bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential transfection of RUNX2/SP7 and ATF4 coated onto dexamethasone-loaded nanospheres enhances osteogenesis
Authors: Kim Hye Jin , Park Ji Sun , Yi Se Won , Oh Hyun Jyung , Kim Jae-Hwan , Park Keun-Hong 
Published: January 2018

AbstractThe timing of gene transfection greatly influences stem cell differentiation. Sequential transfection is crucial for regulation of cell behavior. When transfected several days after differentiation initiation, genes expressed at the late stage of differentiation can regulate cell behaviors and functions. To determine the optimal timing of key gene delivery, we sequentially transfected human mesenchymal stem cells (hMSCs). This method can easily control osteogenesis of stem cells. hMSCs were first transfected with RUNX2 and SP7 using poly(lactic-co-glycolic acid) nanoparticles to induce osteogenesis, and then with ATF4 after 5, 7, and 14 days. Prior to transfecting hMSCs with all three genes, each gene was individually transfected and its expression was monitored. Transfection of these genes was confirmed by RT-PCR, Western blotting, and confocal microscopy. The pDNAs entered the nuclei of hMSCs, and RUNX2 and SP7 proteins were translated and triggered osteogenesis. Second, the ATF4 gene was delivered when cells were at the pre-osteoblasts stage. To induce the osteogenesis of hMSCs, the optimal timing of ATF4 gene delivery was 14 days after RUNX2/SP7 transfection. Experiments in 2- and 3-dimensional culture systems confirmed that transfection of ATF4 at 14 days after RUNX2/SP7 promoted osteogenic differentiation of hMSCs.
Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue
Authors: Tahara Yu , Yamazaki Mayu , Sukigara Haruna , Motohashi Hiroaki , Sasaki Hiroyuki , Miyakawa Hiroki , Haraguchi Atsushi , Ikeda Yuko , Fukuda Shinji , Shibata Shigenobu 
Published: January 2018

AbstractMicrobiota-derived short-chain fatty acids (SCFAs) and organic acids produced by the fermentation of non-digestible fibre can communicate from the microbiome to host tissues and modulate homeostasis in mammals. The microbiome has circadian rhythmicity and helps the host circadian clock function. We investigated the effect of SCFA or fibre-containing diets on circadian clock phase adjustment in mouse peripheral tissues (liver, kidney, and submandibular gland). Initially, caecal SCFA concentrations, particularly acetate and butyrate, induced significant day-night differences at high concentrations during the active period, which were correlated with lower caecal pH. By monitoring luciferase activity correlated with the clock gene Period2 in vivo, we found that oral administration of mixed SCFA (acetate, butyrate, and propionate) and an organic acid (lactate), or single administration of each SCFA or lactate for three days, caused phase changes in the peripheral clocks with stimulation timing dependency. However, this effect was not detected in cultured fibroblasts or cultured liver slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect modulation of circadian clocks in vivo. Finally, cellobiose-containing diets facilitated SCFA production and refeeding-induced peripheral clock entrainment. SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock adjustment, suggesting prebiotics as novel therapeutic candidates for misalignment.
Abnormal behaviours relevant to neurodevelopmental disorders in Kirrel3-knockout mice
Authors: Hisaoka Tomoko , Komori Tadasuke , Kitamura Toshio , Morikawa Yoshihiro 
Published: January 2018

AbstractIn the nervous system, Kirrel3 is involved in neuronal migration, axonal fasciculation, and synapse formation. Recently, genetic links have been reported between mutations in the KIRREL3 gene and increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability. To elucidate the causal relationship between KIRREL3 deficiency and behavioural abnormalities relevant to neurodevelopmental disorders, we generated global Kirrel3-knockout (Kirrel3−/−) mice and investigated the detailed behavioural phenotypes. In the three-chambered social approach test, Kirrel3−/−mice displayed a significant preference for a mouse over a non-social object but no significant preference for a stranger mouse over a familiar mouse. Ultrasonic communications, including pup-to-mother calls, male-female courtship vocalisation and resident responses to intruder, were significantly impaired in Kirrel3−/−mice. Significant increases in locomotor activity and repetitive rearing were also observed in Kirrel3−/−mice. Furthermore, the performance of Kirrel3−/−mice in the rotarod test was significantly better than that of wild-type mice. In the acoustic startle test, Kirrel3−/−mice were significantly hypersensitive to acoustic stimuli. Anxiety-related behaviours and spatial or fear memory acquisition were normal in Kirrel3−/−mice. These findings suggest that Kirrel3−/−mice exhibit autistic-like behaviours, including social and communicative deficits, repetitive behaviours, and sensory abnormalities, as well as hyperactivity.
Functional metagenomics identifies novel genes ABCTPP, TMSRP1 and TLSRP1 among human gut enterotypes
Authors: Verma Manoj Kumar , Ahmed Vasim , Gupta Shashank , Kumar Jitendra , Pandey Rajesh , Mandhan Vibha , Chauhan Nar Singh 
Published: January 2018

