bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Monitoring of Combinatorial Chemistry Reactions by Infrared Microspectroscopy
Authors: Martoglio Pamela A , Schiering David W , Smith Matthew J , Smith Daniel T
Published: March 2018

What is combinatorial chemistry? Combinatorial chemistry is quickly becoming a very popular technique for organic synthesis in the pharmaceutical and biotechnology fields. Basically, combinatorial methods allow one to obtain thousands of derivatives of chemical compounds in a very quick and efficient manner. The method begins when a molecule of interest is attached to resin beads. Once the molecule is attached, a number of reactions can be run on the beads. The beads can be split up into several subsets, and different reactions can be run on each of the subsets. Because the beads are in the solid phase, it is extremely easy to separate the beads from the liquid layer after the reactions have completed.
Finger Painting or Digital Imaging
Authors: Revel Jean-Paul
Published: March 2018

In the good old days, when microscopists wanted to show others what they had found, they either drew by hand what they saw or hired someone to do same. Besides manual dexterity, and eye-hand coordination, drawing of course requires artistic interpretation, i.e. at least a smidgen of imagination. As a result one always had to be concerned with the objectively of rendering. Such concerns were more or less put to rest once the proper use of photography became established. The manual dexterity was reduced to twisting the focus knob, squeezing the shutter button without also shaking the camera and doing some handwaving in the dark room (artistic interpretation), surprisingly all non-trivial operations.

Today we have entered a different phase yet in the process of sharing morphological information, a phase characterized by digital recording and along with it, digital image processing. The digits now are not literally fingers anymore, but the numbers they stand for Digital image recording and processing was originally devised to improve the quality of images returned by spacecraft and used to require highly sophisticated computing facilities.
Stm at High Temperature: What you see is what you see … usually
Authors: Kersker Michael M
Published: March 2018

There remains two basic axioms of all microscopists: the first….if you look, you're bound to see something, and the second….not everything you will see is artifact. These axioms apply particularly well to scanning probe microscopy at the molecular and atomic level. Fortunately, coarser resolution images share comforting similarities with images from other established scanning methods. Holes in optical discs look like holes when probed with AFM tips, and these holes look very much like SEM images, a subject with which we have some familiarity. At the molecular and atomic level, however, the scanning probe instruments may or may not be “seeing” the sample, though they are clearly seeing something.

Comparison of surface structure observed with indirect surface structural measurements, for example by LEED (Low Energy Electron Diffraction) or RHEED (Reflection High Energy Electron Diffraction) usually under ultra-high vacuum conditions can lead, by inference, to an understanding of the real bulk or average surface structure.
Industrial Mineral Microscopy
Authors: Solebello Louis P
Published: March 2018

What is industrial mineral microscopy? It is the application of any micro-analytical technique used to characterize and identify non-metallic and non-fuel earth materials. Humans have used industrial minerals since ancient times. The earliest known scientific work which dealt expressly with minerals and artificial products derived from them is Theophrastus On Stones. Theophrastus, a pupil and friend of Aristotle, described the use of fuller's earth and gypsum for whitening discolored cloth garments in the latter half of the 4th century, B.C. Fuller's earth is still used today as a decolorizing agent by manufacturers of oil and fat products. Gypsum, of course, is widely used in plaster of paris, cement, and paper.

Today, industrial minerals are encountered often by people in everyday life. Electronic, pharmaceutical, cosmetic, construction, paper, and plastics industries use industrial minerals in a multitude of products.
Telemicroscopy
Authors: Fan Gary , Mercurio Phil , Young Steve , Ellisman Mark
Published: March 2018

While many of us have used a computer network to send E-mail, how about using it to remotely control an electron microscope? That's exactly what Telemicroscopy refers to.

Up to now electron microscopy (EM) has been conducted typically in a darkened enclosure, with the operator sitting in the dark for hours staring at a dim phosphor screen. This paradigm was not, however, closely followed during the telemicroscopy demonstration at the SIGGRAPH 1992 meeting in Chicago, where microscopic images were acquired on-line over the Internet high-speed computer network from the intermediate-high voltage electron microscope located at the San Diego Microscopy and Imaging Resource. Stereo-pairs were displayed on a color projection screen in front of many spectators and camera crews.
Physics of Backscattered Electron Diffraction
Authors: Camus Patrick
Published: March 2018

The scale of features that control the physical properties of engineered materials is ever decreasing. We can investigate the structure of these materials using several techniques. The techniques are usually selected based on the feature size of interest. Typical scales are the millimeter or optical scale, the micron or microscopic scale, and the nanometer or atomic scale. As the feature size decreases, the capabilities of the technique must increase.

Typical features that require at least microscopic characterization include particles in super alloys, grain misorientations in high temperature superconductors and thin films, inclusions in steels, reaction products in gas chambers.
Presentation of the Microscopy Image
Authors: Blystone Robert V
Published: March 2018

Microscopists have special challenges when presenting image data to audiences, Issues such as image size, resolution, and labeling are related to the format of the presented image. Contact prints, transparencies, 35 mm film, and projected video of digital images are some of the output options possible for microscopy presentation. This brings us to a question which Jonathan Krupp of the University of California, Santa Cruz, recently posed to the Microscopy listserver;

“In this age of digital imaging, is a film recorder still useful? The last presentation I went to was all PowerPoint ‘slides’, but shown directly from a computer to a video projector, no film to be seen.”
X-Ray Analysis in the Low Vacuum SEM
Authors: Chemoff Don
Published: March 2018

Low vacuum and environmental SEMs have become commonplace in many labs for many applications. With the rise in popularity of these instruments comes the need to understand their capabilities and limitations. An article I wrote in this publication in August 1997 summarized the issue of beam scatter in the low vacuum SEM, In this first of a series of three articles, I will go into more detail and give more examples on the phenomena of beam scatter in the low vacuum SEM.

