bluuebunny/crossref_metadata_2025 huggingface dataset:
beadplexr: reproducible and automated analysis of multiplex bead assays
Authors: Stervbo Ulrik , Westhoff Timm H. , Babel Nina
Published: November 2018

Multiplex bead assays are an extension of the commonly used sandwich ELISA. The advantage over ELISA is that they make simultaneous evaluation of several analytes possible. Several commercial assay systems, where the beads are acquired on a standard flow cytometer, exist. These assay systems come with their own software tool for analysis and evaluation of the concentration of the analyzed analytes. However, these tools are either tied to particular commercial software or impose other limitations to their licenses, such as the number of events which can be analyzed. In addition, all these solutions are ‘point and click’ which potentially obscures the steps taken in the analysis. Here we presentbeadplexer, an open-source R-package for the reproducible analysis of multiplex bead assay data. The package makes it possible to automatically identify bead clusters, and provides functionality to easily fit a standard curve and calculate the concentrations of the analyzed analytes.beadplexeris available from CRAN and fromhttps://gitlab.com/ustervbo/beadplexr.
A comparison of student performance and satisfaction between a traditional and integrative approach to teaching an introductory radiology course on the extremities
Authors: Jarrett-Thelwell Fiona D. , Burke Jeanmarie R. , Poirier Jean-Nicolas , Petrocco-Napuli Kristina
Published: November 2018

Objective:

The purpose of the study was to compare student performance and student satisfaction ratings for an introductory extremities radiology course taught using 2 different educational methods.

Methods:

One group of students was taught using a traditional face-to-face instruction method, and the other group received an integrative blended-learning approach. A multivariate analysis of scores on lecture and laboratory examinations was performed to detect differences in student performance between the 2 methods. An independent t test was performed to compare the final course averages between the 2 methods. χ2 Analysis was used to compare the distribution of letter grades and levels of satisfaction between the 2 groups.

Results:

Test scores were higher for the integrative approach than for the traditional face-to-face method (p < .05). However, the differences were not meaningful, as the greatest improvement in correct responses was only for 2 questions. Students appeared to be more satisfied with the integrative approach when compared to the traditional method (p < .05).

Conclusion:

Student satisfaction with the educational delivery methods in an introductory extremities radiology course using an integrative approach was greater than for the traditional face-to-face instruction method. Student performance was similar between the 2 cohorts.
The expression signature of cancer‐associated KRAB‐ZNF factors identified in TCGA pan‐cancer transcriptomic data
Authors: Machnik Marta , Cylwa Rafał , Kiełczewski Kornel , Biecek Przemysław , Liloglou Triantafillos , Mackiewicz Andrzej , Oleksiewicz Urszula
Published: November 2018

The KRAB‐ZNF (Krüppel‐associated box domain zinc finger) gene family is composed of a large number of highly homologous genes, gene isoforms, and pseudogenes. The proteins encoded by these genes, whose expression is often tissue‐specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Due to its high complexity, the KRAB‐ZNF family has not been studied in sufficient detail, and the involvement of its members in carcinogenesis remains mostly unexplored. In this study, we aimed to provide a comprehensive description of cancer‐associated KRAB‐ZNFs using publicly available The Cancer Genome Atlas pan‐cancer datasets. We analyzed 6727 tumor and normal tissue samples from 16 cancer types. Here, we showed that a small but distinctive cluster of 16 KRAB‐ZNFs is commonly upregulated across multiple cancer cohorts in comparison to normal samples. We confirmed these observations in the independent panels of lung and breast cancer cell lines and tissues. This upregulation was also observed for most of the KRAB‐ZNF splicing variants, whose expression is simultaneously upregulated in tumors compared to normal tissues. Finally, by analyzing the clinicopathological data for breast and lung cancers, we demonstrated that the expression of cancer‐associated KRAB‐ZNFs correlates with patient survival, tumor histology, and molecular subtyping. Altogether, our study allowed the identification and characterization of KRAB‐ZNF factors that may have an essential function in cancer biology and thus potential to become novel oncologic biomarkers and treatment targets.
Quantifying Colocalisation in Biological Fluorescence Microscopy
Authors: Oheim Martin , Brunstein Maia
Published: November 2018

One of the basic concepts in biological fluorescence microscopy is the separation of photons from spectrally distinct fluorophores into different colour channels for studying questions concerning the colocalisation, coclustering or interaction of fluorescently labelled proteins, organelles or membranes on fluorescence images. The quantitative use of colocalisation information, however, is not without pitfalls, and the validity of arguments based on the comparison of dual‐colour fluorescence images depends on which molecular targets are labelled and how; which combinations of fluorophores, excitation wavelengths and filters are chosen; how images are acquired and at which spatiotemporal resolution and by which means they are analysed. Unfortunately, no consensual metrics for quantifying colocalisation has emerged. Interrogations as to how colocalisation is best quantified currently make surface again in the context of superresolution microscopies that are increasingly being used in the life sciences. We focus on the practice of the colocalisation imaging workflow and point out problematic steps, guiding the reader to make more informed statements beyond the common ‘red‐plus‐green‐equals‐yellow’ approach.

Key Concepts

Colocalisation measurements are only as good as the raw images they are calculated from – hence, the entire imaging workflow must be understood and quality controlled.

Molecules do not occupy the same place. They are, by definition, not ‘colocalised’. Their imperfect images overlap, and both their proximity and the available spatial resolution determine the amount of colocalisation.

