bluuebunny/crossref_metadata_2025 huggingface dataset:
AKARI mid-infrared slit-less spectroscopic catalogue
Authors: Yamagishi Mitsuyoshi , Yamamura Issei , Mizuki Toshiyuki , Ootsubo Takafumi , Baba Shunsuke , Usui Fumihiko , Onaka Takashi
Published: December 2018

AKARI/IRC is capable of conducting slit-less spectroscopy in the mid-infrared (5–13 μm) over a 10΄ × 10΄ area with a spectral resolution of 50, which is suitable for serendipitous surveys. The data reduction is, however, rather complicated by the confusion of nearby sources after dispersing the spectra. To achieve efficient and reliable data reduction, we first compiled a point-source list from the reference image in each field of view and checked the overlaps of the spectra using their relative positions and fluxes. Applying this procedure to 886 mid-infrared slit-less spectroscopic data taken in the cryogenic phase, we obtained 862 mid-infrared spectra from 604 individual non-overlapping sources brighter than 1.5 mJy. We find a variety of objects in the spectroscopic catalogue, ranging from stars to galaxies. We also obtained a by-product catalogue of 9 μm point sources containing 42837 objects brighter than 0.3 mJy. The spectroscopic and point-source catalogues are available online.
Cold Acclimation of the Thermoacidophilic Red Alga Galdieria sulphuraria: Changes in Gene Expression and Involvement of Horizontally Acquired Genes
Authors: Rossoni Alessandro W , Sch�nknecht Gerald , Lee Hyun Jeong , Rupp Ryan L , Flachbart Samantha , Mettler-Altmann Tabea , Weber Andreas P M , Eisenhut Marion
Published: December 2018

Galdieria sulphuraria is a unicellular red alga that lives in hot, acidic, toxic metal-rich, volcanic environments, where few other organisms survive. Its genome harbors up to 5% of genes that were most likely acquired through horizontal gene transfer. These genes probably contributed to G.sulphuraria’s adaptation to its extreme habitats, resulting in today’s polyextremophilic traits. Here, we applied RNA-sequencing to obtain insights into the acclimation of a thermophilic organism towards temperatures below its growth optimum and to study how horizontally acquired genes contribute to cold acclimation. A decrease in growth temperature from 42�C/46�C to 28�C resulted in an upregulation of ribosome biosynthesis, while excreted proteins, probably components of the cell wall, were downregulated. Photosynthesis was suppressed at cold temperatures, and transcript abundances indicated that C-metabolism switched from gluconeogenesis to glycogen degradation. Folate cycle and S-adenosylmethionine cycle (one-carbon metabolism) were transcriptionally upregulated, probably to drive the biosynthesis of betaine. All these cold-induced changes in gene expression were reversible upon return to optimal growth temperature. Numerous genes acquired by horizontal gene transfer displayed temperature-dependent expression changes, indicating that these genes contributed to adaptive evolution in G.sulphuraria.
Obstetric and Pediatric Provider Perspectives on Mandatory Reporting of Prenatal Substance Use
Authors: Jarlenski Marian , Minney Sarah , Hogan Caroline , Chang Judy C.
Published: December 2018

Objective:

In many states, health care providers are legally required to report pregnant women who use substances, or infants affected by prenatal substance use, to child welfare authorities. The objective of this study was to characterize obstetric and pediatric providers’ perceptions of and experiences with policies requiring mandatory reporting of prenatal substance use to child welfare authorities.

Methods:

We conducted a qualitative interview study among 20 obstetric and pediatric providers to elicit participants’ perspectives about and experience with current policy requiring mandatory reporting of prenatal substance use. Two investigators used an iterative content analysis approach to code interview transcripts and identify themes.

Results:

Study participants included obstetrician/gynecologists (N = 7), midwives (N = 5), and pediatricians (N = 8). Providers noted that implementation of the policy was often targeted and that targeted screening can be biased. Most providers reported that they incorporated information about mandatory reporting policies into patient counseling about substance use. They described not knowing what happens to patients after mandatory reporting and concerns regarding unintended consequences. Providers indicated that changes are needed to improve outcomes for patients and their families and suggested increased research into best practices, more funding for social services, and eliminating the policy altogether.

Conclusions:

Health care providers expressed concern about the targeted screening process used to identify women with substance use whose children are reported to child welfare authorities. Most providers believed that mandatory reporting processes could be modified in ways that would support the health of women and children.
Perceptions of Attractive and Healthy-Looking Lips
Authors: Hwang Kun , Kim Young Suk , Kim Hun
Published: December 2018

The aim of this study was to characterize Koreans’ perceptions of attractive and healthy-looking lips.

A survey was conducted among 258 women and 72 men who were asked to view illustrations of various examples of the 4 lip-related ratios (lip thickness-to-width ratio [LTW]; upper-to-lower vermillion ratio [ULR]; upper vermillion thickness-to-upper lip height ratio [VUL]; and lip-to-nose width ratio [LNW]) and to choose which they thought were attractive or healthy-looking.

