bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-comatose patients with minimal consciousness tend to preserve reading comprehension skills but neglect syntax and spelling
Authors: Kwiatkowska Agnieszka , Lech Michał , Odya Piotr , Czyżewski Andrzej
Published: December 2019

Modern eye tracking technology provides a means for communication with patients suffering from disorders of consciousness (DoC) or remaining in locked-in-state. However, being able to use an eye tracker for controlling text-based contents by such patients requires preserved reading ability in the first place. To our knowledge, this aspect, although of great social importance, so far has seemed to be neglected. In the paper, we presented the possibility of using an eye-tracking technology for assessing reading comprehension skills in post-comatose patients with minimal consciousness. We prepared various syllable-, word- and sentence-based tasks, controlled by gaze, used for assessing the reading comprehension skills. The obtained results showed that people with minimal consciousness preserved the reading comprehension skills, in most cases to a high extent, but had difficulties with recognizing errors in the written text. The ability to maintain attention during performing the tasks was in statistically significant correlation with motivation, and that one was in a statistically significant correlation with the reading ability. The results indicate that post-comatose patients with minimal consciousness can read words and sentences, hence some useful hints may be provided for the development of gaze tracking-based human-computer interfaces for these people.
Spatio-temporal expression and distribution of collagen VI during zebrafish development
Authors: Tonelotto Valentina , Trapani Valeria , Bretaud Sandrine , Heumüller Stefanie Elisabeth , Wagener Raimund , Ruggiero Florence , Bonaldo Paolo
Published: December 2019

Collagen VI (ColVI) is an extracellular matrix (ECM) protein involved in a range of physiological and pathological conditions. Zebrafish (Danio rerio) is a powerful model organism for studying vertebrate development and for in vivo analysis of tissue patterning. Here, we performed a thorough characterization of ColVI gene and protein expression in zebrafish during development and adult life. Bioinformatics analyses confirmed that zebrafish genome contains single genes encoding for α1(VI), α2(VI) and α3(VI) ColVI chains and duplicated genes encoding for α4(VI) chains. At 1 day post-fertilization (dpf) ColVI transcripts are expressed in myotomes, pectoral fin buds and developing epidermis, while from 2 dpf abundant transcript levels are present in myosepta, pectoral fins, axial vasculature, gut and craniofacial cartilage elements. Using newly generated polyclonal antibodies against zebrafish α1(VI) protein, we found that ColVI deposition in adult fish delineates distinct domains in the ECM of several organs, including cartilage, eye, skin, spleen and skeletal muscle. Altogether, these data provide the first detailed characterization of ColVI expression and ECM deposition in zebrafish, thus paving the way for further functional studies in this species.
A genetic toolkit for the analysis of metabolic changes in Drosophila provides new insights into metabolic responses to stress and malignant transformation
Authors: Gándara L. , Durrieu L. , Behrensen C. , Wappner P.
Published: December 2019

Regulation of the energetic metabolism occurs fundamentally at the cellular level, so analytical strategies must aim to attain single cell resolution to fully embrace its inherent complexity. We have developed methods to utilize a toolset of metabolic FRET sensors for assessing lactate, pyruvate and 2-oxoglutarate levels of Drosophila tissues in vivo by imaging techniques. We show here how the energetic metabolism is altered by hypoxia: While some larval tissues respond to low oxygen levels by executing a metabolic switch towards lactic fermentation, the fat body and salivary glands do not alter their energetic metabolism. Analysis of tumor metabolism revealed that depending on the genetic background, some tumors undergo a lactogenic switch typical of the Warburg effect, while other tumors do not. This toolset allows for developmental and physiologic studies in genetically manipulated Drosophila individuals in vivo.
Detection and genotyping of CMV and HPV in tumors and fallopian tubes from epithelial ovarian cancer patients
Authors: Paradowska Edyta , Jabłońska Agnieszka , Studzińska Mirosława , Wilczyński Miłosz , Wilczyński Jacek R.
Published: December 2019

Viral and bacterial infections are detected in epithelial ovarian cancer (EOC) tissues. Since the fallopian tubes are often affected by pelvic inflammatory disease (PID) and the majority of serous EOCs appear to originate from dysplastic lesions in the distal tube, it is relevant to consider the potential role that infectious agents may play in ovarian carcinogenesis. We sought to analyze the prevalence of human papillomavirus (HPV) and cytomegalovirus (CMV) in EOC tissue and fallopian tube specimens obtained at tumor resection. Ovarian cancer and fallopian tube tissue samples obtained from patients with EOC were analyzed by both qualitative and quantitative PCR to detect and quantify viral DNA. The presence of CMV and HPV DNA was detected in 70% and 74% cancerous ovarian tissues, respectively, and was significantly higher in EOC than in benign tumor cases (P ≤ 0.01). CMV or HPV infection was observed also in the fallopian tube samples. Infection with HPV16 was determined in 70% of EOC cases. Almost two thirds of EOC patients demonstrated coinfection with CMV and HPV in the pathological samples. The results revealed that the presence of CMV and HPV in EOC samples is common. CMV and HPV infections can be potential risks for EOC development.
Phenoxyethyl Piperidine/Morpholine Derivatives as PAS and CAS Inhibitors of Cholinesterases: Insights for Future Drug Design
Authors: Pourshojaei Yaghoub , Abiri Ardavan , Eskandari Khalil , Haghighijoo Zahra , Edraki Najmeh , Asadipour Ali
Published: December 2019

