bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Regional Management Needs into a Mid-Atlantic Shorelines Research Project
Authors: Turner Elizabeth , Jordan Thomas
Published: June 2017

We provide an example of how one estuarine research project engaged regional managers to help guide the research towards the needs of managers and policymakers dealing with shoreline management in the Mid-Atlantic region of the USA. Elements of the approach that contributed to success included a well-targeted initial request for proposals, a review process that included management input both as a review criterion and on the review panel, a careful process in choosing advisory members at the appropriate level in the agencies, regular opportunities for interactions between the management advisory group and the science team, and active involvement of a program manager as liaison throughout the life of the project. Engagement of a management advisory group changed some of the scientific approaches, helped to communicate results, and formed a foundation for incorporation into regional management and initiatives.
A ‘Suitable Soil’: Plague’s Urban Breeding Grounds at the Dawn of the Third Pandemic
Authors: Lynteris Christos
Published: June 2017

A pressing question during the first half-decade of the third plague pandemic (1894–9) was what was a ‘suitable soil’ for the disease. The question related to plague’s perceived ability to disappear from a given city only to reappear at some future point; a phenomenon that became central to scientific investigations of the disease. However, rather than this simply having a metaphorical meaning, the debate around plague’s ‘suitable soil’ actually concerned the material reality of the soil itself. The prevalence of plague in the working-class neighbourhood of Taipingshan during the first major outbreak of the pandemic, in 1894 in Hong Kong, led to an extensive debate regarding the ability of the soil to harbour and even spread the disease. Involving experiments, which were seen as able to procure evidence for or against the demolition or even torching of the area, scientific and administrative concerns over the soil rendered it an unstable yet highly productive epistemic thing. The spread of plague to India further fuelled concerns over the ability of the soil to act as the medium of the disease’s so-called true recrudescence. Besides high-profile scientific debates, hands-on experiments on purifying the soil of infected houses by means of highly intrusive methods allowed scientists and administrators to act upon and further solidify plague’s supposed invisibility in the urban terrain. Rather than being a short-lived, moribund object of epidemiological concern, this paper will demonstrate that the soil played a crucial role in the development of plague as a scientifically knowable and actionable category for modern medicine.
Lives in the Asylum Record, 1864 to 1910: Utilising Large Data Collection for Histories of Psychiatry and Mental Health
Authors: McCarthy Angela , Coleborne Catharine , O’Connor Maree , Knewstubb Elspeth
Published: June 2017

This article examines the research implications and uses of data for a large project investigating institutional confinement in Australia and New Zealand. The cases of patients admitted between 1864 and 1910 at four separate institutions, three public and one private, provided more than 4000 patient records to a collaborative team of researchers. The utility and longevity of this data and the ways to continue to understand its significance and contents form the basis of this article’s interrogation of data collection and methodological issues surrounding the history of psychiatry and mental health. It examines the themes of ethics and access, record linkage, categories of data analysis, comparison and record keeping across colonial and imperial institutions, and constraints and opportunities in the data itself. The aim of this article is to continue an ongoing conversation among historians of mental health about the role and value of data collection for mental health and to signal the relevance of international multi-sited collaborative research in this field.
Taxes and the Choice of Organizational Form in Late Nineteenth Century Japan
Authors: Onji Kazuki , Tang John P.
Published: June 2017

How do changes to taxation policy affect the organizational choices of firms? Using historical firm data constructed from Japanese corporate genealogies, we examine the short-run impact of introducing a personal income tax (PIT) in 1887 on tax-motivated incorporation. Between 1880 and 1892, we find that the introduction of PIT increased the share of incorporated firms by more than 3 percentage points, indicating firms chose their organizational structure to avoid new taxation. Furthermore, our results suggest that a corporate income tax may have acted as a backstop to maintain revenue collected through PIT.
Laeonereis watsoni(Annelida, Nereididae), a new species from western Mexico
Authors: de León-González J. A. , Méndez N. , Navedo J. G.
Published: June 2017

A new species ofLaeonereisfrom a shrimp farm associated with a subtropical coastal lagoon on the Mexican Pacific coast is described. The new species is characterized by a deep anterior groove on the prostomium, which is shared only withL. culveri. However, longer tentacular cirri extending back to the anterior margin of chaetiger two, the number of papillae of each group on the maxillary ring of the pharynx, and the relative size of the homogomph falcigers in the new species, allow us to separate the two species. Although the species has not been previously detected in the coastal lagoon surrounding the shrimp farm, we postulate thatL. watsonin. sp. is likely to be part of the invertebrate communities of the upper parts of similar coastal lagoons that are common along the tropical coasts of Mexico.
MULTIMODALITY p**-FORMULA AND CONFIDENCE REGIONS
Authors: Van Garderen Kees Jan , Sowell Fallaw
Published: June 2017

