bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene
Authors: Akerman Ildem , Maestro Miguel Angel , Grau Vane , García-Hurtado Javier , Mittler Gerhard , Ravassard Philippe , Piemonti Lorenzo , Ferrer Jorge
Published: June 2020

Despite the central role of chromosomal context in gene transcription, human noncoding DNA variants are generally studied outside of their endogenous genomic location. This poses major limitations to understand the true consequences of causal regulatory variants. We focused on a cis-regulatory mutation (c.-331C>G) in theINSgene promoter that is recurrently mutated in unrelated patients with recessive neonatal diabetes. We created mice in which a ~3.1 kb humanINSupstream region carrying −331C or −331G alleles replaced the orthologous mouseIns2region. This human sequence drove cell-specific transcription in mice. It also recapitulated poised chromatin during pancreas development and active chromatin in differentiated β-cells. The c.-331C>G mutation, however, blocked active chromatin formation in differentiated b-cells. We further show that another neonatal diabetes gene product, GLIS3, had a singular pioneer-like ability to activateINSchromatin in non-pancreatic cells, which was hampered by the c.-331C>G mutation. Thisin vivoanalysis of human regulatory defects, therefore, uncoveredcisandtranscomponents of a mechanism that is essential to activate the endogenousINSgene.
Nasal immunization with the C-terminal domain of BclA3 induced specific IgG production and attenuated disease symptoms in mice infected withClostridioides difficilespores
Authors: Maia Ana Raquel , Reyes-Ramírez Rodrigo , Pizarro-Guajardo Marjorie , Saggese Anella , Ricca Ezio , Baccigalupi Loredana , Paredes-Sabja Daniel
Published: June 2020

Clostridioides difficileis a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance a strong immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets of new therapeutic treatments. In this context, spore surface proteins ofC. difficile, are potential antigens for the development of vaccines targetingC. difficilespores. Here we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced inEscherichia coliand tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTDwas also exposed on the surface ofB. subtilisspores, a well-established mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTDinduced antibody production in mice and attenuated some CDI symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization route need to be optimized, our results suggest BclA3CTDas a potentially effective antigen to develop a new vaccination strategy targetingC. difficilespores.
Transfer learning between preclinical models and human tumors identifies conserved NK cell activation signature in anti-CTLA-4 responsive tumors
Authors: Davis-Marcisak Emily F. , Fitzgerald Allison A. , Kessler Michael D. , Danilova Ludmila , Jaffee Elizabeth M. , Zaidi Neeha , Weiner Louis M. , Fertig Elana J.
Published: June 2020

Background

Tumor response to therapy is affected by both the cell types and the cell states present in the tumor microenvironment. This is true for many cancer treatments, including notably immune checkpoint inhibitors (ICIs). While it is well-established that ICIs promote T cell activation, their broader impact on other intratumoral immune cells is unclear; this information is needed to identify new mechanisms of action and improve ICI efficacy. Many preclinical studies have begun to use single cell analysis to delineate therapeutic responses in individual immune cell types within tumors. One major limitation to this approach is that therapeutic mechanisms identified in preclinical models have failed to fully translate to human disease, restraining efforts to improve ICI efficacy in bench to bedside research.

Method

We previously developed a computational transfer learning approach to identify shared biology between independent high-throughput single-cell RNA sequencing (scRNA-seq) datasets. In the present study, we test this framework’s ability to identify conserved and clinically relevant transcriptional changes in complex tumor scRNA-seq data and further expand its application beyond comparison of scRNA-seq datasets into comparison of scRNA-seq datasets with additional data types such as bulk RNA-seq and mass cytometry.

Results

We found a conserved signature of NK cell activation in anti-CTLA-4 responsive mice and human tumors. In human melanoma, we found that the NK cell activation signature correlates with longer overall survival and is predictive of anti-CTLA-4 (ipilimumab) response. Additional molecular approaches to confirm the computational findings demonstrated that human NK cells express CTLA-4 and bind anti-CTLA-4 independent of the antibody binding receptor (FcR), and that similar to T cells, CTLA-4 expression by NK cells is modified by cytokine-mediated and target cell-mediated NK cell activation.

Conclusions

These data demonstrate the ability of our transfer learning approach to identify cell state transitions conserved in preclinical models and human tumors. This approach can be adapted to explore many immuno-oncology questions, enhancing bench to bedside research and enabling better understanding and treatment of disease.

Graphical Abstract
TMEM106BandCPOXare genetic determinants of cerebrospinal fluid Alzheimer’s disease biomarker levels
Authors: Hong Shengjun , Dobricic Valerija , Bos Isabelle , Vos Stephanie J. B. , Prokopenko Dmitry , Tijms Betty M. , Andreasson Ulf , Blennow Kaj , Vandenberghe Rik , Gabel Silvy , Scheltens Philip , Teunissen Charlotte E. , Engelborghs Sebastiaan , Frisoni Giovanni , Blin Olivier , Richardson Jill C. , Bordet Regis , Lleó Alberto , Alcolea Daniel , Popp Julius , Clark Christopher , Peyratout Gwendoline , Martinez-Lage Pablo , Tainta Mikel , Dobson Richard J. B. , Legido-Quigley Cristina , Sleegers Kristel , Van Broeckhoven Christine , Tanzi Rudolph E , ten Kate Mara , Wittig Michael , Franke Andre , Barkhof Frederik , Lovestone Simon , Streffer Johannes , Zetterberg Henrik , Visser Pieter Jelle , Bertram Lars
Published: June 2020

Background

Neurofilament light (NF-L), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are utilized as biomarkers for Alzheimer’s disease (AD), to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Here we performed genome-wide association study (GWAS) analyses using all three biomarkers as outcome.