Acetylcholinesterase (AChE) catalyzes the conversion of Aβ peptide to its aggregated form and the peripheral anionic site (PAS) of AChE is mainly involved in this phenomenon. Also catalytic active site (CAS) of donepezil stimulates the break-down of acetylcholine (ACh) and depletion of ACh in cholinergic synapses are well established in brains of patients with AD. In this study, a set of compounds bearing phenoxyethyl amines were synthesized and their inhibitory activity toward electric eel AChE (eeAChE) and equine butyrylcholinesterase (eqBuChE) were evaluated. Molecular dynamics (MD) was employed to record the binding interactions of best compounds against human cholinesterases (hAChE and hBuChE) as well as donepezil as reference drug. In vitro results revealed that compound 5c is capable of inhibiting eeAChE activity at IC50 of 0.50 µM while no inhibitory activity was found for eqBuChE for up to 100 µM concentrations. Compound 5c, also due to its facile synthesis, small structure and high selectivity for eeAChE would be very interesting candidate in forthcoming studies. The main interacting parts of compound 5c and compound 7c (most potent eeAChE and eqBuChE inhibitors respectively) with receptors which confer selectivity for AChE and BuChE inhibition were identified, discussed, and compared with donepezil’s interactions. Also during MD simulation it was discovered for the first time that binding of substrates like donepezil to dual CAS and PAS or solely CAS region might have a suppressive impact on 4-α-helical bundles near the tryptophan amphiphilic tetramerization (WAT) domain of AChE and residues which are far away from AChE active site. The results proposed that residues involved in donepezil interactions (Trp86 and Phe295) which are located in CAS and mid-gorge are the mediator of conformational changes in whole protein structure.
Soybean yield, biological N2 fixation and seed composition responses to additional inoculation in the United States
Authors: Carciochi Walter D. , Rosso Luiz H. Moro , Secchi Mario A. , Torres Adalgisa R. , Naeve Seth , Casteel Shaun N. , Kovács Péter , Davidson Dan , Purcell Larry C. , Archontoulis Sotirios , Ciampitti Ignacio A.
Published: December 2019

It is unclear if additional inoculation with Bradyrhizobia at varying soybean [Glycine max (L.) Merr.] growth stages can impact biological nitrogen fixation (BNF), increase yield and improve seed composition [protein, oil, and amino acid (AA) concentrations]. The objectives of this study were to evaluate the effect of different soybean inoculation strategies (seed coating and additional soil inoculation at V4 or R1) on: (i) seed yield, (ii) seed composition, and (iii) BNF traits [nodule number and relative abundance of ureides (RAU)]. Soybean field trials were conducted in 11 environments (four states of the US) to evaluate four treatments: (i) control without inoculation, (ii) seed inoculation, (iii) seed inoculation + soil inoculation at V4, and (iv) seed inoculation + soil inoculation at R1. Results demonstrated no effect of seed or additional soil inoculation at V4 or R1 on either soybean seed yield or composition. Also, inoculation strategies produced similar values to the non-inoculated control in terms of nodule number and RAU, a reflection of BNF. Therefore, we conclude that in soils with previous history of soybean and under non-severe stress conditions (e.g. high early-season temperature and/or saturated soils), there is no benefit to implementing additional inoculation on soybean yield and seed composition.
Degree of Quantumness in Quantum Synchronization
Authors: Eneriz H. , Rossatto D. Z. , Cárdenas-López F. A. , Solano E. , Sanz M.
Published: December 2019

We introduce the concept of degree of quantumness in quantum synchronization, a measure of the quantum nature of synchronization in quantum systems. Following techniques from quantum information, we propose the number of non-commuting observables that synchronize as a measure of quantumness. This figure of merit is compatible with already existing synchronization measurements, and it captures different physical properties. We illustrate it in a quantum system consisting of two weakly interacting cavity-qubit systems, which are coupled via the exchange of bosonic excitations between the cavities. Moreover, we study the synchronization of the expectation values of the Pauli operators and we propose a feasible superconducting circuit setup. Finally, we discuss the degree of quantumness in the synchronization between two quantum van der Pol oscillators.
Vaginoscopic Incision of Oblique Vaginal Septum in Adolescents with OHVIRA Syndrome
Authors: Cheng Chunxia , Subedi Jigyasa , Zhang Aiqian , Johnson Grace , Zhao Xingping , Xu Dabao , Guan Xiaoming
Published: December 2019

This study is to evaluate the efficacy and safety of vaginoscopic incision of oblique vaginal septum in adolescents with Obstructed hemi-vagina and ipsilateral renal agenesis (OHVIRA) syndrome. It is about Fourteen adolescents with OHVIRA syndrome managed by vaginoscopic incision of the oblique vaginal septum using a “No-touch” technique over an 8-year period. In all fourteen adolescents with OHVIRA the oblique vaginal septum was incised successfully without any intraoperative complications. Postoperative pain was unremarkable and each patient’s symptoms resolved postoperatively. The 3-month postoperative follow up office vaginoscopy revealed that the vaginal septum had not reformed nor was any vaginal stenosis noted. Vaginoscopic incision of the oblique vaginal septum using a “No-Touch” technique is a safe, minimally invasive, and effective approach for treating OHVIRA syndrome in adolescents with hematocolpos. This technique may be utilized to minimize disruption to the undeveloped vaginal wall and postoperative pain while providing excellent surgical visualization throughout the procedure.
Antiplatelet effects of citalopram in patients with ischaemic stroke: A randomized, placebo-controlled, double-blind study
Authors: Kraglund Kristian Lundsgaard , Mortensen Janne Kaergaard , Johnsen Søren Paaske , Andersen Grethe , Grove Erik Lerkevang
Published: December 2019

