bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational considerations in injectable cell-based therapeutics for neurological applications: concepts, progress and challenges
Authors: Amer Mahetab H. , Rose Felicity R. A. J. , Shakesheff Kevin M. , Modo Michel , White Lisa J. 
Published: August 2017

AbstractSignificant progress has been made during the past decade towards the clinical adoption of cell-based therapeutics. However, existing cell-delivery approaches have shown limited success, with numerous studies showing fewer than 5% of injected cells persisting at the site of injection within days of transplantation. Although consideration is being increasingly given to clinical trial design, little emphasis has been given to tools and protocols used to administer cells. The different behaviours of various cell types, dosing accuracy, precise delivery, and cell retention and viability post-injection are some of the obstacles facing clinical translation. For efficient injectable cell transplantation, accurate characterisation of cellular health post-injection and the development of standardised administration protocols are required. This review provides an overview of the challenges facing effective delivery of cell therapies, examines key studies that have been carried out to investigate injectable cell delivery, and outlines opportunities for translating these findings into more effective cell-therapy interventions.
Progress in genome-wide association studies of schizophrenia in Han Chinese populations
Authors: Yue Weihua , Yu Xin , Zhang Dai 
Published: August 2017

AbstractSince 2006, genome-wide association studies of schizophrenia have led to the identification of numerous novel risk loci for this disease. However, there remains a geographical imbalance in genome-wide association studies, which to date have primarily focused on Western populations. During the last 6 years, genome-wide association studies in Han Chinese populations have identified both the sharing of susceptible loci across ethnicities and genes unique to Han Chinese populations. Here, we review recent progress in genome-wide association studies of schizophrenia in Han Chinese populations. Researchers have identified and replicated the sharing of susceptible genes, such as within the major histocompatibility complex, microRNA 137 (MIR137), zinc finger protein 804A (ZNF804A), vaccinia related kinase 2 (VRK2), and arsenite methyltransferase (AS3MT), across both European and East Asian populations. Several copy number variations identified in European populations have also been validated in the Han Chinese, including duplications at 16p11.2, 15q11.2-13.1, 7q11.23, and VIPR2 and deletions at 22q11.2, 1q21.1-q21.2, and NRXN1. However, these studies have identified some potential confounding factors, such as genetic heterogeneity and the effects of natural selection on tetraspanin 18 (TSPAN18) or zinc finger protein 323 (ZNF323), which may explain the population differences in genome-wide association studies. In the future, genome-wide association studies in Han Chinese populations should include meta-analyzes or mega-analyses with enlarged sample sizes across populations, deep sequencing, precision medicine treatment, and functional exploration of the risk genes for schizophrenia.
Low Serum Albumin level as a Predictor of Hemorrhage Transformation after Intravenous Thrombolysis in Ischemic Stroke Patients
Authors: Che Ruiwen , Huang Xiaoqin , Zhao Wenbo , Jiang Fang , Wu Longfei , Zhang Zhen , Bian Tingting , Ma Qingfeng , Yu Zhipeng , Zhang Qian , Dong Kai , Song Haiqing , Ji Xunming 
Published: August 2017

AbstractSerum albumin levels has been shown to predict outcome in ischemic stroke patients. We aimed to investigate the relationship between serum albumin levels and hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute stroke. 428 patients receiving intravenous rt-PA therapy were included from 2013 to 2016 and were categorized into two groups: low level (<35 mmol/L) and normal level (35–55 mmol/L) group. Demographic, clinical and laboratory information, HT and functional outcomes were analyzed. Hemorrhagic transformation was comfirmed by CT scan or MRI within 7 days. The functional outcome was measured by modified Barthel Index and modified Rankin Scale (mRS) at 7 days and 90 days. Patients with lower albumin had significantly higher risk of HT (15.3% vs. 4.2%, P = 0.002) and sICH (6.2% vs. 1.4%, P = 0.03) than those with normal level of albumin. In univariate analysis for HT, atrial fibrillation and level of albumin were identified as significant factors (P < 0.001, P = 0.001 respectively). On multivariate logistic regression analysis, serum albumin level remained independent predictor of HT (OR = 4.369, 95% CI = 1.626–11.742, P = 0.003). No significantly difference were found in the clinical outcome at 7 days and 90 days between two groups ﻿(P > 0.05). Low level of serum albumin within 24 hours may be an independent predictor of post-thrombolytic HT.
Radiation Interception, Chlorophyll Fluorescence and Senescence of Flag leaves in Winter Wheat under Supplemental Irrigation
Authors: Man Jianguo , Yu Zhenwen , Shi Yu 
Published: August 2017