Methods

DNA and cerebrospinal fluid (CSF) samples originated from the European Medical Information Framework AD Multimodal Biomarker Discovery (EMIF-AD MBD) study. Overlapping genotype/phenotype data were available for n=671 (NF-L), 677 (YKL-40), and 672 (Ng) individuals. GWAS analyses applied linear regression models adjusting for relevant covariates.

Findings

We identify novel genome-wide significant associations with markers inTMEM106Band CSF levels of NF-L. Additional novel signals were observed with DNA variants inCPOXand CSF levels of YKL-40. Lastly, we confirmed previous work suggesting that YKL-40 levels are regulated bycisprotein quantitative trait loci (pQTL) inCHI3L1.

Interpretation

Our study provides important new insights into the genetic architecture underlying inter-individual variation in all three tested AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
Alteration of Substrate-Induced Conformational Changes ofEscherichia coliMelibiose Permease by Mutating Arg149
Authors: Lin Yibin
Published: June 2020

Fourier transform infrared difference spectroscopy and fluorescence spectroscopic techniques have been used to obtain information about substrate-induced structural changes of the melibiose permease mutant R149C, compared with the Cys-less, which were reconstituted into liposomes. ATR-FTIR evidences show that Na+-induced difference spectra of R149C and Cys-less are similar. However, Na+induces some new peaks for R149C mutant permease. This means that replacement of Arg-149 by Cys may affect the structure of MelB, and then affect the binding of Na+. Melibiose-induced difference spectra of R149C in the presence of Na+show some peaks in the amide I region not seen in Cys-less, corresponding to turns, β-sheets, α-helix changes. This suggests that R149C mutant permease undergo some different secondary structure changes compared to Cys-less mutant permease, when binding melibiose. Comparison of the permease intrinsic fluorescence variations of R149C and Cys-less indicate that there are similar substrate binding properties between R149C and Cys-less. When analyzing the effects of different sugars it appears that the R149C mutant is more sensitive to the sugar. All these data indicate that replacement of Arg-149 by Cys will affect Na+and sugar binding, and enhance the selectivity and sensitivity to sugars.
UPMaBoSS: a novel framework for dynamic cell population modeling
Authors: Stoll Gautier , Naldi Aurélien , Noël Vincent , Viara Eric , Barillot Emmanuel , Kroemer Guido , Thieffry Denis , Calzone Laurence
Published: June 2020

One of the aims of mathematical modeling is to understand and simulate the effects of biological perturbations and suggest ways to intervene and reestablish proper cell functioning. However, it remains a challenge, especially when considering the dynamics at the level of a cell population, with cells dying, dividing and interacting. Here, we introduce a novel framework for the dynamical modelling of cell populations packaged into a dedicated tool, UPMaBoSS. We rely on the preexisting tool MaBoSS, which enables probabilistic simulations of cellular networks, and add a novel layer to account for cell interactions and population dynamics. We illustrate our methodology by means of a case study dealing with TNF-induced cell death. Interestingly, the simulation of cell population dynamics with UPMaBoSS reveals a mechanism of resistance triggered by TNF treatment. This appoach can be applied to diverse models of cellular networks, for example to study the impact of ligand release or drug treatments on cell fate decisions, such as commitment to proliferation, differentiation, apoptosis, etc. Relatively easy to encode, UPMaBoSS simulations require only moderate computational power and execution time.

To ease the reproduction of simulations, we provide several Jupyter notebooks that can be accessed within a new release of the CoLoMoTo Docker image, which contains all required software and the example models.
Implementation of Genomic Variant Calling: A Novel Approach
Authors: Kumar Ambarish , Bangash Ali Haider
Published: June 2020

Genomics has emerged as one of the major sources of big data. The task of augmenting data-driven challenges into bioinformatics can be met using technologies of parallel and distributed computing. GATK4 tools for genomic variants detection are enabled for high-performance computing platforms – SPARK Map Reduce framework. GATK4+WDL+CROMWELL+SPARK+DOCKER is proposed as the way forward in achieving automation, reproducibility, reusability, customization, portability and scalability. SPARK-based tools perform equally well in genomic variants detection with that of standard implementation of GATK4 tools over a command-line interface. Implementation of workflows over cloud-based high-performance computing platforms will enhance usability and will be a way forward in community research and infrastructure development for genomic variant discovery.
Dense Computer Replica of Cortical Microcircuits Unravels Cellular Underpinnings of Auditory Surprise Response
Authors: Amsalem Oren , King James , Reimann Michael , Ramaswamy Srikanth , Muller Eilif , Markram Henry , Nelken Israel , Segev Idan
Published: June 2020

