bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcribed B lymphocyte genes and multiple sclerosis risk genes are underrepresented in Epstein–Barr Virus hypomethylated regions
Authors: Ong Lawrence T. C. , Parnell Grant P. , Afrasiabi Ali , Stewart Graeme J. , Swaminathan Sanjay , Booth David R.
Published: October 2019

Epstein–Barr Virus (EBV) infection appears to be necessary for the development of Multiple Sclerosis (MS), although the specific mechanisms are unknown. More than 200 single-nucleotide polymorphisms (SNPs) are known to be associated with the risk of developing MS. About a quarter of these are also highly associated with proximal gene expression in B cells infected with EBV (lymphoblastoid cell lines—LCLs). The DNA of LCLs is hypomethylated compared with both uninfected and activated B cells. Since methylation can affect gene expression, and so cell differentiation and immune evasion, we hypothesised that EBV-driven hypomethylation may affect the interaction between EBV infection and MS. We interrogated an existing dataset comprising three individuals with whole-genome bisulfite sequencing data from EBV transformed B cells and CD40L-activated B cells. DNA methylation surrounding MS risk SNPs associated with gene expression in LCLs (LCLeQTL) was less likely to be hypomethylated than randomly selected chromosomal regions. Differential methylation was independent of genomic features such as promoter regions, but genes preferentially expressed in EBV-infected B cells, including the LCLeQTL genes, were underrepresented in the hypomethylated regions. Our data does not indicate MS genetic risk is affected by EBV hypomethylation.
Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion
Authors: Centeno Patricia P. , Herberger Amanda , Mun Hee-Chang , Tu Chialing , Nemeth Edward F. , Chang Wenhan , Conigrave Arthur D. , Ward Donald T.
Published: October 2019

Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). However, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration, the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.
Modular quantum computation in a trapped ion system
Authors: Zhang Kuan , Thompson Jayne , Zhang Xiang , Shen Yangchao , Lu Yao , Zhang Shuaining , Ma Jiajun , Vedral Vlatko , Gu Mile , Kim Kihwan
Published: October 2019

Modern computation relies crucially on modular architectures, breaking a complex algorithm into self-contained subroutines. A client can then call upon a remote server to implement parts of the computation independently via an application programming interface (API). Present APIs relay only classical information. Here we implement a quantum API that enables a client to estimate the absolute value of the trace of a server-provided unitary operation $$U$$
U
. We demonstrate that the algorithm functions correctly irrespective of what unitary $$U$$
U
the server implements or how the server specifically realizes $$U$$
U
. Our experiment involves pioneering techniques to coherently swap qubits encoded within the motional states of a trapped $${}^{171}{{\rm{Yb}}}^{+}\,$$

171

Yb

+

ion, controlled on its hyperfine state. This constitutes the first demonstration of modular computation in the quantum regime, providing a step towards scalable, parallelization of quantum computation.
A genome-wide assessment of the ancestral neural crest gene regulatory network
Authors: Hockman Dorit , Chong-Morrison Vanessa , Green Stephen A. , Gavriouchkina Daria , Candido-Ferreira Ivan , Ling Irving T. C. , Williams Ruth M. , Amemiya Chris T. , Smith Jeramiah J. , Bronner Marianne E. , Sauka-Spengler Tatjana
Published: October 2019

The neural crest (NC) is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional and epigenomic profiles of NC cells in the sea lamprey, in order to gain insight into the ancestral state of the NC gene regulatory network (GRN). Transcriptome analyses identify clusters of co-regulated genes during NC specification and migration that show high conservation across vertebrates but also identify transcription factors (TFs) and cell-adhesion molecules not previously implicated in NC migration. ATAC-seq analysis uncovers an ensemble of cis-regulatory elements, including enhancers of Tfap2B, SoxE1 and Hox-α2 validated in the embryo. Cross-species deployment of lamprey elements identifies the deep conservation of lamprey SoxE1 enhancer activity, mediating homologous expression in jawed vertebrates. Our data provide insight into the core GRN elements conserved to the base of the vertebrates and expose others that are unique to lampreys.
Controlled creation of a singular spinor vortex by circumventing the Dirac belt trick
Authors: Weiss L. S. , Borgh M. O. , Blinova A. , Ollikainen T. , Möttönen M. , Ruostekoski J. , Hall D. S.
Published: October 2019

Persistent topological defects and textures are particularly dramatic consequences of superfluidity. Among the most fascinating examples are the singular vortices arising from the rotational symmetry group SO(3), with surprising topological properties illustrated by Dirac’s famous belt trick. Despite considerable interest, controlled preparation and detailed study of vortex lines with complex internal structure in fully three-dimensional spinor systems remains an outstanding experimental challenge. Here, we propose and implement a reproducible and controllable method for creating and detecting a singular SO(3) line vortex from the decay of a non-singular spin texture in a ferromagnetic spin-1 Bose–Einstein condensate. Our experiment explicitly demonstrates the SO(3) character and the unique spinor properties of the defect. Although the vortex is singular, its core fills with atoms in the topologically distinct polar magnetic phase. The resulting stable, coherent topological interface has analogues in systems ranging from condensed matter to cosmology and string theory.
Tracking human genes along the translational continuum
Authors: Lee Kyubum , Clyne Mindy , Yu Wei , Lu Zhiyong , Khoury Muin J.
Published: October 2019