More often than not, colocalisation will be partial, and therefore only interpretable with some reference or when compared among conditions.

Measures of colocalisation need to be held against the random colocalisation arising when structures are placed independently at the same density on an equivalent area.

Colocalisation measurements are more meaningful when presented along with positive and negative controls and when the fluctuation of colocalisation within subfields of view, or – for live cells – over time, is reported.

Fluorophore concentrations, acquisition parameters, intensity ranges and image processing and segmentation rules should be made explicit to allow comparison of data across experiments and laboratories.

Colocalisation studies must always be considered relative to the available spectral, spatial (and for live cells also temporal) resolution, which needs to be explicitly stated.
Can There Be a ‘Liberal Eugenics’?
Authors: Davis Dena S
Published: November 2018

It is possible to have a liberal eugenics, in which certain population outcomes are neither coerced nor predetermined, but driven by individual parental choice. There is, however, a paradox. There will always be disabled people among us, if not as a result of genetic disease, then from trauma, disease and old age. How do we create a society where parents are free to choose not to give birth to disabled children, but where we still value and support the disabled members of our community?

Key Concepts

The debate over ‘liberal eugenics’ is actually a number of debates, made murkier by semantic confusion.

It is possible to have a liberal eugenics, in which certain population outcomes are neither coerced nor predetermined, but driven by individual parental choice.

Authoritarian eugenics was scientifically ignorant, used coercive means and treated people as means to eugenic ends.

Liberal genetics is propelled primarily by individual prospective parents making free choices.

‘Eugenic’ efforts have shifted from a focus on those who should not reproduce to those who should not be produced.

While early eugenics focused on poor and marginalised people, it is now wealthier people who have better access to scientific means of preventing the birth of disabled children.
Interleukin‐1
Authors: Etti Azulay E , Assy Nimer , Idan Cohen
Published: November 2018

The interleukin‐1 (IL‐1) family of ligands and receptors plays a central role in the generation and regulation of inflammation as a part of the immune response. IL‐1 molecules are best known as members of the pro‐inflammatory protein family called cytokines. They have been shown to play a role, not only during inflammation, but also in influencing additional physiological and pathological functions such as auto‐immune diseases, malignancies and many others. Moreover, the biological balance between pro‐inflammatory and inhibitory activities is crucial, since any shift in IL‐1 family expression has the potential to cause disease.

Key Concepts

Interleukin‐1 proteins play a central role in the generation and regulation of inflammatory processes.

The IL‐1α and IL1‐β ligands are pro‐inflammatory cytokines. IL‐1Ra and IL‐1RII are natural inhibitors of IL‐1 signalling.

Shifts in the balance between agonistic and antagonistic signals of IL‐1 family members are crucial for a proper immune response.

Changes in production and secretion of IL‐1 proteins, which determine the balance between activating and neutralising IL‐1R signalling, are widely associated with many human diseases.

IL‐1 neutralisation is now considered as an attractive therapeutic strategy for many diseases, including cancer.
Molecular Genetics of
B
irt–
H
ogg–
D
ubé Syndrome
Authors: Schmidt Laura S
Published: November 2018

Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant hereditary cancer disorder that predisposes at‐risk individuals to develop cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothoraces and kidney tumours. Germline mutations in the
FLCN
gene on chromosome 17 are responsible for BHD. BHD‐associated kidney tumours are most frequently hybrid oncocytic tumours or chromophobe renal carcinoma and show inactivation of the wild‐type
FLCN
allele either by somatic mutation or chromosomal loss, confirming that
FLCN
is a classic tumour suppressor. The FLCN protein interacts with two binding partners, FNIP1 and FNIP2, and with AMPK – an important negative regulator of mTOR. Studies in
Flcn
‐deficient animal models support a role for FLCN in modulating mTOR activity. Emerging evidence suggests that FLCN interacts in a number of molecular pathways important for cell homeostasis that are often dysregulated in cancer including regulation of TFE3/TFEB transcriptional activity, amino acid‐dependent mTOR activation through Rag GTPases, TGF‐β signalling, PGC1‐α‐driven mitochondrial biogenesis and autophagy.

Key Concepts

Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant hereditary syndrome that predisposes at‐risk individuals to develop cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax and increased risk for kidney tumours.

Germline mutations in the
FLCN
gene on chromosome 17 are responsible for Birt–Hogg–Dubé syndrome.

BHD‐associated kidney tumours are characterised by inactivation of the wild‐type copy of
FLCN
by somatic mutation or loss of chromosome 17p sequences confirming that
FLCN
is a classic tumour suppressor gene that follows the two‐hit model of tumourigenesis.

Kidney tumours that develop in BHD‐affected individuals are most frequently hybrid oncocytic tumours or chromophobe renal carcinoma.

The FLCN protein interacts with two novel binding partners, FNIP1 and FNIP2, and also with AMPK, an important negative regulator of mTOR.

Studies in
Flcn
‐deficient animal models support a role for FLCN in modulating mTOR activity.

