bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Synthesis, SAR and Molecular Modeling Studies of Novel Imidazo[2,1‐b][1,3,4]Thiadiazole Derivatives as Highly Potent Antimicrobial Agents
Authors: Tahtaci Hakan , Karacık Hatice , Ece Abdulilah , Er Mustafa , Şeker Mine Gül
Published: September 2017

In this study, a novel series of phenyl substituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives were synthesized, characterized and explored for antibacterial activity against Gram‐negative Escherichia coli, Gram‐positive Staphylococcus aureus and Bacillus subtilis and antifungal activity against Candida albicans. Most of the synthesized compounds exhibited remarkable antimicrobial activities, some of which being ten times more potent than positive controls. The most promising compound showed excellent activity with MIC value of 0.03 μg/ml against both S. aureus and B. subtilis (MIC values of positive compound Chloramphenicol are 0.4 μg/ml and 0.85 μg/ml, respectively). Furthermore, structure‐activity relationship was also investigated with the help of computational tools. Some physicochemical and ADME properties of the compounds were calculated too. The combination of electronic structure calculations performed at PM6 level and molecular docking simulations using Glide extra‐precision mode showed that the hydrophobic nature of keto aryl ring with no electron withdrawing substituents at para position enhances activity while electron‐donating substituents at the second aryl ring is detrimental to activity.
Identification of Signaling Pathways Targeted by the Food Contaminant FB1: Transcriptome and Kinome Analysis of Samples from Pig Liver and Intestine
Authors: Régnier Marion , Gourbeyre Pascal , Pinton Philippe , Napper Scott , Laffite Joëlle , Cossalter Anne‐Marie , Bailly Jean‐Denis , Lippi Yannick , Bertrand‐Michel Justine , Bracarense Ana Paula F.R.L. , Guillou Hervé , Loiseau Nicolas , Oswald Isabelle P.
Published: September 2017

Scope

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium species. In mammals, this toxin causes widespread organ‐specific damage; it promotes hepatotoxicity, is immunotoxic, alters intestinal functions etc. Despite its inhibitory effect on de novo ceramide synthesis, its molecular mechanism of action and toxicity is not totally elucidated.

Methods and results

To explore the mechanism of FB1 toxicity, we analyzed the transcriptome and the kinome of two organs targeted by FB1: the liver and the jejunum. Pigs were fed for 4 weeks a control diet or a FB1‐contaminated diet (10 mg/kg). As expected, FB1‐exposed pigs gained less weight and displayed a higher sphinganine/sphingosine ratio. Comparison of the transcriptomes and the kinomes of treated versus control pigs showed striking differences. Among the disrupted pathways in liver and jejunum, we highlight Protein Kinase B (AKT) / Phosphatase and tensin homolog (PTEN) at the intersection of the FB1‐modulated pathways.

Conclusion

Most of the effects of FB1 are mediated by the regulation of ceramide level, which influences protein phosphatase 2 (PP2A) and the phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway. This pathway might be a new target to counteract toxic effect of Fumonisin B1, which is one of the most spread food contaminant in the world.
Clinical features and evolution of juvenile myasthenia gravis in a French cohort
Authors: Barraud Coline , Desguerre Isabelle , Barnerias Christine , Gitiaux Cyril , Boulay Christophe , Chabrol Brigitte
Published: September 2017

Introduction

In this study we determined the clinical, paraclinical, and treatment‐related features of juvenile myasthenia gravis (JMG) as well as the clinical course in a cohort of French children.

Methods

We conducted a retrospective study of 40 patients with JMG at 2 French pediatric neurology departments from April 2004 to April 2014.

Results

Among the patients, 70% had generalized JMG, 52% had positive acetylcholine receptor antibodies, 8% had muscle‐specific kinase antibodies, and 40% were seronegative. Treatment with acetylcholinesterase inhibitors was effective and sufficient in 47% of patients. The 6 patients with generalized JMG treated with rituximab and/or immunoadsorption showed improvement. Thirty percent of the patients required hospitalization in an intensive care unit during follow‐up (mean 4.7 years). Remission without treatment occurred in 18% of patients.