Understanding the drivers of research on human genes is a critical component to success of translation efforts of genomics into medicine and public health. Using publicly available curated online databases we sought to identify specific genes that are featured in translational genetic research in comparison to all genomics research publications. Articles in the CDC’s Public Health Genomics and Precision Health Knowledge Base were stratified into studies that have moved beyond basic research to population and clinical epidemiologic studies (T1: clinical and population human genome epidemiology research), and studies that evaluate, implement, and assess impact of genes in clinical and public health areas (T2+: beyond bench to bedside). We examined gene counts and numbers of publications within these phases of translation in comparison to all genes from Medline. We are able to highlight those genes that are moving from basic research to clinical and public health translational research, namely in cancer and a few genetic diseases with high penetrance and clinical actionability. Identifying human genes of translational value is an important step towards determining an evidence-based trajectory of the human genome in clinical and public health practice over time.
Author Correction: Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF6) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis
Authors: Bocé Mathilde , Tassé Marine , Mallet-Ladeira Sonia , Pillet Flavien , Da Silva Charlotte , Vicendo Patricia , Lacroix Pascal G. , Malfant Isabelle , Rols Marie-Pierre
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation
Authors: Fukunaga Hisanori , Kaminaga Kiichi , Sato Takuya , Butterworth Karl T. , Watanabe Ritsuko , Usami Noriko , Ogawa Takehiko , Yokoya Akinari , Prise Kevin M.
Published: October 2019

Microbeam radiotherapy (MRT) is based on a spatial fractionation of synchrotron X-ray microbeams at the microscale level. Although the tissue-sparing effect (TSE) in response to non-uniform radiation fields was recognized more than one century ago, the TSE of MRT in the testes and its clinical importance for preventing male fertility remain to be determined. In this study, using the combination of MRT techniques and a unique ex vivo testes organ culture, we show, for the first time, the MRT-mediated TSE for the preservation of spermatogenesis. Furthermore, our high-precision microbeam analysis revealed that the survival and potential migration steps of the non-irradiated germ stem cells in the irradiated testes tissue would be needed for the effective TSE for spermatogenesis. Our findings indicated the distribution of dose irradiated in the testes at the microscale level is of clinical importance for delivering high doses of radiation to the tumor, while still preserving male fertility.
The Intrinsic Enzyme Activities of the Classic Polyoxometalates
Authors: Zhang Boyu , Zhao Mingming , Qi Yanfei , Tian Rui , Carter Boye B. , Zou Hangjin , Zhang Chuhan , Wang Chunyan
Published: October 2019

The mimicking enzyme activities of eighteen classic POMs with different structures, Keggin (H3PW12O40, H4SiW12O40, H4GeW12O40, K4GeW12O40, H3PMo12O40, H4SiMo12O40and Eu3PMo12O40), Wells-Dawson (H6P2Mo18O62, α-(NH4)6P2W18O62and α-K6P2W18O62·14H2O), lacunary-Keggin (Na8H[α-PW9O34], Na10[α-SiW9O34], Na10[α-GeW9O34] and K8[γ-SiW10O36]), the transition-metal substituted-type (α-1,2,3-K6H[SiW9V3O34] and H5PMo10V2O40), sandwich-type (K10P2W18Fe4(H2O)2O68) and an isopolyoxotungstate (Na10H2W12O42) were screened and compared. The mechanisms and reaction conditions of POMs with mimicking enzyme-like activities were also analyzed. The results shown that the structures, the hybrid atoms, the coordination atoms, the substituted metal atoms, pH and substrate are the effect factors for the enzyme mimic activities of POM. Among the eighteen POMs, H3PW12O40, H4SiW12O40, H4GeW12O40, α-(NH4)6P2W18O62, α-K6P2W18O62·14H2O, Na8H[α-PW9O34], Na10[α-SiW9O34], Na10[α-GeW9O34], K8[γ-SiW10O36], K10P2W18Fe4(H2O)2O68and Na10H2W12O42had the peroxidase activities. Eu3PMo12O40, H3PMo12O40, H4SiMo12O40, α-1,2,3-K6H [SiW9V3O34], H6P2Mo18O62and H5PMo10V2O40showed the oxidase-like activities. K4GeW12O40did not show the peroxidase and oxidase activities. The Na8H[α-PW9O34], Na10[α-SiW9O34] and Na10[α-GeW9O34] showed intrinsic enzyme activities at alkaline conditions, which were different from other type of POMs. The sandwich-type K10P2W18Fe4(H2O)2O68displayed the strongest peroxidase activity, which is similar to natural horseradish peroxidase.
Synthesis of Magnesium- and Silicon-modified Hydroxyapatites by Microwave-Assisted Method
Authors: Rasskazova Liudmila A. , Zhuk Ilya V. , Korotchenko Natalia M. , Brichkov Anton S. , Chen Yu-Wen , Paukshtis Evgeniy A. , Ivanov Vladimir K. , Kurzina Irina A. , Kozik Vladimir V.
Published: October 2019