We evaluated the effect of SSRI treatment on platelet aggregation in patients with ischaemic stroke and included patients from the randomized double-blind controlled study of citalopram in acute ischaemic stroke (TALOS). Patients on clopidogrel were included 6 months after acute ischaemic stroke. Platelet parameters, including P2Y12 platelet reactivity using the VerifyNow System, were measured at the last day of study treatment and repeated after a 14-day wash-out period. A total of 60 patients were included (n = 32 randomized to citalopram). Platelet aggregation levels did not differ between the citalopram group (mean 116, 95% CI 89 to 143) and the placebo group (mean 136, 95% CI 109 to 163) (On-treatment, p = 0.14). Similarly, there was no significant change in platelet aggregation in the citalopram group from on-treatment to post-treatment (mean difference 2.0; 95% CI −18 to 14). Platelet count, size and turnover were not affected by SSRI treatment. In conclusion, SSRI therapy did not lead to statistically significant inhibition of platelet aggregation in ischaemic stroke patients treated with clopidogrel.
Quantification of ocean heat uptake from changes in atmospheric O2 and CO2 composition
Authors: Resplandy L. , Keeling R. F. , Eddebbar Y. , Brooks M. , Wang R. , Bopp L. , Long M. C. , Dunne J. P. , Koeve W. , Oschlies A.
Published: December 2019

The ocean is the main source of thermal inertia in the climate system. Ocean heat uptake during recent decades has been quantified using ocean temperature measurements. However, these estimates all use the same imperfect ocean dataset and share additional uncertainty due to sparse coverage, especially before 2007. Here, we provide an independent estimate by using measurements of atmospheric oxygen (O2) and carbon dioxide (CO2) – levels of which increase as the ocean warms and releases gases – as a whole ocean thermometer. We show that the ocean gained 1.29 ± 0.79 × 1022Joules of heat per year between 1991 and 2016, equivalent to a planetary energy imbalance of 0.80 ± 0.49 W watts per square metre of Earth’s surface. We also find that the ocean-warming effect that led to the outgassing of O2and CO2can be isolated from the direct effects of anthropogenic emissions and CO2sinks. Our result – which relies on high-precision O2atmospheric measurements dating back to 1991 – leverages an integrative Earth system approach and provides much needed independent confirmation of heat uptake estimated from ocean data.
ABC transporter genes ABC-C6 and ABC-G33 alter plant-microbe-parasite interactions in the rhizosphere
Authors: Cox Deborah Elizabeth , Dyer Steven , Weir Ryan , Cheseto Xavier , Sturrock Matthew , Coyne Danny , Torto Baldwyn , Maule Aaron G. , Dalzell Johnathan J.
Published: December 2019

Plants are master regulators of rhizosphere ecology, secreting a complex mixture of compounds into the soil, collectively termed plant root exudate. Root exudate composition is highly dynamic and functional, mediating economically important interactions between plants and a wide range of soil organisms. Currently we know very little about the molecular basis of root exudate composition, which is a key hurdle to functional exploitation of root exudates for crop improvement. Root expressed transporters modulate exudate composition and could be manipulated to develop beneficial plant root exudate traits. Using Virus Induced Gene silencing (VIGS), we demonstrate that knockdown of two root-expressed ABC transporter genes in tomato cv. Moneymaker, ABC-C6 and ABC-G33, alters the composition of semi-volatile compounds in collected root exudates. Root exudate chemotaxis assays demonstrate that knockdown of each transporter gene triggers the repulsion of economically relevant Meloidogyne and Globodera spp. plant parasitic nematodes, which are attracted to control treatment root exudates. Knockdown of ABC-C6 inhibits egg hatching of Meloidogyne and Globodera spp., relative to controls. Knockdown of ABC-G33 has no impact on egg hatching of Meloidogyne spp. but has a substantial inhibitory impact on egg hatching of G. pallida. ABC-C6 knockdown has no impact on the attraction of the plant pathogen Agrobacterium tumefaciens, or the plant growth promoting Bacillus subtilis, relative to controls. Silencing ABC-G33 induces a statistically significant reduction in attraction of B. subtilis, with no impact on attraction of A. tumefaciens. By inoculating selected differentially exuded compounds into control root exudates, we demonstrate that hexadecaonic acid and pentadecane are biologically relevant parasite repellents. ABC-C6 represents a promising target for breeding or biotechnology intervention strategies as gene knockdown leads to the repulsion of economically important plant parasites and retains attraction of the beneficial rhizobacterium B. subtilis. This study exposes the link between ABC transporters, root exudate composition, and ex planta interactions with agriculturally and economically relevant rhizosphere organisms, paving the way for new approaches to rhizosphere engineering and crop protection.
Metabolic GWAS of elite athletes reveals novel genetically-influenced metabolites associated with athletic performance
Authors: Al-Khelaifi Fatima , Diboun Ilhame , Donati Francesco , Botrè Francesco , Abraham David , Hingorani Aroon , Albagha Omar , Georgakopoulos Costas , Suhre Karsten , Yousri Noha A. , Elrayess Mohamed A.
Published: December 2019