The LTW ratios most often identified as attractive were LTW-1/3 (lip thickness is 1/3 of lip width, 40.0%) and LTW-2/5 (47.3%). The LTW value most often identified as healthy-looking was LTW-2/5 (54.3%). The most attractive ULR ratio was ULR-4/5 (upper vermillion thickness is 4/5 of the lower vermillion, 49.4%). The most healthy-looking ULR ratio was ULR-4/5 (47.0%). The most attractive VUL ratio was VUL-1/2 (thickness of the upper vermillion is 1/2 of upper lip height, 60.3%). The most healthy-looking VUL ratio was VUL-1/2 (61.0%). The most attractive LNW ratio was LNW-3/2 (lip width is 3/2 of nose width, 42.1%). LNW-3/2 was also the most preferred in all age groups below 50 years, while those over 50 preferred LNW-4/3 (55.0%). The most healthy-looking LNW ratios were LNW-3/2 (35.2%) and LNW-4/3 (32.1%). LNW-3/2 was the most preferred in all age groups below 50, while those over 50 preferred LNW-4/3 (40.0%). It therefore seems that older people preferred a narrower lip width than younger people.

The results of this study can be applied in lip augmentations or aesthetic lip surgery.
First detection of tick-borne encephalitis virus in Ixodes ricinus ticks and their rodent hosts in Moscow, Russia
Authors: Makenov Marat , Karan Lyudmila , Shashina Natalia , Akhmetshina Marina , Zhurenkova Olga , Kholodilov Ivan , Karganova Galina , Smirnova Nina , Grigoreva Yana , Yankovskaya Yanina , Fyodorova Marina
Published: December 2018

Here, we report the first confirmed autochthonous tick-borne encephalitis case diagnosed in Moscow in 2016 and describe the detection of Tick-borne encephalitis virus (TBEV) in ticks and small mammals in a Moscow park.

The paper includes data from two patients who were bitten by TBEV-infected ticks within the Moscow city limits; one of these cases led to the development of the meningeal form of TBE. Both TBEV-infected ticks attacked patients in the same area. We collected ticks and trapped small mammals in this area in 2017. All samples were screened for the presence of pathogens causing tick-borne diseases by PCR. The TBEV-positive ticks and small mammals’ tissue samples were subjected to virus isolation. The sequencing of the complete polyprotein gene of the positive samples was performed.

A total of 227 questing ticks were collected. TBEV was detected in five specimens of Ixodes ricinus. We trapped 44 small mammals, mainly bank voles (Myodes glareolus) and pygmy field mice (Apodemus uralensis). Two samples of brain tissue from bank voles yielded a positive signal in RT-PCR for TBEV. We obtained six virus isolates from the ticks and brain tissue of a bank vole. Complete genome sequencing showed that the obtained isolates belong to the European subtype and have low diversity with sequence identities as high as 99.9%. GPS tracking showed that the maximum distance between the exact locations where the TBEV-positive ticks were collected was 185 m. We assume that the forest park was free of TBEV and that the virus was recently introduced.
Culturing primary neurons from rat hippocampus and cortex
Authors: Sahu Madhusmita Priyadarshini , Nikkilä Outi , Lågas Seija , Kolehmainen Sulo , Castrén Eero
Published: December 2018

Primary neurons from rodent brain hippocampus and cortex has served as great tools in biomedical research over the years. However, protocols for the preparation of primary neurons vary, which often leads to conflicting results. This report provides a robust and reliable protocol for the production of primary neuronal cultures from the cortex and hippocampus with minimal contribution of non-neuronal cells. The neurons were grown in serum free media and maintained for several weeks without any additional feeder cells. The neuronal cultures maintained according to this protocol differentiate and by three weeks develop extensive axonal and dendritic branching. The cultures produced by this method show excellent reproducibility and can be used for histological, molecular and biochemical methods.
“Homogenous subgroups of atypical meningiomas defined using oncogenic signatures: basis for a new grading system?”
Authors: Zador Zsolt , Landry Alexander , Saha Ashirbani , Cusimano Michael D.
Published: December 2018

Meningiomas are the most common brain tumor with a prevalence of 3% in the population. Histological grading of meningiomas (1 through 3) has a major role in determining treatment choice and predicting outcome. While largely indolent grade 1 and the highly aggressive grade 3 meningiomas as considered mostly homogenous in clinical behavior, atypical or grade 2 meningiomas have highly diverse biological properties. Our aim was to identify homogenous subgroups of atypical meningiomas with the working hypothesis that these subgroups would share features with grade 1 and grade 3 counterparts. We carried out systems level analysis by gene module discovery using co-expression networks on the transcriptomics of 212 meningiomas. The newly identified subgroups were characterized in terms of recurrence rate and overlapping biological processes in gene ontology. We were able to reclassify 33 of 46 atypical meningiomas (72%) into a benign “grade 1-like” (14/46) and malignant “grade 3-like” (19/46) subgroup based on oncogenic signatures. Recurrence rates of “Grade 1-like” and “grade 3-like” tumors was 0% and 72% respectively. These two new subgroups showed similar recurrence rates and concordant biological processes with the respected grades. Our findings help resolve the heterogeneity/uncertainty around atypical meningioma biology and identify subgroups more homogenous than in prior studies. These results may help reshape prediction, follow-up planning, treatment decisions and recruitment protocols for future and ongoing clinical trials. The findings demonstrate the conceptual advantage of systems biology approaches and underpin the utility of molecular signatures as complements to the current histological grading system.
Environmental heterogeneity drives tsetse fly population dynamics
Authors: Cecilia Hélène , Arnoux Sandie , Picault Sébastien , Dicko Ahmadou , Seck Momar Talla , Sall Baba , Bassène Mireille , Vreysen Marc , Pagabeleguem Soumaïla , Bancé Augustin , Bouyer Jérémy , Ezanno Pauline
Published: December 2018

