bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgenic substitution with Greater Amberjack Seriola dumerili fish insulin 2 in NOD mice reduces beta cell immunogenicity
Authors: Foo Kylie S. , Skowronski Alicja A. , Baum Danielle , Firdessa-Fite Rebuma , Thams Sebastian , Shang Linshan , Creusot Rémi J. , LeDuc Charles A. , Egli Dieter , Leibel Rudolph L. 
Published: March 2019

AbstractType I diabetes (T1D) is caused by immune-mediated destruction of pancreatic beta cells. This process is triggered, in part, by specific (aa 9–23) epitopes of the insulin Β chain. Previously, fish insulins were used clinically in patients allergic to bovine or porcine insulin. Fish and human insulin differ by two amino acids in the critical immunogenic region (aa 9–23) of the B chain. We hypothesized that β cells synthesizing fish insulin would be less immunogenic in a mouse model of T1D. Transgenic NOD mice in which Greater Amberjack fish (Seriola dumerili) insulin was substituted for the insulin 2 gene were generated (mouse Ins1−/− mouse Ins2−/− fish Ins2+/+). In these mice, pancreatic islets remained free of autoimmune attack. To determine whether such reduction in immunogenicity is sufficient to protect β cells from autoimmunity upon transplantation, we transplanted fish Ins2 transgenic (expressing solely Seriola dumerili Ins2), NOD, or B16:A-dKO islets under the kidney capsules of 5 weeks old female NOD wildtype mice. The B:Y16A Β chain substitution has been previously shown to be protective of T1D in NOD mice. NOD mice receiving Seriola dumerili transgenic islet transplants showed a significant (p = 0.004) prolongation of their euglycemic period (by 6 weeks; up to 18 weeks of age) compared to un-manipulated female NOD (diabetes onset at 12 weeks of age) and those receiving B16:A-dKO islet transplants (diabetes onset at 12 weeks of age). These data support the concept that specific amino acid sequence modifications can reduce insulin immunogenicity. Additionally, our study shows that alteration of a single epitope is not sufficient to halt an ongoing autoimmune response. Which, and how many, T cell epitopes are required and suffice to perpetuate autoimmunity is currently unknown. Such studies may be useful to achieve host tolerance to β cells by inactivating key immunogenic epitopes of stem cell-derived β cells intended for transplantation.
Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture
Authors: Reddel Sofia , Del Chierico Federica , Quagliariello Andrea , Giancristoforo Simona , Vernocchi Pamela , Russo Alessandra , Fiocchi Alessandro , Rossi Paolo , Putignani Lorenza , El Hachem May 
Published: March 2019

AbstractAtopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium). Taken togheter these results show an alteration in AD microbiota composition with the depletion or absence of some species, opening the way to future probiotic intervention studies.
Biological Cardiac Tissue Effects of High-Energy Heavy Ions – Investigation for Myocardial Ablation
Authors: Rapp Felicitas , Simoniello Palma , Wiedemann Julia , Bahrami Karola , Grünebaum Valeria , Ktitareva Svetlana , Durante Marco , Lugenbiel P. , Thomas D. , Lehmann H. Immo , Packer Douglas L. , Graeff Christian , Fournier Claudia 
Published: March 2019

AbstractNoninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.
Changes in the Urinary Proteome in a Patient-Derived Xenograft (PDX) Nude Mouse Model of Colorectal Tumor
Authors: Liu Yongtao , Wang Youzhu , Cao Zhixiang , Gao Youhe 
Published: March 2019

AbstractIn this report, the urinary proteome from a patient-derived xenograft (PDX) model was examined at the peptide level to study the origins of urinary proteins in tumor-bearing nude mice. Urine was collected from PDX mice before and after colorectal tumor implantation. A total of 4,318 unique peptides were identified, and 78 unambiguous human-origin peptides were discerned in the PDX model urine. Unlike the differential urinary protein composition of tumor-bearing immunocompetent rat models, the differential urinary proteins in the PDX model did not include host immune-response proteins. This study demonstrates that tumor-secreted proteins can be observed in the urine proteome of the PDX model. However, immune-response proteins, which are very early candidate tumor biomarkers, are not present in the urine of PDX model mice; this absence is due to immune deficiency. Therefore, immunodeficient animals may not be suitable models for searching for early immunity-associated tumor biomarkers in the urine.
A complex of novel protease inhibitor, ovostatin homolog, with its cognate proteases in immature mice uterine luminal fluid
Authors: Huang Hsien-Lu , Li Szu-Chin , Wu Jin-Fong 
Published: March 2019