Genetic research of elite athletic performance has been hindered by the complex phenotype and the relatively small effect size of the identified genetic variants. The aims of this study were to identify genetic predisposition to elite athletic performance by investigating genetically-influenced metabolites that discriminate elite athletes from non-elite athletes and to identify those associated with endurance sports. By conducting a genome wide association study with high-resolution metabolomics profiling in 490 elite athletes, common variant metabolic quantitative trait loci (mQTLs) were identified and compared with previously identified mQTLs in non-elite athletes. Among the identified mQTLs, those associated with endurance metabolites were determined. Two novel genetic loci in FOLH1 and VNN1 are reported in association with N-acetyl-aspartyl-glutamate and Linoleoyl ethanolamide, respectively. When focusing on endurance metabolites, one novel mQTL linking androstenediol (3alpha, 17alpha) monosulfate and SULT2A1 was identified. Potential interactions between the novel identified mQTLs and exercise are highlighted. This is the first report of common variant mQTLs linked to elite athletic performance and endurance sports with potential applications in biomarker discovery in elite athletic candidates, non-conventional anti-doping analytical approaches and therapeutic strategies.
Electrically tuning soft membranes to both a higher and a lower transparency
Authors: Chen Leihao , Ghilardi Michele , Busfield James J. C. , Carpi Federico
Published: December 2019

The possibility to electrically tune the optical transparency of thin membranes is of significant interest for a number of possible applications, such as controllable light diffusers and smart windows, both for residential and mobile use. As a difference from state-of-the-art approaches, where with an applied voltage the transparency can only increase or decrease, this paper presents the first concept to make it electrically tuneable to both higher and lower values, within the same device. The concept is applicable to any soft insulating membrane, by coating both of its surfaces with a circular transparent stretchable conductor, surrounded by a stretchable annular conductor. The two conductors are used as independently addressable electrodes to generate a dielectric elastomer-based actuation of the membrane, so as to electrically control its surface topography. We show that the optical transmittance can electrically be modulated within a broad range, between 25% and 83%. This approach could be especially advantageous for systems that require such a broad tuning range within structures that have to be thin, lightweight and acoustically silent in operation.
An intuitive explanation of dermoscopic structures by digitally reconstructed pathological horizontal top-down view images
Authors: Kasuya Akira , Aoshima Masahiro , Fukuchi Kensuke , Shimauchi Takatoshi , Fujiyama Toshiharu , Tokura Yoshiki
Published: December 2019

Dermoscopy is a convenient tool to diagnose melanocytic lesions, especially nevus and melanoma. Various pigmented structures, including pigment network, dots and globules, and streaks, are observed in dermoscopy. Usually, 2D vertical images are used to explain the correlation of dermoscopy and histopathology. However, because the image of dermoscopy is horizontal, it is difficult for the horizontal view of dermoscopy to refer to the vertical view of histopathology. In our study, we digitally reconstructed 2D horizontal top-down view images and 3D aerial images from 50–100 serial 2D vertical sections by using high-speed scanner and 3D software in 6 cases of melanocytic lesion. Our new technology intuitively explained the histopathological structures corresponding to the dermoscopic structures. This technique could be used as a good educational tool for beginners.
The Novel Notch-induced Long Noncoding RNA LUNAR1 Determines the Proliferation and Prognosis of Colorectal Cancer
Authors: Zhang Zixi , Li Gai , Qiu He , Yang Jingyi , Bu Xin , Zhu Shaojun , Zheng Jianyong , Dang Chengxue , Wang Weizhong , Chu Dake
Published: December 2019

In contrast to what is known about the complicated roles of Notch signalling in human malignancies, the direct target genes of Notch signalling are still unclear. Recently, long noncoding RNAs (lncRNAs) have been found to play various roles in the post-transcriptional regulation of gene expression. In the present study, we investigated the potential role of the Notch-induced lncRNA LUNAR1 in colorectal cancer (CRC). We recruited 196 cases of clinical CRC specimens and investigated LUNAR1 levels in these specimens. The associations of LUNAR1 with tumour aggressiveness and clinical outcomes were evaluated. Moreover, the impact of LUNAR1 on the malignant behaviour of tumour cells was tested in cell lines. Significantly increased expression of LUNAR1 in clinical CRC specimens was detected compared with that in matching normal tissues. LUNAR1 expression in CRC was found to be associated with the tumour aggressiveness, disease-free survival and overall survival of patients. The downregulation of LUNAR1 in SW620 cells inhibited cell proliferation, migration, invasion and tumour growth while inducing apoptosis. Moreover, the inhibition of LUNAR1 can significantly suppress IGF1 signalling in CRC. These results indicated that LUNAR1 was increased in CRC and might promote tumour progression. Thus, LUNAR1 may constitute a promising prognostic marker for the clinical management of CRC.
The production of l- and d-phenylalanines using engineered phenylalanine ammonia lyases from Petroselinum crispum
Authors: Tork Souad Diana , Nagy Emma Zsófia Aletta , Cserepes Lilla , Bordea Diana Monica , Nagy Botond , Toşa Monica Ioana , Paizs Csaba , Bencze László Csaba
Published: December 2019