The nervous system is notorious for its strong response evoked by a surprising sensory input, but the biophysical and anatomical underpinnings of this phenomenon are only partially understood. Here we utilizedin-silicoexperiments of a biologically-detailed model of a neocortical microcircuit to study stimulus specific adaptation (SSA) in the auditory cortex, whereby the neuronal response adapts significantly for a repeated (“expected”) tone but not for a rare (“surprise”) tone. SSA experiments were mimicked by stimulating tonotopically-mapped thalamo-cortical afferents projecting to the microcircuit; the activity of these afferents was modeled based on ourin-vivorecordings from individual thalamic neurons. The modeled microcircuit expressed naturally many experimentally-observed properties of SSA, suggesting that SSA is a general property of neocortical microcircuits. By systematically modulating circuit parameters, we found that key features of SSA depended on synergistic effects of synaptic depression, spike frequency adaptation and recurrent network connectivity. The relative contribution of each of these mechanisms in shaping SSA was explored, additional SSA-related experimental results were explained and new experiments for further studying SSA were suggested.
RapidMycobacterium tuberculosisspoligotyping from uncorrected long reads using Galru
Authors: Page Andrew J. , Alikhan Nabil-Fareed , Strinden Michael , Le Viet Thanh , Skvortsov Timofey
Published: June 2020

Spoligotyping ofMycobacterium tuberculosisprovides a subspecies classification of this major human pathogen. Spoligotypes can be predicted from short read genome sequencing data; however, no methods exist for long read sequence data such as from Nanopore or PacBio. We present a novel software package Galru, which can rapidly detect the spoligotype of aMycobacterium tuberculosissample from as little as a single uncorrected long read. It allows for near real-time spoligotyping from long read data as it is being sequenced, giving rapid sample typing. We compare it to the existing state of the art software and find it performs identically to the results obtained from short read sequencing data. Galru is freely available fromhttps://github.com/quadram-institute-bioscience/galruunder the GPLv3 open source licence.
Deep learning approach for automated cancer detection and tumor proportion score estimation of PD-L1 expression in lung adenocarcinoma
Authors: Wu J. , Liu C. , Liu X. , Sun W. , Li L. , Zhang Y. , Zhang J. , Wang H. , Liu X. , Yang X. , Huang X. , Lin D. , Ling S.
Published: June 2020

Background

This study proposed a computational method to detect the cancer areas and calculate the tumor proportion score (TPS) of PD-L1 immunohistochemistry (IHC) expression for lung adenocarcinoma based on deep learning and transfer learning.

Patients and methods

PD-L1 22C3 and SP142 IHC slides of lung adenocarcinoma samples on digitized whole-slide images (WSI) database were employed. We build a deep convolutional neural network (DCNN) to automatically segment cancer regions. TPS was calculated based on segmented areas and then compared with the interpretations of pathologists.

Results

We trained a DCNN model based on 22C3 dataset and fine-tuned it with SP142 dataset. We obtain a robust performance on cancer region detection on both datasets, with a sensitivity of 93.36% (22C3) and 92.80% (SP142) and a specificity of 93.97% (22C3) and 89.25% (SP142). With all the coefficient of determinations larger than 0.9 and Fleiss’ and Cohen’s Kappa larger than 0.8 (between mean or median of pathologists and TPS calculated by our method), we also found out the strong correlation between the TPS estimated by our computational method and estimation from multiple pathologists’ interpretations of 22C3 and SP142 respectively.

Conclusion

We provide an AI method to efficiently predict cancer region and calculate TPS in PD-L1 IHC slide of lung adenocarcinoma on two different antibodies. It demonstrates the potential of using deep learning methods to conveniently access PD-L1 IHC status. In the future, we will further validate the AI tool for automated scoring PD-L1 in large volume samples.
High temperatures drive offspring mortality in a cooperatively breeding bird
Authors: Bourne Amanda R. , Cunningham Susan J. , Spottiswoode Claire N. , Ridley Amanda R.
Published: June 2020

An improved understanding of life history responses to current environmental variability is required to predict species-specific responses to anthopogenic climate change. Previous research has suggested that cooperation in social groups may buffer individuals against some of the negative effects of unpredictable climates. We use a 15-year dataset on a cooperative-breeding arid-zone bird, the southern pied babbler Turdoides bicolor, to test i) whether environmental conditions and group size correlate with survival of young during three development stages (egg, nestling, fledgling), and ii) whether group size mitigates the impacts of adverse environmental conditions on reproductive success. Exposure to high mean daily maximum temperatures (mean Tmax) during early development was associated with reduced survival probabilities of young in all three development stages. No young survived when mean Tmax > 38°C across all group sizes. Low reproductive success at high temperatures has broad implications for recruitment and population persistence in avian communities given the rapid pace of advancing climate change. That impacts of high temperatures were not moderated by group size, a somewhat unexpected result given prevailing theories around the influence of environmental uncertainty on the evolution of cooperation, suggests that cooperative breeding strategies are unlikely to be advantageous in the face of rapid anthropogenic climate change.
Cognitive tests that identify high risk of conversion to dementia in Parkinson’s disease
Authors: Myall D.J. , Horne K-L. , MacAskill M.R. , Livingston L. , Pitcher T.L. , Melzer T.R. , Geurtsen G.J. , Anderson T.J , Dalrymple-Alford J.C.
Published: June 2020

Background

People with Parkinson’s disease who meet criteria for mild cognitive impairment are at increased risk of dementia. It is not known which tests are more effective than others for identifying the risk of dementia.

