Long-lived crowded-litter mice have an age-dependent increase in protein synthesis to DNA synthesis ratio and mTORC1 substrate phosphorylation
Authors: Drake Joshua C. , Bruns Danielle R. , Peelor Frederick F. , Biela Laurie M. , Miller Richard A. , Hamilton Karyn L. , Miller Benjamin F.
Published: September 2014

Increasing mouse litter size [crowded litter (CL)] presumably imposes a transient nutrient stress during suckling and extends lifespan through unknown mechanisms. Chronic calorically restricted and rapamycin-treated mice have decreased DNA synthesis and mTOR complex 1 (mTORC1) signaling but maintained protein synthesis, suggesting maintenance of existing cellular structures. We hypothesized that CL would exhibit similar synthetic and signaling responses to other long-lived models and, by comparing synthesis of new protein to new DNA, that insight may be gained into the potential preservation of existing cellular structures in the CL model. Protein and DNA synthesis was assessed in gastroc complex, heart, and liver of 4- and 7-mo CL mice. We also examined mTORC1 signaling in 3- and 7-mo aged animals. Compared with controls, 4-mo CL had greater DNA synthesis in gastroc complex with no differences in protein synthesis or mTORC1 substrate phosphorylation across tissues. Seven-month CL had less DNA synthesis than controls in heart and greater protein synthesis and mTORC1 substrate phosphorylation across tissues. The increased new protein-to-new DNA synthesis ratio suggests that new proteins are synthesized more so in existing cells at 7 mo, differing from 4 mo, in CL vs. controls. We propose that, in CL, protein synthesis shifts from being directed toward new cells (4 mo) to maintenance of existing cellular structures (7 mo), independently of decreased mTORC1.
Autophagy and Non-Alcoholic Fatty Liver Disease
Authors: Lavallard Vanessa J. , Gual Philippe
Published: September 2014

Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.
The Role of MicroRNAs in Ovarian Cancer
Authors: Kinose Yasuto , Sawada Kenjiro , Nakamura Koji , Kimura Tadashi
Published: September 2014

Ovarian cancer is the most lethal of malignant gynecological tumors. Its lethality may be due to difficulties in detecting it at an early stage and lack of effective treatments for patients with an advanced or recurrent status. Therefore, there is a strong need for prognostic and predictive markers to diagnose it early and to help optimize and personalize treatment. MicroRNAs are noncoding RNAs that regulate target genes posttranscriptionally. They are involved in carcinogenesis, cell cycle, apoptosis, proliferation, invasion, metastasis, and chemoresistance. The dysregulation of microRNAs is involved in the initiation and progression of human cancers including ovarian cancer, and strong evidence that microRNAs can act as oncogenes or tumor suppressor genes has emerged. Several microRNA signatures that are unique to ovarian cancer have been proposed, and serum-circulating microRNAs have the potential to be useful diagnostic and prognostic biomarkers. Various microRNAs such as those in the miR-200 family, the miR-199/214 cluster, or the let-7 paralogs have potential as therapeutic targets for disseminated or chemoresistant ovarian tumors. Although many obstacles need to be overcome, microRNA therapy could be a powerful tool for ovarian cancer prevention and treatment. In this review, we discuss the emerging roles of microRNAs in various aspects of ovarian cancer.
Vaginoperineal Fistula as a Complication of Perianal Surgery in a Patient with Sjögren’s Syndrome: A Case Report
Authors: Beksac Kemal , Turgal Mert , Basaran Derman , Aran Omer , Beksac M. Sinan
Published: September 2014

Forty-seven-year-old woman with Sjögren’s syndrome had been operated on because of transsphincteric perianal fistula secondary to perianal abscess. Vaginal wall injury occurred during the course of the operation and injured tissue was repaired primarily. Three months later, patient suffered from the recurrence of perianal fistula symptoms and fistulectomy was performed once again under antibiotic suppression. Several months later, perineal discharge continued, and, therefore, patient was admitted to the hospital for the third time and a fistulotomy was performed. Two months after the third operation, patient was admitted with leukorrhea and a perineovaginal fistula was detected. This time, not only her surgical problem but also her immune system disorder was considered in the preoperative workup. Then, patient was hospitalized for the fourth time and “fistulectomy/perineoplasty” was performed successfully. We believe that patients with autoimmune disorders with or without medical treatment may have healing problems during the course of surgical processes and therefore such medical problems must be taken into consideration by the surgeons.
Effective Concentration and Detection of Cryptosporidium, Giardia, and the Microsporidia from Environmental Matrices
Authors: Moss Joseph A. , Gordy John , Snyder Richard A.
Published: September 2014

Cryptosporidium spp., Giardia spp., and members of Microsporidia are enteropathogenic parasites of humans and animals, producing asymptomatic to severe intestinal infections. To circumvent various impediments associated with current detection methods, we tested a method providing multistage purification and separation in a single, confined step. Standard real-time PCR was used as a detection method. Samples spiked with C. parvum and G. intestinalis were split for comparison to standard Method 1623. Results were equivalent to immunomagnetic procedures for Cryptosporidium, and Giardia. Overall percent recovery for Cryptosporidium with Method 1623 averaged 26.89% (std 21.44%; min = 0%; max = 73%) and was similar but less variable for qPCR method at an estimated average of 27.67 (std 17.65%; min = 5%; max = 63%). For Giardia, Method 1623 had an overall average recovery of 27.11% (std 17.98%; min = 1%; max = 58%), while multistage purification and qPCR had an estimated lower overall recovery at 18.58% (std 13.95%; min = 0%; max = 35%). Microsporidia were also readily detected with an estimated recovery of 46.81% overall (std 17.66%; min = 18%; max = 70%) for E. intestinalis and 38.90% (std 14.36%; min = 13%; max = 62%) for E. bieneusi.
Hybrid Electronic Tongues Applied to the Quality Control of Wines
Authors: Gutiérrez-Capitán Manuel , Capdevila Fina , Vila-Planas Jordi , Domingo Carme , Büttgenbach Stephanus , Llobera Andreu , Puig-Pujol Anna , Jiménez-Jorquera Cecilia
Published: September 2014