AbstractWater shortage threatens agricultural sustainability in China, effective water-saving technologies urgently need to be developed. In this study, five treatments were conducted: rainfed (W0), a local supplemental irrigation (SI) practice (W1), and three treatments in which soil water content was tested prior to SI, specifically at 0–20 (W2), 0–40 (W3) and 0–60 cm (W4) soil layers. Soil water consumption in W3 had no differ with W2 but was higher than W1 and W4. Crop evapotranspiration in W1, W3 and W4 treatments were higher than that in W2. W3 treatment had higher leaf area index than W1 and W4 at later grain filling stages. The mean photosynthetically active radiation capture ratio in W3, especially at 20, 40 and 60 cm plant heights, were significantly higher than those in W1, W2 and W4. The chlorophyll content index, actual photosynthetic activities, catalase and superoxide dismutase activities of flag leaves from W3 were the highest after the middle grain filling stages. W3 treatment obtained the highest grain yield (9169 kg ha−1) and water use efficiency (20.8 kg ha−1 mm−1) in the two seasons. These benefits likely accrued through created a suitable soil moisture environment in W3 treatment.
MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing
Authors: Li Xi , Li Dongqing , Wikstrom Jakob D. , Pivarcsi Andor , Sonkoly Enikö , Ståhle Mona , Landén Ning Xu 
Published: August 2017

AbstractMicroRNA (miR)-132 has been identified as a top up-regulated miRNA during skin wound healing and its inhibition impairs wound repair. In a human in vivo surgical wound model, we showed that miR-132 was induced in epidermal as well as in dermal wound–edge compartments during healing. Moreover, in a panel of cells isolated from human skin wounds, miR-132 was found highly expressed in human dermal fibroblasts (HDFs). In HDFs, miR-132 expression was upregulated by TGF-β1. By overexpression or inhibition of miR-132, we showed that miR-132 promoted HDF migration. Mechanistically, global transcriptome analysis revealed that RAS signaling pathway was regulated by miR-132 in HDFs. We found that RAS p21 protein activator 1 (RASA1), a known target of miR-132, was downregulated in HDFs upon miR-132 overexpression. Silencing of RASA1 phenocopied the pro-migratory effect of miR-132. Collectively, our study reveals an important role for miR-132 in HDFs during wound healing and indicates a therapeutic potential of miR-132 in hard-to-heal skin wounds.
Perception of facial expressions reveals selective affect-biased attention in humans and orangutans
Authors: Pritsch Carla , Telkemeyer Silke , Mühlenbeck Cordelia , Liebal Katja 
Published: August 2017

AbstractRapid detection and recognition of another individual’s emotional state plays a pivotal role for humans and, most likely, other social species. Proper reactions contribute to an individual’s survival in potentially dangerous situations; this is ensured by a preferential attention towards salient cues. The predisposition to attend to certain categories of affectively salient stimuli– also referred to as affect-biased attention - is likely shared with other species, since fast detection of and appropriate reaction to threats is crucial to survival. We compared human children and one of our close relatives, Sumatran orangutans (Pongo abelii), and predicted that both look more attentively and longer at emotionally salient facial expressions of their own and corresponding other species, compared to neutral faces. However, in contrast to a bias towards emotions providing relevant information by indicating a threat, both species preferentially looked at the fear-related, but not the angry faces of humans and consistently preferred the silent-bared teeth espressions in orangutans. The differential attention towards certain expressions might derive from their social function and the need to detect a potential threat in the environment. Our findings are consistent with claims rooting this affect-biased attention characteristic of human perception in our evolutionary history.
The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
Authors: Nagasaka Akiomi , Mogi Chihiro , Ono Hiroki , Nishi Toshihide , Horii Yuma , Ohba Yuki , Sato Koichi , Nakaya Michio , Okajima Fumikazu , Kurose Hitoshi 
Published: August 2017

AbstractMyocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the physiological implication of this pH reduction remains largely unknown. T-cell death-associated gene 8 (TDAG8) is a proton-sensing G protein-coupled receptor found on cardiac macrophages that recognise increases in extracellular protons. We demonstrated that TDAG8 negatively regulates the transcription of the chemokine Ccl20. The infarcted hearts of TDAG8 KO mice showed an increase in CCL20 expression and the number of infiltrating IL-17A-producing γδT cells that express CCR6, a receptor for CCL20. Accordingly, excessive IL-17A production, which is linked to the functional deterioration after MI, was observed in MI-operated TDAG8 KO mice. The survival rate and cardiac function significantly decreased in TDAG8 KO mice compared with those in wild-type mice after MI. Thus, our results suggest that TDAG8 is a key regulator of MI and a potential therapeutic target.
A time-varying biased random walk approach to human growth
Authors: Suki Béla , Frey Urs 
Published: August 2017

