bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of insurance status on ability to return for outpatient management of pediatric supracondylar humerus fractures
Authors: Fletcher Nicholas D. , Sirmon Bryan J. , Mansour Ashton S. , Carpenter William E. , Ward Laura A.
Published: August 2016

Purpose

Outcomes are excellent following surgical management of displaced supracondylar humerus fractures. Short delays until surgical fixation have been shown to be equivalent to immediate fixation with regards to complications. We hypothesized that insurance coverage may impact access to care and the patient's ability to return to the operating room for outpatient surgery.

Methods

A retrospective review of supracondylar humerus fractures treated at a large urban pediatric hospital from 2008 to 2012 was performed. Fractures were classified by the modified Gartland classification and baseline demographics were collected. Time from discharge to office visits and subsequent surgical fixation was calculated for all type II fractures discharged from the emergency department. Insurance status and primary carrier were collected for all patients.

Results

2584 supracondylar humerus fractures were reviewed, of which 584 were type II fractures. Of the 577 type II fractures with complete records, 383 patients (61 %) were admitted for surgery and the remaining 194 were discharged with plans for outpatient follow-up. There was no difference in insurance status between patients admitted for immediate surgery. Of the 194 patients who were discharged with type 2 fractures after gentle reduction, 59 patients (30.4 %) ultimately underwent surgical fixation. Of these, 42 patients were privately insured (58.3 % of patients with private insurance), 16 had governmental insurance (15.1 %), and 1 was uninsured (6.3 %). Patients with private insurance were 2.46 times more likely to have surgery than patients with public or no insurance ( p = 0.005). Of the 135 patients who did not eventually have surgery, 92 (68.1 %) were seen in the clinic. Patients with private insurance were 2.78 times more likely to be seen back in the clinic when compared to publicly insured or uninsured patients ( p = 0.0152).

Conclusions

Despite an equivalent number of privately insured and publicly insured patients undergoing immediate surgery for type II fractures, those with public or no insurance who were discharged were 2.46 times less likely to obtain outpatient surgery when compared to privately insured patients. Patient insurance status and the ability to follow up in a timely manner should be assessed at the time of initial evaluation in the emergency department. Level of evidence Level 3
Application of human factors engineering (HFE) to the design of a naloxone auto-injector for the treatment of opioid emergencies
Authors: Raffa Robert B. , Taylor Robert , Pergolizzi Joseph V. , Nalamachu Srinivas , Edwards Eric S. , Edwards Evan T.
Published: August 2016

The increased use of opioids for chronic treatment of pain and the resulting epidemic of opioid overdoses have created a major public health challenge. Parenteral naloxone has been used since the 1970’s to treat opioid overdose. Recently, a novel naloxone auto-injector device (EVZIO, kaleo, Inc., Richmond, VA) was approved by the Food and Drug Administration. In this article, we review the Human Factors Engineering (HFE) process used in the development and testing of this novel naloxone auto-injector currently used in nonmedical settings for the emergency treatment of known or suspected opioid overdose. HFE methods were employed throughout the product development process for the naloxone auto-injector including formative and summative studies in order to optimize the auto-injector’s user interface, mitigate use-related hazards and increase reliability during an opioid emergency use scenario. HFE was also used to optimize the product’s design and user interface in order to reduce or prevent user confusion and misuse. The naloxone auto-injector went through a rigorous HFE process that included perceptual, cognitive, and physical action analysis; formative usability evaluations; use error analysis and summative design validation studies. Applying HFE resulted in the development of a product that is safe, fast, easy and predictably reliable to deliver a potentially life-saving dose of naloxone during an opioid overdose emergency. The naloxone auto-injector may be considered as a universal precaution option for at-risk patients prescribed opioids or those who are at increased risk for an opioid overdose emergency.
Pressure and cold pain threshold reference values in a large, young adult, pain-free population
Authors: Waller Robert , Smith Anne Julia , O’Sullivan Peter Bruce , Slater Helen , Sterling Michele , Alexandra McVeigh Joanne , Straker Leon Melville
Published: August 2016

Background and aims

Currently there is a lack of large population studies that have investigated pain sensitivity distributions in healthy pain free people. The aims of this study were: (1) to provide sex-specific reference values of pressure and cold pain thresholds in young pain-free adults; (2) to examine the association of potential correlates of pain sensitivity with pain threshold values.