AbstractEvery niche in the biosphere is touched by the seemingly endless capacity of microbes to transform the world around them by adapting swiftly and flexibly to the environmental changes, likewise the gastrointestinal tract is no exception. The ability to cope with rapid changes in external osmolarity is an important aspect of gut microbes for their survival and colonization. Identification of these survival mechanisms is a pivotal step towards understanding genomic suitability of a symbiont for successful human gut colonization. Here we highlight our recent work applying functional metagenomics to study human gut microbiome to identify candidate genes responsible for the salt stress tolerance. A plasmid borne metagenomic library of Bacteroidetes enriched human fecal metagenomic DNA led to identification of unique salt osmotolerance clones SR6 and SR7. Subsequent gene analysis combined with functional studies revealed that TLSRP1 within pSR7 and TMSRP1 and ABCTPP of pSR6 are the active loci responsible for osmotolerance through an energy dependent mechanism. Our study elucidates the novel genetic machinery involved in bestowing osmotolerance in Prevotella and Bacteroidetes, the predominant microbial groups in a North Indian population. This study unravels an alternative method for imparting ionic stress tolerance, which may be prevalent in the human gut microbiome.
Discovery of novel bacterial topoisomerase I inhibitors by use of in silico docking and in vitro assays
Authors: Sandhaus Shayna , Chapagain Prem P. , Tse-Dinh Yuk-Ching 
Published: January 2018

AbstractTopoisomerases are important targets for antibacterial and anticancer therapies. Bacterial topoisomerase I remains to be exploited for antibiotics that can be used in the clinic. Inhibitors of bacterial topoisomerase I may provide leads for novel antibacterial drugs against pathogens resistant to current antibiotics. TB is the leading infectious cause of death worldwide, and new TB drugs against an alternative target are urgently needed to overcome multi-drug resistance.Mycobacterium tuberculosistopoisomerase I (MtbTopI) has been validated genetically and chemically as a TB drug target. Here we conductedin silicoscreening targeting an active site pocket of MtbTopI. The top hits were assayed for inhibition of MtbTopI activity. The shared structural motif found in the active hits was utilized in a second round ofin silicoscreening andin vitroassays, yielding selective inhibitors of MtbTopI with IC50s as low as 2 µM. Growth inhibition ofMycobacterium smegmatisby these compounds in combination with an efflux pump inhibitor was diminished by the overexpression of recombinant MtbTopI. This work demonstrates thatin silicoscreening can be utilized to discover new bacterial topoisomerase I inhibitors, and identifies a novel structural motif which could be explored further for finding selective bacterial topoisomerase I inhibitors.
A systematic review and meta-analysis: Association between MGMT hypermethylation and the clinicopathological characteristics of non-small-cell lung carcinoma
Authors: Chen Lin , Wang Yong , Liu Fen , Xu Liyao , Peng Feifei , Zhao Ning , Fu Biqi , Zhu Zijie , Shi Yu , Liu Jiansheng , Wu Renrui , Wang Chen , Yao Shengmin , Li Yong 
Published: January 2018

AbstractThe relationship between O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) has remained controversial and unclear. Therefore, in this study we have undertaken a systematic review and meta-analysis of relevant studies to quantitatively investigate this association. We identified 30 eligible studies investigating 2714 NSCLC patients. The relationship between MGMT hypermethylation and NSCLC was identified based on 20 studies, including 1539 NSCLC patient tissue and 1052 normal and adjacent tissue samples (OR = 4.60, 95% CI = 3.46~6.11,p < 0.00001). MGMT methylation varied with ethnicity (caucasian: OR = 4.56, 95% CI = 2.63~7.92,p < 0.00001; asian: OR = 5.18, 95% CI = 2.03~13.22,p = 0.0006) and control style (autologous: OR = 4.44, 95% CI = 3.32~5.92,p < 0.00001; heterogeneous: OR = 9.05, 95% CI = 1.79~45.71,p = 0.008). In addition, MGMT methylation was observed to be specifically associated with NSCLC clinical stage, and not with age, sex, smoking, pathological types, and differentiation status. Also MGMT methylation did not impact NSCLC patients survival (HR = 1.32, 95% CI = 0.77~2.28,p = 0.31). Our study provided clear evidence about the association of MGMT hypermethylation with increased risk of NSCLC.
Transcriptional profiling of long non-coding RNAs in mantle of Crassostrea gigas and their association with shell pigmentation
Authors: Feng Dandan , Li Qi , Yu Hong , Kong Lingfeng , Du Shaojun 
Published: January 2018