A spatially and temporally heterogeneous environment may lead to unexpected population dynamics, and knowledge still is needed on which of the local environment properties favour population maintenance at larger scale. As regards pathogen vectors, such as tsetse flies transmitting human and animal African trypanosomosis, such a knowledge is crucial for proposing relevant management strategy. We developed an original mechanistic spatio-temporal model of tsetse fly population dynamics, accounting for combined effects of spatial complexity, density-dependence, and temperature on the age-structured population, and parametrized with field and laboratory data. We confirmed the strong impact of temperature and adult mortality on tsetse populations. We showed that patches with the lowest mean temperatures and lowest variations act as refuges when adult mortality is homogeneously increased. Our results highlighted the importance of baseline data collection to characterize the targeted ecosystem before any control measure is implemented to maximize its efficiency.
Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture
Authors: Llorca Alfredo , Ciceri Gabriele , Beattie Robert , Wong Fong K. , Diana Giovanni , Serafeimidou Eleni , Fernández-Otero Marian , Streicher Carmen , Arnold Sebastian J. , Meyer Martin , Hippenmeyer Simon , Maravall Miguel , Marín Oscar
Published: December 2018

The cerebral cortex contains multiple hierarchically organized areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have quantitatively investigated the neuronal output of individual progenitor cells in the ventricular zone of the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. We found that individual cortical progenitor cells show a high degree of stochasticity and generate pyramidal cell lineages that adopt a wide range of laminar configurations. Mathematical modelling these lineage data suggests that a small number of progenitor cell populations, each generating pyramidal cells following different stochastic developmental programs, suffice to generate the heterogenous complement of pyramidal cell lineages that collectively build the complex cytoarchitecture of the neocortex.
Large-scale analyses of human microbiomes reveal thousands of small, novel genes and their predicted functions
Authors: Sberro Hila , Greenfield Nicholas , Pavlopoulos Georgios , Kyrpides Nikos , Bhatt Ami S.
Published: December 2018

Small proteins likely abound in prokaryotes, and may mediate much of the communication that occurs between organisms within a microbiome and their host. Unfortunately, small proteins are traditionally overlooked in biology, in part due to the computational and experimental difficulties in detecting them. To systematically identify novel small proteins, we carried out a large comparative genomics study on 1,773 HMP human-associated metagenomes from four different body sites (mouth, gut, skin and vagina). We describe more than four thousand conserved protein families, the majority of which are novel; ~30% of these protein families are predicted to be secreted or transmembrane. Over 90% of the small protein families have no known domain, and almost half are not represented in reference genomes, emphasizing the incompleteness of knowledge in this space. Our analysis exposes putative novel ‘housekeeping’ small protein families, including a potential novel ribosomally associated protein, as well as ‘mammalian-specific’ or ‘human-specific’ protein families. By analyzing the genomic neighborhood of small genes, we pinpoint a subset of families that are potentially associated with defense against bacteriophage. Finally, we identify families that may be subject to horizontal transfer and are thus potentially involved in adaptation of bacteria to the changing human environment. Our study suggest that small proteins are highly abundant and that those of the human microbiome, in particular, may perform diverse functions that have not been previously reported.
Novel Computational Method to Define RNA PSRs Explains Influenza A Virus Nucleotide Conservation
Authors: Chursov Andrey , Fridlyand Nathan , Sufianov Albert A. , Kiselev Oleg I. , Baranovskaya Irina , Vasin Andrey , Yewdell Jonathan W. , Shneider Alexander
Published: December 2018

RNA molecules often fold into evolutionarily selected functional structures. Yet, the literature offers neither a satisfactory definition for “structured RNA regions”, nor a computational method to accurately identify such regions. Here, we define structured RNA regions based on the premise that both stems and loops in functional RNA structures should be conserved among RNA molecules sharing high sequence homology. In addition, we present a computational approach to identify RNA regions possessing evolutionarily conserved secondary structures, RNA ISRAEU (RNA Identification of Structured Regions As Evolutionary Unchanged). Applying this method to H1N1 influenza mRNAs revealed previously unknown structured RNA regions that are potentially essential for viral replication and/or propagation. Evolutionary conservation of RNA structural elements may explain, in part, why mutations in some nucleotide positions within influenza mRNAs occur significantly more often than in others. We found that mutations occurring in conserved nucleotide positions may be more disruptive for structured RNA regions than single nucleotide polymorphisms in positions that are more prone to changes. Finally, we predicted computationally a previously unknown stem-loop structure and demonstrated that oligonucleotides complementing the stem (but not the loop or unrelated sequences) reduce viral replicationin vitro.These results contribute to understanding influenza A virus evolution and can be applied to rational design of attenuated vaccines and/or drug designs based on disrupting conserved RNA structural elements.