Methods

This study investigated sex specific pressure and cold pain threshold estimates for young pain free adults aged 21–24 years. A cross-sectional design was utilised using participants (n =617) from the Western Australian Pregnancy Cohort (Raine) Study at the 22-year follow-up. The association of site, sex, height, weight, smoking, health related quality oflife, psychological measures and activity with pain threshold values was examined. Pressure pain threshold (lumbar spine, tibialis anterior, neck and dorsal wrist) and cold pain threshold (dorsal wrist) were assessed using standardised quantitative sensory testing protocols.

Results

Reference values for pressure pain threshold (four body sites) stratified by sex and site, and cold pain threshold (dorsal wrist) stratified by sex are provided. Statistically significant, independent correlates of increased pressure pain sensitivity measures were site (neck, dorsal wrist), sex (female), higher waist-hip ratio and poorer mental health. Statistically significant, independent correlates of increased cold pain sensitivity measures were, sex (female), poorer mental health and smoking.

Conclusions

These data provide the most comprehensive and robust sex specific reference values for pressure pain threshold specific to four body sites and cold pain threshold at the dorsal wrist for young adults aged 21–24 years. Establishing normative values in this young age group is important given that the transition from adolescence to adulthood is a critical temporal period during which trajectories for persistent pain can be established.

Implications

These data will provide an important research resource to enable more accurate profiling and interpretation of pain sensitivity in clinical pain disorders in young adults. The robust and comprehensive data can assist interpretation of future clinical pain studies and provide further insight into the complex associations of pain sensitivity that can be used in future research.
Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation
Authors: Huang Xin , Wu Shangze , Wu Wangteng , Li Pengbin , Fu Chunling , Ma Shengming
Published: August 2016

Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C–C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.
Performance of arsenene and antimonene double-gate MOSFETs from first principles
Authors: Pizzi Giovanni , Gibertini Marco , Dib Elias , Marzari Nicola , Iannaccone Giuseppe , Fiori Gianluca
Published: August 2016

In the race towards high-performance ultra-scaled devices, two-dimensional materials offer an alternative paradigm thanks to their atomic thickness suppressing short-channel effects. It is thus urgent to study the most promising candidates in realistic configurations, and here we present detailed multiscale simulations of field-effect transistors based on arsenene and antimonene monolayers as channels. The accuracy of first-principles approaches in describing electronic properties is combined with the efficiency of tight-binding Hamiltonians based on maximally localized Wannier functions to compute the transport properties of the devices. These simulations provide for the first time estimates on the upper limits for the electron and hole mobilities in the Takagi’s approximation, including spin–orbit and multi-valley effects, and demonstrate that ultra-scaled devices in the sub-10-nm scale show a performance that is compliant with industry requirements.
Universal shape and pressure inside bubbles appearing in van der Waals heterostructures
Authors: Khestanova E. , Guinea F. , Fumagalli L. , Geim A. K. , Grigorieva I. V.
Published: August 2016

Trapped substances between a two-dimensional (2D) crystal and an atomically flat substrate lead to the formation of bubbles. Their size, shape and internal pressure are determined by the competition between van der Waals attraction of the crystal to the substrate and the elastic energy needed to deform it, allowing to use bubbles to study elastic properties of 2D crystals and conditions of confinement. Using atomic force microscopy, we analysed a variety of bubbles formed by monolayers of graphene, boron nitride and MoS2. Their shapes are found to exhibit universal scaling, in agreement with our analysis based on the theory of elasticity of membranes. We also measured the hydrostatic pressure induced by the confinement, which was found to reach tens of MPa inside submicron bubbles. This agrees with our theory estimates and suggests that for even smaller, sub-10 nm bubbles the pressure can be close to 1 GPa and may modify properties of a trapped material.
Disordered actomyosin networks are sufficient to produce cooperative and telescopic contractility
Authors: Linsmeier Ian , Banerjee Shiladitya , Oakes Patrick W. , Jung Wonyeong , Kim Taeyoon , Murrell Michael P.
Published: August 2016

While the molecular interactions between individual myosin motors and F-actin are well established, the relationship between F-actin organization and actomyosin forces remains poorly understood. Here we explore the accumulation of myosin-induced stresses within a two-dimensional biomimetic model of the disordered actomyosin cytoskeleton, where myosin activity is controlled spatiotemporally using light. By controlling the geometry and the duration of myosin activation, we show that contraction of disordered actin networks is highly cooperative, telescopic with the activation size, and capable of generating non-uniform patterns of mechanical stress. We quantitatively reproduce these collective biomimetic properties using an isotropic active gel model of the actomyosin cytoskeleton, and explore the physical origins of telescopic contractility in disordered networks using agent-based simulations.
Efficient and transgene-free genome editing in wheat through transient expression of CRISPR/Cas9 DNA or RNA
Authors: Zhang Yi , Liang Zhen , Zong Yuan , Wang Yanpeng , Liu Jinxing , Chen Kunling , Qiu Jin-Long , Gao Caixia
Published: August 2016