The legislation of food industry is becoming increasingly strict with regard to the quality of food products. Therefore, the market is demanding for automatic systems of analysis that allow fast and accurate monitoring of the evolution of quality parameters in agrofood products or permit obtaining information to optimize production processes. In this context, sensors and more specifically microsensors play an important role since they allow fast and reproducible measurement of a large number of quality parameters with good reliability and can be implemented in portable systems. This paper presents a review of the results obtained with an electronic tongue based on different kinds of microsensors applied to wine analysis by the team of IMB-CNM. This multisensor system allows on one hand classifying the wine according to its features like grape variety, geographic origin, year, and organoleptic characteristics and on the other hand quantifying some parameters of interest in quality control, such as alcoholic degree, pH, ions, total acidity, glycerol, and color.
Design of Robust Output Feedback Guaranteed Cost Control for a Class of Nonlinear Discrete-Time Systems
Authors: Zhang Yan , Dong Yali , Li Tianrui
Published: September 2014

This paper investigates static output feedback guaranteed cost control for a class of nonlinear
discrete-time systems where the delay in state vector is inconsistent with the delay in nonlinear
perturbations. Based on the output measurement, the controller is designed to ensure the robust exponentially
stability of the closed-loop system and guarantee the performance of system to achieve an
adequate level. By using the Lyapunov-Krasovskii functional method, some sufficient conditions for
the existence of robust output feedback guaranteed cost controller are established in terms of linear
matrix inequality. A numerical example is provided to show the effectiveness of the results obtained.
Synthesis and Biological Evaluation of Aminonaphthols Incorporated Indole Derivatives
Authors: Anand Raghunath Saundane , Nandibeoor Mathada Kirankumar
Published: September 2014

An efficient one pot condensation of naphthols (1), 2,5-disubstituted indole-3-carboxaldehydes (2), and secondary amines (3) has been achieved using dichloromethane as a solvent, stirring at room temperature. Some of the new [(disubstituted amino)(5-substituted 2-phenyl-1H-indol-3-yl)methyl]naphthalene-ols (4) derivatives were prepared in good yields. The significant features of this method are simple work-up procedure, inexpensive nontoxic solvent, shorter reaction times, and excellent product yields. The structures of newly synthesized compounds (4a–r) are confirmed by their elemental analysis, FTIR, 1H and 13C NMR, and mass spectral data. These compounds were screened for their in vitro antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the synthesized compounds (4a–r), the compound 4e exhibited highest activity for radical scavenging and ferric ions reducing antioxidant power activities; compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and 4q showed excellent antimicrobial activities with MIC value 08 µg/mL against tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular activity with MIC value 12.5 µg/mL. Compounds 4k and 4q exhibited 100% cell lysis at concentration 10 µg/mL against MDA-MB-231 (human adenocarcinoma mammary gland) cell lines.
Comparative Hepatoprotective Activity of Ethanolic Extracts ofCuscuta australisagainst Acetaminophen Intoxication in Wistar Rats
Authors: Folarin Rachael O. , Omirinde Jamiu O. , Bejide Ronald , Isola Tajudeen O. , Usende Levi I. , Basiru Afisu
Published: September 2014

This study investigates the comparative hepatoprotective activity of crude ethanol extracts ofCuscuta australisagainst acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed ofCuscuta australisin doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses ofCuscuta australisstem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably,Cuscuta australis(seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions ofCuscuta australisstem appear to protect the liver from acetaminophen intoxication better than the seed counterpart.
Pesticidal and Mosquitocidal Activities of Clausena excavata Burm. F. (Rutaceae) against Spodoptera litura (Fab.) (Noctuidae: Lepidoptera) and Aedes aegypti L., Anopheles stephensi Liston, and Culex quinquefasciatus Say. (Diptera: Culicidae)
Authors: Thangarasu Mathivanan , Kaliyamoorthy Krishnappa , Kuppusamy Elumalai
Published: September 2014

The aim of this paper is to evaluate the larvicidal and ovicidal activities of hexane, diethyl ether, dichloromethane, ethyl acetate, and methanol extract of Indian medicinal plant, Clausena excavata, at different concentrations against lepidopteran agricultural field pest, Spodoptera litura (Lepidoptera: Noctuidae), and Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus (Diptera: Culicidae). Twenty-five early fourth instar larvae of S. litura and A. aegypti, An. stephensi and C. quinquefasciatus were exposed to various concentrations and were assayed in the laboratory by using specific protocols. The 24 h LC50 and LC90 values of the C. excavata leaf extract was determined by probit analysis. The ovicidal activity were determined against S. litura and A. aegypti, An. stephensi, and C. quinquefasciatus and was assessed 120 hrs after treatment. Results of this study show that the selected Indian medicinal plant C. excavata may be a potential source of natural larvicidal and ovicidal activities against selected pest and vector mosquitoes.