Emerging evidence suggests that FLCN may interact in a number of molecular pathways important for cellular homeostasis that are often dysregulated in cancer.
G
‐Quadruplexes (
G4s
)
Authors: Richter Sara N
Published: November 2018

Guanine‐rich regions of nucleic acids can fold into G‐quadruplex, a secondary structure formed by four strands of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). In the G‐quadruplex, guanines bind via Hoogsteen hydrogen bonds to yield the G‐quartet. Two or more G‐quartets stack on top of each other to form the G‐quadruplex, which can adopt different conformations, based both on the nature and orientation of the strands and on environmental factors such as cations. Both DNA and RNA G‐quadruplexes are found in biological systems: They have been computationally predicted and experimentally demonstrated by several methods in the genomes of several organisms, including humans, other eukaryotes, bacteria and viruses. G‐quadruplexes in the human cell genome are found in pivotal genomic regions, where they mainly act as regulatory elements. Several proteins process the G‐quadruplex. G‐quadruplex ligands that stabilise these structures are investigated against several diseases, as cancer and viral infections. In turn, G‐quadruplexes can themselves act as therapeutics.

Key Concepts

G‐quadruplexes are noncanonical nucleic acid structures that form in guanine‐rich sequences.

G‐quadruplexes can form both in the DNA and RNA and are structurally extremely heterogeneous.

Both computational and experimental methods have shown the presence of G‐quadruplexes in the genome of humans and other organisms, such as bacteria and viruses.

G‐quadruplexes mainly function as epigenetic regulatory elements.

G‐quadruplexes interact with a diverse array of cellular proteins, which induce, stabilise or destabilise them.

Several methods have been developed to study the G‐quadruplex conformation in short oligonucleotides, longer sequences and whole genomes.

Compounds that bind the G‐quadruplex are being studied as inhibitors of important human diseases such as cancer and infective diseases.

G‐quadruplex‐folded aptamers have therapeutic potential.
Novel Strategies Targeting
G
‐Protein‐Coupled Receptors: An Overview
Authors: García‐Cárceles Javier
Published: November 2018

G‐protein‐coupled receptors (GPCRs) represent the largest group of cell surface receptors encoded by the human genome (∼2%) and have been associated to a multitude of human disorders, which makes them the focus of attention of many drug discovery programs. Traditionally, the development of drugs that target GPCRs has been focused on finding agonists or antagonists that displace the natural or endogenous ligand to activate or inhibit the receptor. Emerging knowledge of structure and physiological functions of GPCRs has begun to alter the approaches to drug discovery. Thus, over the past two decades, novel strategies such as the development of biased and bitopic ligands, allosteric modulators, pepducins or ligands targeting GPCR heteromers have appeared. Some of these new approaches have proved to be productive, yielding molecules currently in clinical trials or even marketed.

Key Concepts

GPCRs are cell membrane proteins essential for the survival of eukaryotic cells and they can be classified in four different classes based on their amino acid sequence.

GPCRs are responsible for the realisation of cell functions through the transduction of a wide range of extracellular stimuli such as light, hormones, odours, peptides and neurotransmitters among others.

GPCRs are associated with a multitude of human disorders, in fact, medicines targeting these receptors comprise 35% of the drugs on the market.

Traditional approaches targeting GPCRs, that is development of agonists or antagonists that compete with the orthosteric or endogenous ligand, have become ineffective developing new drugs.

Selectivity across subtypes in a certain receptor family has been the major issue in order to obtain safer drugs.

The emergence of new and more sensitive pharmacological, biochemical and biophysical techniques have helped in designing novel strategies targeting GPCRs. The publication of crystal structures of GPCRs bound to various kind of ligands have been particularly helpful in determining the molecular basis of ligand binding.
Lateral Root Formation: Building a Meristemde novo
Authors: Trinh Chi D , Laplaze Laurent , Guyomarc'h Soazig
Published: November 2018

The complex and adaptable architecture of the plant root system in soil is of paramount importance for crop growth and performance. Root growth depends on the activity of the root apical meristem, an organised population of proliferating progenitor cells continuously replenished from a stem cell niche. Root branching, which greatly contributes to root system architecture in most dicot species, consists ofde novoformation of new root meristems in existing root tissues. This phenomenon illustrates the ability of plants to repeatedly generate new tissues specialised in post‐embryonic continuous growth and greatly impacts the elaboration of the root system architecture and its adaptation to environmental constraints. Here, we review the recent findings and models related to lateral root organogenesis in the dicot speciesArabidopsis thaliana, with emphasis on the mechanisms controllingde novoroot meristem formation. Experimental evidence suggests that critical regulatory modules are common between embryonic and post‐embryonic root meristem organogenesis and that the lateral root formation molecular pathway is in part common with organ regeneration from callus.
MYORG is associated with recessive primary familial brain calcification
Authors: Arkadir David , Lossos Alexander , Rahat Dolev , Abu Snineh Muneer , Schueler‐Furman Ora , Nitschke Silvia , Minassian Berge A. , Sadaka Yair , Lerer Israela , Tabach Yuval , Meiner Vardiella
Published: November 2018

Objective

To investigate the genetic basis of the recessive form of primary familial brain calcification and study pathways linking a novel gene with known dominant genes that cause the disease.

Methods

Whole exome sequencing and Sanger‐based segregation analysis were used to identify possible disease causing mutations. Mutation pathogenicity was validated by structural protein modeling. Functional associations between the candidate gene, MYORG, and genes previously implicated in the disease were examined through phylogenetic profiling.