Editing plant genomes is technically challenging in hard-to-transform plants and usually involves transgenic intermediates, which causes regulatory concerns. Here we report two simple and efficient genome-editing methods in which plants are regenerated from callus cells transiently expressing CRISPR/Cas9 introduced as DNA or RNA. This transient expression-based genome-editing system is highly efficient and specific for producing transgene-free and homozygous wheat mutants in the T0 generation. We demonstrate our protocol to edit genes in hexaploid bread wheat and tetraploid durum wheat, and show that we are able to generate mutants with no detectable transgenes. Our methods may be applicable to other plant species, thus offering the potential to accelerate basic and applied plant genome-engineering research.
A strategy to discover new organizers identifies a putative heart organizer
Authors: Anderson Claire , Khan Mohsin A. F. , Wong Frances , Solovieva Tatiana , Oliveira Nidia M. M. , Baldock Richard A. , Tickle Cheryll , Burt Dave W. , Stern Claudio D.
Published: August 2016

Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development.
First vaccine approval under the FDA Animal Rule
Authors: Beasley David W C , Brasel Trevor L , Comer Jason E
Published: August 2016

The US Food and Drug Administration’s Animal Rule was established to facilitate licensure of new products for life-threatening conditions when traditional efficacy trials in humans are unethical or impractical. In November, 2015 BioThrax became the first vaccine to receive approval for a new indication via this pathway. The basis for this approval and use of Animal Rule or other non-traditional approval pathways for licensure of vaccines for serious conditions are discussed.
Erratum: Efficient second-harmonic imaging of collagen in histological slides using Bessel beam excitation
Authors: Vuillemin Nelly , Mahou Pierre , Débarre Delphine , Gacoin Thierry , Tharaux Pierre-Louis , Schanne-Klein Marie-Claire , Supatto Willy , Beaurepaire Emmanuel
Published: August 2016

Scientific Reports 6: Article number: 29863; published online: 20 July 2016; updated: 25 August 2016 This Article contains typographical errors. In the Results and Discussion section under subheading ‘Properties of second-harmonic generation imaging with Bessel beam excitation’, “Interestingly, in the case of SHG, if all contributions scattered by the sample along the optical axis interfere in a constructive manner, the signal should scale as ρ z × 1/ρ z 2, i.
Correction: Corrigendum: Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis
Authors: Zheng Zengjie , Jiang Hailong , Huang Yan , Wang Jie , Qiu Lei , Hu Zhenlin , Ma Xingyuan , Lu Yiming
Published: August 2016

Scientific Reports 6: Article number: 25672; published online: 09 May 2016; updated: 25 August 2016 This Article contains errors. In the Results section under subheading ‘H. cyanocinctus venom gland T7 phage display library construction and biopanning’, “DEQHLETELHTHLTSVLTANGFQ” should read: “DEQHLETELHTLTSVLTANGFQ”
Erratum: Tsunami-generated magnetic fields may constrain focal mechanisms of earthquakes
Authors: Kawashima Issei , Toh Hiroaki
Published: August 2016

Scientific Reports 6: Article number: 28603; published online: 29 June 2016; updated: 25 August 2016 In the HTML version of this Article, there are typographical errors in Equation 8, should read:
Erratum: A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held
Authors: Guo Jun , Ge Jian-long , Hao Mei , Sun Zhi-cheng , Wu Xin-sheng , Zhu Jian-bing , Wang Wei , Yao Pan-tong , Lin Wei , Xue Lei
Published: August 2016

Scientific Reports 5: Article number: 9517; published online: 31 March 2015; updated: 25 August 2016 In the original version of this Article, there were errors in Affiliation 1 which was incorrectly listed as ‘State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, P.
Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study
Authors: Seyhan Attila A. , Nunez Lopez Yury O. , Xie Hui , Yi Fanchao , Mathews Clayton , Pasarica Magdalena , Pratley Richard E.
Published: August 2016

