bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation muscle-directed gene therapy by in silico vector design
Authors: Sarcar S. , Tulalamba W. , Rincon M. Y. , Tipanee J. , Pham H. Q. , Evens H. , Boon D. , Samara-Kuko E. , Keyaerts M. , Loperfido M. , Berardi E. , Jarmin S. , In’t Veld P. , Dickson G. , Lahoutte T. , Sampaolesi M. , De Bleser P. , VandenDriessche T. , Chuah M. K. 
Published: January 2019

AbstractThere is an urgent need to develop the next-generation vectors for gene therapy of muscle disorders, given the relatively modest advances in clinical trials. These vectors should express substantially higher levels of the therapeutic transgene, enabling the use of lower and safer vector doses. In the current study, we identify potent muscle-specific transcriptional cis-regulatory modules (CRMs), containing clusters of transcription factor binding sites, using a genome-wide data-mining strategy. These novel muscle-specific CRMs result in a substantial increase in muscle-specific gene transcription (up to 400-fold) when delivered using adeno-associated viral vectors in mice. Significantly higher and sustained human micro-dystrophin and follistatin expression levels are attained than when conventional promoters are used. This results in robust phenotypic correction in dystrophic mice, without triggering apoptosis or evoking an immune response. This multidisciplinary approach has potentially broad implications for augmenting the efficacy and safety of muscle-directed gene therapy.
Flexible decapyrrylcorannulene hosts
Authors: Xu Yun-Yan , Tian Han-Rui , Li Shu-Hui , Chen Zuo-Chang , Yao Yang-Rong , Wang Shan-Shan , Zhang Xin , Zhu Zheng-Zhong , Deng Shun-Liu , Zhang Qianyan , Yang Shangfeng , Xie Su-Yuan , Huang Rong-Bin , Zheng Lan-Sun 
Published: January 2019

AbstractThe assembly of spherical fullerenes, or buckyballs, into single crystals for crystallographic identification often suffers from disordered arrangement. Here we show a chiral configuration of decapyrrylcorannulene that has a concave ‘palm’ of corannulene and ten flexible electron-rich pyrryl group ‘fingers’ to mimic the smart molecular ‘hands’ for self-adaptably cradling various buckyballs in a (+)hand-ball-hand(−) mode. As exemplified by crystallographic identification of 15 buckyball structures representing pristine, exohedral, endohedral, dimeric and hetero-derivatization, the pyrryl groups twist with varying dihedral angles to adjust the interaction between decapyrrylcorannulene and fullerene. The self-adaptable electron-rich pyrryl groups, susceptible to methylation, are theoretically revealed to contribute more than the bowl-shaped palm of the corannulene in holding buckyball structures. The generality of the present decapyrrylcorannulene host with flexible pyrryl groups facilitates the visualization of numerous unknown/unsolved fullerenes by crystallography and the assembly of the otherwise close-packed spherical fullerenes into two-dimensional layered structures by intercalation.
Ingestible hydrogel device
Authors: Liu Xinyue , Steiger Christoph , Lin Shaoting , Parada German Alberto , Liu Ji , Chan Hon Fai , Yuk Hyunwoo , Phan Nhi V. , Collins Joy , Tamang Siddartha , Traverso Giovanni , Zhao Xuanhe 
Published: January 2019

AbstractDevices that interact with living organisms are typically made of metals, silicon, ceramics, and plastics. Implantation of such devices for long-term monitoring or treatment generally requires invasive procedures. Hydrogels offer new opportunities for human-machine interactions due to their superior mechanical compliance and biocompatibility. Additionally, oral administration, coupled with gastric residency, serves as a non-invasive alternative to implantation. Achieving gastric residency with hydrogels requires the hydrogels to swell very rapidly and to withstand gastric mechanical forces over time. However, high swelling ratio, high swelling speed, and long-term robustness do not coexist in existing hydrogels. Here, we introduce a hydrogel device that can be ingested as a standard-sized pill, swell rapidly into a large soft sphere, and maintain robustness under repeated mechanical loads in the stomach for up to one month. Large animal tests support the exceptional performance of the ingestible hydrogel device for long-term gastric retention and physiological monitoring.
Photoinduced, reversible phase transitions in all-inorganic perovskite nanocrystals
Authors: Kirschner Matthew S. , Diroll Benjamin T. , Guo Peijun , Harvey Samantha M. , Helweh Waleed , Flanders Nathan C. , Brumberg Alexandra , Watkins Nicolas E. , Leonard Ariel A. , Evans Austin M. , Wasielewski Michael R. , Dichtel William R. , Zhang Xiaoyi , Chen Lin X. , Schaller Richard D. 
Published: January 2019