Results

We studied nine affected individuals from two unrelated families of Middle Eastern origin. The median age of symptom onset was 29.5 years (range 21–57 years) and dysarthria was the most common presenting symptom. We identified in the MYORG gene, a homozygous c.1233delC mutation in one family and c.1060_1062delGAC mutation in another. The first mutation results in protein truncation and the second in deletion of a highly conserved aspartic acid that is likely to disrupt binding of the protein with its substrate. Phylogenetic profiling analysis of the MYORG protein sequence suggests co‐evolution with a number of calcium channels as well as other proteins related to regulation of anion transmembrane transport (False Discovery Rate, FDR < 10−8) and with PDCD6IP, a protein interacting with PDGFRβ which is known to be involved in the disease.

Interpretation

MYORG mutations are linked to a recessive form of primary familial brain calcification. This association was recently described in patients of Chinese ancestry. We suggest the possibility that MYORG mutations lead to calcification in a PDGFRβ‐related pathway.
Direct CVD Growth of Graphene on Traditional Glass: Methods and Mechanisms
Authors: Chen Zhaolong , Qi Yue , Chen Xudong , Zhang Yanfeng , Liu Zhongfan
Published: November 2018

Chemical vapor deposition (CVD) on catalytic metal surfaces is considered to be the most effective way to obtain large‐area, high‐quality graphene films. For practical applications, a transfer process from metal catalysts to target substrates (e.g., poly(ethylene terephthalate) (PET), glass, and SiO2/Si) is unavoidable and severely degrades the quality of graphene. In particular, the direct growth of graphene on glass can avoid the tedious transfer process and endow traditional glass with prominent electrical and thermal conductivities. Such a combination of graphene and glass creates a new type of glass, the so‐called “super graphene glass,” which has attracted great interest from the viewpoints of both fundamental research and daily‐life applications. In the last few years, great progress has been achieved in pursuit of this goal. Here, these growth methods as well as the specific growth mechanisms of graphene on glass surfaces are summarized. The typical techniques developed include direct thermal CVD growth, molten‐bed CVD growth, metal‐catalyst‐assisted growth, and plasma‐enhanced growth. Emphasis is placed on the strategy of growth corresponding to the different natures of glass substrates. A comprehensive understanding of graphene growth on nonmetal glass substrates and the latest status of “super graphene glass” production are provided.
Organic Photovoltaics with Multiple Donor–Acceptor Pairs
Authors: Lee Jungho , Lee Sang Myeon , Chen Shanshan , Kumari Tanya , Kang So‐Huei , Cho Yongjoon , Yang Changduk
Published: November 2018

Compared with conventional organic solar cells (OSCs) based on single donor–acceptor pairs, terpolymer‐ and ternary‐based OSCs featuring multiple donor–acceptor pairs are promising strategies for enhancing the performance while maintaining an easy and simple synthetic process. Using multiple donor–acceptor pairs in the active layer, the key photovoltaic parameters (i.e., short‐circuit current density, open‐circuit voltage, and fill factor) governing the OSC characteristics can be simultaneously or individually improved by positive changes in light‐harvesting ability, molecular energy levels, and blend morphology. Here, these three major contributions are discussed with the aim of offering in‐depth insights in combined terpolymers and ternary systems. Recent exemplary cases of OSCs with multiple donor–acceptor pairs are summarized and more advanced research and perspectives for further developments in this field are highlighted.
Enzyme‐Instructed Supramolecular Self‐Assembly with Anticancer Activity
Authors: Yao Qingxin , Huang Zhentao , Liu Dongdong , Chen Jiali , Gao Yuan
Published: November 2018

Cancer remains one of the leading causes of death, which has continuously stimulated the development of numerous functional biomaterials with anticancer activities. Herein is reviewed one recent trend of biomaterials focusing on the advances in enzyme‐instructed supramolecular self‐assembly (EISA) with anticancer activity. EISA relies on enzymatic transformations to convert designed small‐molecular precursors into corresponding amphiphilic residues that can form assemblies in living systems. EISA has shown some advantages in controlling cell fate from three aspects. 1) Based on the abnormal activity of specific enzymes, EISA can differentiate cancer cells from normal cells. In contrast to the classical ligand–receptor recognition, the targeting capability of EISA relies on dynamic control of the self‐assembly process. 2) The interactions between EISA and cellular components directly disrupt cellular processes or pathways, resulting in cell death phenotypes. 3) EISA spatiotemporally controls the distribution of therapeutic agents, which boosts drug delivery efficiency. Therefore, with regard to the development of EISA, the aim is to provide a perspective on the future directions of research into EISA as anticancer theranostics.
Low‐Temperature De‐NOx Extruded Monolithic Catalysts Based on Highly Dispersive Mn–Ce Oxide Nanoparticles of Low Ce Content
Authors: Ye Bora , Jeong Bora , Lee Minwoo , Kim Hong‐Dae , Baik Jeong Min
Published: November 2018

A facile strategy to produce low‐temperature De‐NOx extruded monolithic catalysts based on the highly dispersive Mn–Ce oxide nanoparticles of low Ce content is described. The design of the materials is based on dual supports composed of reduced graphene oxide and TiO2, which is made by Mn–Ce oxide nanoparticles well separated on the supports without any agglomeration. Compared to the catalysts with only TiO2 support, the specific surface area of the catalysts is significantly increased by 2.8 times. The temperature‐programmed desorption analysis of NH3 shows that the number of Lewis acid sites increases; thus, the binding strength of the NH3 at the surface of the oxides is also increased. Through the temperature‐programmed reduction of the H2, the rate of the reduction reaction also increases. Thus, the efficiency of the overall De‐NOx reaction increases to 90% with a lower Ce content of 40% at 250 °C and shows good stability at a high temperature of 300 °C. By using the above‐mentioned catalysts, a honeycomb‐type extruded monolithic product with De‐NOx efficiency higher than 90% in the temperature range between 200 and 300 °C is made without any additional binders. This indicates a good formability, enough for the fabrication of the commercialized products.
Stress‐Induced Domain Wall Motion in FeCo‐Based Magnetic Microwires for Realization of Energy Harvesting
Authors: Bhatti Sabpreet , Ma Chuang , Liu Xiaoxi , Piramanayagam S. N.
Published: November 2018