Discussion

As with adults, JMG has high morbidity, particularly among children with generalized symptoms, and rituximab should be considered early in the course of the disease as a second‐line treatment. Muscle Nerve 57: 603–609, 2018
Sequenced click chemistry and photopolymerization: a new approach toward semi‐interpenetrating polymer networks
Authors: Retailleau M. , Pierrel J. , Ibrahim A. , Croutxé‐Barghorn C. , Allonas X.
Published: September 2017

The article from this special issue was previously published in Polymers for Advanced Technologies, Volume 28, Issue 4, 2017. For completeness we are including the title page of the article below. The full text of the article can be read in Issue 28:4 on Wiley Online Library: http://onlinelibrary.wiley.com/doi/10.1002/pat.3914/full
Investigating the effects of CNT aspect ratio and agglomeration on elastic constants of crosslinked polymer nanocomposite using multiscale modeling
Authors: Aghadavoudi Farshid , Golestanian Hossein , Tadi Beni Yaghoub
Published: September 2017

Multiscale modeling has been developed to calculate the Young's modulus of carbon nanotube (CNT) reinforced epoxy‐based nanocomposites. Molecular dynamics was used to construct nanocomposite models consisting of crosslinked network structure of epoxy resin as the matrix material and CNT as the reinforcement at nanoscale. Transversely, isotropic stiffness matrices were calculated using constant strain method on four cases with different CNT chiralities. Effective fiber method was employed to scale bridging from nanoscale to microscale. In multiscale calculations, various types of micromechanical methods were investigated and Halpin–Tsai formulation was selected due to its more realistic predictions. The results showed that increasing CNT aspect ratio from 1 to 1,000 results in an increase in nanocomposite Young's modulus by about three times for nanocomposite reinforced with CNT(20,0). Comparing CNT(5,0) with CNT(20,0) reinforced polymer results, suggested that increasing the CNT radius resulted in a decrease in nanocomposite moduli to about one half. Multiscale results indicated that CNT agglomeration can decrease nanocomposite Young's modulus to one‐third compared to the dispersed CNT case. Predicted results were compared with numerical and experimental results found in the literature and good agreement was observed. POLYM. COMPOS., 39:4513–4523, 2018. © 2017 Society of Plastics Engineers
Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon
Authors: Saito Kanako , Kawasoe Ryotaro , Sasaki Hiroshi , Kawaguchi Ayano , Miyata Takaki
Published: September 2017

Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.
Le masochisme dans la relation soignant–soigné en clinique de la douleur
Authors: Lionet B. , Castelain-Devillers D.
Published: September 2017

La relation soignant–soigné est asymétrique. Elle repose sur la demande du patient, étymologiquement « celui qui endure », demande en direction du soignant supposé savoir comment le soulager. Dans cet article, nous interrogeons cette asymétrie initiale autour de la douleur. Nous nous intéressons au masochisme chez chacun des partenaires en regard de l'autre, à la manière dont se décline la relation soignant–soigné entre douleur subie et douleur consentie. Du côté du soigné, le masochisme permet de supporter une position de passivité face à la douleur et face aux soins. Parfois, une dose de douleur contrôlée peut être recherchée en réaction de défense contre cette passivité. Une part de masochisme est également attendue du côté des professionnels qui travaillent en structure douleur. En effet, c'est une clinique complexe nécessitant de se départir d'une maîtrise complète de la situation au profit de l'approche pluriprofessionnelle. Rendre le patient douloureux chronique acteur de sa prise en charge suppose également une certaine retenue du côté des soignants. Enfin, être confronté quotidiennement à la douleur engage le masochisme comme condition de l'empathie. Il nous apparaît important de reconnaître la part masochiste normale chez le patient comme chez le soignant et d'envisager également chez chacun d'entre eux les risques de dérives et d'excès qui peuvent émerger de la relation de soin.
Beyond Sex Differences
Authors: Keverne Eric B.
Published: September 2017

Recent developments in behavioural neuroscience and genomics are providing exciting new tools for understanding mammalian evolution. Drawing on a range of disciplines including genomic reprogramming, immunology, genomic imprinting, placentation and brain development, this book examines the leading role played by the mother's genome and epigenome in the successful evolutionary progression of humans from ancestral mammals. Keverne begins by discussing the historic context of the perceived dominance of males and the patriline, before arguing that it is instead the matriline that exerts the dominant influence in shaping the evolution of our brain development and behaviour, especially the co-adaptive development of brain and placenta. Presenting a balanced outlook on the development of sex differences and an alternative to traditional views, Beyond Sex Differences will be of interest to anyone studying and researching mother and infant development.
The Hidden Rules of Race
Authors: Flynn Andrea , Holmberg Susan R. , Warren Dorian T. , Wong Felicia J.
Published: September 2017

Why do black families own less than white families? Why does school segregation persist decades after Brown v. Board of Education? Why is it harder for black adults to vote than for white adults? Will addressing economic inequality solve racial and gender inequality as well? This book answers all of these questions and more by revealing the hidden rules of race that create barriers to inclusion today. While many Americans are familiar with the histories of slavery and Jim Crow, we often don't understand how the rules of those eras undergird today's economy, reproducing the same racial inequities 150 years after the end of slavery and 50 years after the banning of Jim Crow segregation laws. This book shows how the fight for racial equity has been one of progress and retrenchment, a constant push and pull for inclusion over exclusion. By understanding how our economic and racial rules work together, we can write better rules to finally address inequality in America.
Destroy and Build
Authors: Richardson Thomas
Published: September 2017