Nanopowders of hydroxyapatite (HA), modified by magnesium (MgHA) and by silicon (SiHA) were obtained by liquid-phase microwave synthesis method. X-ray diffraction and IR spectroscopy results showed that Mg2+ and SiO44− ions were present in the synthesized products both as secondary phases and as part of the HA phase. Whitlockite was found in the magnesium-modified HA (MgHA) and larnite was found in the silicon-modified HA (SiHA); ion substitution for both materials resulted in solid solutions. In the synthesized samples of modified HA, the increase of particle size of powders was in the order HA < SiHA < MgHA, which was calculated through data specific surface area and measured pycnometric density of the powders. The Lewis acid sites (Ca2+, Mg2+, Si4+) were present using spectral probes on the surface of the samples of HA, MgHA, and SiHA, and the acidity of these sites decreased in the order SiHA > MgHA > HA. The rates of calcium phosphate layer deposition on the surface of these materials at 37 °C in the model simulated body fluid solution showed similar dependence.
Imbalance in the response of pre- and post-synaptic components to amyloidopathy
Authors: Stephen Terri-Leigh , Tamagnini Francesco , Piegsa Judith , Sung Katherine , Harvey Joshua , Oliver-Evans Alice , Murray Tracey K. , Ahmed Zeshan , Hutton Michael L. , Randall Andrew , O’Neill Michael J. , Jackson Johanna S.
Published: October 2019

Alzheimer’s disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Amyloid β (Aβ) species, both soluble and in plaque deposits, have been causally related to the progressive, structural and functional impairments observed in AD. It is, however, still unclear how Aβ plaques develop over time and how they progressively affect local synapse density and turnover. Here we observed, in a mouse model of AD, that Aβ plaques grow faster in the earlier stages of the disease and if their initial area is >500 µm2; this may be due to deposition occurring in the outer regions of the plaque, the plaque cloud. In addition, synaptic turnover is higher in the presence of amyloid pathology and this is paralleled by a reduction in pre- but not post-synaptic densities. Plaque proximity does not appear to have an impact on synaptic dynamics. These observations indicate an imbalance in the response of the pre- and post-synaptic terminals and that therapeutics, alongside targeting the underlying pathology, need to address changes in synapse dynamics.
A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors
Authors: Ísberg Ólöf Gerdur , Kim Jiyoung , Fridriksdottir Agla J. , Morsing Mikkel , Timmermans-Wielenga Vera , Rønnov-Jessen Lone , Petersen Ole W. , Villadsen René
Published: October 2019

Human breast cancer is believed to arise in luminal progenitors within the normal breast. A subset of these are double positive (DP) for basal and luminal keratins and localizes to a putative stem cell zone within ducts. We here present a new protocol based on a combination of CD146 with CD117 and CD326 which provides an up to thirty fold enrichment of the DP cells. We show by expression profiling, colony formation, and morphogenesis that CD146high/CD117high/CD326high DP cells belong to a luminal progenitor compartment. While these DP cells are located quite uniformly in ducts, with age a variant type of DP (vDP) cells, which is mainly CD146-negative, accumulates in lobules. Intriguingly, in specimens with BRCA1 mutations known to predispose for cancer, higher frequencies of lobular vDP cells are observed. We propose that vDP cells are strong candidates for tracing the cellular origin of breast cancer.
CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
Authors: Tsunekuni Kenta , Konno Masamitsu , Haraguchi Naotsugu , Koseki Jun , Asai Ayumu , Matsuoka Kazuaki , Kobunai Takashi , Takechi Teiji , Doki Yuichiro , Mori Masaki , Ishii Hideshi
Published: October 2019

Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective against CSC-like cells. CD44+CD133+high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of FTD and fluorouracil (5-FU) on CD44+CD133+cells were then measured. CD44+CD133+DLD-1 cells formed substantially more spheres than other cells. Moreover, treating CD44+CD133+DLD-1 cells with subtoxic concentrations of FTD (1 µM) inhibited sphere formation, and this was superior to the effect of subtoxic concentrations (1 µM) of 5-FU. The associated inhibition rates for FTD and 5-FU were 58.2% and 26.1%, respectively. Further, CD44+CD133+DLD-1 cells expressed higher levels of thymidine kinase 1, which is responsible for FTD phosphorylation, than DLD-1 cells, and FTD was incorporated into the DNA of CD44+CD133+DLD-1 cells. Thus, our data show that FTD treatment is effective against CSC-like cells and might be applied as CSC-targeting chemotherapy for tumor subtypes with high CD44 and CD133 expression.
High-resolution transcriptional profiling of Anopheles gambiae spermatogenesis reveals mechanisms of sex chromosome regulation
Authors: Taxiarchi Chrysanthi , Kranjc Nace , Kriezis Antonios , Kyrou Kyros , Bernardini Federica , Russell Steven , Nolan Tony , Crisanti Andrea , Galizi Roberto
Published: October 2019

Although of high priority for the development of genetic tools to control malaria-transmitting mosquitoes, only a few germline-specific regulatory regions have been characterised to date and the presence of global regulatory mechanisms, such as dosage compensation and meiotic sex chromosome inactivation (MSCI), are mostly assumed from transcriptomic analyses of reproductive tissues or whole gonads. In such studies, samples include a significant portion of somatic tissues inevitably complicating the reconstruction of a defined transcriptional map of gametogenesis. By exploiting recent advances in transgenic technologies and gene editing tools, combined with fluorescence-activated cell sorting and RNA sequencing, we have separated four distinct cell lineages from the Anopheles gambiae male gonads: premeiotic, meiotic (primary and secondary spermatocytes) and postmeiotic. By comparing the overall expression levels of X-linked and autosomal genes across the four populations, we revealed a striking transcriptional repression of the X chromosome coincident with the meiotic phase, classifiable as MSCI, and highlighted genes that may evade silencing. In addition, chromosome-wide median expression ratios of the premeiotic population confirmed the absence of dosage compensation in the male germline. Applying differential expression analysis, we highlighted genes and transcript isoforms enriched at specific timepoints and reconstructed the expression dynamics of the main biological processes regulating the key stages of sperm development and maturation. We generated the first transcriptomic atlas of A. gambiae spermatogenesis that will expand the available toolbox for the genetic engineering of vector control technologies. We also describe an innovative and multidimensional approach to isolate specific cell lineages that can be used for the targeted analysis of other A. gambiae organs or transferred to other medically relevant species and model organisms.
Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model
Authors: Kim Tae Yun , Jeng Paul , Hwang JungMin , Pfeiffer Zachary , Patel Divyang , Cooper Leroy L , Kossidas Konstantinos , Centracchio Jason , Peng Xuwen , Koren Gideon , Qu Zhilin , Choi Bum-Rak
Published: October 2019