Energy harvesting is getting significant interest due to the emergence of Internet of Things (IoT). As IoT devices are required to generate power on their own, several researchers are studying ferroelectric materials for voltage generation. However, ferroelectric materials suffer from high resistance at low frequencies, which reduces the output power. Domain wall propagation in ferromagnetic materials, as induced by stress and a pickup voltage using coils, is investigated as an alternate form of energy harvesting. Such studies, which are reported in multiferroic structures, feature a voltage applied to induce the stress, which defeats the purpose of self‐power generation. Here, power generation from mechanical vibrations in purely ferromagnetic structures is shown. These results are achieved by showing that the domain walls can be moved entirely by stress in a trilayer stack of ferromagnetic microwires. The use of flexible substrates with low Young's modulus and a trilayer magnetic stack enables the achievement of significant magnetization rotation or domain wall motion even from ambient vibrations. Here, the rotation of magnetization or domain wall motion is exploited to induce voltages in the pickup coils. The results shown here provide an alternative way to power IoT devices.
Facile Cleavage of the P=P Double Bond in Vinyl‐Substituted Diphosphenes
Authors: Liu Liu Leo , Cao Levy L. , Zhou Jiliang , Stephan Douglas W.
Published: November 2018

The reactions of the cyclic alkyl amino carbene (CAAC)1with phosphaalkynes generate the kinetically unstable CAAC‐derived phosphirenes4and5, which undergo rearrangement/dimerization reactions to give the vinyl‐substituted diphosphenes2,3, and6. The P=P double bond scission of2or3is unprecedentedly effected by S8, [AuCl(tht)], or MeOTf at room temperature, which affords a dithiophosphorane7, a phosphepine Au complex8, or phosphepinium cations9and10, respectively. The cationic species feature little homoaromaticity while representing the first examples of the phosphorus‐containing analogue of the tropylium ion.
Direct Electron Transfer of Enzymes Facilitated by Cytochromes
Authors: Ma Su , Ludwig Roland
Published: November 2018

The direct electron transfer (DET) of enzymes has been utilized to develop biosensors and enzymatic biofuel cells on micro‐ and nanostructured electrodes. Whereas some enzymes exhibit direct electron transfer between their active‐site cofactor and an electrode, other oxidoreductases depend on acquired cytochrome domains or cytochrome subunits as built‐in redox mediators. The physiological function of these cytochromes is to transfer electrons between the active‐site cofactor and a redox partner protein. The exchange of the natural electron acceptor/donor by an electrode has been demonstrated for several cytochrome carrying oxidoreductases. These multi‐cofactor enzymes have been applied in third generation biosensors to detect glucose, lactate, and other analytes. This review investigates and classifies oxidoreductases with a cytochrome domain, enzyme complexes with a cytochrome subunit, and covers designed cytochrome fusion enzymes. The structurally and electrochemically best characterized proponents from each enzyme class carrying a cytochrome, that is, flavoenzymes, quinoenzymes, molybdenum‐cofactor enzymes, iron‐sulfur cluster enzymes, and multi‐haem enzymes, are featured, and their biochemical, kinetic, and electrochemical properties are compared. The cytochromes molecular and functional properties as well as their contribution to the interdomain electron transfer (IET, between active‐site and cytochrome) and DET (between cytochrome and electrode) with regard to the achieved current density is discussed. Protein design strategies for cytochrome‐fused enzymes are reviewed and the limiting factors as well as strategies to overcome them are outlined.
Na2FePO4F Fluorophosphate as Positive Insertion Material for Aqueous Sodium‐Ion Batteries
Authors: Sharma Lalit , Nakamoto Kosuke , Sakamoto Ryo , Okada Shigeto , Barpanda Prabeer
Published: November 2018

Exploring stable and economic cathodes for aqueous sodium‐ion batteries, we have investigated iron‐based fluorophosphate (Na2FePO4F) as a compound for applications in aqueous battery systems. Solution combustion synthesized Na2FePO4F is found to act as an efficient cathode for aqueous Na‐ion batteries delivering a reversible capacity over 85 mAh g−1 (at a rate of 1 mA cm−2) with excellent rate kinetics. Further, this layered Na2FePO4F has been successfully implemented to design a full aqueous cell with NASICON‐type NaTi2(PO4)3 as anode, delivering a reversible capacity of 90 mAh g−1. In conclusion, Na2FePO4F is proposed as a potential cathode material for aqueous Na‐ion batteries.
Zinc‐Mediated Intermolecular Reductive Radical Fluoroalkylsulfination of Unsaturated Carbon–Carbon Bonds with Fluoroalkyl Bromides and Sulfur Dioxide
Authors: Liu Yongan , Lin Qiongzhen , Xiao Zhiwei , Zheng Changge , Guo Yong , Chen Qing‐Yun , Liu Chao
Published: November 2018

