bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring health conditions from fMRI-graph data
Authors: Mana P.G.L. Porta , Bachmann C. , Morrison A.
Published: April 2018

Automated classification methods for disease diagnosis are currently in the limelight, especially for imaging data. Classification does not fully meet a clinician’s needs, however: in order to combine the results of multiple tests and decide on a course of treatment, a clinician needs the likelihood of a given health condition rather than binary classification yielded by such methods. We illustrate how likelihoods can be derived step by step from first principles and approximations, and how they can be assessed and selected, using fMRI data from a publicly available data set containing schizophrenic and healthy control subjects, as a working example. We start from the basic assumption of partial exchangeability, and then the notion of sufficient statistics and the “method of translation” (Edgeworth, 1898) combined with conjugate priors. This method can be used to construct a likelihood that can be used to compare different data-reduction algorithms. Despite the simplifications and possibly unrealistic assumptions used to illustrate the method, we obtain classification results comparable to previous, more realistic studies about schizophrenia, whilst yielding likelihoods that can naturally be combined with the results of other diagnostic tests.
A stimulus artefact undermines the evidence for independent ON and OFF channels in stereopsis
Authors: Read Jenny C. A. , Cumming Bruce G.
Published: April 2018

Early vision proceeds through distinct ON and OFF channels, which encode luminance increments and decrements respectively. It has been argued that these channels also contribute separately to stereoscopic vision. This is based on the fact that observers perform better on a noisy disparity discrimination task when the stimulus is a random-dot pattern consisting of equal numbers of black and white dots (a “mixed-polarity stimulus”, argued to activate both ON and OFF stereo channels), than when it consists of all-white or all-black dots (“same-polarity”, argued to activate only one). However, it is not clear how this theory can be reconciled with our current understanding of disparity encoding. Recently, a binocular convolutional neural network was able to replicate the mixed-polarity advantage shown by human observers, even though it was based on linear filters and contained no mechanisms which would respond separately to black or white dots. Here, we show that the stimuli used in all these experiments contain a subtle artefact. The interocular correlation between left and right images is actually lower for the same-polarity stimuli than for mixed-polarity stimuli with the same amount of disparity noise applied to the dots. Since our current theories suggest stereopsis is based on a correlation-like computation in primary visual cortex, it is then unsurprising that performance was better for the mixed-polarity stimuli. We conclude that there is currently no evidence supporting separate ON and OFF channels in stereopsis.
Biology and taxonomy of crAss-like bacteriophages, the most abundant virus in the human gut
Authors: Guerin Emma , Shkoporov Andrey , Stockdale Stephen R. , Clooney Adam G. , Ryan Feargal J. , Sutton Thomas D. S. , Draper Lorraine A. , Gonzalez-Tortuero Enrique , Ross R. Paul , Hill Colin
Published: April 2018

CrAssphage is yet to be cultured even though it represents the most abundant virus in the gut microbiota of humans. Recently, sequence based classification was performed on distantly related crAss-like phages from multiple environments, leading to the proposal of a familial level taxonomic group [Yutin N, et al. (2018) Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut. Nat Microbiol 3(1):38–46]. Here, we assembled the metagenomic sequencing reads from 702 human faecal virome/phageome samples and obtained 98 complete circular crAss-like phage genomes and 145 contigs ≥70kb. In silico comparative genomics and taxonomic analysis was performed, resulting in a classification scheme of crAss-like phages from human faecal microbiomes into 4 candidate subfamilies composed of 10 candidate genera. Moreover, laboratory analysis was performed on faecal samples from an individual harbouring 7 distinct crAss-like phages. We achieved propagation of crAss-like phages in ex vivo human faecal fermentations and visualised Podoviridae virions by electron microscopy. Furthermore, detection of a crAss-like phage capsid protein could be linked to metagenomic sequencing data confirming crAss-like phage structural annotations.

Significance

CrAssphage is the most abundant biological entity in the human gut, but it remains uncultured in the laboratory and its host(s) is unknown. CrAssphage was not identified in metagenomic studies for many years as its sequence is so different from anything present in databases. To this day, it can only be detected from sequences assembled from metagenomics or viromic datasets (crAss – cross Assembly). In this study, we identified 243 new crAss-like phages from human faecal metagenomic studies. Taxonomic analysis of these crAss-like phages highlighted their extensive diversity within the human microbiome. We also present the first propagation of crAssphage in faecal fermentations and provide the first electron micrographs of this extraordinary bacteriophage.
Using the residual bootstrap to quantify uncertainty in mean apparent propagator MRI
Authors: Gu Xuan , Eklund Anders , Özarslan Evren , Knutsson Hans
Published: April 2018