In 2002, Governor General Michael Jeffrey stated that 'we Australians had everything under control in Phuoc Tuy Province'. This referred not only to military control, but to the policy of 'pacification' employed by the Republic of Vietnam and external 'Free World' allies such as the US and Australia. In the hopes of stemming the tide of Communism, pacification aimed to win the allegiance of the populace through political, economic and social reform. In this new work, Thomas Richardson explores the 1st Australian Task Force's (1ATF) implementation of this policy in Phuoc Tuy between 1966 and 1972. Using material from US and Australian archives, as well as newly translated Vietnamese histories, Destroy and Build: Pacification in Phuoc Tuy, 1966–1972 challenges the accepted historiography of the Western forces' fight against insurgency in Vietnam.
Tidal modulation of ice shelf buttressing stresses
Authors: Robel Alexander A. , Tsai Victor C. , Minchew Brent , Simons Mark
Published: September 2017

Ocean tides influence the flow of marine-terminating glaciers. Observations indicate that the large fortnightly variations in ice flow at Rutford Ice Stream in West Antarctica originate in the floating ice shelf. We show that nonlinear variations in ice shelf buttressing driven by tides can produce such fortnightly variations in ice flow. These nonlinearities in the tidal modulation of buttressing stresses can be caused by asymmetries in the contact stress from migration of the grounding line and bathymetric pinning points beneath the ice shelf. Using a simple viscoelastic model, we demonstrate that a combination of buttressing and hydrostatic stress variations can explain a diverse range of tidal variations in ice shelf flow, including the period, phase and amplitude of flow variations observed at Rutford and Bindschadler Ice Streams.
The Archpriest Controversy: The conservative Appellants against the progressive Jesuits
Authors: Ridgedell Thomas
Published: September 2017

The Archpriest Controversy, a dispute that took place from 1598 to 1602 over the necessity for an archpriest to enforce moral discipline among the English Catholic clergy, has been traditionally seen either as a struggle for hierarchical order within the Catholic Church or a serious ideological breach between the Jesuit faction and the Appellants. In contrast to recent historiography, this paper argues that the Appellants, secular clergy that opposed the archpriest, represented views of conservative English Catholics who believed they could reconcile their political loyalty to their monarch with their Catholicism. The Archpriest Controversy should be reconsidered as a critical moment in a chain of important events from the English Mission of 1580–81 to the Gunpowder Plot of 1605 that reaffirmed the inherently traditionalist nature of the Catholic community in England.
Mrs Helena Aylward: A British Catholic mother, spouse and businesswoman in the Commercial Age (1705–1714)
Authors: Pizzoni Giada
Published: September 2017

Mrs Helena Aylward, as a Catholic merchant and investor, enriches the literature on both female Catholicism and on the Atlantic-Mediterranean trade. Recent historiography has stressed the importance of women in business, but Catholic women have been overlooked in the mercantile world and in the British fiscal-military economy. I contend that female Catholics were accustomed to their husband’s dealings, and after bereavement, took financial responsibility for the family’s business. Helena was proactive and did not limit herself to the exchanges already established by her husband. She moved independently and diversified her trade with financial investments. Mrs Aylward’s involvement in business challenges the prevailing image of Catholic women as wives, patrons or nuns. She suggests a new economic role for British female Catholics: entrepreneurs that succeeded in a Protestant and patriarchal maritime world.1
Growth performance, nutrient utilisation and carcass composition respond to dietary protein concentrations in broiler chickens but responses are modified by dietary lipid levels
Authors: Liu Sonia Y. , Selle Peter H. , Raubenheimer David , Gous Rob M. , Chrystal Peter V. , Cadogan David J. , Simpson Stephen J. , Cowieson Aaron J.
Published: September 2017