AbstractLong non-coding RNAs (lncRNAs) play crucial roles in diverse biological processes and have drawn extensive attention in the past few years. However, lncRNAs remain poorly understood about expression and roles in Crassostrea gigas, a potential model organism for marine molluscan studies. Here, we systematically identified lncRNAs in the mantles of C. gigas from four full-sib families characterized by white, black, golden, and partially pigmented shell. Using poly(A)-independent and strand-specific RNA-seq, a total of 441,205,852 clean reads and 12,243 lncRNA transcripts were obtained. LncRNA transcripts were relatively short with few exons and low levels of expression in comparison to protein coding mRNA transcripts. A total of 427 lncRNAs and 349 mRNAs were identified to differentially express among six pairwise groups, mainly involving in biomineralization and pigmentation through functional enrichment. Furthermore, a total of 6 mRNAs and their cis-acting lncRNAs were predicted to involve in synthesis of melanin, carotenoid, tetrapyrrole, or ommochrome. Of them, chorion peroxidase and its cis-acting lincRNA TCONS_00951105 are implicated in playing an essential role in the melanin synthetic pathway. Our studies provided the first systematic characterization of lncRNAs catalog expressed in oyster mantle, which may facilitate understanding the molecular regulation of shell colour diversity and provide new insights into future selective breeding of C. gigas for aquaculture.
Improving performance of pedestrian positioning by using vehicular communication signals
Authors: Tang Suhua , Obana Sadao 
Published: January 2018

Pedestrian‐to‐vehicle communications, where pedestrian devices transmit their position information to nearby vehicles to indicate their presence, help to reduce pedestrian accidents. Satellite‐based systems are widely used for pedestrian positioning, but have much degraded performance in urban canyon, where satellite signals are often obstructed by roadside buildings. The authors propose a pedestrian positioning method, which leverages vehicular communication signals and uses vehicles as anchors. The performance of pedestrian positioning is improved from three aspects: (i) channel state information instead of received signal strength indicator (RSSI) is used to estimate pedestrian‐vehicle distance with higher precision. (ii) Only signals with line‐of‐sight path are used, and the property of distance error is considered. (iii) Fast mobility of vehicles is used to get diverse measurements, and Kalman filter is applied to smooth positioning results. Extensive evaluations, via trace‐based simulation, confirm that (i) fixing rate of positions can be much improved. (ii) Horizontal positioning error can be greatly reduced, nearly by one order compared with off‐the‐shelf receivers, by almost half compared with RSSI‐based method, and can be reduced further to about 80 cm when vehicle transmission period is 100 ms and Kalman filter is applied. Generally, positioning performance increases with the number of available vehicles and their transmission frequency.
Adaptive nonparametric drift estimation of an integrated jump diffusion process
Authors: Funke Benedikt , Schmisser Émeline 
Published: January 2018

In the present article, we investigate nonparametric estimation of the unknown drift function b in an integrated Lévy driven jump diffusion model. Our aim will be to estimate the drift on a compact set based on a high-frequency data sample.
Instead of observing the jump diffusion process V itself, we observe a discrete and high-frequent sample of the integrated process

Xt := ∫0t Vsds

Based on the available observations of Xt, we will construct an adaptive penalized least-squares estimate in order to compute an adaptive estimator of the corresponding drift function b. Under appropriate assumptions, we will bound the L2-risk of our proposed estimator. Moreover, we study the behavior of the proposed estimator in various Monte Carlo simulation setups.
Fahreignung aus (neuro)ophthalmologischer Sicht
Authors: Rohrschneider Klaus 
Published: January 2018