Estimation of noise-induced variability in MAP-MRI is needed to properly characterize the amount of uncertainty in quantities derived from the estimated MAP-MRI coefficients. Bootstrap metrics, such as the standard deviation, provides additional valuable diffusion information in addition to common MAP-MRI parameters, and can be incorporated in MAP-MRI studies to provide more extensive insight. To the best of our knowledge, this is the first paper to study the uncertainty of MAP-MRI derived metrics. The noise variability of quantities of MAP-MRI have been quantified using the residual bootstrap, in which the residuals are resampled using two sampling schemes. The residual bootstrap method can provide empirical distributions for MAP-MRI derived quantities, even when the exact distributions are not easily derived. The residual bootstrap methods are applied to SPARC data and HCP-MGH data, and empirical distributions are obtained for the zero-displacement probabilities. Here, we compare and contrast the residual bootstrap schemes using all shells and within the same shell. We show that residual resampling within each shell generates larger uncertainty than using all shells for the HCP-MGH data. Standard deviation and quartile coefficient maps of the estimated variability are provided.
Flexible coding of memory and space in the primate hippocampus during virtual navigation
Authors: Gulli Roberto A. , Duong Lyndon , Corrigan Ben , Doucet Guillaume , Williams Sylvain , Fusi Stefano , Martinez-Trujillo Julio C.
Published: April 2018

Hippocampal maps of space change across tasks. The mechanisms of this effect remain unclear. To examine this, we recorded activity of hippocampal neurons in monkeys navigating the same virtual maze during two different tasks: a foraging task requiring only cue guided navigation, and a memory task also requiring context-object association. Within each task, individual neurons had spatially-selective response fields, enabling a linear classifier to decode position in the virtual environment in each task. However, the population code did not generalize across tasks. This was due to sensory and mnemonic coding of non-spatial features and their associations by single neurons during each period of the associative memory task. Thus, sensory and mnemonic representations of non-spatial features shape maps of space in the primate hippocampus during virtual navigation. This may reflect a fundamental role of the hippocampus in compressing information from a variety of sources for efficient memory storage.
An inter-chromosomal transcription hub activates the unfolded protein response in plasma cells
Authors: Bortnick Alexandra , He Zhaoren , Aubrey Megan , Chandra Vivek , Denholtz Matthew , Chen Kenian , Lin Yin C , Murre Cornelis
Published: April 2018

Previous studies have indicated that the transcription signature of antibody-secreting cells is closely associated with the induction of the unfolded protein response pathway (UPR). Here we have used genome-wide and single cell analyses to examine the folding patterns of plasma cell genomes. We found that plasma cells adopt a cartwheel configuration and undergo large-scale changes in chromatin folding at genomic regions associated with a plasma cell specific transcription signature. During plasma cell differentiation, Blimp1 assembles into an inter-chromosomal transcription hub with genes associated with the UPR, biosynthesis of the endoplasmic reticulum (ER) as well as a cluster of genes linked with Alzheimer’s disease. We suggest that the assembly of the Blimp1-UPR-ER transcription hub permits the coordinate activation of a wide spectrum of genes that collectively establish plasma cell identity.
Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
Authors: Gilbertson Sarah , Federspiel Joel D. , Hartenian Ella , Cristea Ileana M. , Glaunsinger Britt
Published: April 2018

Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.
Spontaneous mutations conferring antibiotic resistance to antitubercular drugs at a range of concentrations in Mycobacterium smegmatis
Authors: Nyinoh Iveren W , McFadden Johnjoe
Published: April 2018

Mycobacteria population can undergo mutations in their DNA sequence during replication, which if not repaired, would be transferred to future generations. In this study, in vitro spontaneous mutations in Mycobacterium smegmatis mc2155 (Msm) conferring resistance to isoniazid (INHr), rifampicin (RIFr), kanamycin (KANr) and streptomycin (STRr) were determined at several concentrations in a fluctuation assay. Mutation rate was estimated using the P₀ method, and estimates were then compared with the Lea-Coulson method of the median and Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) method available on the Fluctuation analysis calculator (FALCOR). The mutation rates of RIFr ranged from 9.24 × 10-8 - 2.18 × 10-10, INHr 1.2 × 10-7 - 1.20×10-9, STRr 2.77 × 10-8 - 5.31 × 10-8 and KANr 1.7 × 10-8 mutations per cell division. This study provides mutation rate estimates to key antitubercular drugs at a range of concentrations.
EWI-2 Inhibits Cell-Cell Fusion at the Virological Presynapse
Authors: Whitaker Emily E. , Symeonides Menelaos , Munson Phillip B. , Thali Markus
Published: April 2018

Cell-to-cell transfer of virus particles through the virological synapse (VS) is a highly efficient mode of HIV-1 transmission. Formation of the VS, a transient multiform adhesion structure, is mediated through an interaction between the HIV-1 envelope glycoprotein (Env) and the viral receptor CD4 on the surface of infected cell and target cell, respectively. Given that Env, unlike many other viral fusogens, can mediate the merger of membranes at neutral pH, the close encounter of infected and uninfected cells would seem prone to result in cell-cell fusion and thus the formation of syncytia. However, while it is being recognized now that small, T cell-based syncytia are indeed a defining feature of the natural history of HIV-1, the majority of VSs nevertheless resolve without fusion, thus securing continued virus spread. Gag, the main viral structural component, is partially responsible for restraining Env and preventing it from becoming fusogenic before being incorporated into particles. In addition, a few cellular factors, including tetraspanins and ezrin, have also been shown to inhibit Env’s activity while this fusogen is still part of the producer cell.