The initiation of polymorphic ventricular tachycardia in long QT syndrome type 2 (LQT2) has been associated with a characteristic ECG pattern of short-long RR intervals. We hypothesize that this characteristic pattern increases APD dispersion in LQT2, thereby promoting arrhythmia. We investigated APD dispersion and its dependence on two previous cycle lengths (CLs) in transgenic rabbit models of LQT2, LQT1, and their littermate controls (LMC) using random stimulation protocols. The results show that the short-long RR pattern was associated with a larger APD dispersion in LQT2 but not in LQT1 rabbits. The multivariate analyses of APD as a function of two previous CLs (APDn = C + α1CLn−1 + α2CLn−2) showed that α1 (APD restitution slope) is largest and heterogeneous in LQT2 but uniform in LQT1, enhancing APD dispersion under long CLn−1 in LQT2. The α2 (short-term memory) was negative in LQT2 while positive in LQT1, and the spatial pattern of α1 was inversely correlated to α2 in LQT2, which explains why a short-long combination causes a larger APD dispersion in LQT2 but not in LQT1 rabbits. In conclusion, short-long RR pattern increased APD dispersion only in LQT2 rabbits through heterogeneous APD restitution and the short-term memory, underscoring the genotype-specific triggering of arrhythmias in LQT syndrome.
Uncovering low-level mosaicism in human embryonic stem cells using high throughput single cell shallow sequencing
Authors: Keller Alexander , Tilleman Laurentijn , Dziedzicka Dominika , Zambelli Filippo , Sermon Karen , Van Nieuwerburgh Filip , Spits Claudia , Geens Mieke
Published: October 2019

Human pluripotent stem cells (hPSCs) have significant levels of low-grade genetic mosaicism, which commonly used techniques fail to detect in bulk DNA. These copy number variations remain a hurdle for the clinical translation of hPSC, as their effect in vivo ranges from unknown to dangerous, and the ability to detect them will be necessary as the field advances. As such there is need for techniques which can efficiently analyse genetic content in single cells with higher throughput and lower costs. We report here on the use of the Fluidigm C1 single cell WGA platform in combination with shallow whole genome sequencing to analyse the genetic content of single hPSCs. From a hPSC line carrying an isochromosome 20, 56 single cells were analysed and found to carry a total of 50 aberrations, across 23% of cells, which could not be detected by bulk analysis. Aberrations were predominantly segmental gains, with a fewer number of segmental losses and aneuploidies. Interestingly, 40% of the breakpoints seen here correspond to known DNA fragile sites. Our results therefore demonstrate the feasibility of single cell shallow sequencing of hPSC and further expand upon the biological importance and frequency of single cell mosaicism in hPSC.
A Predictor of Pathological Complete Response to Neoadjuvant Chemotherapy Stratifies Triple Negative Breast Cancer Patients with High Risk of Recurrence
Authors: Fournier Marcia V. , Goodwin Edward C. , Chen Joan , Obenauer John C. , Tannenbaum Susan H. , Brufsky Adam M.
Published: October 2019

We developed a test to predict which patients will achieve pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) and which will have residual disease (RD). Gene expression data from pretreatment biopsies of patients with all breast cancer subtypes were combined into a 519-patient cohort containing 177 TNBC patients. Two RNA classifiers of 16 genes each were sequentially applied to the total cohort, classifying patients into 3 distinct classes. The test performance was further validated in an independent 304-patient cohort. The test accurately identified 70.5% (79/112) of pCR and 83.5% (340/407) of RD patients in the total population, and 75.0% (45/60) of pCR and 75.2% (88/117) of RD patients in the TNBC subset. For the independent cohort, the test identified 91.5% RD patients in the total population and 86.2% RD patients in the TNBC subset. However, the identification of pCR in both total and TNBC population are as low as 21.1% and 30%, respectively. The TNBC RD patients were subdivided by our classifiers, with one class showing significantly higher levels of Ki67 expression and having significantly poorer survival rates than the other classes. This stratification of patients may allow predicted residual disease classes to be assigned an alternative therapy.
A Super-Learner Model for Tumor Motion Prediction and Management in Radiation Therapy: Development and Feasibility Evaluation
Authors: Lin Hui , Zou Wei , Li Taoran , Feigenberg Steven J. , Teo Boon-Keng K. , Dong Lei
Published: October 2019