AbstractA predominant gelatinolytic enzyme with approximately 26 kDa was observed in gelatin zymogram of immature mice uterine luminal fluid (ULF). Size exclusion analysis revealed that the native size of this enzyme was close to that of human α2-macroglobulin (α2-MG), a 725 kDa protein. This large protease was isolated by a series of chromatographic steps on the Sephacryl S-400 and DEAE-Sepharose columns. The results from gelatin zymography and SDS-PAGE analysis supported that this large protease consists of gelatinolytic enzyme and a 360 kDa protein. Through tandem mass spectrometry analysis followed by MASCOT database search, the 360 kDa protein was identified as ovostatin homolog (accession: NP_001001179.2) assigned as a homolog of chicken ovostatin, a protease inhibitor. The co-fractionation analysis by gel filtration and mouse ovostatin homolog (mOH) co-immunoprecipitation experiments demonstrated that the mOH formed a complex with three gelatinolytic enzymes in immature mice ULF. Substrate zymography analysis revealed that the mOH-associated gelatinolytic enzymes were suitable to digest type I collagen rather than type IV collagen. In addition, the refolded mOH-associated 26 kDa gelatinolytic enzyme displayed the type I collagen-digesting activity in the assay, but the other two enzymes did not have this function. RT-PCR analysis showed that mOH gene was abundantly expressed in brain, spinal cord, lung, uterus, and in 17-day embryo. Taken together, our data suggest that mOH/cognate protease system may play a potential role in regulation of tissue remodeling and fetal development.
Genome-wide analysis of long non-coding RNAs unveils the regulatory roles in the heat tolerance of Chinese cabbage (Brassica rapa ssp.chinensis)
Authors: Wang Aihua , Hu Jihong , Gao Changbin , Chen Guanglong , Wang Bingcai , Lin Chufa , Song Liping , Ding Yi , Zhou Guolin 
Published: March 2019

AbstractLong non-coding RNAs (lncRNAs) mediate important epigenetic regulation in various biological processes related to the stress response in plants. However, the systematic analysis of the lncRNAs expressed in Brassica rapa under heat stress has been elusive. In this study, we performed a genome-wide analysis of the lncRNA expression profiles in non-heading Chinese cabbage leaves using strand-specific RNA-sequencing. A total of 4594 putative lncRNAs were identified with a comprehensive landscape of dynamic lncRNA expression networks under heat stress. Co-expression networks of the interactions among the differentially expressed lncRNAs, mRNAs and microRNAs revealed that several phytohormones were associated with heat tolerance, including salicylic acid (SA) and brassinosteroid (BR) pathways. Of particular importance is the discovery of 25 lncRNAs that were highly co-expressed with 10 heat responsive genes. Thirty-nine lncRNAs were predicted as endogenous target mimics (eTMs) for 35 miRNAs, and five of them were validated to be involved in the heat tolerance of Chinese cabbage. Heat responsive lncRNA (TCONS_00048391) is an eTM for bra-miR164a, that could be a sponge for miRNA binding and may be a competing endogenous RNA (ceRNA) for the target gene NAC1 (Bra030820), affecting the expression of bra-miR164a in Chinese cabbage. Thus, these findings provide new insights into the functions of lncRNAs in heat tolerance and highlight a set of candidate lncRNAs for further studies in non-heading Chinese cabbage.
Single step synthesis of highly conductive room-temperature stable cation-substituted mayenite electride target and thin film
Authors: Khan Karim , Tareen Ayesha khan , Khan Usman , Nairan Adeela , Elshahat Sayed , Muhammad Naseer , Saeed Muhammad , Yadav Ashish , Bibbò Luigi , Ouyang Zhengbiao 
Published: March 2019