Here, we identify EWI-2, a protein that was previously shown to associate with the tetraspanins CD9 and CD81 and also with ezrin, as a host factor that contributes to the inhibition of Env­mediated cell-cell fusion. Using fluorescence microscopy, flow cytometry, and TZM-bl fusion assays, we show that EWI-2, comparable to tetraspanins, while overall being downregulated upon HIV-1 infection, accumulates at the producer cell side of the VS (i.e. the presynapse), where it contributes to the fusion-preventing activities of the other viral and cellular components.
Population structure ofBorrelia gariniifromIxodes uriaecollected in seabird colonies of the northwestern Atlantic Ocean
Authors: Munro Hannah J. , Ogden Nicholas H. , Mechai Samir , Lindsay L. Robbin , Robertson Gregory J. , Whitney Hugh , Lang Andrew S.
Published: April 2018

The occurrence ofBorrelia gariniiin seabird ticks,Ixodes uriae, associated with different species of colonial seabirds has been studied since the early 1990s. Research on the population structure of this bacterium in ticks from seabird colonies in the northeastern Atlantic Ocean has revealed admixture between marine and terrestrial tick populations. We studiedB. gariniipopulation structure inI. uriaecollected from seabird colonies in the northwestern Atlantic Ocean, in Newfoundland and Labrador, Canada. We applied a multi-locus sequence typing (MLST) scheme toB. gariniifound in ticks from four species of seabirds. TheB. gariniistrains found in this seabird colony ecosystem were diverse. Some were very similar to strains from Asia and Europe, including some obtained from human clinical samples, while others formed a divergent group specific to this region of the Atlantic Ocean.

Importance

This study provides the firstB. gariniisequences from North American seabird ticks that were characterized using an MLST approach. This revealed new MLST sequence types and alleles, enhancing our knowledge ofB. gariniidiversity. Our findings highlight the genetic complexity ofB. gariniicirculating among seabird ticks and their avian hosts but also demonstrate surprisingly close connections betweenB. gariniiin this ecosystem and terrestrial sources in Eurasia. Genetic similarities amongB. gariniifrom seabird ticks and humans indicate the possibility thatB. gariniicirculating within seabird tick-avian host transmission cycles could directly, or indirectly via connectivity with terrestrial transmission cycles, have consequences for human health.
Conversion of iPS derived hepatic progenitors into scalable, functional and developmentally relevant human organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold engineered from collagen-coated pores of defined size
Authors: Seng Ng Soon , Saeb-Parsy Kourosh , Segal Joe M , Serra Maria Paola , Blackford Samuel J I , Lopez Marta Horcas , No Da Yoon , Frank Curtis W , Cho Nam Joon , Nakauchi Hiromitsu , Glenn Jeffrey S , Rashid S Tamir
Published: April 2018

Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 µm diameter pores coated with Collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularize and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.
The FBXW7-SHOC2-Raptor axis controls the cross-talks between RAS/ERK and mTORC1 signaling pathways
Authors: Sun Yi , Xie Chuan-Ming , Tan Mingjia , Li Haomin , Ma Yuanyuan , Xiong Xiufang
Published: April 2018

FBXW7 is a tumor suppressive E3 ubiquitin ligase, whereas the RAS/ERK and mTORC1 are two major oncogenic pathways. Whether and how FBXW7 regulates these two oncogenic pathways are unknown. While SHOC2 is a scaffold protein that activates RAS/ERK signal, whether and how SHOC2 regulates mTORC1 is unknown. Here we showed that SHOC2 is a novel substrate of FBXW7. Upon phosphorylation on Thr507 by ATR, SHOC2 is recognized by FBXW7 for targeted ubiquitylation and degradation. Consistently, SHOC2-induced RAS/ERK activation and cell growth are inhibited by FBXW7. Furthermore, SHOC2 selectively binds to Raptor to competitively inhibit the Raptor-mTOR binding to inactivate mTORC1 and induce autophagy, whereas Raptor binding of SHOC2 inhibits the SHOC2-RAS binding to block MAPK pathway and proliferation. Finally, SHOC2 is overexpressed in human pancreatic cancer, which correlated with poor patient survival, and multiple SHOC2 mutations were found in human lung cancer tissues with the gain-of-function activity. Collectively, our study established that SHOC2-Raptor interaction triggers negative cross-talk between the RAS-ERK and mTORC1 pathways, whereas FBXW7 regulates both pathways via targeting SHOC2 for ubiquitylation and degradation.
Cold acclimation ofTrogoderma granariumEverts is tightly linked to regulation of enzyme activity, energy content and ion concentration
Authors: Mohammadzadeh Mozhgan , Izadi Hamzeh
Published: April 2018