The biocatalytic synthesis of l- and d-phenylalanine analogues of high synthetic value have been developed using as biocatalysts mutant variants of phenylalanine ammonia lyase from Petroselinum crispum (PcPAL), specifically tailored towards mono-substituted phenylalanine and cinnamic acid substrates. The catalytic performance of the engineered PcPAL variants was optimized within the ammonia elimination and ammonia addition reactions, focusing on the effect of substrate concentration, biocatalyst:substrate ratio, reaction buffer and reaction time, on the conversion and enantiomeric excess values. The optimal conditions provided an efficient preparative scale biocatalytic procedure of valuable phenylalanines, such as (S)-m-methoxyphenylalanine (Y = 40%, ee > 99%), (S)-p-bromophenylalanine (Y = 82%, ee > 99%), (S)-m-(trifluoromethyl)phenylalanine (Y = 26%, ee > 99%), (R)-p-methylphenylalanine, (Y = 49%, ee = 95%) and (R)-m-(trifluoromethyl)phenylalanine (Y = 34%, ee = 93%).
Transcriptome-wide analysis of the SCNT bovine abnormal placenta during mid- to late gestation
Authors: Gao Guangqi , Wang Shenyuan , Zhang Jiaqi , Su Guanghua , Zheng Zhong , Bai Chunling , Yang Lei , Wei Zhuying , Wang Xiuying , Liu Xiao , Guo Ziru , Li Guangpeng , Su Xiaohu , Zhang Li
Published: December 2019

The dysfunction of placenta is common in somatic cell nuclear transfer (SCNT) cloned cattle and would cause aberrant fetal development and even abortion, which occurred with highest rate at the mid- to late gestation. However, the mechanism of abnormal placentas was unclear. To analyze the transcriptome-wide characteristics of abnormal placentas in SCNT cloned cattle, the mRNA, lncRNA and miRNA of placental cotyledon tissue at day 180 after gestation were sequenced. A total of 19,055 mRNAs, 30,141 lncRNAs and 684 miRNAs were identified. Compared with control group, 362 mRNAs, 1,272 lncRNAs and nine miRNAs (six known and three novel miRNAs) were differentially expressed (fold change ≥ 2 and P-value < 0.05). The differentially expressed genes were functionally enriched in urea and ions transmembrane transport, which indicated that the maternal-fetal interactions were disturbed in impaired placentas. Furthermore, the competing endogenous RNAs (ceRNAs) networks were identified to illustrate their roles in abnormal placental morphology. The present research would be helpful to discover the mechanism of late gestational abnormality of SCNT cattle by provides important genomic information and insights.
Human mesenchymal stem cells are resistant to UV-B irradiation
Authors: Lopez Perez Ramon , Brauer Jannek , Rühle Alexander , Trinh Thuy , Sisombath Sonevisay , Wuchter Patrick , Grosu Anca-Ligia , Debus Jürgen , Saffrich Rainer , Huber Peter E. , Nicolay Nils H.
Published: December 2019

Albeit being an effective therapy for various cutaneous conditions, UV-B irradiation can cause severe skin damage. While multipotent mesenchymal stem cells (MSCs) may aid the regeneration of UV-B-induced skin injuries, the influence of UV-B irradiation on MSCs remains widely unknown. Here, we show that human MSCs are relatively resistant to UV-B irradiation compared to dermal fibroblasts. MSCs exhibited higher clonogenic survival, proliferative activity and viability than dermal fibroblasts after exposure to UV-B irradiation. Cellular adhesion, morphology and expression of characteristic surface marker patterns remained largely unaffected in UV-irradiated MSCs. The differentiation ability along the adipogenic, osteogenic and chondrogenic lineages was preserved after UV-B treatment. However, UV-B radiation resulted in a reduced ability of MSCs and dermal fibroblasts to migrate. MSCs exhibited low apoptosis rates after UV-B irradiation and repaired UV-B-induced cyclobutane pyrimidine dimers more efficiently than dermal fibroblasts. UV-B irradiation led to prolonged p53 protein stability and increased p21 protein expression resulting in a prolonged G2 arrest and senescence induction in MSCs. The observed resistance may contribute to the ability of these multipotent cells to aid the regeneration of UV-B-induced skin injuries.
Proximal femur fat fraction variation in healthy subjects using chemical shift-encoding based MRI
Authors: Gondim Teixeira Pedro Augusto , Cherubin Tanguy , Badr Sammy , Bedri Adrien , Gillet Romain , Albuisson Eliane , Blum Alain
Published: December 2019

The objective of this studywasto describe the normal variation of bone marrow fat content in the proximal femur considering the influence of side, age, sex and body mass index using fat fraction MRI. From September 2012 to July 2016, the MRI of 131 patients (258 hips) considered to have a normal MRI appearance were retrospectively evaluated. Patient records were searched to allow calculation of the body mass index (BMI). Water-fat based chemical shift MRI was available for all patients included. Proton density fat fraction maps were calculated, and measurements were performed in the femoral epiphysis, intertrochanteric region, and greater trochanter. The influence of patient age, sex, hip side and BMI on fat fraction values was assessed. Fat fraction was significantly different in the different locations evaluated (P = 0.0001). Patient sex and age significantly influenced fat fraction values in all regions evaluated (P < 0.02) with the exception of the epiphysis for sex (p = 0.07). In all locations, PDFF values were higher in men compared to women (3.3%, 4.4% and 13.1% higher in the epiphysis, greater trochanter and intertrochanteric region respectively). The intertrochanteric region presented the lowest fat fraction values with the highest variation compared to the greater trochanter and the epiphysis. BMI only influenced fat fraction values in the intertrochanteric region of females over 42 years old (P = 0.014). The interobserver variability of the measurements performed was considered to be excellent (ICC = 0.968). In conclusion, patient sex, age, and measurement location significantly influenced fat fraction values indicating that specific standards of reference are needed depending on these factors.
Phase Segmentation in Atom-Probe Tomography Using Deep Learning-Based Edge Detection
Authors: Madireddy Sandeep , Chung Ding-Wen , Loeffler Troy , Sankaranarayanan Subramanian K. R. S. , Seidman David N. , Balaprakash Prasanna , Heinonen Olle
Published: December 2019