AbstractNovel approaches to synthesize efficient inorganic electride [Ca24Al28O64]4+(e−)4 (thereafter, C12A7:e−) at ambient pressure under nitrogen atmosphere, are actively sought out to reduce the cost of massive formation of nanosized powder as well as compact large size target production. It led to a new era in low cost industrial applications of this abundant material as Transparent Conducting Oxides (TCOs) and as a catalyst. Therefore, the present study about C12A7:e− electride is directed towards challenges of cation doping in C12A7:e− to enhance the conductivity and form target to deposit thin film. Our investigation for cation doping on structural and electrical properties of Sn- and Si-doped C12A7:e− (Si-C12A7:e, and Sn-C12A7:e−) reduced graphene oxide (rGO) composite shows the maximum achieved conductivities of 5.79 S·cm−1 and 1.75 S·cm−1 respectively. On the other hand when both samples melted, then rGO free Sn-C12A7:e− and Si-C12A7:e− were obtained, with conductivities ~280 S.cm−1 and 300 S·cm−1, respectively. Iodometry based measured electron concentration of rGO free Sn-C12A7:e− and Si-C12A7:e−, 3 inch electride targets were ~2.22 × 1021 cm−3, with relative 97 ± 0.5% density, and ~2.23 × 1021 cm−3 with relative 99 ± 0.5% density, respectively. Theoretical conductivity was already reported excluding any associated experimental support. Hence the above results manifested feasibility of this sol-gel method for different elements doping to further boost up the electrical properties.
Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
Authors: Elsafadi Mona , Shinwari Tasneem , Al-Malki Sami , Manikandan Muthurangan , Mahmood Amer , Aldahmash Abdullah , Alfayez Musaad , Kassem Moustapha , Alajez Nehad M. 
Published: March 2019

AbstractTargeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting oppositein vivophenotypes, namely, bone forming (hBMSC+bone) and non-bone forming (hBMSC−Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC−Bonecells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMP signaling in those cells. Concordantly, activation of TGFβ signaling in hBMSC−Bonecells using either recombinant TGFβ1 protein or knockdown ofSERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 orviasiRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC−Bonecells. Concordantly, recombinant NOG impairedex vivoosteoblastic differentiation of hBMSC+Bonecells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between TGFB and BMP signaling that regulates hBMSC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMSCs for clinical applications.
A genome-wide association study on photic sneeze reflex in the Chinese population
Authors: Wang Mengqiao , Sun Xinghan , Shi Yang , Song Xiaojun , Mi Hao 
Published: March 2019

AbstractPhotic sneeze reflex (PSR) is an interesting but yet mysterious phenotype featured by individuals’ response of sneezing in exposure to bright light. To uncover the underlying genetic markers (single nucleotide polymorphisms, SNPs), a genome-wide association study (GWAS) was conducted exclusively in a Chinese population of 3417 individuals (PSR prevalence at 25.6%), and reproducibly identified both a replicative rs10427255 on 2q22.3 and a novel locus of rs1032507 on 3p12.1 in various effect models (additive, as well as dominant and recessive). Minor alleles respectively contributed to increased or reduced risk for PSR with odds ratio (95% confidence interval) at 1.68 ([1.50, 1.88]) for rs10427255 and 0.65 ([0.58, 0.72]) for rs1032507. The two independent SNPs were intergenic, and collectively enhanced PSR classification by lifting the area-under-curve value in ROC curve to 0.657. Together with previous GWAS in other populations, the result substantiated the polygenic and non-ethnicity-specific nature behind the PSR phenotype.
Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase
Authors: Diao Xin , Yang Danfen , Chen Yu , Liu Wentian 
Published: March 2019

AbstractBaicalin is the main bioactive component extracted from the traditional Chinese medicine Baical Skullcap Root, and its anti-tumor activity has been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in many cancer cells and stimulates the tumorigenic properties, and so, it is a pivotal target for agent to cure cancers. We reported for the first time that baicalin suppressed PBK/TOPK activities by directly binding with PBK/TOPK in vitro and in vivo. Ex vivo studies showed that baicalin suppressed PBK/TOPK activity in JB6 Cl41 cells and H441 lung cancer cells. Moreover, knockdown of PBK/TOPK in H441 cells decreased their sensitivity to baicalin. In vivo study indicated that injection of baicalin in H441 tumor-bearing mice effectively suppressed cancer growth. The PBK/TOPK downstream signaling molecules Histone H3 and ERK2 in tumor tissues were also decreased after baicalin treatment. Taken together, baicalin can inhibit proliferation of lung cancer cells as a PBK/TOPK inhibitor both in vitro and in vivo.
Interleukin-1 in cerebrospinal fluid for evaluating the neurological outcome in traumatic brain injury
Authors: Yue Yingming , Shang Chongzhi , Dong Huajiang , Meng Kun 
Published: March 2019