In this study, cold hardiness and some physiological characteristics ofT. granariumlarvae were investigated under different thermal regimes, i.e. warm-acclimated (WA), cold-acclimated (CA), fluctuating-acclimated (FA) and rapid cold-hardened (RCH). In all regimes, the survival rate of the larvae decreased with a decrease in temperature and raise in exposure time. Cold acclimated larvae showed the highest cold hardiness in -15 and -20 ºC. Control larvae had the highest glycogen content (34.4 ± 2.3 µg/gdw). In contrast, cold acclimation larvae had the lowest glycogen content (23.0 ± 1.6 µg/gdw). Change in trehalose content was reversely proportional to change in glycogen content. The greatest myo-inositol and glucose contents were detected in larvae cold acclimation treatment (10.7 ± 0.4 µg/gdw) and control (0.49 ± 0.03 µg/gdw), respectively. In control and treated larvae, the concentration of Na+decreased, though the concentration of K+rose, with rising the exposure time. The shape of the thermal reaction of AMP-depended protein kinase and protein phosphatase IIC followed the same norm, which is different from protein phosphatase I and protein phosphatase IIA. Protein phosphatase IIA and IIC showed a complete difference in thermal reaction norms. In did, thermal fluctuation caused the highest changes in the activity of the enzymes, whereas the RCH showed the lowest changes in the activity of the enzyme. Our results showed a significant enhancement of larval cold tolerance under CA regime that is related to the level of low molecular weight carbohydrates, protein kinase, and phosphatases activity, and hemolymph ions concentration.

SUMMARY STATEMENT

InTrogoderma granarium, cold acclimation enhances the larval cold tolerance that is related to change in the level of low molecular weight carbohydrates, protein kinase, and phosphatases activity, and hemolymph ions concentration.
Critical assessment of approaches for molecular docking to elucidate associations of HLA alleles with Adverse Drug Reactions
Authors: Ramsbottom Kerry A , Carr Dan , Jones Andrew R , Rigden Daniel J
Published: April 2018

Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response. There is growing interest in searching for evidence supporting this model for other ADRs using bioinformatics techniques. In this study, in silico docking was used to assess the utility and reliability of well-known docking programs when addressing these challenging HLA-drug situations. Four docking programs: SwissDock, ROSIE, AutoDock Vina and AutoDockFR, were used to investigate if each software could accurately dock the Abacavir back into the crystal structure for the protein arising from the known risk allele, and if they were able to distinguish between the HLA-associated and non-HLA-associated (control) alleles. The impact of using homology models on the docking performance and how using different parameters such as including receptor flexibility affected the docking performance, were also investigated to simulate the approach where a crystal structure for a given HLA allele may be unavailable. The programs that were best able to predict the binding position of Abacavir were then used to recreate the docking seen for Carbamazepine with B*15:02 and controls alleles. It was found that the programmes investigated were sometimes able to correctly predict the binding mode of Abacavir with B*57:01 but not always. Each of the software packages that were assessed could predict the binding of Abacavir and Carbamazepine within the correct sub-pocket and, with the exception of ROSIE, was able to correctly distinguish between risk and control alleles. We found that docking to homology models could produce poorer quality predictions, especially when sequence differences impact the architecture of predicted binding pockets. Caution must therefore be used as inaccurate structures may lead to erroneous docking predictions. Incorporating receptor flexibility was found to negatively affect the docking performance for the examples investigated. Taken together, our findings help characterise the potential but also the limitations of computational prediction of drug-HLA interactions. These docking techniques should therefore always be used with care and alongside other methods of investigation, in order to be able to draw strong conclusions from the given results.
Observing fear enables plasticity of the dmPFC-BLA pathway during subsequent learning of inhibitory avoidance
Authors: Ito Wataru , Morozov Alexei
Published: April 2018

Observing fear in others is a form of social distress. In mice, it leads to the formation of silent synapses in the prefrontal-amygdala pathway and enhances inhibitory avoidance learning at a later time. Here, we report that observing fear enabled ex vivo LTP. The unsilencing of silent synapses was the prevailing mechanism and the plasticity was occluded by inhibitory avoidance training. In free moving mice with OF experience, the inhibitory avoidance training transiently facilitated local field potentials evoked in BLA by stimulating the prefrontal afferents. The facilitation persisted during the first 4 hours after IA training, which is the time when IA memories consolidate. Thus, the OF-generated silent synapses enable plasticity that may enhance consolidation of IA memories.
Novel functions for integrin-associated proteins revealed by myofibril attachment inDrosophila
Authors: Green Hannah J. , Griffiths Annabel G. M. , Brown Nicholas H.
Published: April 2018

We use the myotendinous junction ofDrosophilaflight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.