A versatile and general zinc‐mediated intermolecular reductive radical fluoroalkylsulfination of unsaturated C−C bonds has been developed using readily available fluoroalkyl bromides and 1,4‐diazabicyclo[2.2.2]octane‐bis(sulfur dioxide) adduct (DABSO) with wide substrate scope and excellent functional group tolerance. Sulfur dioxide anion radical generated in situ from the reduction of sulfur dioxide with zinc may be involved in the reaction mechanism.
Alterations in cortical and thalamic connections of somatosensory cortex following early loss of vision
Authors: Dooley James C. , Krubitzer Leah A.
Published: November 2018

Early loss of vision produces dramatic changes in the functional organization and connectivity of the neocortex in cortical areas that normally process visual inputs, such as the primary and second visual area. This loss also results in alterations in the size, functional organization, and neural response properties of the primary somatosensory area, S1. However, the anatomical substrate for these functional changes in S1 has never been described. In the present investigation, we quantified the cortical and subcortical connections of S1 in animals that were bilaterally enucleated very early in development, prior to the formation of retino‐geniculate and thalamocortical pathways. We found that S1 receives dense inputs from novel cortical fields, and that the density of existing cortical and thalamocortical connections was altered. Our results demonstrate that sensory systems develop in tandem and that alterations in sensory input in one system can affect the connections and organization of other sensory systems. Thus, therapeutic intervention following early loss of vision should focus not only on restoring vision, but also on augmenting the natural plasticity of the spared systems.
Fe3O4/Fe3C@Nitrogen‐Doped Carbon for Enhancing Oxygen Reduction Reaction
Authors: Liu Mincong , Guo Xuhong , Hu Libing , Yuan Huifang , Wang Gang , Dai Bin , Zhang Lili , Yu Feng
Published: November 2018

Oxygen reduction reaction (ORR) catalysts play a key role in energy conversion and storage devices. The preparation of iron‐based carbon materials as non‐precious metal catalysts with a simple and scalable method still presents significant challenges. In this work, partially oxidized Fe embedded in Fe3C nanoparticles encased in nitrogen‐doped carbon shells (Fe3O4/Fe3C@NC) were prepared by directly pyrolyzing a mixture of Prussian blue (PB) and chitosan using a facile one‐step carbon‐bath route. The long‐term stability and methanol tolerance of the optimal catalyst were good and superior to those of commercial Pt/C (20 wt%). More importantly, the catalyst showed stronger ORR activities than Pt/C. We conclude that the high ORR activity of Fe3O4/Fe3C@NC catalysts should be attributed to the synergetic effect between Fe3C nanoparticles wrapped in carbon shells, which improves the activity of ORR and Fe3O4 nanoparticles neighbouring Fe‐Nx and significantly increases the number of active sites on the catalysts. Therefore, we believe that the one‐step carbon‐bath method provided in this work to synthesize highly active Fe‐based carbon materials as ORR catalysts is expected to be widely used in practical applications.
Molecular Dynamics Simulations of Water‐Mediated Cholesterol Capture within an Open‐Ended Single‐Walled Carbon Nanotube
Authors: Gade Hrushikesh M. , Wanjari Piyush P.
Published: November 2018

The excess concentration of cholesterol in the bloodstream can be brought down to a safer level by utilizing a potential cholesterol‐binding agent such as a carbon nanotube (CNT). Here, we have probed solvent‐mediated interactions between cholesterol and CNT by performing molecular dynamics simulations and potential‐of‐mean force (PMF) calculations. Simulations predict favorable interactions between water‐mediated cholesterol and CNT owing to strong mutual interactions between them, whereas water plays an opposing role in the association. The breakdown of PMF into its enthalpic and entropic contributions indicates that contrary to traditional entropy‐driven hydrophobic association, the cholesterol encapsulation within a CNT is primarily driven by enthalpy.
Does the ‘equal management of equal risks’ model cause overtreatment in patients with positive cervical cytology results for ASCUS/non‐HPV16/18 oncogenic types?
Authors: Karaca İbrahim , Öztürk Mustafa , Comba Cihan , Demirayak Gökhan , Erdoğan Şakir Vokan , Hoşgören Murat , Özdemir İsa Aykut
Published: November 2018

Objectives

According to the American Society of Colposcopy and Cervical Pathology (ASCCP), cervical cytology patients who test positive for atypical squamous cells of undetermined significance (ASCUS) and the human papilloma virus (HPV) positive are recommended to undergo colposcopies. This study compared the colposcopic biopsy evaluation results of patients with positive cervical cytology results for ASCUS and HPV with regards to their HPV genotypes.

Methods

This study included 179 patients who underwent cervical cancer screening tests between June 2015 and June 2017 and whose results displayed positive cervical cervical cytology results for ASCUS and HPV. Cytological samples were classified using the Bethesda system in liquid‐based specimens. The Hybrid Capture II system was used to define the HPV‐DNA. Colposcopic diagnoses and biopsy results were compared in terms of the outcomes of the Pap test and HPV genotypes.

Results

There were 107 ASCUS/HPV16/18‐positive patients. Of the HPV 16/18 positive patients; 28 (26.1%) patients were detected with CIN1, 8 (7.5%) patients were detected with CIN2, 6 (6%) patients were detected with CIN3, and 1 (0.9%) patient was detected with cervical cancer. Of the 72 non‐HPV 16‐18 positive patients; 8 (11%) patients were detected with CIN1 and 2 (2.7%) patients were detected with CIN2.