The problem of beam scatter in the low vacuum SEM chamber is well known. Electrons from the primary beam interact with gas molecules in the SEM chamber, scatter, and hit the sample surface some distance away from the primary beam. The result is a “skirt” of electrons much wider than the primary beam. The amount of scatter depends on four variables: chamber pressure, working distance, accelerating voltage, and gas type. I will discuss the first three in this paper. The effect of gas type will be addressed in the next issue.
Contemporary Problems in Science Jobs (Second Edition) Part 1: The Job Crunch and the Grant Crunch
Authors: Sowers Arthur E
Published: March 2018

Earlier versions of these essays have been posted primarily and repeatedly on the internet newsgroup  for approximately one year (March 1995 to March 1996). A number of versions are archived at a number of sites. These essays were written in the public interest and for the benefit of younger people who are in the grad. school to postdoc pipeline. This edition was cleaned up, reorganized somewhat, slightly shortened, and brought up to date.

People who are in the grad. school to postdoc pipeline are, for the most part, hoping to see their dreams come true with a real and decent career job in science. The purpose of this document is to inform these people about the realities that will be in conflict with their dreams.
A Berry Sweet Development: Microscopy of the Future
Authors: Revel Jean-Paul
Published: March 2018

One of the most pervasive problems in microscopy is that of making sure that what one is observing represents reality. The complex specimen preparation steps which have to be followed to obtainimages of biological samples all produce artifacts, at least in the sense that they modify the sample. The investigator has to somehow show that these changes in the sample reveal true microscopic features, rather than structures which do not exist in the living. This, of course, is why polarized light microscopy, phase and interference microscopy and their derived approaches, all of which reveal detail in live untreated specimen, are so important, in spite of the limited resolution which can be achieved.

When electron microscopy was in its infancy there were, and justifiably so, even more severe fears about the reality of what could be seen. Even visionary people like Gabor had their doubts and the first steps in biological microscopy were taken with the realization that if the sample was burned to a crisp, perhaps examination of its cinders would still give valuable information.
Atomic Resolution Microscopy
Authors: Silcox John
Published: March 2018

Although it has been possible for many years to determine the average position of atoms by using diffraction techniques, finding the positions of specific atoms has been an elusive target. This latter goal is now in sight. Individual atoms on surfaces were first seen in the seventies by the Chicago Group using the then newly invented Scanning Transmission Electron Microscope (STEM). More recently atoms on surfaces have also been seen by Scanning Tunneling Microscopy (STM) and associated variants (e.g. Atomic Force Microscopy). Atomic structures in the interior of a material have been imaged in recent years through atomic resolution transmission electron microscopy of thin film specimens. Progress in these developments is following an acceleration path and the Materials Research Division of the NSF recently commissioned a panel to review the area and provide advice on an appropriate response.
Attaboy! Attoboys, or the new Zeptoscopists
Authors: Revel Jean-Paul
Published: March 2018

As the year ends there is a bumper crop of announcements of advances that I find absolutely amazing. First of course is the continued clever use of light as a veritable tool in manipulating everything from atoms (entrapping them in “atomic molasses”) to having tugs of war with biological motors (using “light tweezers”). But these developments will be for discussion another time. What I want to talk about in this installment are advances in Near Field Scanning Optical Microscopy (NSOM), which has now been used by Chichester and Betzig to visualize single molecules.

In classical (far field) optics, resolution is limited by diffraction to about 1/2 the wavelength of the radiation used for imaging. Near field optics overcome this limitation by use of scanning techniques similar to those employed in Scanning Tunneling or Scanning Force Microscopy.
Microwave Cryofixation
Authors: van Hook Lee
Published: March 2018

There is much discussion on the best way to fix biological specimens, often advocating cryofixation or microwave fixation. These discussions sometimes become acrimonious, and we at the P.R.I, fear the eventual division of microscopists into rival lab gangs, the “Waves” and the “Cryos”.