AbstractSignificant interest exists in lead trihalides that present the perovskite structure owing to their demonstrated potential in photovoltaic, lasing, and display applications. These materials are also notable for their unusual phase behavior often displaying easily accessible phase transitions. In this work, time-resolved X-ray diffraction, performed on perovskite cesium lead bromide nanocrystals, maps the lattice response to controlled excitation fluence. These nanocrystals undergo a reversible, photoinduced orthorhombic-to-cubic phase transition which is discernible at fluences greater than 0.34 mJ cm−2 through the loss of orthorhombic features and shifting of high-symmetry peaks. This transition recovers on the timescale of 510 ± 100 ps. A reversible crystalline-to-amorphous transition, observable through loss of Bragg diffraction intensity, occurs at higher fluences (greater than 2.5 mJ cm−2). These results demonstrate that light-driven phase transitions occur in perovskite materials, which will impact optoelectronic applications and enable the manipulation of non-equilibrium phase characteristics of the broad perovskite material class.
Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells
Authors: Zhang Shaopeng , Chen Tianzhi , Chen Naixin , Gao Dengfeng , Shi Bingbo , Kong Shuangbo , West Rachel Claire , Yuan Ye , Zhi Minglei , Wei Qingqing , Xiang Jinzhu , Mu Haiyuan , Yue Liang , Lei Xiaohua , Wang Xuepeng , Zhong Liang , Liang Hui , Cao Suying , Belmonte Juan Carlos Izpisua , Wang Haibin , Han Jianyong 
Published: January 2019

AbstractSpatially ordered embryo-like structures self-assembled from blastocyst-derived stem cells can be generated to mimic embryogenesis in vitro. However, the assembly system and developmental potential of such structures needs to be further studied. Here, we devise a nonadherent-suspension-shaking system to generate self-assembled embryo-like structures (ETX-embryoids) using mouse embryonic, trophoblast and extra-embryonic endoderm stem cells. When cultured together, the three cell types aggregate and sort into lineage-specific compartments. Signaling among these compartments results in molecular and morphogenic events that closely mimic those observed in wild-type embryos. These ETX-embryoids exhibit lumenogenesis, asymmetric patterns of gene expression for markers of mesoderm and primordial germ cell precursors, and formation of anterior visceral endoderm-like tissues. After transplantation into the pseudopregnant mouse uterus, ETX-embryoids efficiently initiate implantation and trigger the formation of decidual tissues. The ability of the three cell types to self-assemble into an embryo-like structure in vitro provides a powerful model system for studying embryogenesis.
Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis
Authors: Ramos-Ibeas Priscila , Sang Fei , Zhu Qifan , Tang Walfred W. C. , Withey Sarah , Klisch Doris , Wood Liam , Loose Matt , Surani M. Azim , Alberio Ramiro 
Published: January 2019

AbstractHigh-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are largely inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and of epiblast and hypoblast in late blastocysts. We show that following an emergent short naive pluripotent signature in early embryos, there is a protracted appearance of a primed signature in advanced embryonic stages. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.
A tetracycline-dependent ribozyme switch allows conditional induction of gene expression in Caenorhabditis elegans
Authors: Wurmthaler Lena A. , Sack Monika , Gense Karina , Hartig Jörg S. , Gamerdinger Martin 
Published: January 2019