Barndorff-Nielsen’s celebrated p*-formula and variations thereof have amongst their various attractions the ability to approximate bimodal distributions. In this paper we show that in general this requires a crucial adjustment to the basic formula. The adjustment is based on a simple idea and straightforward to implement, yet delivers important improvements. It is based on recognizing that certain outcomes are theoretically impossible and the density of the MLE should then equal zero, rather than the positive density that a straight application of p* would suggest. This has implications for inference and we show how to use the new p**-formula to construct improved confidence regions. These can be disjoint as a consequence of the bimodality. The degree of bimodality depends heavily on the value of an approximate ancillary statistic and conditioning on the observed value of this statistic is therefore desirable. The p**-formula naturally delivers the relevant conditional distribution. We illustrate these results in small and large samples using a simple nonlinear regression model and errors in variables model where the measurement errors in dependent and explanatory variables are correlated and allow for weak proxies.
Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia
Authors: Szentpéteri Anita , Zsíros Noémi , Varga Viktória E. , Lőrincz Hajnalka , Katkó Mónika , Seres Ildikó , Fülöp Péter , Paragh György , Harangi Mariann
Published: June 2017

Abstract. Background: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. Patients and methods: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. Results: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. Conclusions: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.
Human Self as Information Agent: Functioning in a Social Environment Based on Shared Meanings
Authors: Baumeister Roy F. , Maranges Heather M. , Vohs Kathleen D.
Published: June 2017

A neglected aspect of human selfhood is that people are information agents. That is, much human social activity involves communicating and discussing information. This occurs in the context of incompletely shared information—but also a group's store of collective knowledge and shared understanding. This article elucidates a preliminary theory of self as information agent, proposing that human evolution instilled both abilities and motivations for the various requisite functions. These basic functions include (a) seeking and acquiring information, (b) communicating one's thoughts to others, (c) circulating information through the group, (d) operating on information to improve it, such as by correcting mistakes, and (e) constructing a shared understanding of reality. Sophisticated information agents exhibit additional features, such as sometimes selectively withholding information or disseminating false information for self-serving reasons, cultivating a reputation as a credible source of information, and cooperating with others to shape the shared worldview in a way that favors one's subgroup. Meaningful information is thus more than a resource for individual action: It also provides the context, medium, and content within which the individual self interacts with its social environment.
Diffusion engineering of ions and charge carriers for stable efficient perovskite solar cells
Authors: Bi Enbing , Chen Han , Xie Fengxian , Wu Yongzhen , Chen Wei , Su Yanjie , Islam Ashraful , Grätzel Michael , Yang Xudong , Han Liyuan
Published: June 2017

Long-term stability is crucial for the future application of perovskite solar cells, a promising low-cost photovoltaic technology that has rapidly advanced in the recent years. Here, we designed a nanostructured carbon layer to suppress the diffusion of ions/molecules within perovskite solar cells, an important degradation process in the device. Furthermore, this nanocarbon layer benefited the diffusion of electron charge carriers to enable a high-energy conversion efficiency. Finally, the efficiency on a perovskite solar cell with an aperture area of 1.02 cm2, after a thermal aging test at 85 °C for over 500 h, or light soaking for 1,000 h, was stable of over 15% during the entire test. The present diffusion engineering of ions/molecules and photo generated charges paves a way to realizing long-term stable and highly efficient perovskite solar cells.
INO80 exchanges H2A.Z for H2A by translocating on DNA proximal to histone dimers
Authors: Brahma Sandipan , Udugama Maheshi I. , Kim Jongseong , Hada Arjan , Bhardwaj Saurabh K. , Hailu Solomon G. , Lee Tae-Hee , Bartholomew Blaine
Published: June 2017

ATP-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition. These chromatin remodellers generally function by translocating along nucleosomal DNA at the H3–H4 interface of nucleosomes. Here we show that, unlike other remodellers, INO80 translocates along DNA at the H2A–H2B interface of nucleosomes and persistently displaces DNA from the surface of H2A–H2B. DNA translocation and DNA torsional strain created near the entry site of nucleosomes by INO80 promotes both the mobilization of nucleosomes and the selective exchange of H2A.Z–H2B dimers out of nucleosomes and replacement by H2A–H2B dimers without any additional histone chaperones. We find that INO80 translocates and mobilizes H2A.Z-containing nucleosomes more efficiently than those containing H2A, partially accounting for the preference of INO80 to replace H2A.Z with H2A. Our data suggest that INO80 has a mechanism for dimer exchange that is distinct from other chromatin remodellers including its paralogue SWR1.
In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells
Authors: Jung Dajung , Xiong Jie , Ye Min , Qin Xunsi , Li Lin , Cheng Shunfeng , Luo Mengyuan , Peng Jia , Dong Ji , Tang Fuchou , Shen Wei , Matzuk Martin M. , Kee Kehkooi
Published: June 2017