Graphical abstract
Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila
Authors: Gultekin Yetis , Steller Hermann
Published: April 2018

The self-renewal of intestinal stem cell is controlled by Wingless/Wnt-β catenin signaling both in Drosophila and mammals. Since Axin is a rate-limiting factor in Wingless signaling its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a critical regulator for degradation of ADP-ribosylated Axin and thus of Wnt/β-catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-of-function mutants of Iduna to investigate its physiological role in Drosophila. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin. Increase of Axin protein in enterocytes non-autonomously enhanced stem cell divisions in the Drosophila midgut. Enterocytes secreted Unpaired and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed both the over-proliferation of stem cells and restored their numbers to normal levels in Iduna mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential to maintain tissue homeostasis in the Drosophila midgut.
Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship
Authors: Brunet Marie A. , Levesque Sébastien A. , Hunting Darel J. , Cohen Alan A. , Roucou Xavier
Published: April 2018

Technological advances promise unprecedented opportunities for whole exome sequencing and proteomic analyses of populations. Currently, data from genome and exome sequencing or proteomic studies are searched against reference genome annotations. This provides the foundation for research and clinical screening for genetic causes of pathologies. However, current genome annotations substantially underestimate the proteomic information encoded within a gene. Numerous studies have now demonstrated the expression and function of alternative (mainly small, sometimes overlapping) ORFs within mature gene transcripts. This has important consequences for the correlation of phenotypes and genotypes. Most alternative ORFs are not yet annotated because of a lack of evidence, and this absence from databases precludes their detection by standard proteomic methods, such as mass spectrometry. Here, we demonstrate how current approaches tend to overlook alternative ORFs, hindering the discovery of new genetic drivers and fundamental research. We discuss available tools and techniques to improve identification of proteins from alternative ORFs and finally suggest a novel annotation system to permit a more complete representation of the transcriptomic and proteomic information contained within a gene. Given the crucial challenge of distinguishing functional ORFs from random ones, the suggested pipeline emphasizes both experimental data and conservation signatures. The addition of alternative ORFs in databases will render identification less serendipitous and advance the pace of research and genomic knowledge. This review highlights the urgent medical and research need to incorporate alternative ORFs in current genome annotations and thus permit their inclusion in hypotheses and models, which relate phenotypes and genotypes.
Between MOFs and molecules: organolead(IV) compounds with chain structures
Authors: Shihada Abdel-Fattah , Weller Frank , Massa Werner
Published: April 2018

Organolead compounds are of interest mainly as catalysts and organolead halides have proved to be very efficient materials for solar cells. Two organolead(IV) dimethylarsinates, namely catena-poly[[triphenyllead(IV)]-μ-chlorido-[triphenyllead(IV)]-μ-dimethylarsinato-κ2
O:O′], [Pb2(C6H5)6(C2H6AsO2)Cl]
n
or [(Ph3Pb)2Cl(O2AsMe2)], (1), and poly[chlorido(μ3-dimethylarsinato-κ3
O:O,O′:O′)diphenyllead(IV)], [Pb(C6H5)2(C2H6AsO2)Cl]
n
or [(Ph2ClPb)(O2AsMe2)], (2), together with the triphenyllead(IV) diphenylphosphinate catena-poly[[triphenyllead(IV)]-μ-diphenylphosphinato-κ2
O:O′], [Pb(C6H5)3(C12H10O2P)]
n
or [(Ph3Pb)(O2PPh2)], (3), have been synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy and mass spectrometry. In (1), a chain structure was found with alternating chloride and Pb—O—As—O—Pb arsinate bridges between five-coordinate PbIV atoms. In (2), bidentate and chelate-like bonded dimethylarsinate ligands form double chains with heptacoordinated PbIV atoms. In (3), a pentacoordinated PbIV atom is connected by Pb—O—P—O—Pb phosphinate bridges to form a linear chain. Obviously, the steric demand of the phenyl ligands at PbIV reduces the possibility of interconnections via polydentate ligands to one dimension only. Thus, no metal–organic frameworks (MOF) are formed but instead various chain structures are observed.
Biotransformation, spectroscopic investigation, crystal structure and electrostatic properties of 3,7α-dihydroxyestra-1,3,5(10)-trien-17-one monohydrate studied using transferred electron-density parameters
Authors: Shahid Ammara , Aziz Ambreen , Noureen Sajida , Ahmed Maqsood , Yousuf Sammer , Choudhary Muhammad Iqbal
Published: April 2018