A total of ten experimental diets with protein concentrations ranging from 154 to 400 g/kg and two lipid levels (46 and 85 g/kg) with identical energy densities were offered to 240 male Ross 308 broilers from 7 to 28 d post-hatch. Growth performance was monitored and nutrient utilisation (apparent metabolisable energy (AME), N-corrected AME (AMEn), AME daily intake, AME:gross energy ratios, N retention) was determined. The weight gain response of broiler chickens to dietary protein concentrations in diets containing high and low lipid levels was diverse, with the relevant quadratic regressions being significantly different (P<0·05). With low lipid levels, the predicted maximum weight gain of 1809 g/bird equated to 342 g/kg dietary protein, whereas, for high lipid levels the predicted maximum weight gain of 1694 g/bird equated to 281 g/kg dietary protein. AME was linearly correlated with dietary protein concentration but regressions in diets with different lipid content were not significantly different (P>0·05). AMEn was also linearly (P<0·0001) increased with dietary protein concentrations but regressions in diets with low and high lipid content were significantly different (P<0·03). Carcass protein content increased linearly with dietary protein content in diets containing high lipid concentrations (r 0·933, P<0·0001); by contrast, this relationship was quadratic (R2=0·93, P<0·0001) in diets with low lipid levels. In conclusion, predictably, the effects of dietary protein concentrations on broiler performance were profound; however, the impact of dietary protein on performance in broiler chickens was modified by dietary lipid concentrations.
Seas, oceans and cosmologies in Southeast Asia
Authors: Andaya Barbara Watson
Published: September 2017

This article discusses the changing spirit world of maritime communities in Southeast Asia by differentiating ‘oceans’ from ‘seas’ and by linking historical evidence to modern anthropological studies. Since the lives of seagoing peoples are fraught with unpredictability, propitiation of local sea spirits was a traditional means of ensuring good fortune and protection. As long-distance voyages expanded in the early modern period, the global reach of the world religions, extending beyond familiar seas into the more extensive ocean environment, held out particular appeal. Not only were the gods, deities and saints attached to larger religious systems themselves ocean travellers; in contrast to the unpredictability of indigenous spirits, they were always amenable to requests for help, even when the suppliant was far from home waters. At the same time, as world religions were incorporated into indigenous cosmologies, maritime peoples gained greater agency in negotiating relationships with the local spirits that still wield power in Southeast Asian seas.
Islam and matriliny along the Indian Ocean rim: Revisiting the old ‘paradox’ by comparing the Minangkabau, Kerala and coastal northern Mozambique
Authors: Bonate Liazzat J.K.
Published: September 2017

The coexistence of Islam and matriliny has been viewed as a ‘paradox’ because of strict patriliny that Islam prescribes. This article attempts to disentangle this enigma by comparing the Minangkabau, Kerala and coastal northern Mozambique that represent the most well-known cases of simultaneous practice of Islam and matrilineal kinship, which initially was a result of peaceful Islamisation through Indian Ocean networks. In the nineteenth century, the Dutch and British colonial regimes helped matriliny to survive, despite all the efforts of the Islamists to the contrary, by codifying local juridical rules. The Portuguese integration of the local matrilineal nobility into their colonial administrative system preserved matriliny within the local Muslim order. Nowadays these communities are influenced by modernisation, nation-state policies, and Islamic reformist movements, but matrilineal principles still regulate the use of the ancestral land.
Premorbid social adjustment and association with attenuated psychotic symptoms in clinical high-risk and help-seeking youth
Authors: Tarbox-Berry S. I. , Perkins D. O. , Woods S. W. , Addington J.
Published: September 2017

Background

Attenuated positive symptom syndrome (APSS), characterized by ‘putatively prodromal’ attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of ‘true’ prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals.

Method

Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis.

Results

Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria.

Conclusions

Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.
CME: Erythema nodosum
Authors: Rebsamen Ursina , Guenova Emmanuella , Vallelian Florence
Published: September 2017

Zusammenfassung. Erythema nodosum ist die häufigste Form einer akuten Pannikulitis. Klinisch manifestiert es sich als erythematöse bis livide, druckdolente, subkutane Plaques und Knoten. Diese treten meist symmetrisch im Bereich der Unterschenkelstreckseiten auf. Die häufigsten Auslöser sind Infekte und entzündliche Erkrankungen; in etwa der Hälfte der Fälle lässt sich keine Ursache finden. Aufgrund der Heterogenität der Trigger und des meist selbstlimitierenden Verlaufes stellt sich in der Praxis die Frage, was die Ursache ist und inwieweit sie gesucht werden soll. In diesem Artikel möchten wir auf die Abklärungsstrategie und die wichtigsten Auslöser des Erythema nodosum eingehen.
White House Announces Picks for NASA Chief and NOAA Deputy Head
Authors: Showstack Randy
Published: September 2017

If the administration’s selection of Rep. Jim Bridenstine to lead NASA is confirmed, the congressman would be the first politician to head the agency.
Rapid global ocean-atmosphere response to Southern Ocean freshening during the last glacial
Authors: Turney Chris S. M. , Jones Richard T. , Phipps Steven J. , Thomas Zoë , Hogg Alan , Kershaw A. Peter , Fogwill Christopher J. , Palmer Jonathan , Bronk Ramsey Christopher , Adolphi Florian , Muscheler Raimund , Hughen Konrad A. , Staff Richard A. , Grosvenor Mark , Golledge Nicholas R. , Rasmussen Sune Olander , Hutchinson David K. , Haberle Simon , Lorrey Andrew , Boswijk Gretel , Cooper Alan
Published: September 2017