Understanding the unique mechanisms of human oogenesis necessitates the development of an in vitro system of stem cell differentiation into oocytes. Specialized cell types and organoids have been derived from human pluripotent stem cells in vitro, but generating a human ovarian follicle remains a challenge. Here we report that human embryonic stem cells can be induced to differentiate into ovarian follicle-like cells (FLCs) in vitro. First, we find that two RNA-binding proteins specifically expressed in germ cells, DAZL and BOULE, regulate the exit from pluripotency and entry into meiosis. By expressing DAZL and BOULE with recombinant human GDF9 and BMP15, these meiotic germ cells are further induced to form ovarian FLCs, including oocytes and granulosa cells. This robust in vitro differentiation system will allow the study of the unique molecular mechanisms underlying human pluripotent stem cell differentiation into late primordial germ cells, meiotic germ cells and ovarian follicles.
Immiscible hydrocarbon fluids in the deep carbon cycle
Authors: Huang Fang , Daniel Isabelle , Cardon Hervé , Montagnac Gilles , Sverjensky Dimitri A.
Published: June 2017

The cycling of carbon between Earth’s surface and interior governs the long-term habitability of the planet. But how carbon migrates in the deep Earth is not well understood. In particular, the potential role of hydrocarbon fluids in the deep carbon cycle has long been controversial. Here we show that immiscible isobutane forms in situ from partial transformation of aqueous sodium acetate at 300 °C and 2.4–3.5 GPa and that over a broader range of pressures and temperatures theoretical predictions indicate that high pressure strongly opposes decomposition of isobutane, which may possibly coexist in equilibrium with silicate mineral assemblages. These results complement recent experimental evidence for immiscible methane-rich fluids at 600–700 °C and 1.5–2.5 GPa and the discovery of methane-rich fluid inclusions in metasomatized ophicarbonates at peak metamorphic conditions. Consequently, a variety of immiscible hydrocarbon fluids might facilitate carbon transfer in the deep carbon cycle.
Well-defined porous membranes for robust omniphobic surfaces via microfluidic emulsion templating
Authors: Zhu Pingan , Kong Tiantian , Tang Xin , Wang Liqiu
Published: June 2017

Durability is a long-standing challenge in designing liquid-repellent surfaces. A high-performance omniphobic surface must robustly repel liquids, while maintaining mechanical/chemical stability. However, liquid repellency and mechanical durability are generally mutually exclusive properties for many omniphobic surfaces—improving one performance inevitably results in decreased performance in another. Here we report well-defined porous membranes for durable omniphobic surfaces inspired by the springtail cuticle. The omniphobicity is shown via an amphiphilic material micro-textured with re-entrant surface morphology; the mechanical durability arises from the interconnected microstructures. The innovative fabrication method—termed microfluidic emulsion templating—is facile, cost-effective, scalable and can precisely engineer the structural topographies. The robust omniphobic surface is expected to open up new avenues for diverse applications due to its mechanical and chemical robustness, transparency, reversible Cassie–Wenzel transition, transferability, flexibility and stretchability.
Genetic diagnosis of Mendelian disorders via RNA sequencing
Authors: Kremer Laura S. , Bader Daniel M. , Mertes Christian , Kopajtich Robert , Pichler Garwin , Iuso Arcangela , Haack Tobias B. , Graf Elisabeth , Schwarzmayr Thomas , Terrile Caterina , Koňaříková Eliška , Repp Birgit , Kastenmüller Gabi , Adamski Jerzy , Lichtner Peter , Leonhardt Christoph , Funalot Benoit , Donati Alice , Tiranti Valeria , Lombes Anne , Jardel Claude , Gläser Dieter , Taylor Robert W. , Ghezzi Daniele , Mayr Johannes A. , Rötig Agnes , Freisinger Peter , Distelmaier Felix , Strom Tim M. , Meitinger Thomas , Gagneur Julien , Prokisch Holger
Published: June 2017