AUTHOR SUMMARY

RNA structures play key biological roles. However, the literature offers neither a satisfactory definition for “structured RNA regions” nor the computational methodology to identify such regions. We define structured RNA regions based on the premise that functionally relevant RNA structures should be evolutionarily conserved, and devise a computational method to identify RNA regions possessing evolutionarily conserved secondary structural elements. Applying this method to influenza virus mRNAs of pandemic and seasonal H1N1 influenza A virus generated Predicted Structured Regions (PSRs), which were previously unknown. This explains the previously mysterious sequence conservation among evolving influenza strains. Also, we have experimentally supported existence of a computationally predicted stem-loop structure predicted computationally. Our approach may be useful in designing live attenuated influenza vaccines and/or anti-viral drugs based on disrupting necessary conserved RNA structures.
Unpredictable effects of the genetic background of transgenic lines in physiological quantitative traits
Authors: Evangelou Amalia , Ignatiou Anastasia , Antoniou Chloi , Kalanidou Sofia , Chatzimatthaiou Sotiroula , Shianiou Gavriella , Ellina Soteroulla , Athanasiou Rafaella , Panagi Myrofora , Apidianakis Yiorgos , Pitsouli Chrysoula
Published: December 2018

Physiological, fitness and disease phenotypes are complex traits exhibiting continuous variation in natural populations. To understand complex trait gene functions transgenic lines of undefined genetic background are often combined to assess quantitative phenotypes ignoring the impact of genetic polymorphisms. Here, we used inbred wild-type strains of theDrosophilaGenetics Reference Panel to assess the phenotypic variation of six physiological and fitness traits, namely, female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. We found continuous variation in the approximately 150 strains tested for each trait, with extreme values differing by more than four standard deviations for all traits. In addition, we assessed the effects of commonly usedDrosophila UAS-RNAitransgenic strains and their backcrossed isogenized counterparts, in the same traits plus baseline intestinal mitosis and tracheal branching in normoxia, in heterozygous conditions, when only half of the genetic background was different among strains. We tested 20 non-isogenic strains (10 KK and 10 GD) from the ViennaDrosophilaResource Center and their isogenized counterparts without Gal4 induction. Survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other traits were affected in only 10-25% of the cases. Upon Gal4-inducedUAS-RNAiexpression, 4 out of 11 isogenic vs. non-isogenic pairs tested exhibited differences in survival to infection. Andvice versa, crossing a singleUAS-RNAiline with a Gal4 transgene inserted in different genetic backgrounds exhibited quantitative variations that were unpredictable on the basis of pure line performance. Thus, irrespective of the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.
Data from an electronic health informatics pipeline to describe clearance dynamics of Hepatitis B surface antigen (HBsAg) and e-Antigen (HBeAg) in chronic HBV infection
Authors: Downs Louise , Smith David , Lumley Sheila F , Patel Meha , McNaughton Anna L , Mokaya Jolynne , Ansari M Azim , Salih Hizni , Várnai Kinga A , Freeman Oliver , Cripps Sarah , Phillips Jane , Collier Jane , Woods Kerrie , Channon Keith , Davies Jim , Barnes Eleanor , Jeffery Katie , Matthews Philippa C
Published: December 2018

HBsAg and HBeAg have gained traction as biomarkers of control and clearance during monitoring of chronic hepatitis B virus infection (CHB). An improved understanding of the correlates of clearance of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR-HIC), adopting an unbiased approach to generating a robust longitudinal dataset for adults testing HBsAg-positive from a large UK teaching hospital over a six year period (2011-2016 inclusive). From 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. HBsAg clearance rate was similar in individuals on NA therapy (n=4, median clearance time 150 weeks) vs those not on NA therapy (n=9, median clearance time 157 weeks). Those who cleared HBsAg were significantly older, and less likely to be on NA therapy compared to non-clearers (p=0.003 and p=0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (p=0.025). HBeAg clearance occurred both on NA therapy (n=24, median time 49 weeks) and off NA therapy (n=19, median time 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematised approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and underpin improvements in clinical care provision.

IMPORTANCE

Advances in the diagnosis, monitoring and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical datasets that can help to inform advances in patient care, and provide clues that inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been under-represented in the literature. Tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualised clinical care and may provide important clues into the immune events that underpin disease control.
Neural dynamics of the impact of font style on lexical decision making in adult dyslexia
Authors: Franzen Léon , Philiastides Marios G.
Published: December 2018