The biologically transformed product of estradiol valerate, namely 3,7α-dihydroxyestra-1,3,5(10)-trien-17-one monohydrate, C18H22O3·H2O, has been investigated using UV–Vis, IR,1H and13C NMR spectroscopic techniques, as well as by mass spectrometric analysis. Its crystal structure was determined using single-crystal X-ray diffraction based on data collected at 100 K. The structure was refined using the independent atom model (IAM) and the transferred electron-density parameters from the ELMAM2 database. The structure is stabilized by a network of hydrogen bonds and van der Waals interactions. The topology of the hydrogen bonds has been analyzed by the Bader theory of `Atoms in Molecules' framework. The molecular electrostatic potential for the transferred multipolar atom model reveals an asymmetric character of the charge distribution across the molecule due to a substantial charge delocalization within the molecule. The molecular dipole moment was also calculated, which shows that the molecule has a strongly polar character.
Crystal structure of an iridium(III) complex of the [C(dppm)2] PCP pincer ligand system and its conjugate CH acid form
Authors: Reitsamer Christian , Schlapp-Hackl Inge , Partl Gabriel , Schuh Walter , Kopacka Holger , Wurst Klaus , Peringer Paul
Published: April 2018

After the successful creation of the newly designed PCP carbodiphosphorane (CDP) ligand [Reitsamer et al. (2012). Dalton Trans.
41, 3503–3514; Stallinger et al. (2007). Chem. Commun. pp. 510–512], the treatment of this PCP pincer system with the transition metal iridium and further the analysis of the structures by single-crystal diffraction and by NMR spectroscopy were of major interest. Two different iridium complexes, namely (bis{[(diphenylphosphanyl)methyl]diphenylphosphanylidene}methane-κ3
P,C,P′)carbonylchloridohydridoiridium(III) chloride dichloromethane trisolvate, [IrIII(CO){C(dppm)2-κ3
P,C,P′}ClH]Cl·3CH2Cl2 (1) and the closely related (bis{[(diphenylphosphanyl)methyl]diphenylphosphanylidene}methanide(1+)-κ3
P,C,P′)carbonylchloridohydridoiridium(III) dichloride–hydrochloric acid–water (1/2/5.5), [IrIII(CO){CH(dppm)2-κ3
P,C,P′)ClH]Cl}2 (2), have been designed and both complexes show a slightly distorted octahedral coordinated IrIII centre. The PCP pincer ligand system is arranged in a meridional manner, the CO ligand is located trans to the central PCP carbon and a hydride and chloride are located perpendicular above and below the P2C2 plane. With an Ir—CCDP distance of 2.157 (5) Å, an Ir—CO distance of 1.891 (6) Å and a quite short C—O distance of 1.117 (7) Å, complex 1 presents a strong carbonyl bond. Complex 2, the corresponding CH acid of 1, shows an additionally attached proton at the carbodiphosphorane carbon atom located antiperiplanar to the hydride of the metal centre. In comparison with complex 1, the Ir—CCDP distance of 2.207 (3) Å is lengthened and the Ir—C—O values indicate a weaker trans influence of the central carbodiphosphorane carbon atom.
Crystal structures and Hirshfeld surface analyses of (N-hexyl-N-methyldithiocarbamato-κ2S,S′)triphenyltin(IV) and [N-methyl-N-(2-phenylethyl)dithiocarbamato-κ2S,S′]triphenyltin(IV)
Authors: Mohamad Rapidah , Awang Normah , Kamaludin Nurul Farahana , Jotani Mukesh M. , Tiekink Edward R. T.
Published: April 2018

The crystal and molecular structures of two triphenyltin dithiocarbamate compounds,viz. [Sn(C6H5)3(C8H16NS2)], (I), and [Sn(C6H5)3(C10H12NS2)], (II), are described. The dithiocarbamate ligand in each molecule coordinates in an asymmetric fashion resulting in heavily distorted tetrahedral C3S coordination geometries for the Sn atoms, with the distortions traced to the close approach of the non-coordinating thione-S atom. The molecular packing in both compounds features C—H...π(Sn-phenyl) interactions. In (I), the donors are Sn-phenyl-C—H groups leading to centrosymmetric aggregates, while in (II), the donors are both Sn-phenyl-C—H and methyl-C—H groups leading to supramolecular chains propagating along thebaxis. The identified aggregates assemble into their respective crystals with no directional interactions between them. An analysis of the Hirshfeld surfaces show distinctive patterns, but an overwhelming predominance (>99% in each case) of H...H, C...H/H...C and S...H/H...S contacts on the respective Hirshfeld surface.
1-[(1-Butyl-1H-1,2,3-triazol-5-yl)methyl]-3-methylquinoxalin-2(1H)-one
Authors: Abad Nadeem , Ramli Youssef , Sebbar Nada Kheira , Kaur Manpreet , Essassi El Mokhtar , Jasinski Jerry P.
Published: April 2018

In the title compound, C16H19N5O, the quinoxaline and triazole rings are almost orthogonal, inclined to one another at an angle of 79.8 (3)°. A weak intramolecular C—H...O interaction locks the conformation of the molecule. The crystal packing features weak intermolecular C—H...O and C—H...N interactions, which form chains along the b-axis direction. In addition, weak C—H...π intermolecular interactions further influence the crystal packing.
Digital preservation: some underlying issues for long-term preservation
Authors: Tripathi Sneha
Published: April 2018

Purpose

The purpose of this study is to investigate the concept of digital preservation and traditional preservation per se and discusses various issues related to long-term preservation in a digital environment.