Across a variety of Mendelian disorders, ∼50–75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in principle reveals all genetic variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to molecularly diagnose 10% (5 of 48) of mitochondriopathy patients and identify candidate genes for the remainder. We find a median of one aberrantly expressed gene, five aberrant splicing events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establish disease-causing roles for each kind. Private exons often arise from cryptic splice sites providing an important clue for variant prioritization. One such event is found in the complex I assembly factor TIMMDC1 establishing a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants and provides examples of intronic loss-of-function variants with pathological relevance.
Quantum tunnelling and charge accumulation in organic ferroelectric memory diodes
Authors: Ghittorelli Matteo , Lenz Thomas , Sharifi Dehsari Hamed , Zhao Dong , Asadi Kamal , Blom Paul W. M. , Kovács-Vajna Zsolt M. , de Leeuw Dago M. , Torricelli Fabrizio
Published: June 2017

Non-volatile memories—providing the information storage functionality—are crucial circuit components. Solution-processed organic ferroelectric memory diodes are the non-volatile memory candidate for flexible electronics, as witnessed by the industrial demonstration of a 1 kbit reconfigurable memory fabricated on a plastic foil. Further progress, however, is limited owing to the lack of understanding of the device physics, which is required for the technological implementation of high-density arrays. Here we show that ferroelectric diodes operate as vertical field-effect transistors at the pinch-off. The tunnelling injection and charge accumulation are the fundamental mechanisms governing the device operation. Surprisingly, thermionic emission can be disregarded and the on-state current is not space charge limited. The proposed model explains and unifies a wide range of experiments, provides important design rules for the implementation of organic ferroelectric memory diodes and predicts an ultimate theoretical array density of up to 1012 bit cm−2.
All-optical observation and reconstruction of spin wave dispersion
Authors: Hashimoto Yusuke , Daimon Shunsuke , Iguchi Ryo , Oikawa Yasuyuki , Shen Ka , Sato Koji , Bossini Davide , Tabuchi Yutaka , Satoh Takuya , Hillebrands Burkard , Bauer Gerrit E. W. , Johansen Tom H. , Kirilyuk Andrei , Rasing Theo , Saitoh Eiji
Published: June 2017

To know the properties of a particle or a wave, one should measure how its energy changes with its momentum. The relation between them is called the dispersion relation, which encodes essential information of the kinetics. In a magnet, the wave motion of atomic spins serves as an elementary excitation, called a spin wave, and behaves like a fictitious particle. Although the dispersion relation of spin waves governs many of the magnetic properties, observation of their entire dispersion is one of the challenges today. Spin waves whose dispersion is dominated by magnetostatic interaction are called pure-magnetostatic waves, which are still missing despite of their practical importance. Here, we report observation of the band dispersion relation of pure-magnetostatic waves by developing a table-top all-optical spectroscopy named spin-wave tomography. The result unmasks characteristics of pure-magnetostatic waves. We also demonstrate time-resolved measurements, which reveal coherent energy transfer between spin waves and lattice vibrations.
Glycated hemoglobin A1C and vitamin D and their association with diabetic retinopathy severity
Authors: Long M , Wang C , Liu D
Published: June 2017

Objectives:

This retrospective, population-based, cross-sectional study evaluated the association between vitamin D deficiency and retinopathy severity in diabetic patients with poorly or well controlled glycaemia. Other potential risk factors for diabetic retinopathy severity were also assessed.

Methods:

The National Health and Nutrition Examination Survey (NHANES) 2005–2008 data were used for the study. Outcomes assessed included retinopathy severity, HbA1c levels, socioeconomic, behavioral, and biological factors. Univariate and multivariate regression analysis was used to evaluate association of different parameters with retinopathy severity. The interaction among HbA1c control, vitamin D deficiency, and retinopathy severity were also explored.

Results:

The population included 842 adults (52.8% women) with mean age of 61.2 years. Retinopathy was detected in 301 subjects (35.7%). Mild non-proliferative retinopathy (NPR) was present in 195 subjects (23.2%), severe non-proliferative and proliferative retinopathy in 106 subjects (12.6%). Multivariate ordinal regression analysis found being male (odds ratio (OR): 1.602, P=0.001), increased duration of diabetes (OR: 1.072, P=3.77E−7) and poorly controlled HbA1c (OR: 3.522, P=2.00E−5) were associated with greater retinopathy severity. The association between vitamin D deficiency and retinopathy severity only found in diabetic patients with well controlled glycaemia.