AbstractGrowth and development are dominated by gene-environment interactions. Many approaches have been proposed to model growth, but most are either descriptive or describe population level phenomena. We present a random walk-based growth model capable of predicting individual height, in which the growth increments are taken from time varying distributions mimicking the bursting behaviour of observed saltatory growth. We derive analytic equations and also develop a computational model of such growth that takes into account gene-environment interactions. Using an independent prospective birth cohort study of 190 infants, we predict height at 6 years of age. In a subset of 27 subjects, we adaptively train the model to account for growth between birth and 1 year of age using a Bayesian approach. The 5-year predicted heights compare well with actual data (measured height = 0.838*predicted height + 18.3; R2 = 0.51) with an average error of 3.3%. In one patient, we also exemplify how our growth prediction model can be used for the early detection of growth deficiency and the evaluation of the effectiveness of growth hormone therapy.
A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
Authors: Wang Decai , Pan Xinyuan , Ji Jiangdong , Gu Shun , Sun Xiantao , Jiang Chao , Xia Weiyi , Qiu Zhihua , Kang Xiaoli , Ding Sijia , Liu Qinghuai , Chen Xue , Lu Fang , Zhao Chen 
Published: August 2017

AbstractCongenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestations included bilateral excavated optic disc with multiple cilioretinal vessels emerging and bilateral retinoschisis with great variability in the range of extension and severity. Other intra-familial phenotypic diversities were also noted, including severity in retinal atrophy, onset age of visual impairment and presence of congenital nystagmus and strabismus. Genome-wide linkage analysis and fine mapping mapped a novel locus for CODA to a 34.3 cM interval between D14S972 and D14S139 at 14q12-q22.1. A maximum multi-point log odds score of 3.901 was reached at D14S275. However, no mutation was identified by exome sequencing or direct sequencing of PAX6 and PAX2 genes, suggesting that the mutation may reside within a regulatory element. In conclusion, we find retinoschisis as a necessary consequence of optic nerve head (ONH) anomalies. The complicated phenotype observed in the family provided additional insights into the inherited ONH anomalies. Mapping of a novel locus, 14q12-q22.1, implies a new disease-causing gene and potential distinct pathogenesis for CODA.
Portable wireless electrocorticography system with a flexible microelectrodes array for epilepsy treatment
Authors: Xie Kejun , Zhang Shaomin , Dong Shurong , Li Shijian , Yu Chaonan , Xu Kedi , Chen Wanke , guo Wei , Luo Jikui , Wu Zhaohui 
Published: August 2017

AbstractIn this paper, we present a portable wireless electrocorticography (ECoG) system. It uses a high resolution 32-channel flexible ECoG electrodes array to collect electrical signals of brain activities and to stimulate the lesions. Electronic circuits are designed for signal acquisition, processing and transmission using Bluetooth Low Energy 4 (LTE4) for wireless communication with cell phone. In-vivo experiments on a rat show that the flexible ECoG system can accurately record electrical signals of brain activities and transmit them to cell phone with a maximal sampling rate of 30 ksampling/s per channel. It demonstrates that the epilepsy lesions can be detected, located and treated through the ECoG system. The wireless ECoG system has low energy consumption and high brain spatial resolution, thus has great prospects for future application.
Small amphipathic peptides are responsible for the assembly of cruciferin nanoparticles
Authors: Hong Hui , Akbari Ali , Wu Jianping 
Published: August 2017

AbstractAmphipathic peptides are versatile building blocks for fabricating well-ordered nanostructures, which have gained much attention owing to their enormous design possibilities and bio-functionalities. However, using amphipathic peptides from natural proteins to create tunable nanostructures is challenging because of their heterogeneity and great tendency to form aggregates. Here we fabricated two well-defined nanoparticles from cruciferin amphipathic peptides by integrating top-down and bottom-up approach. Alkali hydrolysis (pH 12, 120 °C for 30 min) was introduced to break down intact cruciferin into peptides (top–down). The cruciferin peptides and their fractions were then assembled into nanoparticles (bottom–up) in the presence of calcium ions. The permeate fraction from 10 kDa cut-off membrane formed smaller nanoparticles (F1-NPs) (around 82 nm) than that of unfractionated cruciferin peptides (CRU-NPs, around 185 nm); the electrostatic and hydrophobic interactions were the main driving forces for particle formation. LC-MS/MS analysis characterised that the small amphipathic peptides (Xn1Zn2Xn3Zn4, n1–4 = 0~5), composed of alternating hydrophobic (X) and hydrophilic (Z) amino acid with a length of 5–15 and 5–20 residues for F1-NPs and CRU-NPs, respectively, were responsible for particle formation. Our study established the mechanism of particle formation of the cold gelation is through assembly of amphipathic peptides.
Retinoblastoma protein (Rb) links hypoxia to altered mechanical properties in cancer cells as measured by an optical tweezer
Authors: Khakshour S. , Labrecque M. P. , Esmaeilsabzali H. , Lee F. J. S. , Cox M. E. , Park E. J. , Beischlag T. V. 
Published: August 2017