Atom-probe tomography (APT) facilitates nano- and atomic-scale characterization and analysis of microstructural features. Specifically, APT is well suited to study the interfacial properties of granular or heterophase systems. Traditionally, the identification of the interface between, for precipitate and matrix phases, in APT data has been obtained either by extracting iso-concentration surfaces based on a user-supplied concentration value or by manually perturbing the concentration value until the iso-concentration surface qualitatively matches the interface. These approaches are subjective, not scalable, and may lead to inconsistencies due to local composition inhomogeneities. We introduce a digital image segmentation approach based on deep neural networks that transfer learned knowledge from natural images to automatically segment the data obtained from APT into different phases. This approach not only provides an efficient way to segment the data and extract interfacial properties but does so without the need for expensive interface labeling for training the segmentation model. We consider here a system with a precipitate phase in a matrix and with three different interface modalities—layered, isolated, and interconnected—that are obtained for different relative geometries of the precipitate phase. We demonstrate the accuracy of our segmentation approach through qualitative visualization of the interfaces, as well as through quantitative comparisons with proximity histograms obtained by using more traditional approaches.
Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model
Authors: Zhuo Qian , Yu Bohai , Zhou Jing , Zhang Jingyun , Zhang Runling , Xie Jingyan , Wang Qingling , Zhao Shuli
Published: December 2019

Previous reports have suggested that many gut microbiomes were associated with the development of colorectal cancer (CRC), and could modulate response to numerous forms of cancer therapy, including checkpoint blockade immunotherapy. Here we evaluated the protective efficacy of Lactobacillus acidophilus (L. acidophilus) cell lysates combined with an anti-CTL antigen-4 blocking antibody (CTLA-4 mAb) in syngeneic BALB/c mice CRC models induce by a single intraperitoneal injection of 10 mg/kg azoxymethane (AOM), followed by three cycles of 2% dextran sulfate sodium (DSS) in drinking water. In contrast to CTLA-4 mAb monotherapy, L. acidophilus lysates could attenuate the loss of body weight and the combined administration significantly protected mice against CRC development, which suggested that the lysates enhanced antitumor activity of CTLA-4 mAb in model mice. The enhanced efficacy was associated with the increased CD8 + T cell, increased effector memory T cells (CD44 + CD8 + CD62L+), decreased Treg (CD4 + CD25 + Foxp3+) and M2 macrophages (F4/80 + CD206+) in the tumor microenvironment. In addition, our results revealed that L. acidophilus lysates had an immunomodulatory effect through inhibition the M2 polarization and the IL-10 expressed levels of LPS-activated Raw264.7 macrophages. Finally, the 16S rRNA gene sequencing of fecal microbiota demonstrated that the combined administration significantly inhibited the abnormal increase in the relative abundance of proteobacteria and partly counterbalance CRC-induced dysbiosis in model mice. Overall, these data support promising clinical possibilities of L. acidophilus lysates with CTLA-4 mAb in cancer patients and the hypothesis that probiotics help shape the anticancer immune response.
Yeast R2TP Interacts with Extended Termini of Client Protein Nop58p
Authors: Yu Ge , Zhao Yu , Tian Shaoxiong , Rai Jay , He Huan , Spear John , Sousa Duncan , Fan Jinbo , Yu Hong-Guo , Stagg Scott M. , Li Hong
Published: December 2019

The AAA + ATPase R2TP complex facilitates assembly of a number of ribonucleoprotein particles (RNPs). Although the architecture of R2TP is known, its molecular basis for acting upon multiple RNPs remains unknown. In yeast, the core subunit of the box C/D small nucleolar RNPs, Nop58p, is the target for R2TP function. In the recently observed U3 box C/D snoRNP as part of the 90 S small subunit processome, the unfolded regions of Nop58p are observed to form extensive interactions, suggesting a possible role of R2TP in stabilizing the unfolded region of Nop58p prior to its assembly. Here, we analyze the interaction between R2TP and a Maltose Binding Protein (MBP)-fused Nop58p by biophysical and yeast genetics methods. We present evidence that R2TP interacts largely with the unfolded termini of Nop58p. Our results suggest a general mechanism for R2TP to impart specificity by recognizing unfolded regions in its clients.
Hepatic Mitochondrial Oxidative Metabolism and Lipogenesis Synergistically Adapt to Mediate Healthy Embryonic-to-Neonatal Transition in Chicken
Authors: Surugihalli Chaitra , Porter Tom E. , Chan Angela , Farley Linda S. , Maguire Meghan , Zhang Christine , Kattapuram Nathan , Muyyarikkandy Muhammed S. , Liu Hsiao-Ching , Sunny Nishanth E.
Published: December 2019