In cancer radiation therapy, large tumor motion due to respiration can lead to uncertainties in tumor target delineation and treatment delivery, thus making active motion management an essential step in thoracic and abdominal tumor treatment. In current practice, patients with tumor motion may be required to receive two sets of CT scans – the initial free-breathing 4-dimensional CT (4DCT) scan for tumor motion estimation and a second CT scan under appropriate motion management such as breath-hold or abdominal compression. The aim of this study is to assess the feasibility of a predictive model for tumor motion estimation in three-dimensional space based on machine learning algorithms. The model was developed based on sixteen imaging features extracted from non-4D diagnostic CT images and eleven clinical features extracted from the Electronic Health Record (EHR) database of 150 patients to characterize the lung tumor motion. A super-learner model was trained to combine four base machine learning models including the Random Forest, Multi-Layer Perceptron, LightGBM and XGBoost, the hyper-parameters of which were also optimized to obtain the best performance. The outputs of the super-learner model consist of tumor motion predictions in the Superior-Inferior (SI), Anterior-Posterior (AP) and Left-Right (LR) directions, and were compared against tumor motions measured in the free-breathing 4DCT scans. The accuracy of predictions was evaluated using Mean Absolute Error (MAE) and Root Mean Square Error (RMSE) through ten rounds of independent tests. The MAE and RMSE of predictions in the SI direction were 1.23 mm and 1.70 mm; the MAE and RMSE of predictions in the AP direction were 0.81 mm and 1.19 mm, and the MAE and RMSE of predictions in the LR direction were 0.70 mm and 0.95 mm. In addition, the relative feature importance analysis demonstrated that the imaging features are of great importance in the tumor motion prediction compared to the clinical features. Our findings indicate that a super-learner model can accurately predict tumor motion ranges as measured in the 4DCT, and could provide a machine learning framework to assist radiation oncologists in determining the active motion management strategy for patients with large tumor motion.
De novo transcriptome of Gymnema sylvestre identified putative lncRNA and genes regulating terpenoid biosynthesis pathway
Authors: Ayachit Garima , Shaikh Inayatullah , Sharma Preeti , Jani Bhavika , Shukla Labdhi , Sharma Priyanka , Bhairappanavar Shivarudrappa B. , Joshi Chaitanya , Das Jayashankar
Published: October 2019

Gymnema sylvestre is a highly valuable medicinal plant in traditional Indian system of medicine and used in many polyherbal formulations especially in treating diabetes. However, the lack of genomic resources has impeded its research at molecular level. The present study investigated functional gene profile of G. sylvestre via RNA sequencing technology. The de novo assembly of 88.9 million high quality reads yielded 23,126 unigenes, of which 18116 were annotated against databases such as NCBI nr database, gene ontology (GO), KEGG, Pfam, CDD, PlantTFcat, UniProt & GreeNC. Total 808 unigenes mapped to 78 different Transcription Factor families, whereas 39 unigenes assigned to CYP450 and 111 unigenes coding for enzymes involved in the biosynthesis of terpenoids including transcripts for synthesis of important compounds like Vitamin E, beta-amyrin and squalene. Among them, presence of six important enzyme coding transcripts were validated using qRT-PCR, which showed high expression of enzymes involved in methyl-erythritol phosphate (MEP) pathway. This study also revealed 1428 simple sequence repeats (SSRs), which may aid in molecular breeding studies. Besides this, 8 putative long non-coding RNAs (lncRNAs) were predicted from un-annotated sequences, which may hold key role in regulation of essential biological processes in G. sylvestre. The study provides an opportunity for future functional genomic studies and to uncover functions of the lncRNAs in G. sylvestre.
Anatomical Pathology of Subtle Lisfranc Injury
Authors: Haraguchi Naoki , Ota Koki , Ozeki Takuma , Nishizaka Shingo
Published: October 2019

The extent and patterns of Lisfranc joint complex disruption in subtle Lisfranc injuries have not been well clarified. We reviewed the direct intraoperative findings for 87 patients, examined computed tomography images that had been obtained preoperatively for 73 of the patients, and classified the injuries according to the Kaar  et al. criteria as the transverse type (instability between the first cuneiform [C1] and the second metatarsal [M2] and between the second cuneiform [C2] and M2) or longitudinal type (instability between C1 and M2 and between C1 and C2). Our patients’ injuries were classified as follows: longitudinal type (38%), transverse type (30%), transverse type and first tarsometatarsal (TMT) joint injury (20%), longitudinal type plus transverse type (7%), longitudinal type and first TMT joint injury (3%), and longitudinal type, transverse type, and first TMT joint injury (2%). In 11 patients, the longitudinal injury extended into the naviculo-first cuneiform joint. In 41 (56%) of the 73 patients for whom CT images were obtained, 1 or more fractures (not counting small avulsion fragments between C1 and M2) were found. Orthopedic surgeons should be aware of the various injury patterns possible in cases of subtle Lisfranc injury.
Altered serum Zinc and Copper in Iranian Adults who were of normal weight but metabolically obese
Authors: Darroudi Susan , Fereydouni Narges , Tayefi Maryam , Esmaily Habibollah , Sadabadi Fatemeh , Khashyarmanesh Zahra , Tayefi Batool , Haghighi Hamideh Moalemzadeh , Timar Ameneh , Mohammadpour Amir Hooshang , Gonoodi Kayhan , Ferns Gordon A. , Hoseini Seyed Javad , Ghayour-Mobarhan Majid
Published: October 2019