Conclusions:

The findings of this study indicate that vitamin D deficiency associated with severe diabetic retinopathy in patients with well controlled diabetes. The findings provide possible relationship for the previous conflict results, and highlight the need for controlling modifiable risk factors to reduce the development of sever diabetic retinopathy.
Sequential self-assembly of DNA functionalized droplets
Authors: Zhang Yin , McMullen Angus , Pontani Lea-Laetitia , He Xiaojin , Sha Ruojie , Seeman Nadrian C. , Brujic Jasna , Chaikin Paul M.
Published: June 2017

Complex structures and devices, both natural and manmade, are often constructed sequentially. From crystallization to embryogenesis, a nucleus or seed is formed and built upon. Sequential assembly allows for initiation, signaling, and logical programming, which are necessary for making enclosed, hierarchical structures. Although biology relies on such schemes, they have not been available in materials science. Here, we demonstrate programmed sequential self-assembly of DNA functionalized emulsions. The droplets are initially inert because the grafted DNA strands are pre-hybridized in pairs. Active strands on initiator droplets then displace one of the paired strands and thus release its complement, which in turn activates the next droplet in the sequence, akin to living polymerization. Our strategy provides time and logic control during the self-assembly process, and offers a new perspective on the synthesis of materials.
Use of a self-rating scale of the nature and severity of symptoms in Parkinson’s Disease (PRO-PD): Correlation with quality of life and existing scales of disease severity
Authors: Mischley Laurie K. , Lau Richard C. , Weiss Noel S.
Published: June 2017

A self-rating scale was developed to permit patient-reported, remote assessment of Parkinson’s disease symptom severity. The goal was to create a continuous outcome measure that does not require a clinical exam, does not fluctuate in response to dopaminergic medications, takes only a few minutes to complete, allows for stratification by symptom(s), and captures both motor and non-motor Parkinson’s disease symptoms, major contributors to quality of life. The Patient Reported Outcomes in Parkinson’s Disease (PRO-PD) is the cumulative score of 32 slider bars, each evaluating a common Parkinson’s disease symptom. The PRO-PD has been used as an outcome measure in three studies. The baseline data from each of these studies were pooled for this analysis. Symptom frequency and severity are described, as well as correlation coefficients with existing measures of Parkinson's disease severity. Data on 1031 participants with Parkinson's disease were available for analysis. Fatigue, impaired handwriting, daytime sleepiness, slowness, tremor, muscle cramps, and forgetfulness were the most frequently reported symptoms. Persons with a relatively long duration of Parkinson's disease tended to report more, and more severe, symptoms. The PRO-PD was most highly correlated with the Parkinson’s Disease Questionaire-39 (r  =  0.763, P  <  0.000) and Patient-Reported Outcome Measurement Information System Global quality of life (r  =  −0.7293, P  <  0.000), other patient-reported quality of life measures. The PRO-PDnon-motor subset was highly correlated with the Non-Motor Symptom Score (r  =  0.7533, P  <  0.000). There was a moderate correlation seen with Hoehn & Yahr (r  =  0.5922, P  <  0.000), total Unified Parkinson’s disease Rating Scale (r  =  0.4724, P  <  0.000), and the Timed-Up-&-Go (r  =  0.4709, P  <  0.000). The PRO-PD may have utility for patients, providers, and researchers as a patient-centered measure of Parkinson’s disease symptom severity. Further PRO-PD validation efforts are warranted.
Generation of high-density biskyrmions by electric current
Authors: Peng Licong , Zhang Ying , He Min , Ding Bei , Wang Wenhong , Tian Huanfang , Li Jianqi , Wang Shouguo , Cai Jianwang , Wu Guangheng , Liu J. Ping , Kramer Matthew J. , Shen Bao-gen
Published: June 2017

Much interest has been focused on the manipulation of magnetic skyrmions, including the generation, annihilation, and motion behaviors, for potential applications in spintronics. Here, we experimentally demonstrate that a high-density Bloch-type biskyrmion lattice in MnNiGa can be generated by applying electric current. It is revealed that the density of biskyrmions can be remarkably increased by increasing the electric current, in contrast to the scattered biskyrmions induced by a magnetic field alone. Furthermore, the transition from the ferromagnetic state to the stripe domain structure can be terminated by the electric current, leading to the biskyrmions dominated residual domain pattern. These biskyrmions in such residual domain structure are extremely stable at zero magnetic and electric fields and can further evolve into the high-density biskyrmion lattice over a temperature range from 100 to 330 K. Our experimental findings open up a new pathway for the generation of skyrmion lattice by electric current manipulation.
Social learning through prediction error in the brain
Authors: Joiner Jessica , Piva Matthew , Turrin Courtney , Chang Steve W. C.
Published: June 2017