ZusammenfassungDie Anforderungen an das Sehvermögen zur Fahreignung sind in Anlage 6 zur Fahrerlaubnisverordnung festgelegt. Bei Störungen ist in der Regel
eine augenärztliche Beurteilung erforderlich. Der begutachtende Augenarzt sollte es als seine primäre Aufgabe ansehen, bei der Beurteilung
der Fahrerlaubnis alle augenärztlichen Möglichkeiten auszuschöpfen, den Bewerber um eine Fahrerlaubnis tauglich zu machen oder zu halten. In
der überwiegenden Mehrzahl der Fälle gelingt dies auch.Allerdings ist es unvermeidlich, bei plötzlichem schwerwiegendem einseitigem Sehverlust für 3 Monate ab dem Auftreten die gesetzlich
vorgeschriebene Fahruntauglichkeit zu attestieren. Bei Motilitätsstörungen entscheiden vor allem die Ausdehnung der Doppelbildbereiche im
Blickfeld und die dadurch hervorgerufene subjektive Einschränkung; die zentralen 20 Grad müssen doppelbildfrei sein.Absolute homonyme Gesichtsfeldausfälle, sowohl als Hemianopsie als auch bei Quadrantenausfällen, die bis an das Zentrum heranreichen, sind
nach der Fahrerlaubnisverordnung nicht mit dem Führen eines Kraftfahrzeugs zu vereinen. Hieran ändern auch Trainingsmaßnahmen, die subjektiv
zu einer problemlosen Orientierung führen, nichts.Grundsätzlich sollte bei wesentlichen Störungen des Sehvermögens die zusätzliche Expertise eines Augenarztes eingeholt werden, ehe positiv
über die Fahrtauglichkeit entschieden wird.
Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase Inhibitors
Authors: Roy Subhajit , Narang Bawneet , Gupta Manish , Abbot Vikrant , Singh Virender , Rawal Ravindra 
Published: January 2018

AbstractFlexible docking simulations were carried out on a series of isocytosine analogs as xanthine oxidase (XO) inhibitors. This was done by analysing the interaction of these compounds at the active site of XO. The binding free energies of the analogs were calculated using GoldScore. The binding modes of the best-fit conformation were studied, providing some handy important interactions. The results obtained henceforth provided an insight into the pharmacophoric structural requirements for XO inhibition for this class of molecules.
Degradation of FBXO31 by APC/C is regulated by AKT- and ATM-mediated phosphorylation
Authors: Choppara Srinadh , Malonia Sunil K. , Sankaran Ganga , Green Michael R. , Santra Manas Kumar 
Published: January 2018

SignificanceThe tumor suppressor protein FBXO31 is maintained at low levels in unstressed (normal cycling) cells, but rapidly increases following genotoxic stress (DNA damage), leading to induction of growth arrest or senescence. The mechanism that underlies physiological regulation of FBXO31 is unknown. Here we show that in unstressed cells FBXO31 is maintained at low levels by anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets cell-cycle regulatory substrates for proteasomal degradation. APC/C coactivators CDH1 and CDC20 interact with FBXO31 and coordinate its degradation, which requires phosphorylation by the prosurvival kinase AKT. Following genotoxic stress, FBXO31 is phosphorylated by another kinase, ATM, disrupting its interaction with CDH1 and CDC20 and preventing its degradation. Thus, altered phosphorylation underlies physiological regulation of FBXO31 levels.
Mechanogenetics for the remote and noninvasive control of cancer immunotherapy
Authors: Pan Yijia , Yoon Sangpil , Sun Jie , Huang Ziliang , Lee Changyang , Allen Molly , Wu Yiqian , Chang Ya-Ju , Sadelain Michel , Shung K. Kirk , Chien Shu , Wang Yingxiao 
Published: January 2018

Significance
There is a lack of a general method to noninvasively and remotely manipulate cells with high spatiotemporal precisions. We developed an ultrasound-based mechanogenetics system to achieve this goal. Cells were engineered with the mechanosensor Piezo1 and genetic transducing modules to perceive the mechanical perturbation generated by the ultrasound wave and transduce it into genetic activities. Mechanosensitive and ultrasound-controllable T cells were further engineered to target and eradicate tumor cells with inducible chimeric antigen receptors. This mechanogenetics approach can be extended to remotely control, in principle, any gene activity in live cells for the reprogramming of cellular functions. This method should also provide a general approach to remotely control molecular functions for biological studies and clinical applications, particularly cell-based cancer immunotherapy.
Therapeutic biomaterials based on extracellular vesicles: classification of bio‐engineering and mimetic preparation routes
Authors: García‐Manrique Pablo , Matos María , Gutiérrez Gemma , Pazos Carmen , Blanco‐López María Carmen 
Published: January 2018