Good reading comprehension is indispensable in many situations including contract-based transactions that have become so prevalent in our everyday lives. People with dyslexia often exhibit impairments in this important cognitive process. Although the effects of italics — a commonly used style for highlighting important content in a range of documents — and font in general, have been explored with behavioural measures, their impact on human brain dynamics remains poorly understood. Here, we used electroencephalography (EEG) to investigate the specific effects of italics in a sentence reading lexical decision task in adult dyslexics and an age-matched non-dyslexia group. Overall, the performance of dyslexics was worse. Cluster-based event-related potential (ERP) analysis revealed that brain responses within the first 300 ms following the decision stimulus differed in amplitude and spatial distribution between dyslexics and non-dyslexics when processing italicised text. An initial ERP component over occipitotemporal electrode sites started to differ between the groups as early as 167 ms following the onset of short italicised decision words. A subsequent ERP component over centrofrontal electrodes showed differences lasting until about 300 ms post-stimulus onset. Inter-individual amplitude differences in this centrofrontal neural signal were predictive of behavioural performance across participants, further highlighting the role of fast post-sensory linguistic processes in lexical decision making. Crucially, our findings emphasise the importance of choosing font style carefully to optimise word processing and reading comprehension by everyone.
Biophysical and physiological causes of coral reef microbialization
Authors: Silveira Cynthia B. , Roach Ty N. F. , Villela Helena , Barno Adam , Reyes Brandon , Rubio-Portillo Esther , Le Tram , Mead Spencer , Hatay Mark , Luque Antoni , Wegley-Kelly Linda , Vermeij Mark , Bailey Barbara , Takeshita Yui , Haas Andreas , Rohwer Forest
Published: December 2018

Coral reefs are declining globally as their primary producer communities shift from stony coral to fleshy macroalgae dominance. Previously, we have shown that the rise of fleshy macroalgae produces dissolved organic carbon (DOC) that lead to microbialization and coral death. Here we test the hypothesis that the biophysical cause of bacterial biomass accumulation is a relative decrease in electron acceptors relative to electron donors due to O2loss from macroalgae. We show that 37 % of photosynthetic O2produced by reef fleshy macroalgae is lost in the form of gas through ebullition from algae surfaces. O2loss increases DOC:O2ratios, decoupling the photosynthetically fixed carbon from oxidative potential for respiration. This biogeochemical environment drives heterotrophic microbes to increase cell-specific DOC consumption and cell sizes, accumulating biomass. In contrast, corals do not lose oxygen and support the growth of smaller and fewer bacteria.In situbiomass and metagenomic analyses of 87 reefs across the Pacific and Caribbean show that on algae-dominated reefs bacteria accumulate organic carbon through a Warburg-like increase in aerobic glycolytic metabolism. Because of its biophysical basis, microbialization is predicted to occur in other marine ecosystems shifting primary producer assemblages, such as planktonic communities in warming and acidifying conditions.
The Bellerophon pipeline, improving de novo transcriptomes and removing chimeras
Authors: Kerkvliet Jesse , de Fouchier Arthur , van Wijk Michiel , Groot Astrid T.
Published: December 2018

Transcriptome quality control is an important step in RNA-seq experiments. However, the quality of de novo assembled transcriptomes is difficult to assess, due to the lack of reference genome to compare the assembly to. We developed a method to assess and improve the quality of de novo assembled transcriptomes by focusing on the removal of chimeric sequences. These chimeric sequences can be the result of faulty assembled contigs, merging two transcripts into one. The developed method is incorporated into a pipeline, that we named Bellerophon, which is broadly applicable and easy to use. Bellerophon first uses the quality-assessment tool TransRate to indicate the quality, after which it uses a Transcripts Per Million (TPM) filter to remove lowly expressed contigs and CD-HIT-EST to remove highly identical contigs. To validate the quality of this method, we performed three benchmark experiments: 1) a computational creation of chimeras, 2) identification of chimeric contigs in a transcriptome assembly, 3) a simulated RNAseq experiment using a known reference transcriptome. Overall, the Bellerophon pipeline was able to remove between 40 to 91.9% of the chimeras in transcriptome assemblies and removed more chimeric than non-chimeric contigs. Thus, the Bellerophon sequence of filtration steps is a broadly applicable solution to improve transcriptome assemblies.
The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer's disease.
Authors: Ameen-Ali Kamar Eleanor , Simpson Julie E , Wharton Stephen B , Heath Paul R , Sharp Paul , Brezzo Gaia , Berwick Jason
Published: December 2018

The role of cellular changes in the neurovascular unit is increasingly being investigated to understand the pathogenesis of Alzheimers disease. The aim of the current study was to determine the time course of recognition memory impairment in the J20 mouse model of AD, in relation to neuroinflammatory responses and the pathology of Aβ. Male hAPP-J20 and wild-type mice were assessed at 3, 6, 9, and 12 months of age. The spontaneous object recognition (SOR) task provided a measure of memory, with assessment of both a short delay (1 min) and a long delay (4 hrs). Immunohistochemistry was used to characterise Aβ-deposition, and quantify astrocyte and microglial responses. At all ages tested J20 mice had impaired long-term, but preserved short-term, recognition memory. Wild-types demonstrated preserved long-term memory up to 9 months of age, and preserved short-term memory at all ages tested. Plaque pathology in the J20 mice was present from 6 months onwards, with co-localisation of reactive microglia and activated astrocytes. Reactive microglia and astrocyte activation in the hippocampus were significantly greater in the J20 mice at 9 months, compared to wild-types. This study contributes to our understanding of the pathological and cognitive mechanisms at play in AD. J20 mice showed impairment in retaining information over longer periods from an early age, preceding the deposition of Aβ and glial activation. Defining early physiological changes in relation to cognitive decline could provide insight into new therapeutic targets early in the disease process, when intervention is most likely to effectively slow disease progression.
The impact of stroma on the discovery of molecular subtypes and prognostic gene signatures in serous ovarian cancer
Authors: Schwede Matthew , Waldron Levi , Mok Samuel C. , Wei Wei , Basunia Azfar , Merritt Melissa A. , Parmigiani Giovanni , Harrington David , Quackenbush John , Birrer Michael J. , Culhane Aedín C.
Published: December 2018