Conclusion

This study believes that the ASCCP recommendations, which state that a ‘colposcopy should be performed on all women with positive cytology for ASCUS/non‐HPV16/18 oncogenic types’, is required to be revised. This will reduce the rate of the colposcopy procedures by 40% in women with ASCUS/HPV positivity.
Developmental roles of microglia: A window into mechanisms of disease
Authors: Anderson Sarah R. , Vetter Monica L.
Published: November 2018

Microglia are engineers of the central nervous system (CNS) both in health and disease. In addition to the canonical immunological roles of clearing damaging entities and limiting the spread of toxicity and death, microglia remodel the CNS throughout life. While they have been extensively studied in disease and injury, due to their highly variable functions, their precise role in these contexts still remains uncertain. Over the past decade, we have greatly expanded our understanding of microglial function, including their essential homeostatic roles during development. Here, we review these developmental roles, identify parallels in disease, and speculate whether developmental mechanisms re‐emerge in disease and injury. Developmental Dynamics 248:98–117, 2019. © 2018 Wiley Periodicals, Inc.
Solvothermal Synthesis, Crystal Structures, and Photocatalytic Properties of Iodoplumbate Hybrids with Nickel(II) Complex Templates
Authors: Zhang Limei , Tang Chunying , Zheng Wei , Jiang Wenqing , Jia Dingxian
Published: November 2018

Organic–inorganic iodoplumbate hybrids [Ni(en)2]2Pb3I10 (1), [Ni(en)3]Pb2I6 (2) (en = ethylenediamine), [Ni(dien)2]Pb2I6·H2O (3) (dien = diethylenetriamine), [Ni(14‐TMC)][PbI3]2·DMF (4), and [Ni(14‐TMC)]2[Pb5I14(DMSO)2] (5) (14‐TMC = 1,4,8,11‐tetramethyl‐1,4,8,11‐tetraazacyclotetradecane) were prepared using different NiII complex cation as structural directing agents under solvothermal conditions. Compounds 1–4 consist of 1‐D [Pb3I104–]n, [PbI3–]n and [Pb2I62–]n polymeric anions constructed by PbI6 octahedra via corner‐, edge‐ or face‐sharing, respectively. The novel organic hybrid iodoplumbate anion [Pb5I14(DMSO)24–]n in 5 is composed of PbI6 and PbI5O octahedra via edge‐ and face‐sharing. The formation of polymeric iodoplumbate anions in 1–5 indicates different structure‐directing effect of the NiII complex cations with various polyamino ligands under appropriate reaction and crystallization conditions. Compounds 1–5 exhibit tunable band gaps varying in the range of 2.18–2.61 eV. Compounds 4 and 5 are more effective than 1 and 3 in the photocatalytic degradation of methylene blue.
Ruthenium Porphyrin Catalyzed Synthesis of Oxazolidin‐2‐ones by Cycloaddition of CO2 to Aziridines
Authors: Carminati Daniela , Gallo Emma , Damiano Caterina , Caselli Alessandro , Intrieri Daniela
Published: November 2018

The reaction between N‐substituted‐2‐arylaziridines and CO2 is efficiently promoted by ruthenium(VI) imidoporphyrin complexes and yields a mixture of 5‐aryl (A) and 4‐aryl (B) substituted oxazolidin‐2‐ones with a regioisomeric A/B ratio up to 99:1. Several oxazolidin‐2‐one molecules were synthesized at 100 °C and 0.6 MPa of carbon dioxide by using the low catalytic loading of 1 mol‐%. The formation of a deactivated compound, deriving from the ruthenium catalyst, suggested a possible catalytic role of imido nitrogen atoms.
Substituent Effects on the Reactivity of the 2,4,6‐Tridehydropyridinium Cation, an Aromatic σ,σ,σ‐Triradical
Authors: Gao Jinshan , Jankiewicz Bartłomiej J. , Sheng Huaming , Kirkpatrick Lindsey , Ma Xin , Nash John J. , Kenttämaa Hilkka I.
Published: November 2018

2,4,6‐Tridehydropyridinium cation (7) undergoes three consecutive atom or atom group abstractions from reagent molecules in the gas phase. By placing a π‐electron‐donating hydroxyl group between two radical sites, their reactivity can be quenched by enhancing their through‐space coupling via a favorable resonance structure. Indeed, 3‐hydroxy‐2,4,6‐tridehydropyridinium cation (8) abstracts only one atom or group of atoms from reagents. On the other hand, an electron‐withdrawing cyano group between two of the radical sites (9) destabilizes the analogous resonance structure and diminishes through‐space coupling between the radical sites, resulting in abstraction of three atoms, just like 7. However, the cyano‐substituent also increases acidity to the point that 9 reacts predominantly via proton transfer instead of undergoing radical reactions. Therefore, acidic triradicals may undergo nonradical, barrierless proton transfer reactions faster than radical reactions, which are usually accompanied by barriers. Examination of the analogous cyano‐substituted mono‐ and biradicals revealed behavior similar to that of the corresponding unsubstituted species, with the exception of substantially greater reactivities due to their greater (calculated) vertical electron affinities. Finally, the 3‐cyano‐2,6‐didehydropyridinium cation with a singlet ground state (S‐T splitting: –11.9 kcal mol–1) was found to react exclusively from the lowest‐energy triplet state by fast proton transfer reactions.
Stereocontrolled Synthesis of Fluorine‐Containing Piperidine γ‐Amino Acid Derivatives
Authors: Ouchakour Lamiaa , Ábrahámi Renáta A. , Forró Enikő , Haukka Matti , Fülöp Ferenc , Kiss Loránd
Published: November 2018