AbstractThe nematode Caenorhabditis elegans represents an important research model. Convenient methods for conditional induction of gene expression in this organism are not available. Here we describe tetracycline-dependent ribozymes as versatile RNA-based genetic switches in C. elegans. Ribozyme insertion into the 3’-UTR converts any gene of interest into a tetracycline-inducible gene allowing temporal and, by using tissue-selective promoters, spatial control of expression in all developmental stages of the worm. Using the ribozyme switches we established inducible C. elegans polyglutamine Huntington’s disease models exhibiting ligand-controlled polyQ-huntingtin expression, inclusion body formation, and toxicity. Our approach circumvents the complicated expression of regulatory proteins. Moreover, only little coding space is necessary and natural promoters can be utilized. With these advantages tetracycline-dependent ribozymes significantly expand the genetic toolbox for C. elegans.
ATM phosphorylation of the actin-binding protein drebrin controls oxidation stress-resistance in mammalian neurons and C. elegans
Authors: Kreis Patricia , Gallrein Christian , Rojas-Puente Eugenia , Mack Till G. A. , Kroon Cristina , Dinkel Viktor , Willmes Claudia , Murk Kai , tom-Dieck Susanne , Schuman Erin M. , Kirstein Janine , Eickholt Britta J. 
Published: January 2019

AbstractDrebrin (DBN) regulates cytoskeletal functions during neuronal development, and is thought to contribute to structural and functional synaptic changes associated with aging and Alzheimer’s disease. Here we show that DBN coordinates stress signalling with cytoskeletal dynamics, via a mechanism involving kinase ataxia-telangiectasia mutated (ATM). An excess of reactive oxygen species (ROS) stimulates ATM-dependent phosphorylation of DBN at serine-647, which enhances protein stability and accounts for improved stress resilience in dendritic spines. We generated a humanized DBN Caenorhabditis elegans model and show that a phospho-DBN mutant disrupts the protective ATM effect on lifespan under sustained oxidative stress. Our data indicate a master regulatory function of ATM-DBN in integrating cytosolic stress-induced signalling with the dynamics of actin remodelling to provide protection from synapse dysfunction and ROS-triggered reduced lifespan. They further suggest that DBN protein abundance governs actin filament stability to contribute to the consequences of oxidative stress in physiological and pathological conditions.
Shape-directed rotation of homogeneous micromotors via catalytic self-electrophoresis
Authors: Brooks Allan M. , Tasinkevych Mykola , Sabrina Syeda , Velegol Darrell , Sen Ayusman , Bishop Kyle J. M. 
Published: January 2019

AbstractThe pursuit of chemically-powered colloidal machines requires individual components that perform different motions within a common environment. Such motions can be tailored by controlling the shape and/or composition of catalytic microparticles; however, the ability to design particle motions remains limited by incomplete understanding of the relevant propulsion mechanism(s). Here, we demonstrate that platinum microparticles move spontaneously in solutions of hydrogen peroxide and that their motions can be rationally designed by controlling particle shape. Nanofabricated particles with n-fold rotational symmetry rotate steadily with speed and direction specified by the type and extent of shape asymmetry. The observed relationships between particle shape and motion provide evidence for a self-electrophoretic propulsion mechanism, whereby anodic oxidation and cathodic reduction occur at different rates at different locations on the particle surface. We develop a mathematical model that explains how particle shape impacts the relevant electrocatalytic reactions and the resulting electrokinetic flows that drive particle motion.
Enhanced strength–ductility synergy in ultrafine-grained eutectic high-entropy alloys by inheriting microstructural lamellae
Authors: Shi Peijian , Ren Weili , Zheng Tianxiang , Ren Zhongming , Hou Xueling , Peng Jianchao , Hu Pengfei , Gao Yanfei , Zhong Yunbo , Liaw Peter K. 
Published: January 2019