Wishing to forestall this, and because Leonard Bernstein is no longer with us to write West Lab Story, we have been working on a method of combining the two fixation methods. Less romantic than rival gang members falling in love perhaps, but more practical.
Combined Pressure-Cooker and Microwave Antigen Retrieval
Authors: Kennedy Allan
Published: March 2018

The use of antigen retrieval techniques has been the foundation of the development of immunocytochemistry (ICC). After the pioneering work done on cryostat sections, the use of enzyme digestion made formalin-fixed archival and current material available for study by ICC. However, the relationship between the duration of fixation and the digestion time necessary for optimum results is a major drawback associated with enzyme digestion. The longer the tissue has been in fixative, the longer the required digestion time will be. Even after a standardised fixation time, some antigens require greatly extended digestion times. Whereas 10-15 minutes in trypsin may be a standard protocol after overnight fixation, immunoglobulin deposits in renal glomeruli may require 60-90 minutes.
For Lack of a Nail
Authors: Revel Jean-Paul
Published: March 2018

A few months ago I read a most exciting article in a scientific magazine. It seemed to me that the ideas presented had the potential to revolutionize all of microscopy and I got very excited at the vistas opened by this unexpected departure from the accepted dogma. The article was only a summary of the current status of the research in the field and I resolved to probe deeper. Since I read the piece just as I was ready to go to sleep I trusted my memory in the unreasonable belief that, should my memory fail, I could always access a computer database to retrieve the information when I needed it. I even recollect feeling very virtuous when, the very next morning, I entered the data into my files. At least I think I remember that.
Microscopy for Middle Schools
Authors: Schooley Caroline
Published: March 2018

The Microscopy Society of America (MSA) is beginning a long-term educational effort; the first goal of the program is to bring the excitement of microscopy to middle schools. We'll begin by developing a curriculum manual that integrates an understanding of how lenses magnify with observation of the microworld; examples will be from both physical and biological sciences. Funding will come from NSF and private foundations, and science education expertise will be provided by the Lawrence Hall of Science in Berkeley, a leading developer of science curriculum. As educators often use acronyms, we've named ours MICRO, for Microscopy In Curriculum - Research Outreach.

Writing a manual is just the beginning. MSA is directing its first effort at middle schools, because teachers at that level who want and need to teach science often lack the background to do so as anything more than a dull textbook exercise; teacher training workshops will be offered nationally.
Modern Microscopy on the Light Side - - - Fibers, Fibers Fibers Everywhere
Authors: Bisbing Richard E
Published: March 2018

In antiquity men and women consumed more labor to produce products from fiber bearing plants and animals than any other activity. Today the manmade fiber industry has reached dazzling heights frying to improve on the quality of natural fibers like wool, cotton, and asbestos and at the same time trying to offer the product at a better price. The identification of the tiny textile fiber fragments which cover our clothes and floors and contaminate our manufactured products illustrates how light microscopy can help improve the work environment, keep our products clean, and solve the most serious crimes. The consulting microscopist sees fibers as penultimately a problem of materials identification and finally as part of an intriguing mystery. In other words, from an archaeologist's point of view, fabric analysis always reveals something of the weaver in the same way as a forensic scientist learns something of the criminal through identification of extraneous fibers on the victim's clothing.
Stars of Snow
Authors: Delly John Gustav
Published: March 2018

“Hast thou entered into the treasures of the snow? Or hast thou seen the treasures of the hail.” Job 38:22

A number of years ago, I produced a Christmas card which featured a snowflake in the unusual form of a Christmas tree. To enhance the suggestion of “evergreen”, I photographed it by transmitted light with a green filter (Wratten No. 58) in the light path. It has been almost twenty years since the card appeared, and in that time I have had many occasions to project the original 35-mm transparency, When I do show it, I mention that particular snowflake was captured during a snowfall in Chicago on January 17, 1971.
Quantifying Heterogeneity with Microbeam Analysis
Authors: Shaffer Michael
Published: March 2018

Electron probe microanalysis (EPMA) is not only an excellent technique for measuring the chemical composition of a wide variety of materials, but also provides an effective means to quantitatively evaluate the chemical homogeneity of the material, In this contribution I present an easy approach for determining the chemical homogeneity of specimens in a statistically meaningful way.

The decree of chemical heterogeneity may be determined by a variety of methods varying both in ease snd rigor. One might apply a simple test for the sake of classifying the material as homogeneous or heterogeneous.
Microscopists & Spectroscopists
Authors: Katon Jack E , Sommer Andre' J
Published: March 2018

Our attention was caught by a recent article in this newsletter (Issue #7, September, 1992) entitled “Modern Microscopy on the Light Side. The FTIR Microscope” by Mr. Skip Palenik. Mr. Palenik makes some cogent points but we feel there is a bit more to the story. We are spectroscopists by training and experience and “...have done some reading and/or taken a short course...”, but we have not “...set ourselves up as microscopists...”, at least so far. We have, however, for the past nine years attempted to educate microscopists, spectroscopists. chemists and even non-scientists regarding the benefits of combining optical microscopy and molecular spectroscopy. We are convinced the whole is greater than the sum of the parts.

The very rapid acceptance of infrared microspeetroscopy by the analytical chemistry community reflects its power to solve diverse problems. One of the long time characteristics of infrared spectroscopy has been that its users vary greatly in their needs and thus in the sophistication in their systems. In connection with this, it must be realized that the fundamental laws of physics prevent the coupling of a microscope and an infrared spectrometer, in such a way as to optimize the performance of both, at a cost which can be borne by all users. As a result, some infrared microscopes have "been optimized for viewing capabilities while compromising spectroscopic capabilities and vice versa. Such compromises are not unusual in the field of infrared spectroscopy and the advantages gained by them constitute part of the reason for such widespread use of infrared in chemical analysis.
Score NoSAS: un outil de dépistage du syndrome d’apnées du sommeil pour le médecin de premier recours
Authors: Mitropoulou Georgia , Haba-Rubio José , Heinzer Raphaël
Published: March 2018

