bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomic Resolution Microscopy
Authors: Silcox John 
Published: March 2018

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
“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

Abstract
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

Abstract
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.
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

AbstractGenome-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

AbstractClassical 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

AbstractMicroRNAs (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

AbstractIt 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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractUsing 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.