Methods

At baseline, we assessed performance on 21 neuropsychological test measures spanning five cognitive domains in a prospective longitudinal study of 196 non-demented people with Parkinson’s. Elastic net logistic regression was used to identify a pair of tests from each cognitive domain that best predicted conversion to dementia over a four year period. The optimal tests most predictive of dementia were also determined when mild cognitive impairment was derived from a logistic-regression classifier that used all 21 measures simultaneously.

Results

With two tests per domain, the resulting mild cognitive impairment group (N=87/196) captured 44 of 51 individuals who converted to PDD; the out-of-sample relative risk of PDD was 8.0 (95% CI [4.3, 24]), similar to that achieved with the full battery (N=102/196, capturing 45/51, relative risk = 6.9). When selecting tests regardless of domain, there was strong evidence for three tests: Trail Making part B (Executive), Map Search (Attention), and CVLT-II word list acquisition (Episodic Memory). The logistic-regression classifier achieved an out-of-sample AUC of 0.90 [0.84, 0.96] and a relative risk of 12 [6, 39].

Conclusions

An abbreviated selection of neuropsychological tests can identify non-demented patients who have a high relative risk of progression to PDD.
ON THE UNCERTAINTY ABOUT HERD IMMUNITY LEVELS REQUIRED TO STOP COVID-19 EPIDEMICS
Authors: Gianola Daniel
Published: June 2020

COVID-19 evolved into a pandemic in 2020 affecting more than 150 countries. Given the absence of a vaccine, discussion has taken place on the strategy of allowing the virus to spread in a population, to increase population “herd immunity”. Knowledge of the minimum proportion of a population required to have recovered from COVID-19 infection in order to attain “herd” immunity, Pcrit, is important for formulating epidemiological policy. A method for measuring uncertainty about Pcrit based on a widely used package, EpiEstim, is derived. The procedure is illustrated using data from twelve countries at two early times during the COVID-19 epidemic. It is shown that simple plug-in measures of confidence on estimates of Pcrit are misleading, but that a full characterization of statistical uncertainty can be derived from EpiEstim, which reports percentiles only. Because of the important levels of uncertainty, it is risky to design epidemiological policy based on guidance provided by a single point estimate.
A Highly Sensitive Fluorogenic Assay for the Detection of Nephrotoxin-Induced Oxidative Stress in Live Cells and Renal Tissue
Authors: Mukherjee Kamalika , Chio Tak Ian , Gu Han , Sackett Dan L. , Bane Susan L. , Sever Sanja
Published: June 2020

A common manifestation of drug toxicity is kidney injury or nephrotoxicity. Nephrotoxicity frequently leads to termination of clinical trials and drug withdrawals, which jeopardize biomedical progress. Efficient preclinical screening platforms capable of detecting mild signs of kidney damage, which may elicit considerable toxic responsein vivo,are essential. A common manifestation of chemical toxicity is oxidative modification of cellular biomolecules. Therefore, we have developed a facile biomolecule carbonyl detection assay that well surpasses the sensitivity of the standard assays in identifying modest forms of renal injury. Using a novel fluorogenic sensor, TFCH, we have demonstrated the applicability of the assay in live kidney cells and in renal tissue. This robust assay can help inform preclinical decisions to recall unsafe drug candidates. Application of this assay in identifying and analyzing diverse pathologies is envisioned.
A genetic history of the pre-contact Caribbean
Authors: Fernandes Daniel M. , Sirak Kendra A. , Ringbauer Harald , Sedig Jakob , Rohland Nadin , Cheronet Olivia , Mah Matthew , Mallick Swapan , Olalde Iñigo , Culleton Brendan J. , Adamski Nicole , Bernardos Rebecca , Bravo Guillermo , Broomandkhoshbacht Nasreen , Callan Kimberly , Candilio Francesca , Demetz Lea , Carlson Kellie Sara Duffett , Eccles Laurie , Freilich Suzanne , Lawson Ann Marie , Mandl Kirsten , Marzaioli Fabio , Oppenheimer Jonas , Özdogan Kadir T. , Schattke Constanze , Schmidt Ryan , Stewardson Kristin , Terrasi Filippo , Zalzala Fatma , Antúnez Carlos Arredondo , Canosa Ercilio Vento , Colten Roger , Cucina Andrea , Genchi Francesco , Kraan Claudia , Pastina Francesco La , Lucci Michaela , Maggiolo Marcio Veloz , Marcheco-Teruel Beatriz , Maria Clenis Tavarez , Martinez Cristian , París Ingeborg , Pateman Michael , Simms Tanya , Sivoli Carlos Garcia , Vilar Miguel , Kennett Douglas J. , Keegan William F. , Coppa Alfredo , Lipson Mark , Pinhasi Ron , Reich David
Published: June 2020