AbstractRealizing improved strength–ductility synergy in eutectic alloys acting as in situ composite materials remains a challenge in conventional eutectic systems, which is why eutectic high-entropy alloys (EHEAs), a newly-emerging multi-principal-element eutectic category, may offer wider in situ composite possibilities. Here, we use an AlCoCrFeNi2.1 EHEA to engineer an ultrafine-grained duplex microstructure that deliberately inherits its composite lamellar nature by tailored thermo-mechanical processing to achieve property combinations which are not accessible to previously-reported reinforcement methodologies. The as-prepared samples exhibit hierarchically-structural heterogeneity due to phase decomposition, and the improved mechanical response during deformation is attributed to both a two-hierarchical constraint effect and a self-generated microcrack-arresting mechanism. This work provides a pathway for strengthening eutectic alloys and widens the design toolbox for high-performance materials based upon EHEAs.
Methamphetamine functions as a novel CD4+ T-cell activator via the sigma-1 receptor to enhance HIV-1 infection
Authors: Prasad Anil , Kulkarni Rutuja , Shrivastava Ashutosh , Jiang Shuxian , Lawson Kaycie , Groopman Jerome E. 
Published: January 2019

AbstractMethamphetamine (Meth) exacerbates HIV-1 pathobiology by increasing virus transmission and replication and accelerating clinical progression to AIDS. Meth has been shown to alter the expression of HIV-1 co-receptors and impair intrinsic resistance mechanisms of immune cells. However, the exact molecular mechanisms involved in augmenting HIV-1 replication in T-cells are still not yet clear. Here, we demonstrate that pretreatment with Meth of CD4+T-cells enhanced HIV-1 replication. We observed upregulation of CD4+T-cell activation markers and enhanced expression of miR-34c-5p and miR-155 in these cells. Further, we noted activation of the sigma-1 receptor and enhanced intracellular Ca2+concentration and cAMP release in CD4+T-cells upon Meth treatment, which resulted in increased phosphorylation and nuclear translocation of transcription factors NFκB, CREB, and NFAT1. Increased gene expression of IL-4 and IL-10 was also observed in Meth treated CD4+T-cells. Moreover, proteasomal degradation of Ago1 occurred upon Meth treatment, further substantiating the drug as an activator of T-cells. Taken together, these findings show a previously unreported mechanism whereby Meth functions as a novel T-cell activator via the sigma-1 signaling pathway, enhancing replication of HIV-1 with expression of miR-34c-5p, and transcriptional activation of NFκB, CREB and NFAT1.
Testing the feasibility and safety of feeding preterm infants fresh mother’s own milk in the NICU: A pilot study
Authors: Sun Huiqing , Han Shuping , Cheng Rui , Hei Mingyan , Kakulas Foteini , Lee Shoo K. 
Published: January 2019

AbstractNecrotizing enterocolitis (NEC) is the leading cause of death among infants born at <30 weeks’ gestation, but donor human milk can reduce the incidence of NEC. Unfortunately, freezing or pasteurizing human milk deactivates beneficial bioactive components. We evaluated the feasibility, safety, and impact of feeding very preterm infants fresh (unprocessed) mother’s own milk within 4 hours of expression. In our multicentre prospective cohort analytic study, we fed 109 control and 98 intervention infants previously frozen donor or mother’s own milk; only the intervention group was fed fresh mother’s own milk once daily from enrollment until 32 weeks’ corrected age. Control group mothers could not commit to provide fresh milk daily and were less likely receive antenatal corticosteroids than mothers in the intervention group. In the intervention group, 87.5% (98/112) of mothers were able to provide at least one feed of fresh milk a day. No critical incidents or non-compliance with the protocol were reported. The duration of mechanical ventilation and total parenteral nutrition use were shorter in the intervention group than controls (P < 0.01) but the length of hospital stay was similar (P = 0.57). Although the study might be underpowered, the intervention group had lower unadjusted rates of the composite outcome NEC ≥ stage 2 or mortality (8% vs 20%, P = 0.04), sepsis (22% vs 38%, P = 0.02), retinopathy of prematurity (17% vs 39%, P < 0.01) and bronchopulmonary dysplasia (32% vs 47%, P < 0.01) than the control. These results indicated that feeding fresh mother’s own milk once daily was safe, feasible, and may reduce morbidity.
Association of muscle and visceral adipose tissues with the probability of Alzheimer’s disease in healthy subjects
Authors: Kim Jahae , Choi Kang-Ho , Cho Sang-Geon , Kang Sae-Ryung , Yoo Su Woong , Kwon Seong Young , Min Jung-Joon , Bom Hee-Seung , Song Ho-Chun 
Published: January 2019