Zusammenfassung. Schlafbezogene Atmungsstörungen (SBAS) sind in der Bevölkerung weit verbreitet, sie sind mit einem erhöhten kardiovaskulären Risiko und einer übermässigen Tagesschläfrigkeit verbunden, die wiederum das Risiko von Autounfällen erhöht. Die Diagnose erfordert Atemaufnahmen während des Schlafs, die oft schwierig durchzuführen sind. Daher werden Screening-Verfahren benötigt, um die Prätest-Wahrscheinlichkeit von SBAS abzuschätzen und über den geeigneten Diagnosetest entscheiden zu können. Derzeit sind die beiden Fragebögen, die am häufigsten als Screening-Tools für SBAS in der Primärversorgung verwendet werden, der Berliner Fragebogen und der STOP-Bang-Fragebogen; ihr Vorhersagewert in der Allgemeinbevölkerung wurde jedoch nicht validiert. Der NoSAS-Score ist ein neues Screening-Tool, das auf Grundlage der Ergebnisse der HypnoLaus-Studie entwickelt wurde, einer grossen bevölkerungsbezogenen Kohorte mit 2121 Teilnehmern, die sich zu Hause einer vollständigen Polysomnografie (PSG) unterzogen haben. Die Punktzahl ist die gewichtete Summe der Punkte, die fünf Parametern zugeordnet werden: Halsumfang, Adipositas gemessen am Body-Mass-Index, Schnarchen, Alter und Geschlecht. Es reicht von 0 bis 17, wobei ≥8 als positiv für ein hohes Risiko einer klinisch signifikanten SBAS angesehen wird. Der NoSAS-Score schnitt bei der Vorhersage von SBAS besser ab als der Berliner und der STOP-Bang-Fragebogen, wie anhand von Polysomnografie ermittelt wurde – sowohl in der HypnoLaus-Studie als auch in einer unabhängigen populationsbasierten Kohorte (EPISONO). Eine der Stärken des NoSAS-Scores ist die nahezu ausschliessliche Verwendung von objektiven Variablen, die aus Patientenakten leicht zugänglich sind, wobei Schnarchen der einzige subjektive Parameter ist. Zusammenfassend ist der NoSAS-Score ein zuverlässiges und einfach zu verwendendes Screening-Tool für SBAS in der Allgemeinbevölkerung. Eine weitere Validierung in verschiedenen klinischen Populationen ist notwendig, um den Wert in der klinischen Praxis zu bestätigen.
Fieber bei monoklonaler Gammopathie und Immunneuropathie – ein differenzialdiagnostischer Sple(e)n
Authors: Lüscher Daniel , Diethelm Markus , Hundsberger Thomas , Hitz Felicitas
Published: March 2018

Zusammenfassung. Wir stellen den Fall einer 81-jährigen Patientin mit Fieber unklarer Ursache bei bekannter chronisch inflammatorischer demyelinisierender Polyneuropathie (CIDP) und monoklonaler Gammopathie unklarer Signifikanz vor. Nach langer Hospitalisation konnte die Diagnose eines diffus grosszelligen B-Zell-Lymphoms erst nach einer Splenektomie gestellt werden. Die Abklärungen bei Diagnosestellung und die Nachsorgeuntersuchungen bei einer monoklonalen Gammopathie werden diskutiert.
Soziale Disparitäten im Kontext von Mutter-Kind-Interaktionen und frühen Entwicklungsmaßen von Kindern
Authors: Attig Manja , Weinert Sabine
Published: March 2018

Zusammenfassung. Lange vor Schuleintritt sind bereits vielfältige bildungsrelevante Entwicklungsunterschiede im Zusammenhang mit dem jeweiligen familiären Hintergrund der Kinder (z.B. Bildung, Familienstatus, Einkommen) beobachtbar und dokumentiert. Anhand von Daten der Säuglingskohorte des Nationalen Bildungspanels (NEPS; LIfBi, 2016 ) wurde die Entstehung solcher Disparitäten bei 16 bis 17 Monate alten Kindern und ihren Familien untersucht. Im Fokus stand die Analyse von Unterschieden in frühen Lernressourcen der Kinder sowie im mütterlichen und kindlichen Interaktionsverhalten in Abhängigkeit von sozialen (Familienstatus, Einkommen) und bildungsbezogenen familiären Charakteristika. Die Befunde zeigten Effekte der mütterlichen Bildung auf ihr Interaktionsverhalten in Mutter-Kind-Interaktionen sowie Assoziationen zwischen dem mütterlichen und kindlichen Interaktionsverhalten. Bezogen auf die erfassten Kindmerkmale fanden sich keine herkunftsbedingten Unterschiede in den frühkindlichen Lernressourcen der Kinder. Die geringen mit der mütterlichen Bildung assoziierten Disparitäten in sozio-emotionalen Facetten des kindlichen Interaktionsverhaltens erwiesen sich als nicht mehr signifikant, wenn die Unterschiede im mütterlichen Interaktionsverhalten berücksichtigt wurden. Die Befunde werden mit Blick auf die Entstehung von Disparitäten in der Kindesentwicklung aufgrund sozialer und bildungsbezogener Ungleichheit diskutiert.
A Systematic Review of Theory of Mind’s Precursors and Functions
Authors: Derksen Daniel G. , Hunsche Michelle C. , Giroux Megan E. , Connolly Deborah A. , Bernstein Daniel M.
Published: March 2018