Learning about the world is critical to survival and success. In social animals, learning about others is a necessary component of navigating the social world, ultimately contributing to increasing evolutionary fitness. How humans and nonhuman animals represent the internal states and experiences of others has long been a subject of intense interest in the developmental psychology tradition, and, more recently, in studies of learning and decision making involving self and other. In this review, we explore how psychology conceptualizes the process of representing others, and how neuroscience has uncovered correlates of reinforcement learning signals to explore the neural mechanisms underlying social learning from the perspective of representing reward-related information about self and other. In particular, we discuss self-referenced and other-referenced types of reward prediction errors across multiple brain structures that effectively allow reinforcement learning algorithms to mediate social learning. Prediction-based computational principles in the brain may be strikingly conserved between self-referenced and other-referenced information.
Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes
Authors: Bogaert Delfien J. , Dullaers Melissa , Kuehn Hye Sun , Leroy Bart P. , Niemela Julie E. , De Wilde Hans , De Schryver Sarah , De Bruyne Marieke , Coppieters Frauke , Lambrecht Bart N. , De Baets Frans , Rosenzweig Sergio D. , De Baere Elfride , Haerynck Filomeen
Published: June 2017

Syndromic primary immunodeficiencies are rare genetic disorders that affect both the immune system and other organ systems. More often, the immune defect is not the major clinical problem and is sometimes only recognized after a diagnosis has been made based on extra-immunological abnormalities. Here, we report two sibling pairs with syndromic primary immunodeficiencies that exceptionally presented with a phenotype resembling early-onset common variable immunodeficiency, while extra-immunological characteristics were not apparent at that time. Additional features not typically associated with common variable immunodeficiency were diagnosed only later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed KMT2A-associated Wiedemann-Steiner syndrome in one sibling pair and their mother. In the other sibling pair, targeted testing of the known disease gene for Roifman syndrome (RNU4ATAC) provided a definite diagnosis. With this study, we underline the importance of an early-stage and thorough genetic assessment in paediatric patients with a common variable immunodeficiency phenotype, to establish a conclusive diagnosis and guide patient management. In addition, this study extends the mutational and immunophenotypical spectrum of Wiedemann-Steiner and Roifman syndromes and highlights potential directions for future pathophysiological research.
Updating the Phylogenetic Dating of New Caledonian Biodiversity with a Meta-analysis of the Available Evidence
Authors: Nattier Romain , Pellens Roseli , Robillard Tony , Jourdan Hervé , Legendre Frédéric , Caesar Maram , Nel André , Grandcolas Philippe
Published: June 2017

For a long time, New Caledonia was considered a continental island, a fragment of Gondwana harbouring old clades that originated by vicariance and so were thought to be locally ancient. Recent molecular phylogenetic studies dating diversification and geological data indicating important events of submergence during the Paleocene and Eocene (until 37 Ma) brought evidence to dismiss this old hypothesis. In spite of this, some authors still insist on the idea of a local permanence of a Gondwanan biota, justifying this assumption through a complex scenario of survival by hopping to and from nearby and now-vanished islands. Based on a comprehensive review of the literature, we found 40 studies dating regional clades of diverse organisms and we used them to test the hypothesis that New Caledonian and inclusive Pacific island clades are older than 37 Ma. The results of this meta-analysis provide strong evidence for refuting the hypothesis of a Gondwanan refuge with a biota that originated by vicariance. Only a few inclusive Pacific clades (6 out of 40) were older than the oldest existing island. We suggest that these clades could have extinct members either on vanished islands or nearby continents, emphasizing the role of dispersal and extinction in shaping the present-day biota.
EV-3, an endogenous human erythropoietin isoform with distinct functional relevance
Authors: Bonnas Christel , Wüstefeld Liane , Winkler Daniela , Kronstein-Wiedemann Romy , Dere Ekrem , Specht Katja , Boxberg Melanie , Tonn Torsten , Ehrenreich Hannelore , Stadler Herbert , Sillaber Inge
Published: June 2017

Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures. Using LC-ESI-MS/MS, we provide first evidence for the existence of hEPOΔ3 derived protein EV-3 in human serum from healthy donors. Contrary to EPO, recombinant EV-3 did not promote early erythroid progenitors in cultures of human CD34+ haematopoietic stem cells. Repeated intraperitoneal administration of EV-3 in mice did not affect the haematocrit. Similar to EPO, EV-3 acted anti-apoptotic in rat hippocampal neurons exposed to oxygen-glucose deprivation. Employing the touch-screen paradigm of long-term visual discrimination learning, we obtained first in vivo evidence of beneficial effects of EV-3 on cognition. This is the first report on the presence of a naturally occurring EPO protein isoform in human serum sharing non-erythropoietic functions with EPO.
Dipeptidyl Peptidase-4 and Adolescent Idiopathic Scoliosis: Expression in Osteoblasts
Authors: Normand Emilie , Franco Anita , Moreau Alain , Marcil Valérie
Published: June 2017