Contrasting Greenland and Antarctic temperatures during the last glacial period (115,000 to 11,650 years ago) are thought to have been driven by imbalances in the rates of formation of North Atlantic and Antarctic Deep Water (the ‘bipolar seesaw’). Here we exploit a bidecadally resolved 14C data set obtained from New Zealand kauri (Agathis australis) to undertake high-precision alignment of key climate data sets spanning iceberg-rafted debris event Heinrich 3 and Greenland Interstadial (GI) 5.1 in the North Atlantic (~30,400 to 28,400 years ago). We observe no divergence between the kauri and Atlantic marine sediment 14C data sets, implying limited changes in deep water formation. However, a Southern Ocean (Atlantic-sector) iceberg rafted debris event appears to have occurred synchronously with GI-5.1 warming and decreased precipitation over the western equatorial Pacific and Atlantic. An ensemble of transient meltwater simulations shows that Antarctic-sourced salinity anomalies can generate climate changes that are propagated globally via an atmospheric Rossby wave train.
Comparison of quality of life between Billroth-І and Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: A randomized controlled trial
Authors: Yang Kun , Zhang Wei-Han , Liu Kai , Chen Xin-Zu , Zhou Zong-Guang , Hu Jian-Kun
Published: September 2017

Studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) anastomosis are still lacking and inconsistent. The aim of this trial was to compare the quality of life (QoL) of B-I with R-Y reconstruction after curative distal gastrectomy for gastric cancer. A total of 140 patients were randomly assigned to the B-I group (N = 70) and R-Y group (N = 70) with the comparable baseline characteristics. The overall postoperative morbidity rates were 18.6% and 25.7% in the B-I group and R-Y group without significant difference. More estimated blood loss and longer surgical duration were found in the R-Y group. At the postoperative 1 year time point, the B-I group had a higher score in pain, but lower score in global health. However, the R-Y anastomosis was associated with lower incidence of reflux symptoms at postoperative 6 months (P = 0.002) and postoperative 9 months (P = 0.007). The multivariable analyses of variance did not show any interactions between the time trend and grouping. For the results of endoscopic examination, the degree and extent of remnant gastritis were milder significantly in the R-Y group. The stronger anti-reflux capability of R-Y anastomosis contributes to the higher QoL by reducing the reflux related gastritis and pain symptoms, and promotes a better global health.
Nectin-like molecule-4/cell adhesion molecule 4 inhibits the ligand-induced dimerization of ErbB3 with ErbB2
Authors: Mizutani Kiyohito , Kedashiro Shin , Maruoka Masahiro , Ueda Yuki , Takai Yoshimi
Published: September 2017

The ligand-induced dimerization of cell surface single-transmembrane receptors is essential for their activation. However, physiological molecules that inhibit their dimerization and activation have not been identified. ErbB3 dimerizes with ErbB2 upon binding of heregulin (HRG) to ErbB3, causing the ErbB2-catalyzed tyrosine phosphorylation of ErbB3, which leads to the activation of the signalling pathways for cell movement and survival. Genetic disorders of this receptor cause tumorigenesis and metastasis of cancers. We show here that nectin-like molecule-4/cell adhesion molecule 4, known to serve as a tumour suppressor, interacts with ErbB3 in the absence of HRG and inhibits the HRG-induced dimerization of ErbB3 with ErbB2 and its activation. The third immunoglobulin-like domain of nectin-like molecule-4 cis-interacts with the extracellular domain 3 of ErbB3. We describe here a novel regulatory mechanism for the activation and signalling of cell surface single-transmembrane receptors.
Genetic Ablation of Fgf23 or Klotho Does not Modulate Experimental Heart Hypertrophy Induced by Pressure Overload
Authors: Slavic Svetlana , Ford Kristopher , Modert Magalie , Becirovic Amarela , Handschuh Stephan , Baierl Andreas , Katica Nejla , Zeitz Ute , Erben Reinhold G. , Andrukhova Olena
Published: September 2017