Metabolically obese normal weight (MONW) individuals are potentially at increased risk of developing metabolic syndrome. Serum zinc and copper concentrations were assessed in individuals with MONW to determine whether MONW is associated with altered serum zinc and/or copper status. Normal weight subjects (total n = 2419; 1298 men and 1121 women), were recruited as part of Mashhad Stroke and Heart Association Disorder (MASHAD) Study cohort. They were divided into two groups according to the presence or absence of MetS, defined using IDF criteria. Serum zinc and copper concentrations were determined by atomic absorption. Of the 2419 normal weight adults, 377 had MetS. Of this group, 53.7% and 49.7% had a serum zinc <70 µg/dl (Q1) (p = 0.001) or a serum copper <79 µg/dl (Q1) respectively. Furthermore, 27.3% had a serum copper >131 µg/dl (Q4) (p = 0.034), and 18.8% had a serum zinc >95 µg/dl (Q4). Logistic regression analysis was performed to determine the odds ratio (OR) for an association of serum zinc, copper and zinc to copper ratio with MetS in normal weight subjects. The subjects with a serum zinc >95 µg/dl (Q4) had 0.386 [OR: 0.614(95%CI 0.457–0.823)] lower chance of MetS (p = 0.001) and the subjects with a serum copper >131 (Q4) had OR 1.423 (95% CI: 1.09–1.857) higher chance of MetS (p = 0.009). These data remained significant after adjustment for age and sex, for serum zinc and copper, respectively. Furthermore, our results strongly suggested that zinc and copper were the independent risk factor for metabolic syndrome in normal weight subjects. There is an imbalance between serum copper and zinc concentrations among individuals with MONW when compared with normal BMI individuals without MetS. This may increase the risk of individuals with MONW developing conditions associated with this imbalance, such as diabetes and cardiovascular disease.
Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism
Authors: Nishimura Kenji , Murakami Taichi , Sakurai Toshihiro , Miyoshi Masashi , Kurahashi Kiyoe , Kishi Seiji , Tamaki Masanori , Tominaga Tatsuya , Yoshida Sumiko , Nagai Kojiro , Abe Hideharu , Hui Shu-Ping , Kotani Kazuhiko , Doi Toshio
Published: October 2019

Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = −0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.
Expression regulation of myo-inositol 3-phosphate synthase 1 (INO1) in determination of phytic acid accumulation in rice grain
Authors: Perera Ishara , Fukushima Ayaka , Akabane Tatsuki , Horiguchi Genki , Seneweera Saman , Hirotsu Naoki
Published: October 2019

Phytic acid (PA) is the primary phosphorus (P) storage compound in the seeds of cereals and legumes. Low PA crops, which are considered an effective way to improve grain nutrient availability and combat environmental issues relating to seed P have been developed using mutational and reverse genetics approaches. Here, we identify molecular mechanism regulating PA content among natural rice variants. First, we performed genome-wide association (GWA) mapping of world rice core collection (WRC) accessions to understand the genetic determinants underlying PA trait in rice. Further, a comparative study was undertaken to identify the differences in PA accumulation, protein profiles, and gene expression in low (WRC 5) and high PA (WRC 6) accessions. GWA results identified myo-inositol 3-phosphate synthase 1 (INO1) as being closely localized to a significant single nucleotide polymorphism. We found high rates of PA accumulation 10 days after flowering, and our results indicate that INO1 expression was significantly higher in WRC 6 than in WRC 5. Seed proteome assays found that the expression of INO1 was significantly higher in WRC 6. These results suggest that not only the gene itself but regulation of INO1 gene expression at early developmental stages is important in determining PA content in rice.
Author Correction: Fornix white matter glia damage causes hippocampal gray matter damage during age-dependent limbic decline
Authors: Metzler-Baddeley Claudia , Mole Jilu P. , Sims Rebecca , Fasano Fabrizio , Evans John , Jones Derek K. , Aggleton John P. , Baddeley Roland J.
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Molecular marker assisted breeding and genome composition analysis of Zhengmai 7698, an elite winter wheat cultivar
Authors: Li Chun-xin , Xu Wei-gang , Guo Rui , Zhang Jian-zhou , Qi Xue-li , Hu Lin , Zhao Ming-zhong
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer’s disease
Authors: Sundaram S. , Nagaraj S. , Mahoney H. , Portugues A. , Li W. , Millsaps K. , Faulkner J. , Yunus A. , Burns C. , Bloom C. , Said M. , Pinto L. , Azam S. , Flores M. , Henriksen A. , Gamsby J. , Gulick D.
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Competition of individual domain folding with inter-domain interaction in WW domain engineered repeat proteins
Authors: Dave Kapil , Gasic Andrei G. , Cheung Margaret S. , Gruebele M.
Published: October 2019

Engineered repeat proteins have proven to be a fertile ground for studying the competition between folding, misfolding and transient aggregation of tethered protein domains.
Antibacterial and hydroxyapatite-forming coating for biomedical implants based on polypeptide-functionalized titania nanospikes
Authors: Gao Qiang , Feng Tao , Huang Danni , Liu Peng , Lin Peng , Wu Yan , Ye Zhaoming , Ji Jian , Li Peng , Huang Wei
Published: October 2019

The immobilization of mussel-inspired polypeptide onto biomimetic titania nanospike coating enhanced its antibacterial ability and bioactivity, thus holding great promise for utilization for orthopedic and dental implants.
Facile construction of hierarchical ellipsoid-shaped TiO2 porous nanostructures with enhanced photocatalytic activity
Authors: Meng Lili , Chang Yi , Ma Xiaoming , Liu Peng , Liu Tingting , Guo Yuming , Yang Lin
Published: October 2019

Hierarchical ellipsoid-shaped TiO2 porous nanostructures with efficient photocatalytic activity for the degradation of MB are constructed by hierarchical assembly of TiO2 nanoparticles.
Heteroepitaxy of perovskite (111) SrTiO3 on wurtzite (0002) GaN using an artificial interface lattice design
Authors: Li Guanjie , Li Xiaomin , Zhao Junliang , Zhu Qiuxiang , Gao Xiangdong
Published: October 2019