An efficient synthetic approach for the construction of fluorine‐containing piperidine γ‐amino acid derivatives has been developed. The synthetic concept was based on oxidative ring opening of an unsaturated bicyclic γ‐lactam (Vince‐lactam) through its ring C=C bond, followed by double reductive amination of the diformyl intermediate performed with various fluoroalkylamines. The method has been extended towards the access of alkylated and perfluoroalkylated substances and for γ‐lactam derivatives. The transformations proceeded with stereocontrol: the configuration of the stereocenters in the products were predetermined by the configuration of the chiral centers of the starting γ‐lactam. The method could be extended for the access to enantiopure piperidine γ‐amino esters.
Formal Synthesis of (–)‐Perhydrohistrionicotoxin Using a Thorpe‐Ziegler Cyclization Approach. Synthesis of Functionalized Aza‐Spirocycles
Authors: Vu Van Ha , Bouvry Christelle , Roisnel Thierry , Golhen Stéphane , Hurvois Jean‐Pierre
Published: November 2018

The formal synthesis of (–)‐PHTX is described. Our approach was based on the anodic cyanation of (S)‐1‐(1‐phenylethyl)‐piperidine (–)‐1 to afford α‐aminonitrile 2 in 85 % yield in a 53:47 dr. The presence of the α‐phenylethyl group as the chiral auxiliary ensured the control of the absolute configuration of the future C6 spiro‐center during the alkylation step of 2, which was carried out with 1‐bromo‐4‐chlorobutane. Next, elaboration of the 1‐azaspiro[5,5]undecane‐7‐one ring system was achieved in a two‐step sequence, involving (a) a Thorpe‐Ziegler annulation, and (b) the hydrolysis–decarboxylation of enaminonitrile (–)‐5 to afford spiroketone (+)‐6 in >99:1 dr. Finally, the incorporation of the future C7 butyl chain was carried out stereoselectively through a new reaction sequence which involved the synthesis of tricyclic oxazolidinone (–)‐11 and alkylation of the intermediary syn‐fluorohydrin (+)‐13 with nBuMgCl to form oxazolidinone (+)‐15 in an overall 19 % yield from (–)‐1.
Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood‐retinal barrier in diabetic retinopathy
Authors: Jo Dong Hyun , Yun Jang‐Hyuk , Cho Chang Sik , Kim Jin Hyoung , Kim Jeong Hun , Cho Chung‐Hyun
Published: November 2018

Inner and outer blood‐retinal barriers (BRBs), mainly composed of retinal endothelial cells and retinal pigment epithelial (RPE) cells, respectively, maintain the integrity of the retinal tissues. In this study, we aimed to investigate the mechanisms of the outer BRB disruption regarding the interaction between RPE and microglia. In mice with high‐fat diet‐induced obesity and streptozotocin‐induced hyperglycemia, microglia accumulated on the RPE layer, as in those after intravitreal injection of interleukin (IL)‐6, which is elevated in ocular fluids of patients with diabetic retinopathy. Although IL‐6 did not directly affect the levels of zonula occludens (ZO)‐1 and occludin in RPE cells, IL‐6 increased VEGFA mRNA in RPE cells to recruit microglial cells. In microglial cells, IL‐6 upregulated the mRNA levels of MCP1, MIP1A, and MIP1B, to amplify the recruitment of microglial cells. In this manner, IL‐6 modulated RPE and microglial cells to attract microglial cells on RPE cells. Furthermore, IL‐6‐treated microglial cells produced and secreted tumor necrosis factor (TNF)‐α, which activated NF‐κB and decreased the levels of ZO‐1 in RPE cells. As STAT3 inhibition reversed the effects of IL‐6‐treated microglial cells on the RPE monolayer in vitro, it reduced the recruitment of microglial cells and the production of TNF‐α in RPE tissues in streptozotocin‐treated mice. Taken together, IL‐6‐treated RPE and microglial cells amplified the recruitment of microglial cells and IL‐6‐treated microglial cells produced TNF‐α to disrupt the outer BRB in diabetic retinopathy.
The influence of the Community‐based Health Planning and Services (CHPS) program on community health sustainability in the Upper West Region of Ghana
Authors: Woods Hannah , Haruna Umar , Konkor Irenius , Luginaah Isaac
Published: November 2018

Ghana introduced Community‐based Health Planning and Services (CHPS) to improve primary health care in rural areas. The extension of health care services to rural areas has the potential to increase sustainability of community health. Drawing on the capitals framework, this study aims to understand the contribution of CHPS to the sustainability of community health in the Upper West Region of Ghana—the poorest region in the country. We conducted in‐depth interviews with community members (n = 25), key informant interviews with health officials (n = 8), and focus group discussions (n = 12: made up of six to eight participants per group) in six communities from two districts. Findings show that through their mandate of primary health care provision, CHPS contributed directly to improvement in community health (eg, access to family planning services) and indirectly through strengthening social, human, and economic capital and thereby improving social cohesion, awareness of health care needs, and willingness to take action at the community level. Despite the current contributions of CHPS in improving the sustainability of community health, there are several challenges, based on which we recommend, that government should increase staffing and infrastructure in order to strengthen and maintain the functionality of CHPS.