Abstract
Objective Severe traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Inflammation induced by TBI is complex, individual-specific, and associated with morbidity and mortality. The aim of the present study was to discover the differentially expressed cerebrospinal fluid (CSF) proteins and identify which can improve the clinical outcomes in TBI patients.
Methods In the present study, we reported 145 patients with TBI and found the change in patients’ leukocytes in serum and interleukin-1 (IL-1) in CSF, which strongly correlated with the neurological outcome. In terms of results of leukocytes in blood and IL-1 in CSF, we retained the patient’s CSF specimens and conducted a proteomic analysis.
Results A total of 119 differentially expressed proteins were detected between samples of TBI and the normal, which were commonly expressed in all samples, indicating the differentially expressed proteins. When the patients’ Glasgow outcome score (GOS) improved, IL-1 was down-regulated, and when the patients’ GCS score deteriorated, IL-1 was up-regulated accompanied with the progression in TBI.
Conclusion The differentially expressed proteins in CSF may be the novel therapeutic targets for TBI treatment. The leukocytes in blood samples and the IL-1 in CSF may be two important indicators for predicting the prognosis of TBI patients.
Bioinformatics analysis revealing prognostic significance of RRM2 gene in breast cancer
Authors: Chen Wei-xian , Yang Liang-gen , Xu Ling-yun , Cheng Lin , Qian Qi , Sun Li , Zhu Yu-lan 
Published: March 2019

Abstract
Background: Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. However, the prognostic significance of RRM2 gene in breast cancer remains to be investigated. Methods:RRM2 expression was initially evaluated using the Oncomine database. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results:RRM2 was overexpressed in different subtypes of breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with RRM2 expression. Conversely, the Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Patients with increased RRM2 showed worse overall survival, relapse-free survival, distant metastasis-free survival, disease-specific survival, and disease-free survival. RRM2 also exerted positive effect on metastatic relapse event. Besides, a positive correlation between RRM2 and KIF11 genes was confirmed. Conclusion: Bioinformatics analysis revealed that RRM2 might be used as a predictive biomarker for prognosis of breast cancer. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis.
Verbal Learning and Memory in Early-Implanted, Prelingually Deaf Adolescent and Adult Cochlear Implant Users
Authors: Chandramouli Suyog H. , Kronenberger William G. , Pisoni David B. 
Published: March 2019

Purpose

The purpose of this study was to investigate the information-processing strategies of early-implanted, prelingually deaf cochlear implant (CI) users with the California Verbal Learning Test–Second Edition (CVLT-II;
Delis, Kramer, Kaplan, & Ober, 2000
), a well-established normed measure of verbal learning and memory used in neuropsychological assessments of memory loss.

Method
Verbal learning and memory skills were compared in 20 older adolescent and young adult prelingually deaf long-term early-implanted CI users and their 24 normal hearing (NH) peers using the CVLT-II, a widely used multitrial free recall test of verbal learning and memory.

Results
On average, CI users recalled fewer words than their NH peers across the immediate, delayed, and cued recall trials of the CVLT-II but were comparable to their NH peers on yes/no recognition memory. CI users showed little evidence of semantic clustering of words during free recall but greater serial clustering compared to their NH peers, suggesting fundamental disturbances in automatic semantic activation of words from long-term memory. No differences were found in verbal memory between CI users and their NH peers on measures of retroactive interference and encoding/retrieval interactions. Performance on the 2nd word list of the CVLT-II (List B) and amount of semantic clustering of words during recall were correlated with sentence recognition in the CI group.

Conclusion
Study findings demonstrate significant differences in free recall performance and information-processing strategies that early-implanted, prelingually deaf CI users use to encode, organize, store, and retrieve spoken words in conventional verbal list learning paradigms, compared to their NH peers. Because verbal learning and memory are core foundational processes routinely used in daily functioning for a wide range of neurocognitive and language processing operations, these findings suggest potential domains for assessment and novel interventions to promote the development of optimal outcomes in prelingually deaf early-implanted long-term CI users.