Epitaxial integration of perovskite SrTiO3 on wurtzite GaN was realized using novel designed hexagonal Ti and spinel MgAl2O4 buffer layers.
A computational approach to get insights into multiple faces of additives in modulation of protein aggregation pathways
Authors: Katyal Nidhi , Deep Shashank
Published: October 2019

Computer simulations can be exploited to extract useful information about the effect of an additive at different stages of protein aggregation.
Odd–even harmonic generation from oriented CO molecules in linearly polarized laser fields and the influence of the dynamic core-electron polarization
Authors: Phan Ngoc-Loan , Le Cam-Tu , Hoang Van-Hung , Le Van-Hoang
Published: October 2019

We present a detailed theoretical study of the odd–even harmonics generated from the polar molecule CO by the method based on numerically solving the time-dependent Schrödinger equation within the single-active-electron approximation.
Interface-induced enhancement of piezoelectricity in the (SrTiO3)m/(BaTiO3)M−m superlattice for energy harvesting applications
Authors: Zvejnieks Guntars , Rusevich Leonid L. , Gryaznov Denis , Kotomin Eugene A.
Published: October 2019

A six-fold increase of the e33 piezoelectric constant is theoretically predicted for a lead-free perovskite superlattice.
First-principles theory of atomic-scale friction explored by an intuitive charge density fluctuation surface
Authors: Zhang Bozhao , Cheng Ziwen , Zhang Guangan , Lu Zhibin , Ma Fei , Zhou Feng
Published: October 2019

Atomic-scale friction theory, and even superlubricity, is inseparable from charge redistribution, but lacks a bridge to establish the potential link between them.
Ni@PC as a stabilized catalyst toward the efficient hydrogenation of quinoline at ambient temperature
Authors: Yun Ruirui , Ma Wanjiao , Hong Lirui , Hu Yang , Zhan Feiyang , Liu Shoujie , Zheng Baishu
Published: October 2019

A novel and efficient strategy, namely as starch-assistant-confine, was used to design and rationally construct a series of porous carbons featuring uniform dispersal of Ni@PC-T-h with highly-efficient catalytic hydrogenation of quinoline.
The chemically reduced CuO–Co3O4 composite as a highly efficient electrocatalyst for oxygen evolution reaction in alkaline media
Authors: Aftab Umair , Tahira Aneela , Mazzaro Raffaello , Abro Muhammad Ishaq , Baloch Muhammad Moazam , Willander Magnus , Nur Omer , Yu Cong , Ibupoto Zafar Hussain
Published: October 2019

The fabrication of efficient, alkaline-stable and nonprecious electrocatalysts for the oxygen evolution reaction is highly needed; however, it is a challenging task.
Ferrocenyl palladacycles derived from unsymmetrical pincer-type ligands: evidence of Pd(0) nanoparticle generation during the Suzuki–Miyaura reaction and applications in the direct arylation of thiazoles and isoxazoles
Authors: Maji Ankur , Singh Anshu , Mohanty Aurobinda , Maji Pradip K. , Ghosh Kaushik
Published: October 2019

Design palladium complexes Pd1 and Pd2 derived from unsymmetrical pincer-type ligands were employed as catalysts for Suzuki Miyaura cross-coupling reaction and direct arylation of Csp2–H functionalization of thiazole and isoxazole dervatives.
A porous and redox active ferrocenedicarboxylic acid based aluminium MOF with a MIL-53 architecture
Authors: Benecke Jannik , Mangelsen Sebastian , Engesser Tobias A. , Weyrich Thomas , Junge Jannik , Stock Norbert , Reinsch Helge
Published: October 2019

A new redox active MOF Al-MIL-53-FcDC based on 1,1′-ferrocenedicarboxylate exhibits reversible electrochemical activity and permanent porosity.
Substituents lead to differences in the formation of two different butterfly-shaped NiII2DyIII2 clusters: structures and multistep assembly mechanisms
Authors: Mo Kai-Qiang , Zhu Zhong-Hong , Wang Hai-Ling , Ma Xiong-Feng , Peng Jin-Mei , Zou Hua-Hong , Bai Juan , Liang Fu-Pei
Published: October 2019

This study is the second to investigate the assembly mechanism of 3d–4f heterometallic clusters by HRESI-MS. Meanwhile, this study is the first to determine the effect of substitution on the assembly mechanism of 3d–4f heterometallic clusters.
Correction: A comparative study of Ir(iii) complexes with pyrazino[2,3-f][1,10]phenanthroline and pyrazino[2,3-f][4,7]phenanthroline ligands in light-emitting electrochemical cells (LECs)
Authors: González Iván , Dreyse Paulina , Cortés-Arriagada Diego , Sundararajan Mahesh , Morgado Claudio , Brito Iván , Roldán-Carmona Cristina , Bolink Henk J. , Loeb Bárbara
Published: October 2019

Correction for ‘A comparative study of Ir(iii) complexes with pyrazino[2,3-f][1,10]phenanthroline and pyrazino[2,3-f][4,7]phenanthroline ligands in light-emitting electrochemical cells (LECs)’ by Iván González et al., Dalton Trans., 2015, 44, 14771–14781.
The determination of two emerging perfluoroalkyl substances and related halogenated sulfonic acids and their significance for the drinking water supply chain
Authors: Vughs D. , Baken K. A. , Dingemans M. M. L. , de Voogt P.
Published: October 2019