AbstractIncreasing evidence indicates that sarcopenia and obesity can be risk factors for incident dementia. We investigated the association of body composition including muscle and visceral adipose tissue (VAT) with the probability of Alzheimer’s disease (AD) in healthy middle-aged and elderly subjects using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). This study included 110 healthy subjects with available whole-body FDG PET/CT scans and medical records. Muscle and VAT tissues were measured on the abdominal CT slice, and the PMOD Alzheimer’s discrimination FDG PET analysis tool (PALZ) score was evaluated on the brain PET of the same subject using software PALZ. Skeletal muscle index (r: −0.306; P = 0.031) was significantly negatively associated with the PALZ score in the elderly patients. Muscle area (β: −0.640; P = 0.043) and skeletal muscle index (β: −0.557; P = 0.043) were independently associated with the PALZ score in elderly subjects after adjustments for sex, duration of education, hypertension, diabetes mellitus, and smoking and drinking status. Increased muscle tissue was associated with a lower probability of AD in elderly subjects, but VAT was not associated with a lower probability of AD in middle-or older-aged adults.
Prenatal diagnosis of fetal intraabdominal extralobar pulmonary sequestration: a 12-year 3-center experience in China
Authors: Xu Ganqiong , Zhou Jiawei , Zeng Shi , Zhang Ming , Ouyang Zhu , Zhao Yili , Yuan Hongxia , Tong Lili , Yin Chan , Zhou Qichang 
Published: January 2019

AbstractTo provide useful information for diagnosing and predicting fetal intraabdominal extralobar pulmonary sequestration (IEPS), a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed serially in 21 fetuses with IEPS from 2005 to 2017. Prenatal sonographic features, treatment, and outcomes of each case were evaluated and collected. These cases of IEPS were also compared to 43 cases previously reported by other researchers from 1986 to 2017. Of the 21 sonographic features, 14 (67%) were hyperechoic, 21 (100%) were well circumscribed, and 17 (81%) depicted a mass that shifted with fetal breaths/hiccups non-synchronized with adjacent organs (sliding sign). Feeding arteries were detected prenatally in 18 patients (86%). The lesion volume was 10.17 ± 4.66 cm3, the congenital cystic adenomatoid malformation volume ratio and cardiothoracic ratio were in normal range. The gestational age at diagnosis, location and echotexture of the lesion, and rate of surgical treatment were similar to previous studies, but with a significantly higher rate of detected feeding arteries (P < 0.01), and associated anomalies (P < 0.01). All infants who underwent surgery after birth had satisfactory outcomes. The sliding sign and feeding artery are essential features of IEPS in prenatal diagnosis.
Reduced neural representation of arm/hand actions in the medial posterior parietal cortex
Authors: Bosco A. , Breveglieri R. , Filippini M. , Galletti C. , Fattori P. 
Published: January 2019

AbstractSeveral investigations at a single-cell level demonstrated that the medial posterior parietal area V6A is involved in encoding reaching and grasping actions in different visual conditions. Here, we looked for a “low-dimensional” representation of these encoding processes by studying macaque V6A neurons tested in three different tasks with a dimensionality reduction technique, the demixed principal component analysis (dPCA), which is very suitable for neuroprosthetics readout. We compared neural activity in reaching and grasping tasks by highlighting the portions of population variance involved in the encoding of visual information, target position, wrist orientation and grip type. The weight of visual information and task parameters in the encoding process was dependent on the task. We found that the distribution of variance captured by visual information in the three tasks did not differ significantly among the tasks, whereas the variance captured by target position and grip type parameters were significantly higher with respect to that captured by wrist orientation regardless of the number of conditions considered in each task. These results suggest a different use of relevant information according to the type of planned and executed action. This study shows a simplified picture of encoding that describes how V6A processes relevant information for action planning and execution.