Humans settled the Caribbean ~6,000 years ago, with intensified agriculture and ceramic use marking a shift from the Archaic Age to the Ceramic Age ~2,500 years ago. To shed new light on the history of Caribbean people, we report genome-wide data from 184 individuals predating European contact from The Bahamas, Cuba, Hispaniola, Puerto Rico, Curaçao, and northwestern Venezuela. A largely homogeneous ceramic-using population most likely originating in northeastern South America and related to present-day Arawak-speaking groups moved throughout the Caribbean at least 1,800 years ago, spreading ancestry that is still detected in parts of the region today. These people eventually almost entirely replaced Archaic-related lineages in Hispaniola but not in northwestern Cuba, where unadmixed Archaic-related ancestry persisted into the last millennium. We document high mobility and inter-island connectivity throughout the Ceramic Age as reflected in relatives buried ~75 kilometers apart in Hispaniola and low genetic differentiation across many Caribbean islands, albeit with subtle population structure distinguishing the Bahamian islands we studied from the rest of the Caribbean and from each other, and long-term population continuity in southeastern coastal Hispaniola differentiating this region from the rest of the island. Ceramic-associated people avoided close kin unions despite limited mate pools reflecting low effective population sizes (2Ne=1000-2000) even at sites on the large Caribbean islands. While census population sizes can be an order of magnitude larger than effective population sizes, pan-Caribbean population size estimates of hundreds of thousands are likely too large. Transitions in pottery styles show no evidence of being driven by waves of migration of new people from mainland South America; instead, they more likely reflect the spread of ideas and people within an interconnected Caribbean world.
Comprehensive evaluation of deconvolution methods for human brain gene expression
Authors: Sutton Gavin J , Poppe Daniel , Simmons Rebecca K , Walsh Kieran , Nawaz Urwah , Lister Ryan , Gagnon-Bartsch Johann A , Voineagu Irina
Published: June 2020

Gene expression measurements, similar to DNA methylation and proteomic measurements, are influenced by the cellular composition of the sample analysed. Deconvolution of bulk transcriptome data aims to estimate the cellular composition of a sample from its gene expression data, which in turn can be used to correct for composition differences across samples. Although a multitude of deconvolution methods have been developed, it is unclear whether their performance is consistent across tissues with different complexities of cellular composition. The human brain is unique in its transcriptomic diversity, expressing the highest diversity of alternative splicing isoforms and non-coding RNAs. It comprises a complex mixture of cell-types including transcriptionally similar sub-types of neurons, which undergo gene expression changes in response to neuronal activity. However, a comprehensive assessment of the accuracy of transcriptome deconvolution methods on human brain data is currently lacking.

Here we carry out the first comprehensive comparative evaluation of the accuracy of deconvolution methods for human brain transcriptome data, and assess the tissue-specificity of our key observations by comparison with transcriptome data from human pancreas and heart.

We evaluate 8 transcriptome deconvolution approaches, covering all main classes: 4 partial deconvolution methods, each applied with 9 different cell-type signatures, 2 enrichment methods, and 2 complete deconvolution methods. We test the accuracy of cell-type estimates usingin silicomixtures of single-cell RNA-seq data, mixtures of neuronal and glial RNA, as well as nearly 2,000 human brain samples.

Our results bring several important insights into the performance of transcriptome deconvolution:(a)We find that cell-type signature data has a stronger impact on brain deconvolution accuracy than the choice of method.(b)We demonstrate that biological factors influencing brain cell-type signature data (e.g.brain region,in vitrocell culturing), have stronger effects on the deconvolution outcome than technical factors (e.g.RNA sequencing platform).(c)We find that partial deconvolution methods outperform complete deconvolution methods on human brain data. To facilitate wider implementation of correction for cellular composition, we develop a webtool that implements the best performing methods, and is available athttps://voineagulab.shinyapps.io/BrainDeconvShiny/.
An enormousParis polyphyllagenome sheds light on genome size evolution and polyphyllin biogenesis
Authors: Li Jing , Lv Meiqi , Du Lei , Yunga A , Hao Shijie , Zhang Yaolei , Zhang Xingwang , Guo Lidong , Gao Xiaoyang , Deng Li , Zhang Xuan , Shi Chengcheng , Guo Fei , Liu Ruxin , Fang Bo , Su Qixuan , Hu Xiang , Su Xiaoshan , Lin Liang , Liu Qun , Wang Yuehu , Qin Yating , Zhang Wenwei , Li Shengying , Liu Changning , Li Heng
Published: June 2020