Analytical methodologies were developed for two emerging PFAS, F3-MSA and HFPO-DA, in order to assess their occurrence and levels in Dutch and Belgian waters and evaluate human health risks due to their presence in drinking water.
The fabrication of activated carbon and metal-carbide 2D framework-based asymmetric electrodes for the capacitive deionization of Cr(vi) ions toward industrial wastewater remediation
Authors: Bharath G. , Hai Abdul , Rambabu K. , Savariraj Dennyson , Ibrahim Yazan , Banat Fawzi
Published: October 2019

A new asymmetric pseudocapacitive deionization (CDI) cell was assembled with date seed-derived activated carbon (DSAC) as an anode and MAX (Ti3AlC2) as a cathode for the deionization of the Cr(vi) ions from industrial effluents.
The influence of hydrofluoric acid etching processes on the photocatalytic hydrogen evolution reaction using mesoporous silicon nanoparticles
Authors: Martell Sarah A. , Werner-Zwanziger Ulrike , Dasog Mita
Published: October 2019

In this work, the response of the photocatalytic activity of mp-Si nanoparticles to a series of HF acid treatments was investigated.
Quantitative analysis of gadolinium doped cerium oxide thin films via online-LASIL-ICP-OES
Authors: Herzig C. , Frank J. , Opitz A. K. , Fleig J. , Limbeck A.
Published: October 2019

LASIL-ICP-OES is used to determine the stoichiometry of gadolinium doped cerium oxide thin films ranging from 220 to 14 nm with high accuracy and precision.
Wash-free non-spectroscopic optical immunoassay by controlling retroreflective microparticle movement in a microfluidic chip
Authors: Kim Ka Ram , Chun Hyeong Jin , Lee Kyung Won , Jeong Kwan Young , Kim Jae-Ho , Yoon Hyun C.
Published: October 2019

A wash-free nonspectroscopic optical immunoassay system by controlling retroreflective Janus microparticles movement in a microfluidic chip was developed to minimize random errors under the point-of-care testing environment.
Clean rhodium nanoparticles prepared by laser ablation in liquid for high performance electrocatalysis of the hydrogen evolution reaction
Authors: Volpato Giulia Alice , Muneton Arboleda David , Brandiele Riccardo , Carraro Francesco , Sartori Giovanni Battista , Cardelli Andrea , Badocco Denis , Pastore Paolo , Agnoli Stefano , Durante Christian , Amendola Vincenzo , Sartorel Andrea
Published: October 2019

Rhodium nanoparticles prepared by a facile laser ablation procedure show excellent activity towards the hydrogen evolution reaction.
Recent advances in carbon dots for bioimaging applications
Authors: Li Hongxia , Yan Xu , Kong Deshuai , Jin Rui , Sun Chunyan , Du Dan , Lin Yuehe , Lu Geyu
Published: October 2019

This review summarized recent advances in CDs-based bioimaging including in vitro imaging in delivering CDs into different types of cells and in vivo applications in distribution and uptake of CDs, imaging-guild drug delivery and tumor therapeutics.
Visual detection of H2O2 and melamine based on PW11MO39n− (M = Cu2+, Co2+, Mn2+, Fe3+) and PW9M3O34n− (M = Cu2+, Co2+, Mn2+, Fe3+)
Authors: Li Yiming , Wang Shengtian , Tang Zhijie , Bawa Mbage , Ji Yu , Wang Xiaohong , Zhang Kaizhi
Published: October 2019

The peroxidase-like activity of transition metal-substituted polyoxometalates (PW11MO39n−, PW9M3O34n−, abbreviated as PW11M and PW9M3, where M = Cu2+, Co2+, Mn2+, Fe3+) in the oxidation of 3,3′,5,5′-tetramethylbenzidine by H2O2 was valuated.
A stretchable and rapidly self-healable polysiloxane elastomer based on reversible aluminum–amino coordination
Authors: Lei Yufeng , Huang Qiuping , Shan Shijie , Lin Yaling , Zhang Anqiang
Published: October 2019

Dynamic coordination between aluminum and amines promotes rapid self-healing for polysiloxane elastomers at lower temperature.
A polyaniline-coated ZnS/ZnO/FTO photoelectrode for improving photocorrosion prevention and visible light absorption
Authors: Kim Hyun , Yang Bee Lyong
Published: October 2019

To enhance the absorption of visible light for wide-bandgap semiconductors, methods such as sensitizing with nanoparticles or quantum dots and bandgap engineering using dopants have been reported.
Combined experimental, DFT theoretical calculations and biological activity of sulfaclozine azo dye with 1-hydroxy-2-naphthoic acid and its complexes with some metal ions
Authors: Abdel-Kader Nora S. , Abdel-Latif Samir A. , El-Ansary Aida L. , Sayed Amira G.
Published: October 2019

Sulfaclozine-1-hydroxy-2-naphthoic acid azo dye (Scna) and its metal complexes with Ni(ii) Cu(ii), Zn(ii) and Pd(ii) metal ions have been prepared and characterized using different techniques.
Nonuniform functional group distribution of carbon nanotubes studied by energy dispersive X-ray spectrometry imaging in SEM
Authors: Nakajima Hideaki , Morimoto Takahiro , Zhou Ying , Kobashi Kazufumi , Ata Seisuke , Yamada Takeo , Okazaki Toshiya
Published: October 2019

Light elemental mapping with a high spatial resolution of <10 nm is successfully conducted by the advanced SEM–EDS technique.