It has been proposed that girls with adolescent idiopathic scoliosis (AIS) tend to have a taller stature and a lower body mass index. Energy homeostasis, that is known to affect bone growth, could contribute to these characteristics. In circulation, dipeptidyl peptidase-4 (DPP-4) inactivates glucagon-like peptide-1 (GLP-1), an incretin that promotes insulin secretion and sensitivity. Our objectives were to investigate DPP-4 status in plasma and in osteoblasts of AIS subjects and controls and to evaluate the regulatory role of metabolic effectors on DPP-4 expression. DPP-4 activity was assessed in plasma of 113 girls and 62 age-matched controls. Osteoblasts were isolated from bone specimens of AIS patients and controls. Human cells were incubated with glucose, insulin, GLP-1 and butyrate. Gene and protein expressions were evaluated by RT-qPCR and Western blot. Our results showed 14% inferior plasma DPP-4 activity in AIS patients when compared to healthy controls (P = 0.0357). Similarly, osteoblasts derived from AIS subjects had lower DPP-4 gene and protein expression than controls by 90.5% and 57.1% respectively (P < 0.009). DPP-4 expression was regulated in a different manner in osteoblasts isolated from AIS participants compared to controls. Our results suggest a role for incretins in AIS development and severity.
Divergent Regulation of Actin Dynamics and Megakaryoblastic Leukemia-1 and -2 (Mkl1/2) by cAMP in Endothelial and Smooth Muscle Cells
Authors: Smith Madeleine C. , Hudson Claire A. , Kimura Tomomi E. , White Stephen J. , Sala-Newby Graciela B. , Newby Andrew C. , Bond Mark
Published: June 2017

Proliferation and migration of vascular smooth muscle cells (VSMCs) or endothelial cell (ECs) promote or inhibit, respectively, restenosis after angioplasty, vein graft intimal thickening and atherogenesis. Here we investigated the effects of cAMP-induced cytoskeletal remodelling on the serum response factor (SRF) co-factors Megakaryoblastic Leukemia-1 and -2 (MKL1 and MKL2) and their role in controlling VSMC and EC proliferation and migration. Elevation of cAMP using forskolin, dibutyryl-cAMP (db-cAMP), BAY60-6583 or Cicaprost induced rapid cytoskeleton remodelling and inhibited proliferation and migration in VSMCs but not EC. Furthermore, elevated cAMP inhibited mitogen-induced nuclear-translocation of MKL1 and MKL2 in VSMCs but not ECs. Forskolin also significantly inhibited serum response factor (SRF)-dependent reporter gene (SRE-LUC) activity and mRNA expression of pro-proliferative and pro-migratory MKL1/2 target genes in VSMCs but not in ECs. In ECs, MKL1 was constitutively nuclear and MKL2 cytoplasmic, irrespective of mitogens or cAMP. Pharmacological or siRNA inhibition of MKL1 significantly inhibited the proliferation and migration of VSMC and EC. Our new data identifies and important contribution of MKL1/2 to explaining the strikingly different response of VSMCs and ECs to cAMP elevation. Elucidation of these pathways promises to identify targets for specific inhibition of VSMC migration and proliferation.
Rapid discrimination of human oesophageal squamous cell carcinoma by mass spectrometry based on differences in amino acid metabolism
Authors: Jianyong Zhang , Jianjun Xu , Yongzhong Ouyang , Junwen Liu , Haiyan Lu , Dongliang Yu , Jinhua Peng , Junwen Xiong , Huanwen Chen , Yiping Wei
Published: June 2017

Oesophageal cancer (OC) is associated with high morbidity and mortality, and surgery is the most effective approach to treat it. In order to reduce surgical risks and duration of surgery, we explored a new strategy to determine tumour margins in surgery. In this study, we included 128 cancerous and 128 noncancerous database entries obtained from 32 human patients. Using internal extractive electrospray ionization-MS, in positive ion detection mode, the relative abundances of m/z 104.13, m/z 116.10, m/z 132.13, and m/z 175.13 were higher in cancer tissue while the relative abundances of m/z 82.99, m/z 133.11, m/z 147.08, m/z 154.06, and m/z 188.05 were higher in normal tissue. Using partial least squares analysis, the mass spectra of cancer samples was discriminated from those of normal tissues, and the discriminatory ions were obtained from loading plots. Dimethylglycine(m/z 104), proline(m/z 116), isoleucine(m/z 132), asparagine(m/z 133), glutamine(m/z 147), and arginine(m/z 175) were identified by collision-induced dissociation experiments. Using the ROC curve analysis, we verified the validity of six amino acids for the identification of tumour tissue. Further investigations of tissue amino acids may allow us to better understand the underlying mechanisms involved in OC and develop novel means to identify tumour tissue during operation.
Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study
Authors: Tang Zhenzhu , Pan Stephen W. , Ruan Yuhua , Liu Xuanhua , Su Jinming , Zhu Qiuying , Shen Zhiyong , Zhang Heng , Chen Yi , Lan Guanghua , Xing Hui , Liao Lingjie , Feng Yi , Shao Yiming
Published: June 2017