Left ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage. Aldosterone receptor blocker spironolactone normalizes serum intact Fgf23 levels after TAC by reducing bony Fgf23 transcription. Notably, genetic Fgf23 or Klotho deficiency does not influence TAC-induced hypertrophic remodelling, LV functional impairment, or LV fibrosis. Despite the profound, aldosterone-mediated increase in circulating intact Fgf23 after TAC, our data do not support an essential role of Fgf23 or Klotho in the pathophysiology of pressure overload-induced cardiac hypertrophy.
A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients
Authors: Tsai Hui-Jen , Jiang Shih Sheng , Hung Wen-Chun , Borthakur Gautam , Lin Sheng-Fung , Pemmaraju Naveen , Jabbour Elias , Bomalaski John S. , Chen Ya-Ping , Hsiao Hui-Hua , Wang Ming-Chung , Kuo Ching-Yuan , Chang Hung , Yeh Su-Peng , Cortes Jorge , Chen Li-Tzong , Chen Tsai-Yun
Published: September 2017

Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 μM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.
The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
Authors: Kosack Lindsay , Gawish Riem , Lercher Alexander , Vilagos Bojan , Hladik Anastasiya , Lakovits Karin , Bhattacharya Anannya , Schliehe Christopher , Mesteri Ildiko , Knapp Sylvia , Bergthaler Andreas
Published: September 2017

Lipid metabolism is increasingly being appreciated to affect immunoregulation, inflammation and pathology. In this study we found that mice infected with lymphocytic choriomeningitis virus (LCMV) exhibit global perturbations of circulating serum lipids. Mice lacking the lipid-sensing surface receptor triggering receptor expressed on myeloid cells 2 (Trem2−/−) were protected from LCMV-induced hepatitis and showed improved virus control despite comparable virus-specific T cell responses. Non-hematopoietic expression of TREM2 was found to be responsible for aggravated hepatitis, indicating a novel role for TREM2 in the non-myeloid compartment. These results suggest a link between virus-perturbed lipids and TREM2 that modulates liver pathogenesis upon viral infection. Targeted interventions of this immunoregulatory axis may ameliorate tissue pathology in hepatitis.
Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial
Authors: Matsuzaki Sachiko , Vernis Lise , Bonnin Martine , Houlle Celine , Fournet-Fayard Aurelie , Rosano Giuseppe , Lafaye Anne Laure , Chartier Christian , Barriere Agnes , Storme Brigitte , Bazin Jean-Etienne , Canis Michel , Botchorishvili Revaz
Published: September 2017

Laparoscopic surgery technology continues to advance. However, much less attention has been focused on how alteration of the laparoscopic surgical environment might improve clinical outcomes. We conducted a randomized, 2 × 2 factorial trial to evaluate whether low intraperitoneal pressure (IPP) (8 mmHg) and/or warmed, humidified CO2 (WH) gas are better for minimizing the adverse impact of a CO2 pneumoperitoneum on the peritoneal environment during laparoscopic surgery and for improving clinical outcomes compared to the standard IPP (12 mmHg) and/or cool and dry CO2 (CD) gas. Herein we show that low IPP and WH gas may decrease inflammation in the laparoscopic surgical environment, resulting in better clinical outcomes. Low IPP and/or WH gas significantly lowered expression of inflammation-related genes in peritoneal tissues compared to the standard IPP and/or CD gas. The odds ratios of a visual analogue scale (VAS) pain score >30 in the ward was 0.18 (95% CI: 0.06, 0.52) at 12 hours and 0.06 (95% CI: 0.01, 0.26) at 24 hours in the low IPP group versus the standard IPP group, and 0.16 (95% CI: 0.05, 0.49) at 0 hours and 0.29 (95% CI: 0.10, 0.79) at 12 hours in the WH gas group versus the CD gas group.
Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion
Authors: Daimon Makoto , Kamba Aya , Murakami Hiroshi , Mizushiri Satoru , Osonoi Sho , Matsuki Kota , Sato Eri , Tanabe Jutaro , Takayasu Shinobu , Matsuhashi Yuki , Yanagimachi Miyuki , Terui Ken , Kageyama Kazunori , Tokuda Itoyo , Kurauchi Shizuka , Nakaji Shigeyuki
Published: September 2017

How the association between the hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based 2015 Iwaki study were enrolled (n: 1,016; age: 54.4 ± 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-β). Univariate linear regression analyses showed a correlation between PC2 and HOMA-β (β = −0.248, p < 0.0001), but not between PC1 and HOMA-β (β = −0.004, p = 0.9048). The correration between PC2 and HOMA-β persisted after adjustment for multiple factors (β = −0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-β (≤68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35–2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population.
Profiling of the metabolic transcriptome via single molecule molecular inversion probes
Authors: de Bitter Tessa , van de Water Carlijn , van den Heuvel Corina , Zeelen Carolien , Eijkelenboom Astrid , Tops Bastiaan , Oosterwijk Egbert , Kolev Dimitar , Mulders Peter , ter Laan Mark , van Lith Sanne , Leenders William
Published: September 2017