Abstract. We conducted a systematic review of longitudinal theory of mind (ToM) studies, focusing on the precursors to and functional outcomes of ToM in typically-developing samples. Our search yielded 87 longitudinal studies, all of which involved children and adolescents. Early attention skills, executive function development, and the use of language are precursors to ToM development. Additionally, quality interaction with parents and older siblings can foster early improvements in ToM. Healthy ToM development improves social relationships with peers and produces greater desire to engage in prosocial behaviors. However, victimized individuals with highly-developed ToM may engage in increased aggression. Future longitudinal research is needed to investigate the functional outcomes resulting from ToM changes in adulthood.
Does the Past Shape Anticipation for the Future?
Authors: Hansen Lagattuta Kristin , Tashjian Sarah M. , Kramer Hannah J.
Published: March 2018

Abstract. A positive association between executive function (a set of higher order, self-regulatory cognitive skills) and theory of mind (beliefs about mental states) has been well documented during early childhood. As investigations extend beyond false belief understanding (that the mind can misrepresent reality), there is growing interest in examining contributions of executive function to more advanced aspects of theory of mind in older age groups. To add to this literature, we showed 4- to 10-year-olds and adults (N = 274) scenarios in which a perpetrator acted positively (P) and/or negatively (N) toward a focal character on two separate days (PP, NN, NP, and PN). Participants inferred focal characters’ future-oriented mental states upon seeing perpetrators for the third time. Children and adults also completed executive function measures (working memory and inhibitory control). Both age and executive function independently predicted higher life history theory of mind: Recognition that prior life experiences influence how individuals think, feel, and make decisions about the future.
The integrated landscape of causal genes and pathways in schizophrenia
Authors: Ma Changguo , Gu Chunjie , Huo Yongxia , Li Xiaoyan , Luo Xiong-Jian
Published: March 2018

Genome-wide association studies (GWAS) have identified more than 100 loci that show robust association with schizophrenia risk. However, due to the complexity of linkage disequilibrium and gene regulatory, it is challenging to pinpoint the causal genes at the risk loci and translate the genetic findings from GWAS into disease mechanism and clinical treatment. Here we systematically predicted the plausible candidate causal genes for schizophrenia at genome-wide level. We utilized different approaches and strategies to predict causal genes for schizophrenia, including Sherlock, SMR, DAPPLE, Prix Fixe, NetWAS, and DEPICT. By integrating the results from different prediction approaches, we identified six top candidates that represent promising causal genes for schizophrenia, including CNTN4, GATAD2A, GPM6A, MMP16, PSMA4, and TCF4. Besides, we also identified 35 additional high-confidence causal genes for schizophrenia. The identified causal genes showed distinct spatio-temporal expression patterns in developing and adult human brain. Cell-type-specific expression analysis indicated that the expression level of the predicted causal genes was significantly higher in neurons compared with oligodendrocytes and microglia (P < 0.05). We found that synaptic transmission-related genes were significantly enriched among the identified causal genes (P < 0.05), providing further support for the dysregulation of synaptic transmission in schizophrenia. Finally, we showed that the top six causal genes are dysregulated in schizophrenia cases compared with controls and knockdown of these genes impaired the proliferation of neuronal cells. Our study depicts the landscape of plausible schizophrenia causal genes for the first time. Further genetic and functional validation of these genes will provide mechanistic insights into schizophrenia pathogenesis and may facilitate to provide potential targets for future therapeutics and diagnostics.
Kir6.1/K-ATP channel modulates microglia phenotypes: implication in Parkinson’s disease
Authors: Du Ren-Hong , Sun Hong-Bin , Hu Zhao-Li , Lu Ming , Ding Jian-Hua , Hu Gang
Published: March 2018

Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson’s disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6.1/K-ATP) channel switched microglia from the detrimental M1 phenotype toward the beneficial M2 phenotype. Kir6.1 knockdown inhibited M2 polarization and simultaneously exaggerated M1 microglial inflammatory responses, while Kir6.1 overexpression promoted M2 polarization and synchronously alleviated the toxic phase of M1 microglia polarization. Furthermore, we observed that the Kir6.1 deficiency dramatically exacerbated dopaminergic neuron death companied by microglia activation in mouse model of PD. Mechanistically, Kir6.1 deficiency enhanced the activation of p38 MAPK–NF-κB pathway and increased the ratio of M1/M2 markers in the substantia nigra compacta of mouse model of PD. Suppression of p38 MAPK in vivo partially rescued the deleterious effects of Kir6.1 ablation on microglia phenotype and dopaminergic neuron death. Collectively, our findings reveal that Kir6.1/K-ATP channel modulates microglia phenotypes transition via inhibition of p38 MAPK–NF-κB signaling pathway and Kir6.1/K-ATP channel may be a promising therapeutic target for PD.
miR199a-5p inhibits hepatic insulin sensitivity via suppression of ATG14-mediated autophagy
Authors: Li Bo , Wu Xiangsong , Chen Hanbei , Zhuang Chengle , Zhang Zhiguo , Yao Shuangshuang , Cai Dongsheng , Ning Guang , Su Qing
Published: March 2018