The monocot family Melanthiaceae with varying genome sizes in a range of 230-fold is an ideal model to study the genome size fluctuation in plants. Its family memberParisgenus demonstrates an evolutionary trend of bearing huge genomes characterized by an average c-value of 49.22 pg. Here, we report a 70.18 Gb genome assembly out of the 82.55 Gb genome ofParis polyphyllavar. yunnanensis (PPY), which represents the biggest sequenced genome to date. We annotate 69.53% repetitive sequences in this genome and 62.50% of which are long-terminal repeat (LTR) transposable elements. Further evolution analysis indicates that the giant genome likely results from the joint effect of common and species-specific expansion of different LTR superfamilies, which might contribute to the environment adaptation after speciation. Moreover, we identify the candidate pathway genes for the biogenesis of polyphyllins, the PPY-specific medicinal saponins, by complementary approaches including genome mining, comprehensive analysis of 31 next-generation RNA-seq data and 55.23 Gb single-molecule circular consensus sequencing (CCS) RNA-seq reads, and correlation of the transcriptome and phytochemical data of five different tissues at four growth stages. This study not only provides significant insights into plant genome size evolution, but also paves the way for the following polyphyllin synthetic biology.
Low convergent validity of [11C]raclopride binding in extrastriatal brain regions: a PET study of within-subject correlations with [11C]FLB 457
Authors: Freiburghaus Tove , Svensson Jonas E. , Matheson Granville J. , Plavén-Sigray Pontus , Lundberg Johan , Farde Lars , Cervenka Simon
Published: June 2020

Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test-retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [11C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centres. Instead, the medium affinity radioligand [11C]raclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of [11C]raclopride in extrastriatal regions in a pharmacological competition study. Here, we utilise a data set of 16 healthy control subjects examined with both [11C]raclopride and [11C]FLB 457 to assess the correlation in binding potential (BPND) in extrastriatal brain regions. BPND was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BPND values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between [11C]raclopride and [11C]FLB 457 BPNDextrastriatally (Pearson’s R: 0.30 - 0.56), in contrast to very strong correlations between repeated [11C]FLB 457 measurements (Pearson’s R: 0.82 - 0.98). These results are likely related to low signal to noise ratio of [11C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [11C]raclopride should be interpreted with caution.
A miR-124-mediated post-transcriptional mechanism controlling the cell fate switch of astrocytes to induced-neurons
Authors: Papadimitriou Elsa , Koutsoudaki Paraskevi N. , Thanou Irini , Karamitros Timokratis , Karagkouni Dimitra , Chroni-Tzartou Dafni , Gaitanou Maria , Gkemisis Christos , Margariti Maria , Xingi Evangelia , Tzartos Socrates J. , Hatzigeorgiou Artemis G. , Thomaidou Dimitra
Published: June 2020

The miRNA miR-124 has been employed supplementary to neurogenic TFs and other miRNAs to enhance direct neurogenic conversion by suppressing multiple non-neuronal targets. Aim of the study was to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced-neurons (iNs) on its own and elucidate its independent mechanism of reprogramming action. Our data show that miR-124 is a potent driver of the reprogramming switch of astrocytes towards an immature neuronal fate, by directly targeting the RNA-binding protein Zfp36l1 implicated in ARE-mediated mRNA decay and subsequently de-repressing Zfp36l1 neurogenic interactome. To this end miR-124 contribution in iNs’ production largely recapitulates endogenous neurogenesis pathways, being further enhanced upon addition of the neurogenic compound ISX9, which greatly improves both miR-124-induced reprogramming efficiency and iNs’ functional maturation. Importantly, miR-124 is potent to guide direct conversion of reactive astrocytes to immature iNs of cortical identityin vivofollowing cortical trauma, confirming its ‘master’ reprogramming capacity within the injured cortical microenvironment, while ISX9 supplementation confers a survival advantage to newly produced iNs.
The Inoue Method for Preparation and Transformation of Competent Escherichia coli: “Ultracompetent” Cells
Authors: Green Michael R. , Sambrook Joseph
Published: June 2020

This protocol differs from other transformation procedures in that the bacterial culture is grown at 18°C rather than the conventional 37°C. Otherwise, the protocol is unremarkable and follows a fairly standard course. Under standard laboratory conditions, efficiencies of 1 × 108 to 3 × 108 transformed colonies/µg of plasmid DNA are typical.
Purification of Fusion Proteins by Affinity Chromatography on Glutathione Resin
Authors: Kielkopf Clara L. , Bauer William , Urbatsch Ina L.
Published: June 2020

Fusion proteins that contain a glutathione S-transferase (GST) moiety can be purified to near homogeneity by affinity chromatography on glutathione-linked resins. Glutathione immobilized on a chromatography matrix, such as agarose or Sepharose, acts as a substrate for the GST moiety of fusion proteins. Contaminating proteins are washed away, and the bound GST fusion proteins are then readily displaced from the resin by elution with buffers containing free glutathione.
Immunoblotting
Authors: Litovchick Larisa
Published: June 2020

Immunoblotting allows detection of a protein antigen immobilized on the protein-retaining membrane support such as nitrocellulose or polyvinylidene fluoride (PVDF). The detection of the protein of interest relies on the binding of an antibody that specifically recognizes the protein of interest exposed on the membrane. The protein of interest can be purified or mixed with other proteins as in cell or tissue extracts. Usually immunoblotting combines the resolution of proteins by gel electrophoresis with immunochemical detection and is referred to as “western blotting.” Immunoblotting can be used to determine the presence and the steady-state level of the protein of interest in the sample, its relative molecular weight, and the distribution of the protein between cellular fractions. Immunoblotting can be performed using the antibodies raised against synthetic peptide antigens modified to mimic posttranslational modifications of proteins, such as phosphorylation and acetylation, to study these modifications in the protein of interest in vivo. When antibodies against the protein of interest are not available, immunoblotting can be performed using antibodies that specifically recognize the recombinant epitope tags (hemagglutinin [HA]-, Flag-, cMyc-, or glutathione-S-transferase [GST]) fused to the protein of interest using recombinant DNA techniques. Immunoblotting has a variety of research, clinical, and forensic medicine applications. It is also one of the standard techniques for characterization of antibodies from different samples of polyclonal sera or hybridoma supernatants.
Novel phasing method using the origin-free modulus sum function expressed in terms of the absolute electron density
Authors: Rius Jordi
Published: June 2020