Cancer-specific metabolic alterations are of high interest as therapeutic targets. These alterations vary between tumor types, and to employ metabolic targeting to its fullest potential there is a need for robust methods that identify candidate targetable metabolic pathways in individual cancers. Currently, such methods include 13C-tracing studies and mass spectrometry/ magnetic resonance spectroscopic imaging. Due to high cost and complexity, such studies are restricted to a research setting. We here present the validation of a novel technique of metabolic profiling, based on multiplex targeted next generation sequencing of RNA with single molecule molecular inversion probes (smMIPs), designed to measure activity of and mutations in genes that encode metabolic enzymes. We here profiled an isogenic pair of cell lines, differing in expression of the Von Hippel Lindau protein, an important regulator of hypoxia-inducible genes. We show that smMIP-profiling provides relevant information on active metabolic pathways. Because smMIP-based targeted RNAseq is cost-effective and can be applied in a medium high-throughput setting (200 samples can be profiled simultaneously in one next generation sequencing run) it is a highly interesting approach for profiling of the activity of genes of interest, including those regulating metabolism, in a routine patient care setting.
Evaluation of Bleb Fluid After Baerveldt Glaucoma Implantation Using Magnetic Resonance Imaging
Authors: Iwasaki Kentaro , Kanamoto Masayuki , Takihara Yuji , Arimura Shogo , Takamura Yoshihiro , Kimura Hirohiko , Inatani Masaru
Published: September 2017

We evaluated bleb fluid images taken after Baerveldt glaucoma implantation. T2-weighted images of bleb fluid were scanned with 3 Tesla magnetic resonance imaging in 52 patients who had undergone tube-shunt surgery using the 350-mm2 endplate Baerveldt glaucoma implant; three-dimensional images were constructed from these images. Bleb fluid images were classified into either a layer of bleb fluid on either side of the endplate (double bleb layer group; n = 24) or one layer outside the endplate (single bleb layer group; n = 28). Despite there being no correlation between the bleb volume and the postoperative IOP (r = −0.080; P = 0.57), the double bleb layer group had significantly lower postoperative IOPs than the single bleb layer group (12.3 ± 3.8 mmHg vs. 14.7 ± 4.1 mmHg, respectively; P = 0.033). The single bleb layer was significantly related to higher numbers of prior intraocular surgeries (relative risk = 2.85; P = 0.0014). Formation of a layer of bleb fluid on either side of the endplate may have resulted in the lower postoperative IOPs after Baerveldt glaucoma implantation. Repeated intraocular surgery adversely affects formation of the double bleb layer.
Dual Roles of Two Isoforms of Autophagy-related Gene ATG10 in HCV-Subgenomic replicon Mediated Autophagy Flux and Innate Immunity
Authors: Zhao Qiong , Hu Zhan-Ying , Zhang Jing-Pu , Jiang Jian-Dong , Ma Yuan-yuan , Li Jian-rui , Peng Zong-gen , Chen Jin-hua
Published: September 2017

Autophagy and immune response are two defense systems that human-body uses against viral infection. Previous studies documented that some viral mechanisms circumvented host immunity mechanisms and hijacked autophagy for its replication and survival. Here, we focus on interactions between autophagy mechanism and innate-immune-response in HCV-subgenomic replicon cells to find a mechanism linking the two pathways. We report distinct effects of two autophagy-related protein ATG10s on HCV-subgenomic replication. ATG10, a canonical long isoform in autophagy process, can facilitate HCV-subgenomic replicon amplification by promoting autophagosome formation and by combining with and detaining autophagosomes in cellular periphery, causing impaired autophagy flux. ATG10S, a non-canonical short isoform of ATG10 proteins, can activate expression of IL28A/B and immunity genes related to viral ds-RNA including ddx-58, tlr-3, tlr-7, irf-3 and irf-7, and promote autophagolysosome formation by directly combining and driving autophagosomes to perinuclear region where lysosomes gather, leading to lysosomal degradation of HCV-subgenomic replicon in HepG2 cells. ATG10S also can suppress infectious HCV virion replication in Huh7.5 cells. Another finding is that IL28A protein directly conjugates ATG10S and helps autophagosome docking to lysosomes. ATG10S might be a new host factor against HCV replication, and as a target for screening chemicals with new anti-virus mechanisms.
New model for predicting preterm delivery during the second trimester of pregnancy
Authors: Zhu Ya-zhi , Peng Guo-qin , Tian Gui-xiang , Qu Xue-ling , Xiao Shui-yuan
Published: September 2017