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm3 at ART initiation, HIV patients with >500 CD4+ cells/mm3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40–0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03–1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.
Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
Authors: Lee Young-Sun , Kim So Yeon , Ko Eunjung , Lee Jun-Hee , Yi Hyon-Seung , Yoo Yang Jae , Je Jihye , Suh Sang Jun , Jung Young Kul , Kim Ji Hoon , Seo Yeon Seok , Yim Hyung Joon , Jeong Won-Il , Yeon Jong Eun , Um Soon Ho , Byun Kwan Soo
Published: June 2017

Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.
Investigation of the 2312 flexoelectric coefficient component of polyvinylidene fluoride: Deduction, simulation, and mensuration
Authors: Zhang Shuwen , Liu Kaiyuan , Xu Minglong , Shen Hao , Chen Kai , Feng Bo , Shen Shengping
Published: June 2017

Flexoelectric effects hold promising applications in sensing, actuating, and energy capturing, and thus it is demanded to measure the flexoelectric coefficient tensors of dielectric materials accurately. In this work, an approach to measuring the effective flexoelectric coefficient tensor component μ2312 of polymeric materials is developed by imposing a torque load upon a half cylindrical specimen. It is proven that μ2312 can be calculated by assessing the electric charge on the axial plane and the strain gradient along the radial direction, both induced by the torque. To overcome the difficulty in experimental measurements, the relationship between the strain gradient and torque is deduced theoretically and further verified with finite element analysis. This approach is applied to testing bars machined from bulk polyvinylidene fluoride (PVDF). Potential errors from the piezoelectric effects and the non-uniform strain gradient are discussed to verify the validity of the measurement. The experimental results show good reproducibility and agreement with other measured effective flexoelectric tensor components of PVDF. This work indicates a potential application of PVDF-based mechanical sensors and provides a method to investigate the effective flexoelectric coefficient component of polymers.
Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
Authors: Presta Luana , Bosi Emanuele , Mansouri Leila , Dijkshoorn Lenie , Fani Renato , Fondi Marco
Published: June 2017

Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections.
In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study
Authors: Luo Jie , Abaci Turk Esra , Bibbo Carolina , Gagoski Borjan , Roberts Drucilla J. , Vangel Mark , Tempany-Afdhal Clare M. , Barnewolt Carol , Estroff Judy , Palanisamy Arvind , Barth William H. , Zera Chloe , Malpica Norberto , Golland Polina , Adalsteinsson Elfar , Robinson Julian N. , Grant Patricia Ellen
Published: June 2017

Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.
Molecular Identification of Multiple Antibiotic Resistant Fish Pathogenic Enterococcus faecalis and their Control by Medicinal Herbs
Authors: Rahman Muntasir , Rahman Md. Mahbubur , Deb Suzan Chandra , Alam Md. Shahanoor , Alam Md. Jahangir , Islam Md. Tofazzal
Published: June 2017

The opportunistic fish pathogen, Enterococcus faecalis has been reported to cause mass mortality in several fish species in different countries. The objectives of this study were to (i) identify E. faecalis from the diseased fishes through molecular techniques; (ii) assess the antibiotic susceptibility profile of E. faecalis isolates; and (iii) control disease in tilapia fish by treatment with medicinal plant extracts. A total of 48 isolates were phenotypically identified as Enterococcus species from tilapia, stinging catfish and walking catfish cultivated in several fish farms in Gazipur. Ten randomly selected isolates were identified as E.faecalis by 16S rRNA gene sequencing. Artificial infection revealed that most of the isolates caused moderate to high mortality in fishes with characteristic disease symptoms. These isolates exhibited resistance to multiple antibiotics in vitro. Bioassay revealed that organic extracts of Tamarindus indica and Emblica officinalis leaves, Allium sativum bulb, and Syzygium aromaticum bud inhibited the growth of E. faecalis. Methanol extracts of A. sativum and methanol and acetone extracts of S. aromaticum significantly reduced the mortality of fish artificially infected with E. faecalis as both preventive and therapeutic agents. This is the first report on molecular identification, and herbal control of fish pathogenic E. faecalis in Bangladesh.