Purpose

Recent efforts to improve outcomes for high-grade serous ovarian cancer, a leading cause of cancer death in women, have focused on identifying molecular subtypes and prognostic gene signatures, but existing subtypes have poor cross-study robustness. We tested the contribution of cell admixture in published ovarian cancer molecular subtypes and prognostic gene signatures.

Experimental Design

Public gene expression data, two molecular subtype classifications, and 61 published gene signatures of ovarian cancer were examined. Using microdissected data, we developed gene signatures of ovarian tumor and stroma. Computational simulations of increasing stromal cell proportion were performed by mixing gene expression profiles of paired microdissected ovarian tumor and stroma.

Results

Established ovarian cancer molecular subtypes are strongly associated with the cell admixture. Tumors were classified as different molecular subtypes in simulations, when the percentage of stromal cells increased. Stromal gene expression in bulk tumor was weakly prognostic, and in one dataset, increased stroma was associated with anatomic sampling location. Five published prognostic gene signatures were no longer prognostic in a multivariate model that adjusted for stromal content alone.

Conclusions

The discovery that molecular subtypes of high grade serous ovarian cancer is influenced by cell admixture, and stromal cell gene expression is crucial for interpretation and reproduction of ovarian cancer molecular subtypes and gene signatures derived from bulk tissue. Single cell analysis may be required to refine the molecular subtypes of high grade serous ovarian cancer. Because stroma proportion was weakly prognostic, elucidating the role of the tumor microenvironment’s components will be important.

Translational relevance

Ovarian cancer is a leading cause of cancer death in women in the United States. Although the tumor responds to standard therapy for the majority of patients, it frequently recurs and becomes drug-resistant. Recent efforts have focused on identifying molecular subtypes and prognostic gene signatures of ovarian cancer in order to tailor therapy and improve outcomes. This study demonstrates that molecular subtype identification depends on the ratio of tumor to stroma within the specimen. We show that the specific anatomic location of the biopsy may influence the proportion of stromal involvement and potentially the resulting gene expression pattern. It will be crucial for these factors to be taken into consideration when interpreting and reproducing ovarian cancer molecular subtypes and gene signatures derived using bulk tissue and single cells. Furthermore, it will be important to define the relative proportions of stromal cells and model their prognostic importance in the tumor microenvironment.
Inference of Nonlinear Spatial Subunits in Primate Retina with Spike-Triggered Clustering
Authors: Shah Nishal P. , Brackbill Nora , Rhoades Colleen E. , Kling Alexandra , Goetz Georges , Litke Alan , Sher Alexander , Simoncelli Eero P. , Chichilnisky E.J.
Published: December 2018

Integration of rectified synaptic inputs is a widespread nonlinear motif in sensory neuroscience. We present a novel method for maximum likelihood estimation of nonlinear subunits by soft-clustering spike-triggered stimuli. Subunits estimated from parasol ganglion cells recorded in macaque retina partitioned the receptive field into compact regions, likely representing bipolar cell inputs. Joint clustering with multiple RGCs revealed shared subunits in neighboring cells, producing a parsimonious population model. Closed-loop subunit validation was then performed by projecting white noise into the null space of the linear receptive field. Responses to these null stimuli were more accurately explained by a model with multiple subunits, and were stronger in OFF cells than ON cells. Presentation of natural stimuli containing jittering edges and textures also revealed greater response prediction accuracy with the subunit model. Finally, the generality of the approach was demonstrated by application to V1 data.
Anchorene is an endogenous diapocarotenoid required for anchor root formation in Arabidopsis
Authors: Jia Kun-Peng , Dickinson Alexandra J. , Mi Jianing , Cui Guoxin , Kharbatia Najeh M. , Guo Xiujie , Sugiono Erli , Aranda Manuel , Rueping Magnus , Benfey Philip N. , Al-Babili Salim
Published: December 2018

Arabidopsis root development is predicted to be regulated by yet unidentified carotenoid-derived metabolite(s). In this work, we screened known and putative carotenoid cleavage products and identified anchorene, a predicted carotenoid-derived dialdehyde (diapocarotenoid) that triggers anchor root development. Anchor roots are the least characterized type of root in Arabidopsis. They form at the root-shoot junction, particularly upon damage to the root apical meristem. Using Arabidopsis reporter lines, mutants and chemical inhibitors, we show that anchor roots originate from pericycle cells and that the development of this root type is auxin-dependent and requires carotenoid biosynthesis. Transcriptome analysis and treatment of auxin-reporter lines indicate that anchorene triggers anchor root development by modulating auxin homeostasis. Exogenous application of anchorene restored anchor root development in carotenoid-deficient plants, indicating that this compound is the carotenoid-derived signal required for anchor root development. Chemical modifications of anchorene led to a loss of anchor root promoting activity, suggesting that this compound is highly specific. Furthermore, we demonstrate by LC-MS analysis that anchorene is a natural, endogenous Arabidopsis metabolite. Taken together, our work reveals a new member of the family of carotenoid-derived regulatory metabolites and hormones.