ABSTRACTExtracellular vesicles (EVs) are emerging as novel theranostic tools. Limitations related to clinical uses are leading to a new research area on design and manufacture of artificial EVs. Several strategies have been reported in order to produce artificial EVs, but there has not yet been a clear criterion by which to differentiate these novel biomaterials. In this paper, we suggest for the first time a systematic classification of the terms used to build up the artificial EV landscape, based on the preparation method. This could be useful to guide the derivation to clinical trial routes and to clarify the literature. According to our classification, we have reviewed the main strategies reported to date for their preparation, including key points such as: cargo loading, surface targeting strategies, purification steps, generation of membrane fragments for the construction of biomimetic materials, preparation of synthetic membranes inspired in EV composition and subsequent surface decoration.
Differential Regulation of PAI-1 in Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever With Renal Syndrome
Authors: Bellomo Carla , Korva Miša , Papa Anna , Mäkelä Satu , Mustonen Jukka , Avšič-Županc Tatjana , Vaheri Antti , Martinez Valeria P , Strandin Tomas 
Published: January 2018

AbstractWe analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)–1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of tPA commonly increased in both diseases, whereas PAI-1 correlated with disease severity in HCPS but not in HFRS.
Minimally Invasive Lateral Retroperitoneal Approach for Resection of Extraforaminal Lumbar Plexus Schwannomas: Operative Techniques and Literature Review
Authors: Safaee Michael M , Ames Christopher P , Deviren Vedat , Clark Aaron J 
Published: January 2018

Abstract

BACKGROUND
Traditional approaches for retroperitoneal lumbar plexus schwannomas involve anterior open or laparoscopic resection. For select tumors, the lateral retroperitoneal approach provides a minimally invasive alternative.

OBJECTIVE
To describe a minimally invasive lateral transpsoas approach for the resection of retroperitoneal schwannomas.

METHODS
A lateral retroperitoneal transpsoas approach was used to resect a 3.1 × 2.7 × 4.1 cm schwannoma embedded within the psoas muscle. A minimally invasive retractor system allows for appropriate visualization and complete resection with the aid of the microscope. The patient tolerated the procedure without complication and was discharged on postoperative day 2 in good condition at her neurological baseline.

RESULTS
The lateral retroperitoneal approach provides a minimally invasive alternative for select retroperitoneal schwannomas. In theory, this procedure allows for faster recovery and less blood loss compared to traditional open anterior approaches. For a subset of tumors, anterior laparoscopy may provide better access, but the lateral approach is well known to most neurosurgeons who perform lateral interbody fusions and can be easily tailored to extraforaminal tumor resection.

CONCLUSION
Retroperitoneal schwannomas pose a challenge due to their deep location. The lateral retroperitoneal approach provides a useful alternative for resection of a subset of retroperitoneal schwannomas.
Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency
Authors: Ahn Tae Hwan , Cho Sung Bin 
Published: January 2018

Summary:
Most cases of severely contracted nose require revision rhinoplasty and septoplasty, wherein preoperative and/or intraoperative expansion of nasal soft tissue is necessary for tension-free revision surgery. The present study aimed to evaluate the efficacy and safety of pre- and postoperative adjuvant therapy using polydeoxyribonucleotide (PDRN) and invasive, pulsed-type, bipolar, alternating current radiofrequency (RF) for revision surgery of a contracted nose. In total, 30 patients were treated with 16 sessions (8 preoperative sessions and 8 postoperative sessions) of intralesional injection of PDRN and invasive RF treatment using microneedle electrodes at 1-week intervals. One week after the final combined pretreatment using PDRN and invasive bipolar RF, the skin of contracted noses was sufficiently softened, and nasal skin mobility was notably improved in all the patients. During revision rhinoplasty and septoplasty, the contracted nasal skin in each patient was adequately released for proper covering of the nasal tip without tension. Postoperatively, 8 sessions of adjuvant therapy elicited marked clinical improvements in persistent nasal tip dimpling and contracture, septal deviation, and warping from the incomplete recovery of nasal contracture after revision surgery. In conclusion, our pre- and postoperative adjuvant therapies using PDRN and invasive bipolar RF remarkably improved the therapeutic outcomes of revision rhinoplasty and septoplasty for contracted skin of the nose without major side effects.