During the normal embryonic-to-neonatal development, the chicken liver is subjected to intense lipid burden from high rates of yolk-lipid oxidation and also from the accumulation of the yolk-derived and newly synthesized lipids from carbohydrates. High rates of hepatic lipid oxidation and lipogenesis are also central features of non-alcoholic fatty liver disease (NAFLD) in both rodents and humans, but is associated with impaired insulin signaling, dysfunctional mitochondrial energetics and oxidative stress. However, these adverse effects are not apparent in the liver of embryonic and neonatal chicken, despite lipid burden. Utilizing comprehensive metabolic profiling, we identify that steady induction of hepatic mitochondrial tricarboxylic acid (TCA) cycle and lipogenesis are central features of embryonic-to-neonatal transition. More importantly, the induction of TCA cycle and lipogenesis occurred together with the downregulation of hepatic β-oxidation and ketogenesis in the neonatal chicken. This synergistic remodeling of hepatic metabolic networks blunted inflammatory onset, prevented accumulation of lipotoxic intermediates (ceramides and diacylglycerols) and reduced reactive oxygen species production during embryonic-to-neonatal development. This dynamic remodeling of hepatic mitochondrial oxidative flux and lipogenesis aids in the healthy embryonic-to-neonatal transition in chicken. This natural physiological system could help identify mechanisms regulating mitochondrial function and lipogenesis, with potential implications towards treatment of NAFLD.
A microfluidics-based wound-healing assay for studying the effects of shear stresses, wound widths, and chemicals on the wound-healing process
Authors: Lin Jin-Young , Lo Kai-Yin , Sun Yung-Shin
Published: December 2019

Collective cell migration plays important roles in various physiological processes. To investigate this collective cellular movement, various wound-healing assays have been developed. In these assays, a “wound” is created mechanically, chemically, optically, or electrically out of a cellular monolayer. Most of these assays are subject to drawbacks of run-to-run variations in wound size/shape and damages to cells/substrate. Moreover, in all these assays, cells are cultured in open, static (non-circulating) environments. In this study, we reported a microfluidics-based wound-healing assay by using the trypsin flow-focusing technique. Fibroblasts were first cultured inside this chip to a cellular monolayer. Then three parallel fluidic flows (containing normal medium and trypsin solution) were introduced into the channels, and cells exposed to protease trypsin were enzymatically detached from the surface. Wounds of three different widths were generated, and subsequent wound-healing processes were observed. This assay is capable of creating three or more wounds of different widths for investigating the effects of various physical and chemical stimuli on wound-healing speeds. The effects of shear stresses, wound widths, and β-lapachone (a wound healing-promoting chemical) on wound-healing speeds were studied. It was found that the wound-healing speed (total area healed per unit time) increased with increasing shear stress and wound width, but under a shear stress of 0.174 mPa the linear healing speed (percent area healed per unit time) was independent of the wound width. Also, the addition of β-lapachone up to 0.5 μM did not accelerate wound healing. This microfluidics-based assay can definitely help in understanding the mechanisms of the wound-healing process and developing new wound-healing therapies.
Bidirectional Selector Utilizing Hybrid Diodes for PCRAM Applications
Authors: Shuang Yi , Hatayama Shogo , An Junseop , Hong Jinpyo , Ando Daisuke , Song Yunheub , Sutou Yuji
Published: December 2019

Three-dimensional crossbar technology has been of great significance for realizing high density and multiple terabytes of data storage in memory devices. However, to further scale down the size of memory devices, a selector exhibiting nonlinear electrical properties should be in series with a memory layer in case of unwanted sneak current disturbance. Conventional selectors usually utilize a complicated multilayer structure to realize the high nonlinearity of current, which might be incompatible with certain manufacturing processes or limit the scalability of memory. Herein, we propose a simple heterojunction diode using an n-type oxide semiconductor, specifically, InGaZnO4(IGZO), and a p-type phase change material (PCM), specifically, N-doped Cr2Ge2Te6(NCrGT), to realize self-selective performance. The electrode/IGZO/NCrGT/plug-electrode structure with an IGZO/NCrGT pn diode and NCrGT/plug-electrode Schottky diode can realize bidirectional, self-selective phase change random access memory (PCRAM) for either amorphous or crystalline NCrGT. The approximate equilibrium energy band diagrams for the IGZO/NCrGT pn junction and the IGZO/NCrGT/W hybrid junction were proposed to explain the possible conduction mechanism. We demonstrated that hybrid diode-type PCM memory exhibits both selectivity and resistive switching characteristics. The present findings offer new insight into selector technology for PCM.
Real-world safety evaluation of musculoskeletal adverse events associated with Korean pediatric fluoroquinolone use: a nationwide longitudinal retrospective cohort study
Authors: Kim Yoonhye , Paik Minwoo , Khan Chanjoo , Kim Yae-Jean , Kim EunYoung
Published: December 2019

Though the pediatric use of fluoroquinolones (FQs) is limited for musculoskeletal safety concerns, the clinical usefulness still exists. This study examined the association between FQs and musculoskeletal adverse events (AEs) as well as the possible risk factors associated with the pediatric FQs uses. This population-based, longitudinal, retrospective study was conducted using Korean National Sample Cohort database originating between 2002 and 2015. An FQ-treated pediatric cohort (<18 years old) was compared to a control treated with amoxicillin. Propensity score matching (PSM) and a Cox proportional hazard model was used to estimate the hazard ratio (HR) for a diagnosis of musculoskeletal AEs within 60 days of the first prescription. Among one million participants, total of 15,706 and 147,840 children were eligible for the FQ and amoxicillin cohorts, respectively. The PSM cohorts showed a slightly increased risk of musculoskeletal AEs after FQ treatment (HR, 1.19; 95% confidence interval, 1.01–1.40; p = 0.042). This association was stronger in males, older patients, and some FQs users. This study indicates that pediatric FQ use is associated with a risk of musculoskeletal AEs and that FQ use should be carefully monitored in groups with certain risk factors. Well-designed pragmatic trials could be expected to clarify these issues.
Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling
Authors: Park Sung-Soo , Lee Yeon-Joo , Kang Hyuno , Yang Garam , Hong Eun Jeong , Lim Jin Yeong , Oh Sejong , Kim Eungseok
Published: December 2019