Significance

Unknown carotenoid-derived compounds are predicted to regulate different aspects of plant development. Here, we characterize the development of anchor roots, the least characterized root type in Arabidopsis, and show that this process depends on auxin and requires a carotenoid-derived metabolite. We identified a presumed carotenoid-derivative, anchorene, as the likely, specific signal involved in anchor root formation. We further show that anchorene is a natural metabolite that occurs in Arabidopsis. Based on the analysis of auxin reporter lines and transcriptome data, we provide evidence that anchorene triggers the growth of anchor roots by modulating auxin homeostasis. Taken together, our work identifies a novel carotenoid-derived growth regulator with a specific developmental function.
Structure and electrostatic properties of the pyrimethamine–3,5-dihydroxybenzoic acid cocrystal in water solvent studied using transferred electron-density parameters
Authors: Faroque Muhammad Umer , Noureen Sajida , Mirza Shafaat Hussain , Tahir Muhammad Nawaz , Ahmed Maqsood
Published: December 2018

Pyrimethamine is an antimalarial drug. The cocrystal salt form of pyrimethamine with 3,5-dihydroxybenzoic acid in water solvent has been synthesized, namely 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 3,5-dihydroxybenzoate hemihydrate, C12H14ClN4+·C7H5O4−·0.5H2O. X-ray diffraction data were collected at room temperature. Refinement of the crystal structure was carried out using the classical Independent Atom Model (IAM), while the electrostatic properties were studied by transferring electron-density parameters from an electron-density database. The Cl atom was refined anharmonically. The results of both refinement methods were compared. Topological analyses were carried out using Bader's theory of Atoms in Molecules (AIM). The three-dimensional Hirshfeld surface analysis and the two-dimensional fingerprint maps of individual molecules revealed that the crystal structures are dominated by H...O/O...H and H...H contacts. Other close contacts are also present, including weak C...H/H...C contacts. Charge transfer between the pyrimethamine and 3,5-dihydroxybenzoic acid molecules results in a molecular assembly based on strong intermolecular hydrogen bonds. This is further validated by the calculation of the electrostatic potential based on transferred electron-density parameters. The current work proves the significance of the transferability principle in studying the electron-density-derived properties of molecules in cases where high-resolution diffraction data at low temperature are not available.
Energetic propane-1,3-diaminium and butane-1,4-diaminium salts of N,N′-dinitroethylenediazanide: syntheses, crystal structures and thermal properties
Authors: Roodt Gerhard T. , Uprety Bhawna , Levendis Demetrius C. , Arderne Charmaine
Published: December 2018

The acidity of the amine H atoms and the consequent salt formation ability of ethylenedinitramine (EDNA) were analyzed in an attempt to improve the thermal stability of EDNA. Two short-chain alkanediamine bases, namely propane-1,3-diamine and butane-1,4-diamine, were chosen for this purpose. The resulting salts, namely propane-1,3-diaminium N,N′-dinitroethylenediazanide, C3H12N2
2+·C2H4N4O4
2−, and butane-1,4-diaminium N,N′-dinitroethylenediazanide, C4H14N2
2+·C2H4N4O4
2−, crystallize in the orthorhombic space group Pbca and the monoclinic space group P21/n, respectively. The resulting salts display extensive hydrogen-bonding networks because of the presence of ammonium and diazenide ions in the crystal lattice. This results in an enhanced thermal stability and raises the thermal decomposition temperatures to 202 and 221 °C compared to 180 °C for EDNA. The extensive hydrogen bonding present also plays a crucial role in lowering the sensitivity to impact of these energetic salts.
Construction of a supramolecule comprising [2,3,9,10,16,17,23,24-octakis(2,6-dimethylphenoxy)phthalocyaninato]zinc(II) and (5,10,15,20-tetraphenylporphyrinato)zinc(II)
Authors: Makino Masatomo , Matsubayashi Kazuhiko , Kodama-Oda Yukiko , Imawaka Naoto , Mizuno Nobuhiro , Kumasaka Takashi , Yoshino Katsumi
Published: December 2018