MicroRNAs (miRNAs) are known to contribute to many metabolic diseases, including diabetes. In this study, we investigated the role of miR199a-5p in the regulation of hepatic insulin sensitivity. Ad-anti-miR199a-5p adenoviruses were injected into male C57BL/6J WT mice fed a high-fat diet to inhibit miR199a-5p expression before the glucose levels and insulin resistance were assessed. Similarly, Ad-miR199a-5p adenoviruses were injected into male C57BL/6J WT mice to cause the overexpression of miR199a-5p. To investigate the roles of autophagy-related protein 14 (ATG14) and miR199a-5p in the regulation of insulin sensitivity, we injected Ad-miR199a-5p with or without Ad-ATG14 viruses into WT C57BL/6J mice before performing functional assays. Moreover, we infected HepG2 cells or primary hepatocytes with Ad-anti-miR199a-5p or Ad-miR199a-5p viruses to determine the effect of miR199a-5p on insulin resistance in vitro. Finally, we explored the clinical relevance of miR199a-5p by examining the expression level of miR199a-5p in liver samples derived from diabetes patients. We first demonstrated that knocking down miR199a-5p led to decreased glucose tolerance and clearance in vivo, whereas the overexpression of miR199a-5p had the opposite effect. We further identified ATG14 as the target of miR199a-5p, and ATG14 partially rescued miR199a-5p-potentiated glucose and insulin tolerance. In addition, transmission electron microscopy data and western blot data regarding ATG14, LC3 and BECLIN1 illustrated that miR199a-5p regulates autophagy via ATG14. Knocking down miR199a-5p in primary hepatocytes and HepG2 cells suppressed the insulin-stimulated phosphorylation of insulin receptor β, glycogen synthase kinase 3β and protein kinase B, whereas the overexpression of miR199a-5p further potentiated their phosphorylation. Finally, we detected upregulated miR199a-5p levels, which were correlated with reduced ATG14 mRNA levels and downregulated autophagy in liver samples obtained from diabetes patients. Our study uncovered a novel biological role of miR199a-5p in the regulation of hepatic insulin sensitivity via ATG14-mediated autophagy.
Decreased autophagy induced by β1-adrenoceptor autoantibodies contributes to cardiomyocyte apoptosis
Authors: Wang Li , Li Yang , Ning Na , Wang Jin , Yan Zi , Zhang Suli , Jiao Xiangying , Wang Xiaohui , Liu Huirong
Published: March 2018

It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1-AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1-AAB-immunized rat model. Rapamycin, an mTOR inhibitor, restored myocardial apoptosis in the presence of β1-AABs. Further, we found that the early increase of autophagy was an adaptive stress response that is possibly unrelated to β1-AR, and the activation of the β1-AR and PKA contributed to late decreased autophagy. Then, after upregulating or inhibiting autophagy with rapamycin, Atg5 overexpression adenovirus or 3-methyladenine in cultured primary neonatal rat cardiomyocytes, we found that autophagy decline promoted myocardial apoptosis effectively through the mitochondrial apoptotic pathway. In conclusion, the reduction of apoptosis through the proper regulation of autophagy may be important for treating patients with β1-AAB-positive heart dysfunction.
Redefining the ancestral origins of the interleukin-1 superfamily
Authors: Rivers-Auty Jack , Daniels Michael J. D. , Colliver Isaac , Robertson David L. , Brough David
Published: March 2018

The interleukin-1 (IL-1) receptor and ligand families are components of the immune system. Knowledge of their evolutionary history is essential to understand their function. Using chromosomal anatomy and sequence similarity, we show that IL-1 receptor family members are related and nine members are likely formed from duplication and modification of a proto-IL-1R1 receptor. The IL-1 ligands have a different evolutionary history. The first proto-IL-1β gene coincided with proto-IL-1R1 and duplication events resulted in the majority of IL-1 ligand family members. However, large evolutionary distances are observed for IL-1α, IL-18 and IL-33 proteins. Further analysis show that IL-33 and IL-18 have poor sequence similarity and no chromosomal evidence of common ancestry with the IL-1β cluster and therefore should not be included in the IL-1 ligand ancestral family. IL-1α formed from the duplication of IL-1β, and moonlighting functions of pro-IL-1α acted as divergent selection pressures for the observed sequence dissimilarity.
Architecture of the Saccharomyces cerevisiae NuA4/TIP60 complex
Authors: Wang Xuejuan , Ahmad Salar , Zhang Zhihui , Côté Jacques , Cai Gang
Published: March 2018

The NuA4/TIP60 acetyltransferase complex is required for gene regulation, DNA repair and cell cycle progression. The limited structural information impeded understanding of NuA4/TIP60 assembly and regulatory mechanism. Here, we report the 4.7 Å cryo-electron microscopy (cryo-EM) structure of a NuA4/TIP60 TEEAA assembly (Tra1, Eaf1, Eaf5, actin and Arp4) and the 7.6 Å cryo-EM structure of a TEEAA-piccolo assembly (Esa1, Epl1, Yng2 and Eaf6). The Tra1 and Eaf1 constitute the assembly scaffold. The Eaf1 SANT domain tightly binds to the LBE and FATC domains of Tra1 by ionic interactions. The actin/Arp4 peripherally associates with Eaf1 HSA domain. The Eaf5/7/3 (TINTIN) and piccolo modules largely pack against the FAT and HEAT repeats of Tra1 and their association depends on Eaf1 N-terminal and HSA regions, respectively. These structures elucidate the detailed architecture and molecular interactions between NuA4 subunits and offer exciting insights into the scaffolding and regulatory mechanisms of Tra1 pseudokinase.
Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis
Authors: Mugridge Jeffrey S. , Tibble Ryan W. , Ziemniak Marcin , Jemielity Jacek , Gross John D.
Published: March 2018