AbstractHypoxia modulates actin organization via multiple pathways. Analyzing the effect of hypoxia on the biophysical properties of cancer cells is beneficial for studying modulatory signalling pathways by quantifying cytoskeleton rearrangements. We have characterized the biophysical properties of human LNCaP prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress using an oscillating optical tweezer. Hypoxia and Rb-loss increased cell stiffness in a fashion that was dependent on activation of the extracellular signal-regulated kinase (ERK) and the protein kinase B (AKT)- mammalian target of rapamycin (MTOR) pathways. Pharmacological inhibition of MEK1/2, AKT or MTOR impeded hypoxia-inducible changes in the actin cytoskeleton and inhibited cell migration in Rb-deficient cells conditioned with hypoxia. These results suggest that loss of Rb in transformed hypoxic cancer cells affects MEK1/2-ERK/AKT-MTOR signalling and promotes motility. Thus, the mechanical characterization of cancer cells using an optical tweezer provides an additional technique for cancer diagnosis/prognosis and evaluating therapeutic performance.
Characterization of Circulating Low-Density Neutrophils Intrinsic Properties in Healthy and Asthmatic Horses
Authors: Herteman Nicolas , Vargas Amandine , Lavoie Jean-Pierre 
Published: August 2017

AbstractLow-density neutrophils (LDNs) are a subset of neutrophils first described in the bloodstream upon pathological conditions, and recently, in the blood of healthy humans. LDNs may have an enhanced pro-inflammatory (low-density granulocytes, LDGs) or an immunosuppressive (Granulocytic myeloid-derived suppressor cells, G-MDSCs) profile. Whether these characteristics are specific to LDNs or related to disease states is unknown. Thus, we sought to investigate the properties of LDNs in both health and disease states, and to compare them to those of autologous normal-density neutrophils (NDNs). We studied 8 horses with severe equine asthma and 11 healthy animals. LDNs were smaller and contained more N-formylmethionine-leucyl-phenylalanine receptors than NDNs, but the myeloperoxidase content was similar in both cell populations. They also had an increased capacity to produce neutrophil extracellular traps, and were more sensitive to activation by phorbol-12-myristate-13-acetate. This profile is suggestive of LDGs. These characteristics were similar in both healthy and diseased animals, indicating that these are intrinsic properties of LDNs. Furthermore, these results suggest that LDNs represent a population of primed and predominantly mature cells. This study is the first to characterize LDNs in health, and to compare their properties with those of NDNs and of animals with a naturally occurring disease.
Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects
Authors: Li Fu , Du Bao-Wen , Lu Dan-Feng , Wu Wen-Xuan , Wongkrajang Kanjana , Wang Lun , Pu Wen-Chen , Liu Chang-Lu , Liu Han-Wei , Wang Ming-Kui , Wang Fei 
Published: August 2017

AbstractEpimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1–4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.
Identification of competing endogenous RNAs of the tumor suppressor gene PTEN: A probabilistic approach
Authors: Zarringhalam Kourosh , Tay Yvonne , Kulkarni Prajna , Bester Assaf C. , Pandolfi Pier Paolo , Kulkarni Rahul V. 
Published: August 2017

AbstractRegulation by microRNAs (miRNAs) and modulation of miRNA activity are critical components of diverse cellular processes. Recent research has shown that miRNA-based regulation of the tumor suppressor gene PTEN can be modulated by the expression of other miRNA targets acting as competing endogenous RNAs (ceRNAs). However, the key sequence-based features enabling a transcript to act as an effective ceRNA are not well understood and a quantitative model associating statistical significance to such features is currently lacking. To identify and assess features characterizing target recognition by PTEN-regulating miRNAs, we analyze multiple datasets from PAR-CLIP experiments in conjunction with RNA-Seq data. We consider a set of miRNAs known to regulate PTEN and identify high-confidence binding sites for these miRNAs on the 3′ UTR of protein coding genes. Based on the number and spatial distribution of these binding sites, we calculate a set of probabilistic features that are used to make predictions for novel ceRNAs of PTEN. Using a series of experiments in human prostate cancer cell lines, we validate the highest ranking prediction (TNRC6B) as a ceRNA of PTEN. The approach developed can be applied to map ceRNA networks of critical cellular regulators and to develop novel insights into crosstalk between different pathways involved in cancer.