The supramolecular features in the title compound, [2,3,9,10,16,17,23,24-octakis(2,6-dimethylphenoxy)phthalocyaninato]zinc(II) bis[(5,10,15,20-tetraphenylporphyrinato)zinc(II)] chloroform tetrasolvate, [Zn(C96H80N8O8)][Zn(C44H28N4)]2·4CHCl3 or [Zn(Pc)][Zn(TPP)]2·4CHCl3, result from a self-assembly of one molecule of [2,3,9,10,16,17,23,24-octakis(2,6-dimethylphenoxy)phthalocyaninato]zinc(II) (ZnPc) and two molecules of (5,10,15,20-tetraphenylporphyrinato)zinc(II) (ZnTPP). One half ZnPc, one ZnTPP and two chloroform molecules define the asymmetric unit, with the zinc(II) cation of ZnPc situated on an inversion centre. In the supramolecule, the central ZnPc moiety is sandwiched between two ZnTPPs moieties in a co-facial conformation with a π-conjugated system, leading to a nearly H-type aggregate with a distance of 3.4967 (5) Å between adjacent zinc sites. The ZnTPP units are slightly glided away to form a partial ecliptic arrangement. Each phenyl group of the TPP ligand is anchored above the N atom of the isoindole linker of the Pc ligand through weak C—H...N hydrogen bonds and is held into the crevice between the two dimethylphenoxy groups of phthalocyanine via van der Waals interactions. In the crystal, chloroform solvent molecules are situated between the supramolecules. There is another solvent-accessible void of 341 (2) Å3. The contribution of disordered solvent molecules situated in this void was removed from the diffraction data using SQUEEZE in PLATON [Spek (2015). Acta Cryst. C71, 9–18]. The given chemical formula and other crystal data do not consider this unknown solvent molecule(s).
Do no harm and do more good too: connecting the SDGs with business and human rights and political CSR theory
Authors: Buhmann Karin , Jonsson Jonas , Fisker Mette
Published: December 2018

Purpose

This paper aims to explain how companies can benefit from their human rights due diligence process to identify opportunities for sustainable development goals (SDGs) activities in an operationalisation of political corporate social responsibility (PCSR).

Design/methodology/approach

Combining PCSR, SDGs and business and human rights (BHR) literature, the paper develops an extension of the risk-based due diligence process described by the BHR literature, helping companies identify societal needs to which they may contribute in accordance with PCSR through engaging in the SDGs.

Findings

Companies can benefit from resources they already invest in due diligence to identify their adverse human rights impacts, by drawing on the insights gained on broader needs, including human rights, to which they may contribute. This can help them develop appropriate interventions to address local needs and advance their moral legitimacy through assisting in SDG-relevant fulfilment of human rights.

Research limitations/implications

The paper provides theory-based guidance on how companies can assess their capacity for contributing societal value through human rights-oriented SDG interventions. Future empirical research may explore how companies apply the extended due diligence process to assess needs and determine relevant actions.

Practical implications

The paper offers a principle-based analytical approach for integrating the “do no harm” imperative of BHR theory with PCSR’s call for business assistance in the delivery of public goods and the SDGs’ call for business action to “do good’.

Social implications

This paper enables enhanced business implementation of the SDGs in line with PCSR and human rights theory, especially the emergent field of business and human rights.

Originality/value

This study gives theory-based guidance for companies for SDG contributions based on innovative combination of literatures.
A data-driven neural network architecture for sentiment analysis
Authors: Çano Erion , Morisio Maurizio
Published: December 2018

Purpose

The fabulous results of convolution neural networks in image-related tasks attracted attention of text mining, sentiment analysis and other text analysis researchers. It is, however, difficult to find enough data for feeding such networks, optimize their parameters, and make the right design choices when constructing network architectures. The purpose of this paper is to present the creation steps of two big data sets of song emotions. The authors also explore usage of convolution and max-pooling neural layers on song lyrics, product and movie review text data sets. Three variants of a simple and flexible neural network architecture are also compared.

Design/methodology/approach

The intention was to spot any important patterns that can serve as guidelines for parameter optimization of similar models. The authors also wanted to identify architecture design choices which lead to high performing sentiment analysis models. To this end, the authors conducted a series of experiments with neural architectures of various configurations.

Findings

The results indicate that parallel convolutions of filter lengths up to 3 are usually enough for capturing relevant text features. Also, max-pooling region size should be adapted to the length of text documents for producing the best feature maps.

Originality/value

Top results the authors got are obtained with feature maps of lengths 6–18. An improvement on future neural network models for sentiment analysis could be generating sentiment polarity prediction of documents using aggregation of predictions on smaller excerpt of the entire text.
Novel reliable routing method for engineering of internet of vehicles based on graph theory
Authors: Zhang De-gan , Tang Ya-meng , Cui Yu-ya , Gao Jing-xin , Liu Xiao-huan , Zhang Ting
Published: December 2018

Purpose

The communication link in the engineering of Internet of Vehicle (IOV) is more frequent than the communication link in the Mobile ad hoc Network (MANET). Therefore, the highly dynamic network routing reliability problem is a research hotspot to be solved.

Design/methodology/approach

The graph theory is used to model the MANET communication diagram on the highway and propose a new reliable routing method for internet of vehicles based on graph theory.

Findings

The expanded graph theory can help capture the evolution characteristics of the network topology and predetermine the reliable route to promote quality of service (QoS) in the routing process. The program can find the most reliable route from source to the destination from the MANET graph theory.

Originality/value

The good performance of the proposed method is verified and compared with the related algorithms of the literature.