The origin-free modulus sum function S
M refines the set Φ of phases of the structure factors by maximizing the coincidence between the experimental origin-free modulus function and the calculated one in terms of the ρ(Φ)2 density function [Rius, J. (1993). Acta Cryst. A49, 406–409]. Maximization is normally achieved through the recursive application of a Fourier-based algorithm. The purpose of the present study is: (i) to show that ρ(Φ)2 can be replaced by |ρ(Φ)| in S
M; (ii) to illustrate the viability of the corresponding phasing algorithm with experimental data.
Spherical-wave X-ray dynamical diffraction Talbot effect inside a crystal
Authors: Balyan Minas K. , Levonyan Levon V. , Trouni Karapet G.
Published: June 2020

Two-wave dynamical diffraction of an X-ray spherical wave in a crystal, when the wave passes through an object with a periodic amplitude transmission function, is considered. The behavior of the diffracted wave (spherical-wave Talbot effect) in the crystal is investigated. The Talbot effect inside the crystal is accompanied by the focusing effect and the pendulum effect. Peculiarities of the effect before the focus point, in the focusing plane and in the region after the focus point inside the crystal are revealed. An expression is found for the Talbot depth and the spherical-wave Talbot effect in these three regions is investigated. The spherical-wave dynamical diffraction Talbot effect in a crystal is compared with the classical spherical-wave Talbot effect and also with spherical-wave effects inside the crystal without a periodic object.
Design of H_/H∞ fault detection observer for closed-loop nonlinear system with disturbance
Authors: Chen Zhengquan , Han Lu , Hou Yandong
Published: June 2020

Purpose

This paper proposes a novel method of fault detection, which is based on H_/H∞ Runge–Kutta observer and an adaptive threshold for a class of closed-loop non-linear systems. The purpose of this paper is to improve the rapidity and accuracy of fault detection.

Design/methodology/approach

First, the authors design the H_/H∞ Runge–Kutta fault detection observer, which is used as a residual generator to decouple the residual from the input. The H_ performance index metric in the specified frequency domain is used to describe how sensitive the residual to the fault. The H∞ norm is used to describe the residual robustness to the external disturbance of the systems. The residual generator is designed to achieve the best tradeoff between robustness against unknown disturbances but sensitivity to faults, thus realizing the accurate detection of the fault by suppressing the influence of noise and disturbance on the residual. Next, the design of the H_/H∞ fault detection observer is transformed into a convex optimization problem and solved by linear matrix inequality. Then, a new adaptive threshold is designed to improve the accuracy of fault detection.

Findings

The effectiveness and correctness of the method are tested in simulation experiments.

Originality/value

This paper presents a novel approach to improve the accuracy and rapidity of fault detection for closed-loop non-linear system with disturbances and noise.
Gender of the family head and food insecurity in urban and rural Nigeria
Authors: Nwaka Ikechukwu Darlington , Akadiri Seyi Saint , Uma Kalu Ebi
Published: June 2020

Purpose

Are the urban and rural male-headed households (MHHs) or female-headed households (FHHs) poorer and food (in)secured? Such question is of very important policy concern in the drive towards achieving the first two of the Sustainable Development Goals.

Design/methodology/approach

This paper uses 2010–2012 waves of General Household Survey cross-sectional panel data to investigate food (in)security and poverty dynamics amongst MHHs and FHHs in Nigeria, with particular attention to rural and urban dimensions.

Findings

Applying the tobit and probit regressions while controlling for poverty and other household characteristics, we observed that female-headed families are more vulnerable to higher incidences of food insecurity than male-headed ones and with an overall significant urban food security advantage compared to rural areas. Comparing urban and rural results in terms of land access rights, urban food insecurity manifests more amongst urban FHHs non–Agri-land owners which however falls as food expenditure rises. However, the rise in per capita food consumption, agricultural characteristics and years of schooling reduces the likelihood of food insecurity for all households.

Originality/value

This study, therefore, offers relevant policy inputs towards addressing poverty and food insecurity in a typical developing country such as Nigeria.
A retrospective overview of the Asian Review of Accounting during 1992–2019
Authors: Kumar Satish , Sureka Riya , Pandey Nitesh
Published: June 2020

Purpose

Asian Review of Accounting (ARA), a leading journal in the field of accounting, completed its 29 years of active publishing in the year 2019. The primary objective of this study is to provide a comprehensive overview of the journal's publishing activities over these years.