The conserved decapping enzyme Dcp2 recognizes and removes the 5′ eukaryotic cap from mRNA transcripts in a critical step of many cellular RNA decay pathways. Dcp2 is a dynamic enzyme that functions in concert with the essential activator Dcp1 and a diverse set of coactivators to selectively and efficiently decap target mRNAs in the cell. Here we present a 2.84 Å crystal structure of K. lactis Dcp1–Dcp2 in complex with coactivators Edc1 and Edc3, and with substrate analog bound to the Dcp2 active site. Our structure shows how Dcp2 recognizes cap substrate in the catalytically active conformation of the enzyme, and how coactivator Edc1 forms a three-way interface that bridges the domains of Dcp2 to consolidate the active conformation. Kinetic data reveal Dcp2 has selectivity for the first transcribed nucleotide during the catalytic step. The heterotetrameric Edc1–Dcp1–Dcp2–Edc3 structure shows how coactivators Edc1 and Edc3 can act simultaneously to activate decapping catalysis.
3-pyridyl inhibitors with novel activity against Trypanosoma cruzi reveal in vitro profiles can aid prediction of putative cytochrome P450 inhibition
Authors: Sykes Melissa L. , Avery Vicky M.
Published: March 2018

Using high throughput, high-content imaging, a proprietary library was screened against intracellular Trypanosoma cruzi amastigotes to identify compounds with novel activity against the parasite. Five inhibitors were discovered, which did not clear all of the parasites from 3T3 host cells following 48 hours exposure, and were identified as putative T. cruzi cytochrome P450 (TcCYP51) inhibitors. TcCYP51 inhibitors are not favourable for the drug discovery pipeline for treatment of Chagas Disease infection due to clinical and pre-clinical failures. To determine if there were in vitro inhibitory characteristics of these compounds that could aid the prediction of TcCYP51 inhibition further profiling using imaging and fluorescence based assays was undertaken. It was determined that in vitro profiles, coupled with analysis of chemical structure, could support the early prediction of putative TcCYP51 activity and thus enable early de-prioritisation of these compounds from progression through the drug discovery pipeline.
Characterization of a murine model of non-lethal, symptomatic dengue virus infection
Authors: Sarathy Vanessa V. , White Mellodee , Li Li , Kaiser Jaclyn A. , Campbell Gerald A. , Milligan Gregg N. , Bourne Nigel , Barrett Alan D. T.
Published: March 2018

The mosquito-borne disease dengue is caused by four serologically- and genetically-related viruses, termed DENV-1 to DENV-4. Historical setbacks due to lack of human-like mouse models of dengue were partially remedied with characterization of lethal DENV-2 infection in immunocompromised AG129 mice (deficient in IFN-α/β/γ receptors). Recently, our group established lethal AG129 mouse infection models of DENV-1, DENV-3, and DENV-4 using human isolates. Here we compare a non-lethal, disseminated model of DENV-3 infection using strain D83-144 to that of the lethal outcome following infection by strain C0360/94. Both strains belong to DENV-3 genotype II and differ by only 13 amino acids. Intraperitoneal inoculation of AG129 mice with strain D83-144 led to clinical signs of dengue infection, such as cytokine induction, thrombocytopenia, and systemic infection. However, C0360/94 infection led to features of severe human dengue, including coagulopathy and lethal outcome, whereas D83-144 infection does not. This study is the first to investigate a low passage, non-mouse lethal strain in AG129 mice and demonstrates that D83-144 infection induces milder features of human dengue than those induced by lethal C0360/94 infection. The results suggest that the AG129 mouse model has applications to investigate factors associated with mild or severe disease.
In vitro effects of hydroxyapatite containing toothpastes on dentin permeability after multiple applications and ageing
Authors: Hiller Karl-Anton , Buchalla Wolfgang , Grillmeier Isabel , Neubauer Christina , Schmalz Gottfried
Published: March 2018

Thisin vitrostudy evaluated the effect of toothpastes with different active ingredients on dentin permeability using an extended protocol including multiple applications and several thermal ageing cycles in the presence or absence of human saliva. The Null hypothesis was that dentin permeability of a hydroxyapatite containing toothpaste (BR), a potassium nitrate (SP) and an arginine and calcium carbonate (EH) containing toothpaste were similar. Dentin permeability was measured as hydraulic conductance using a commercially available capillary flow system (Flodec, Geneva) and results were expressed as % relative to matching controls. Without saliva, the ranking (best first) of dentin permeability was BR(61%) < SP(87%) < EH(118%), with saliva EH(63%) < SP(72%) < BR(88%). Saliva increased or decreased permeability dependent upon the test material. BR reduced dentin permeability significantly more in absence of saliva, with saliva EH was superior to BR. Repeated material application decreased and thermal ageing increased dentin permeability. The different tooth pastes reduced permeability differently, the best being BR without saliva, the least EH without saliva. The newly introduced test conditions (ageing, saliva, multiple applications) influenced single results significantly, and as they better simulate thein vivosituation they should be considered to be included in furtherin vitropermeability testing of desensitizing preparations.
Solar cyclic variability can modulate winter Arctic climate
Authors: Roy Indrani
Published: March 2018