Design/methodology/approach

The study attempts to look into the various aspects of preservation in context of digital objects (borne or digitalized) especially. Bundling of an object (digital), digital storage, quality control and risk preparedness are some of the pointers studied to perceive an overall scenario for long-term preservation of an object.

Findings

Various methods have been suggested to deal with the issues related to long-term preservation of an object which can be used to frame an organization’s policy for long-term preservation.

Originality/value

The study emphasizes on collective measures incorporating traditional and digital means to ensure long-term preservation. It lists down various checklists to deal with various issues pertinent to long-term digital preservation.
Should clinical guidelines dictate clinical care?
Authors: Chien Patrick
Published: April 2018

Deputy Editor‐in‐Chief, Dr Patrick Chien, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/April-editors-choice-2018
Diagnosis and management of ADA2 deficient polyarteritis nodosa
Authors: Human Andrea , Pagnoux Christian
Published: April 2018

Deficiency of ADA2 (DADA2) is a recently described systemic inflammatory vasculopathy caused by mutations in the CERC1 gene that often, but not always, clinically resembles polyarteritis nodosa (PAN). The condition was originally characterized by livedoid rash, systemic inflammation, variable hypogammaglobulinemia, and early‐onset stroke. The phenotypic spectrum has expanded to include patients with immunodeficiency syndromes and bone marrow dysfunction, which are not typical features of PAN. Exploration into the pathogenesis and treatment options of DADA2 has added to our understanding of this condition, but more studies are needed. The purpose of this article is to review the various clinical phenotypes of DADA2, and raise awareness among rheumatologists to consider DADA2 when evaluating patients presenting with PAN‐like disease.
Air bronchogram in pleomorphic carcinoma of the lung is associated with favorable prognosis
Authors: Onoda Hideko , Kimura Tokuhiro , Tao Hiroyuki , Okabe Kazunori , Matsumoto Tsuneo , Ikeda Eiji
Published: April 2018

Background

Pleomorphic carcinoma (PC) of the lung is a rare histological type of lung carcinoma. The association between computed tomography (CT) findings and histology with outcome remains unclear. We examined the relationships between CT features and histopathologic findings, and evaluated the impact of CT features and other clinicopathologic factors on survival.

Methods

Thirty‐five consecutive patients with PC of the lung who underwent surgery between October 2010 and December 2015 were enrolled in this study. The 35 tumors were classified with or without air bronchogram in the tumors, and with or without intratumoral ground glass opacity (GGO) on CT.

Results

Air bronchogram and GGO were detected in 12 (34.3%) and 5 (14.3%) tumors, respectively. Multivariate analysis revealed that air bronchogram was significantly associated with the presence of adenocarcinoma components with lepidic growth patterns (P = 0.005), and predominance of adenocarcinomas (P = 0.026). GGO was significantly associated with the presence of adenocarcinoma component with lepidic growth pattern (P = 0.010). Air bronchogram was an independent favorable prognostic factor for overall survival, whereas GGO did not have a significant effect on survival.

Conclusion

Air bronchogram observed in PCs of the lung is strongly related with histological components of the tumor and favorable outcome.
Hydro One IPO
Authors: Partovi Adel , Magnan Michel
Published: April 2018

The case describes the initial public offering of Hydro One, one of the largest ever in Canada. The focus is on the financial statement analysis and business valuation of Hydro One from the perspective of a potential institutional investor. The case discusses several alternative valuation methodologies, with particular emphasis on the peculiarities of performing a prospective analysis for a rate‐regulated entity.
Financial literacy and risky asset holdings: evidence from China
Authors: Liao Li , Xiao Jing Jian , Zhang Weiqiang , Zhou Congyi
Published: April 2018

Although financial literacy is important for participating in financial markets, the level of financial literacy of Chinese consumers is low compared with those in developed countries. Using data from the 2014 China Survey of Consumer Finances, we examine the relation between financial literacy and the risky asset holding behaviour of Chinese households, in the context of an emerging financial market with a distinct institutional background. The findings reveal that consumers with higher levels of financial literacy are more likely to hold risky financial assets than those with lower levels. The potential impacts are derived mainly from advanced financial literacy.
Political connections of the board of directors and credit financing: evidence from Chinese private enterprises
Authors: Peng Hongfeng , Zhang Xiao , Zhu Xiaoquan
Published: April 2018