In this study, a new model for predicting preterm delivery (PD) was proposed. The primary model was constructed using ten selected variables, as previously defined in seventeen different studies. The ability of the model to predict PD was evaluated using the combined measurement from these variables. Therefore, a prospective investigation was performed by enrolling 130 pregnant patients whose gestational ages varied from 17+0 to 28+6 weeks. The patients underwent epidemiological surveys and ultrasonographic measurements of their cervixes, and cervicovaginal fluid and serum were collected during a routine speculum examination performed by the managing gynecologist. The results showed eight significant variables were included in the present analysis, and combination of the positive variables indicated an increased probability of PD in pregnant patients. The accuracy for predicting PD were as follows: one positive – 42.9%; two positives – 75.0%; three positives – 81.8% and four positives – 100.0%. In particular, the combination of ≥2× positives had the best predictive value, with a relatively high sensitivity (82.6%), specificity (88.1%) and accuracy rate (79.2%), and was considered the cut-off point for predicting PD. In conclusion, the new model provides a useful reference for evaluating the risk of PD in clinical cases.
Electrostatics of non-neutral biological microdomains
Authors: Cartailler J. , Schuss Z. , Holcman D.
Published: September 2017

Voltage and charge distributions in cellular microdomains regulate communications, excitability, and signal transduction. We report here new electrical laws in a biological cell, which follow from a nonlinear electro-diffusion model. These newly discovered laws derive from the geometrical cell-membrane properties, such as membrane curvature, volume, and surface area. The electro-diffusion laws can now be used to predict and interpret voltage distribution in cellular microdomains such as synapses, dendritic spine, cilia and more.
Propolis envelope in Apis mellifera colonies supports honey bees against the pathogen, Paenibacillus larvae
Authors: Borba Renata S. , Spivak Marla
Published: September 2017

Honey bees have immune defenses both as individuals and as a colony (e.g., individual and social immunity). One form of honey bee social immunity is the collection of antimicrobial plant resins and the deposition of the resins as a propolis envelope within the nest. In this study, we tested the effects of the propolis envelope as a natural defense against Paenibacillus larvae, the causative agent of American foulbrood (AFB) disease. Using colonies with and without a propolis envelope, we quantified: 1) the antimicrobial activity of larval food fed to 1–2 day old larvae; and 2) clinical signs of AFB. Our results show that the antimicrobial activity of larval food was significantly higher when challenged colonies had a propolis envelope compared to colonies without the envelope. In addition, colonies with a propolis envelope had significantly reduced levels of AFB clinical signs two months following challenge. Our results indicate that the propolis envelope serves as an antimicrobial layer around the colony that helps protect the brood from bacterial pathogen infection, resulting in a lower colony-level infection load.
Elastic properties of single-walled carbon nanotube thin film by nanoindentation test
Authors: Tang Xingling , El-Hami Abdelkhalak , El-Hami Khalil , EID Mohamed , Si Chaorun
Published: September 2017

This paper carries out a preliminary study for the elastic properties of single walled carbon nanotube (SWCNT) thin film. The SWCNT thin films (~250 nm) are prepared by a simple and cost effective method of spin-coating technology. Nanoindentation test with a Berkovich indenter is used to determine the hardness and elastic modulus of the SWCNT thin film. It is important to note that the elastic properties of SWCNT film are indirectly derived from the information of load and displacement of the indenter under certain assumptions, deviation of the ‘test value’ is inevitable. In this regard, uncertainty analysis is an effective process in guarantying the validity of the material properties. This paper carries out uncertainty estimation for the tested elastic properties of SWCNT film by nanoindentation. Experimental results and uncertainty analysis indicates that nanoindentation test could be an effective and reliable method in determine the elastic properties of SWCNT thin film. Moreover, the obtained values of hardness and elastic modulus can further benefit the design of SWCNT thin film based components.
Magnetoelectric oxide based stochastic spin device towards solving combinatorial optimization problems
Authors: Sharmin Saima , Shim Yong , Roy Kaushik
Published: September 2017

Solving combinatorial optimization problems is challenging. Mapping onto the ground-state search problem of the Ising Hamiltonian is a promising approach in this field, where the components of the optimization set are modeled as artificial spin units. The search for a suitable physical system to realize these spin units is an active area of research. In this work, we have demonstrated a scheme to model the Ising Hamiltonian with multiferroic oxide/nanomagnet units. Although nanomagnet-based implementation has been shown before, we have utilized the magnetoelectric effect of the multiferroics to make voltagecontrolled spin units with less current flow in the network. Moreover, we have proposed a unique approach of configuring the coupling network of the system directly from the Ising Hamiltonian of a traveling salesman problem (TSP). We have developed a coupled micromagnetic simulation framework and solved TSPs of size 26-city and 15-city with an accuracy of 100% for the latter.