This study investigates the role of the eleven-year solar cycle on the Arctic climate during 1979–2016. It reveals that during those years, when the winter solar sunspot number (SSN) falls below 1.35 standard deviations (or mean value), the Arctic warming extends from the lower troposphere to high up in the upper stratosphere and vice versa when SSN is above. The warming in the atmospheric column reflects an easterly zonal wind anomaly consistent with warm air and positive geopotential height anomalies for years with minimum SSN and vice versa for the maximum. Despite the inherent limitations of statistical techniques, three different methods – Compositing, Multiple Linear Regression and Correlation – all point to a similar modulating influence of the sun on winter Arctic climate via the pathway of Arctic Oscillation. Presenting schematics, it discusses the mechanisms of how solar cycle variability influences the Arctic climate involving the stratospheric route. Compositing also detects an opposite solar signature on Eurasian snow-cover, which is a cooling during Minimum years, while warming in maximum. It is hypothesized that the reduction of ice in the Arctic and a growth in Eurasia, in recent winters, may in part, be a result of the current weaker solar cycle.
Below the Mesophotic
Authors: Baldwin C. C. , Tornabene L. , Robertson D. R.
Published: March 2018

Mesophotic coral ecosystems, which occur at depths of ~40 to 150 m, have received recent scientific attention as potential refugia for organisms inhabiting deteriorating shallow reefs. These ecosystems merit research in their own right, as they harbor both depth-generalist species and a distinctive reef-fish fauna. Reef ecosystems just below the mesophotic are globally underexplored, and the scant recent literature that mentions them often suggests that mesophotic ecosystems transition directly into those of the deep sea. Through submersible-based surveys in the Caribbean Sea, we amassed the most extensive database to date on reef-fish diversity between ~40 and 309 m at any single tropical location. Our data reveal a unique reef-fish assemblage living between ~130 and 309 m that, while taxonomically distinct from shallower faunas, shares strong evolutionary affinities with them. Lacking an existing name for this reef-faunal zone immediately below the mesophotic but above the deep aphotic, we propose “rariphotic.” Together with the “altiphotic,” proposed here for the shallowest reef-faunal zone, and the mesophotic, the rariphotic is part of a depth continuum of discrete faunal zones of tropical reef fishes, and perhaps of reef ecosystems in general, all of which warrant further study in light of global declines of shallow reefs.
Prediction of influenza-like illness based on the improved artificial tree algorithm and artificial neural network
Authors: Hu Hongping , Wang Haiyan , Wang Feng , Langley Daniel , Avram Adrian , Liu Maoxing
Published: March 2018

Because influenza is a contagious respiratory illness that seriously threatens public health, accurate real-time prediction of influenza outbreaks may help save lives. In this paper, we use the Twitter data set and the United States Centers for Disease Control’s influenza-like illness (ILI) data set to predict a nearly real-time regional unweighted percentage ILI in the United States by use of an artificial neural network optimized by the improved artificial tree algorithm. The results show that the proposed method is an efficient approach to real-time prediction.
Improved NO2 Gas Sensing Properties of Graphene Oxide Reduced by Two-beam-laser Interference
Authors: Guo Li , Hao Ya-Wei , Li Pei-Long , Song Jiang-Feng , Yang Rui-Zhu , Fu Xiu-Yan , Xie Sheng-Yi , Zhao Jing , Zhang Yong-Lai
Published: March 2018

We report on the fabrication of a NO2 gas sensor from room-temperature reduction of graphene oxide(GO) via two-beam-laser interference (TBLI). The method of TBLI gives the distribution of periodic dissociation energies for oxygen functional groups, which are capable to reduce the graphene oxide to hierarchical graphene nanostructures, which holds great promise for gaseous molecular adsorption. The fabricated reduced graphene oxide(RGO) sensor enhanced sensing response in NO2 and accelerated response/recovery rates. It is seen that, for 20 ppm NO2, the response (Ra/Rg) of the sensor based on RGO hierarchical nanostructures is 1.27, which is higher than that of GO (1.06) and thermal reduced RGO (1.04). The response time and recovery time of the sensor based on laser reduced RGO are 10 s and 7 s, which are much shorter than those of GO (34 s and 45 s), indicating that the sensing performances for NO2 sensor at room temperature have been enhanced by introduction of nanostructures. This mask-free and large-area approach to the production of hierarchical graphene micro-nanostructures, could lead to the implementation of future graphene-based sensors.
Author Correction: Children’s first handwriting productions show a rhythmic structure
Authors: Pagliarini Elena , Scocchia Lisa , Vernice Mirta , Zoppello Marina , Balottin Umberto , Bouamama Sana , Guasti Maria Teresa , Stucchi Natale
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.