This study explores whether the political connections of the board of directors facilitate credit financing. It addresses the gap concerning the discussion of the substitution or complementary effect on financing terms between political connections and government regulation in China. Using a data set covering 1340 private listed firms, we classify all members on the board of directors into subgroups and show that it is the political connections of nonexecutive directors, rather than executive directors that play an important role in obtaining long‐term credit loans. Moreover, the convenience of obtaining financing is mainly derived from the political connections of official independent directors.
Pairs trading in Chinese commodity futures markets: an adaptive cointegration approach
Authors: Chen Danni , Cui Jing , Gao Yan , Wu Leilei
Published: April 2018

This study comprehensively examines pairs trading in Chinese commodity futures markets, which, although less researched, represents an important scenario for analysing commodity price behaviour. Based on a sample of daily future returns from 2006 to 2016, we propose a cointegration model that employs an adaptive learning process, and we show that our model yields an average annualised return of 26.94 percent before trading costs, using a closed‐loop strategy. Our results are robust to various tests, including parameter uncertainty, holding period constraints, trading period selection and trading costs.
City‐level political uncertainty and city‐level IPO activities
Authors: Luo Danglun , Tong Naqiong , She Guoman
Published: April 2018

Based on the unique city‐level politician turnover data between 1999 and 2012 in China, we document that the number of IPOs at the city level decreases during the city‐level politician turnover period. Such negative shock is more pronounced for non‐state‐owned enterprises (NSOEs) than for SOEs and more pronounced for local SOEs than for central SOEs. Higher political uncertainties amplify the negative shock when the successor politician is nonlocal, when turnover occurs during periods of higher local fiscal deficits or during party member election periods, and when government interventions are higher or confidence‐in‐court is lower. Consequently, IPO firms listed during a political turnover period underperform their counterparts.
Extractions to reconstruction: The Development of Oral & Maxillofacial Surgery in Australian and New Zealand
Authors: Goss AN , Linn R
Published: April 2018

Oral and Maxillofacial Surgery developed initially from Dentistry as exodontia. It then expanded into the surgical management of jaw disorders. As the specialty evolved, it came into increasing conflict with related surgical disciplines. In the 1960s and 1970s these external criticisms were well‐founded as training in oral surgery was individual, solely University‐based and highly variable. In the 1980s the speciality developed a plan which involved hospital‐based surgical training, a mandatory high level college surgical examination and detailed workforce and training studies. These were progressively implemented over the next twenty years with a dual degree (medicine and dentistry) and a final fellowship (FRACDS (OMS)). This resulted in accreditation by the Australian Medical Council and the Australian Dental Council and recognition as a Principal Surgical Speciality by the Commonwealth Department of Health. This development was monitored by published workforce studies over three decades that are important yardsticks to inform the credentialing of dental specialists.
Current and evolving trends in the management of facial fractures
Authors: Vujcich N , Gebauer D
Published: April 2018

The oral and maxillofacial region has a complex regional anatomy including hard and soft tissues. Trauma in this region may affect the airway, cause potentially life threatening bleeding and head injuries. The senses of olfaction, sight and hearing can also be disrupted as well as a profound psychological impact following disfigurement. This oral and maxillofacial trauma update provides information on demographics, incidence, pathophysiology, diagnosis, fracture patterns and management of facial trauma. It also discusses the role of new advancements in the management of facial trauma.
Oral Cancer
Authors: Wong TSC , Wiesenfeld D
Published: April 2018

The management of oral cancer is a multidisciplinary endeavour, as each patient presents the treating clinicians with a unique set of challenges the management of which impacts on both survival and quality of life. This article focuses on the management of oral cancer. We highlight the epidemiology and risk factors for oral cancer in Australia, the various clinical presentations that occur and the staging of oral cancer. In the vast majority of cases surgery remains the mainstay of treatment. Radiation and medical oncology is usually used in an adjuvant context. Dental professionals play a critical role in many stages of management from the initial detection, to optimising pre treatment dental health and managing the short and long term sequelae of treatment. Monitouring for recurrence and the development of second primary tumours is a key role.
The teaching of oral & maxillofacial surgery to dental students in Australia & New Zealand
Authors: Goss AN
Published: April 2018

The teaching of OMS to dental students in Australia & New Zealand was surveyed. Generally the established schools had well developed curricula with good didactic and clinical experience conducted by specialist OMS educators. There was a much greater array of teaching in some of the newer schools with some appearing to barely meet the current minimalist professional competencies of the ADC. The critical element was whether or not the school was associated with a speciality OMS Unit at a Teaching Hospital. Proposals addressing these deficiencies are presented.