Browning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.
Multi-Factor Regulation of the Master Modulator LeuO for the Cyclic-(Phe-Pro) Signaling Pathway in Vibrio vulnificus
Authors: Park Na-Young , Kim In Hwang , Wen Yancheng , Lee Keun-Woo , Lee Sora , Kim Jeong-A , Jung Kwang-Hwan , Lee Kyu-Ho , Kim Kun-Soo
Published: December 2019

LeuO plays the role of a master regulator in the cyclic-L-phenylalanine-L-proline (cFP)-dependent signaling pathway in Vibrio vulnificus. cFP, as shown through isothermal titration calorimetry analysis, binds specifically to the periplasmic domain of ToxR. Binding of cFP triggers a change in the cytoplasmic domain of ToxR, which then activates transcription of leuO encoding a LysR-type regulator. LeuO binds to the region upstream of its own coding sequence, inhibiting its own transcription and maintaining a controlled level of expression. A five-bp deletion in this region abolished expression of LeuO, but a ten-bp deletion did not, suggesting that a DNA bending mechanism is involved in the regulation. Furthermore, binding of RNA polymerase was significantly lower both in the deletion of the ToxR binding site and in the five-bp deletion, but not in the ten-bp deletion, as shown in pull-down assays using an antibody against RNA polymerase subunit α. In summary, multiple factors are involved in control of the expression of LeuO, a master regulator that orchestrates downstream regulators to modulate factors required for survival and pathogenicity of the pathogen.
Fluctuation analysis in the dynamic characteristics of continental glacier based on Full-Stokes model
Authors: Wu Zhen , Zhang Huiwen , Liu Shiyin , Ren Dong , Bai Xuejian , Xun Zhaojie , Ma Zhentao
Published: December 2019

Ice thickness has a great influence on glacial movement and ablation. Over the course of the change in thickness, area and external climate, the dynamic process of how glaciers change and whether a glacier’s changes in melting tend to be stable or irregular is a problem that needs to be studied in depth. In our study, the changes in the dynamic process of the No. 8 Glacier in Hei Valley (H8) under the conditions of different thicknesses in 1969 and 2009 were simulated based on the Full-Stokes code Elmer/Ice (http://www.csc.fi/elmer/). The results were as follows: (1) The thickness reduction in glaciers would lead to a decrease in ice surface tension and basal pressure and friction at the bottom, and the resulting extensional and compressional flow played an important role in the variations in glacial velocity. (2) The force at the bottom of the glacier was key to maintaining the overall stress balance, and the glaciers that often melted and collapsed in bedrock were more easily destroyed by the overall force balance and increased change rate of glacial thaw. (3) Temperature changes at different altitudes affected the ice viscous force. The closer the ice surface temperature was to the melting point, the greater the influence of temperature changes on the ice viscous force and ice surface velocity. Finally, we used the RCP 4.8 and 8.5 climate models to simulate the changes in H8 over the next 40 years. The results showed that with some decreases in ice surface compression and tension, the gravity component changes caused by local topography begin to control the ice flow movement on the surface of glacier, and melting of the glacial surface will appear as an irregular change. The simulation results further confirmed that the fluctuation in glacial dynamic characteristics could be attributed to the change in the gravity component caused by ablation.
Shape characterization and discrimination of single nanoparticles using solid-state nanopores
Authors: Si Wei , Sha Jingjie , Sun Qianyi , He Zhen , Wu Liang , Chen Chang , Yu Shuhong , Chen Yunfei
Published: December 2019

Low-cost and high-throughput shape characterization and differentiation of nanoparticles were realized by simply measuring current blockades through nanopores.
Super stable giant tubes with densely packed multilayer ultrathick membranes self-assembled from amphiphilic polyamide
Authors: Wang Lipeng , Zhu Qing , Ding Liping , Bai Yongping
Published: December 2019

This work reports on the preparation of giant tubes with millimeter-scale length, micron diameter and ultrathick walls above 250 nm, from the aqueous self-assembly of a novel amphiphilic polyamide.
DFT study of various tungstates for photocatalytic water splitting
Authors: Huang Bosi , Hart Judy N.
Published: December 2019

The electronic properties of ternary tungstates can be tuned for photocatalytic water splitting applications by appropriate choice of composition.
A Pickering emulsion of a bifunctional interface prepared from Pd nanoparticles supported on silicane-modified graphene oxide: an efficient catalyst for water-mediated catalytic hydrogenation
Authors: Xue Bing , Xu Tongchun , Li Dongsheng , Xu Jie , Li Yongxin , Wang Fei , Zhu Jie
Published: December 2019

A Pickering emulsion of bifunctional interface that prepared by Pd nanoparticles supported on silicane-modified graphene oxide exhibited high catalytic performance for hydrogenation of CAL.