Design/methodology/approach

The authors use the bibliometric analysis and graphical visualization of bibliographic data to ascertain the publication pattern of ARA. Annual publication and citation structure, leading trends in authorship, institutional affiliation, country affiliation, most cited papers in ARA, documents most cited by ARA and frequency of keyword occurrence are also studied to provide a comprehensive overview of the journal between 1992 and 2019.

Findings

Major findings show that ARA has a progressive trend, in terms of both productivity and stature. The journal is highly influenced by Australia and Malaysia in respect of productivity. Major themes published include auditing, financial accounting, governmental and nonprofit accounting, corporate social responsibility, accounting education and financial reporting.

Originality/value

This study offers the first of its kind comprehensive summary of the research work published in ARA.
Corporate social responsibility and corporate citizenship in sustainable supply chain: a structured literature review
Authors: Akbari Mohammadreza , McClelland Robert
Published: June 2020

Purpose

The purpose of this research is to provide a systematic insight into corporate social responsibility (CSR) and corporate citizenship (CC) in supply chain development, by analyzing the current literature, contemporary concepts, data and gaps for future discipline research.

Design/methodology/approach

This research identifies information from existing academic journals and investigates research designs and methods, data analysis techniques, industry involvement and geographic locations. Information regarding university affiliation, publishers, authors, year of publication is also documented. A collection of online databases from 2001 to 2018 were explored, using the keywords “corporate social responsibility”, “corporate citizenship” and “supply chain” in their title and abstract, to deliver an inclusive listing of journal articles in this discipline area. Based on this approach, a total of 164 articles were found, and information on a chain of variables was collected.

Findings

There has been visible growth in published articles over the last 18 years regarding supply chain sustainability, CSR and CC. Analysis of the data collected shows that only five literature reviews have been published in this area. Further, key findings include 41% of publications were narrowly focused on four sectors of industry, leaving gaps in the research. 85% centered on the survey and conceptual model, leaving an additional gap for future research. Finally, developing and developed nation status should be delineated, researched and analyzed based on further segmentation of the industry by region.

Research limitations/implications

This research is limited to reviewing only academic and professional articles available from Emerald, Elsevier, Wiley, Sage, Taylor and Francis, Springer, Scopus, JSTOR and EBSCO containing the words “corporate social responsibility”, “corporate citizenship” and “supply chain” in the title and abstract.

Originality/value

This assessment provides an enhanced appreciation of the current practices of current research and offers further directions within the CSR and CC in supply chain sustainable development.
Transient quasi-3D magneto-thermal analytical solution in PM induction heating device
Authors: Abdi Ammar , Ouazir Youcef , Barakat Georges , Amara Yacine
Published: June 2020

Purpose

This paper aims to develop a new quasi-three dimensional (3D) analytical model devoted to the study of nonlinear transient magneto-thermal coupled problems in permanent magnet (PM) transverse flux induction heating device (TFIHD).

Design/methodology/approach

The presented work is based on analytical development of strongly coupled problem, including electromagnetic and thermal boundary problems. The electromagnetic problem is first solved by using the separation variables method to evaluate the induced currents in the nonmagnetic plate and the resulting power density loss distribution. The plate temperature profile is then obtained thanks to strong involvement of this magnetic model in a new analytical thermal model combining the separation of variables method and the Green’s functions transient regime analysis method. The coupled model is then used in a simulation procedure of the magneto-thermal process allowing taking into account the workpiece electrothermal nonlinear properties. The developed coupled model is validated by computing the performances of the studied PM TFIHD and comparing them to those obtained by finite element simulations.

Finding

An efficient transient quasi-3D magneto-thermal analytical model is developed allowing rapid analysis of PM induction heating for core heating of parallelepiped parts. The developed model also allows fast and accurate simulations of nonlinear and transient three dimensional (3D) magneto-thermal phenomena for planar induction heaters.

Research limitations implications

The developed quasi-3D magneto-thermal analytical model is limited to design induction heating devices of planar structure with PM inductors.

Originality/value

A new transient quasi-3D magneto-thermal analytical model accounts for non-linearity and edge effect and helps to fast study and fast design of linear permanent magnet induction heating device.
“You can't be an atheist here”: Christianity and Outward Bound in Britain, c.1941–1965
Authors: Freeman Mark
Published: June 2020

Purpose

The purpose of this study is to explore the role of formal religion in the early years of Outward Bound, a significant outdoor education organisation in Britain, from the 1940s to the 1960s.

Design/methodology/approach

This article is based on archival and other documentary research in various archives and libraries, mostly in the United Kingdom.

Findings

The article shows that religious “instruction” was a central feature of the outdoor education that Outward Bound provided. The nature and extent of this aspect of the training was a matter of considerable debate within the Outward Bound Trust and was influenced by older traditions of muscular Christianity as well as the specific context of the early post–Second World War period. However, the religious influences at the schools were marginalised by the 1960s; although formal Christian observances did not disappear, the emphasis shifted to the promotion of a vaguer spirituality associated with the idea that “the mountains speak for themselves”.

Originality/value

The article establishes the importance of organised Christianity and formal religious observances in the early years of Outward Bound, a feature which has generally been overlooked in the historical literature. It contributes to wider analyses of outdoor education, religious education and secularisation in the mid-twentieth century.