The clinical presentation of diabetes sometimes overlaps, contributing to ambiguity in the diagnosis. Thus, circulating pancreatic islet-enriched microRNAs (miRNAs) might be useful biomarkers of β-cell injury/dysfunction that would allow more accurate subtyping of diabetes. We measured plasma levels of selected miRNAs in subjects with prediabetes (n = 12), type 2 diabetes (T2D, n = 31), latent autoimmune diabetes of adults (LADA, n = 6) and type 1 diabetes (T1D, n = 16) and compared them to levels in healthy control subjects (n = 27). The study was conducted at the Translational Research Institute for Metabolism and Diabetes (TRI-MD), Florida Hospital. MiRNAs including miR-375 (linked to β-cell injury), miR-21 (associated with islet inflammation), miR-24.1, miR-30d, miR-34a, miR-126, miR-146, and miR-148a were significantly elevated in subjects with various forms of diabetes compared to healthy controls. Levels of several miRNAs were significantly correlated with glucose responses during oral glucose tolerance testing, HbA1c, β-cell function, and insulin resistance in healthy controls, prediabetes, and T2D. These data suggest that miRNAs linked to β-cell injury and islet inflammation might be useful biomarkers to distinguish between subtypes of diabetes. This information could be used to predict progression of the disease, guide selection of optimal therapy and monitor responses to interventions, thus improving outcomes in patients with diabetes.
Native cellulose nanofibrills induce immune tolerance in vitro by acting on dendritic cells
Authors: Tomić Sergej , Kokol Vanja , Mihajlović Dušan , Mirčić Aleksandar , Čolić Miodrag
Published: August 2016

Cellulose nanofibrills (CNFs) are attractive biocompatible, natural nanomaterials for wide biomedical applications. However, the immunological mechanisms of CNFs have been poorly investigated. Considering that dendritic cells (DCs) are the key immune regulatory cells in response to nanomaterials, our aim was to investigate the immunological mechanisms of CNFs in a model of DC-mediated immune response. We found that non-toxic concentrations of CNFs impaired the differentiation and subsequent maturation of human monocyte-derived (mo)-DCs. In a co-culture with CD4+T cells, CNF-treated mo-DCs possessed a weaker allostimulatory and T helper (Th)1 and Th17 polarizing capacity, but a stronger capacity to induce Th2 cells and CD4+CD25hiFoxP3hi regulatory T cells. This correlated with an increased immunoglobulin-like transcript-4 and indolamine dioxygenase-1 expression by CNF-treated mo-DCs, following the partial internalization of CNFs and the accumulation of CD209 and actin bundles at the place of contacts with CNFs. Cumulatively, we showed that CNFs are able to induce an active immune tolerance by inducing tolerogenic DCs, which could be beneficial for the application of CNFs in wound healing and chronic inflammation therapies.
Correction: Corrigendum: Electron pair escape from fullerene cage via collective modes
Authors: Schüler Michael , Pavlyukh Yaroslav , Bolognesi Paola , Avaldi Lorenzo , Berakdar Jamal
Published: August 2016

Scientific Reports 6: Article number: 24396; published online: 18 April 2016; updated: 25 August 2016 The original version of this Article contained a typographical error in the spelling of the author Paola Bolognesi, which was incorrectly given as Paolo Bolognesi. This has now been corrected in thePDF and HTML versions of the Article.
Erratum: Virtual Planning, Control, and Machining for a Modular-Based Automated Factory Operation in an Augmented Reality Environment
Authors: Pai Yun Suen , Yap Hwa Jen , Md Dawal Siti Zawiah , Ramesh S. , Phoon Sin Ye
Published: August 2016

Scientific Reports 6: Article number: 27380; published online: 07 June 2016; updated: 25 August 2016 In this Article, Hwa Jen Yap, Siti Zawiah Md Dawal, S. Ramesh and Sin Ye Phoon are incorrectly affiliated to ‘Graduate School of Media Design, Keio University, 4-1-1, Hiyoshi, Kohoku, Yokohama, 223-8526, Japan’.
A robust ambient temperature collection and stabilization strategy: Enabling worldwide functional studies of the human microbiome
Authors: Anderson Ericka L. , Li Weizhong , Klitgord Niels , Highlander Sarah K. , Dayrit Mark , Seguritan Victor , Yooseph Shibu , Biggs William , Venter J. Craig , Nelson Karen E. , Jones Marcus B.
Published: August 2016

As reports on possible associations between microbes and the host increase in number, more meaningful interpretations of this information require an ability to compare data sets across studies. This is dependent upon standardization of workflows to ensure comparability both within and between studies. Here we propose the standard use of an alternate collection and stabilization method that would facilitate such comparisons. The DNA Genotek OMNIgene∙Gut Stool Microbiome Kit was compared to the currently accepted community standard of freezing to store human stool samples prior to whole genome sequencing (WGS) for microbiome studies. This stabilization and collection device allows for ambient temperature storage, automation and ease of shipping/transfer of samples. The device permitted the same data reproducibility as with frozen samples and yielded higher recovery of nucleic acids. Collection and stabilization of stool microbiome samples with the DNA Genotek collection device, combined with our extraction and WGS, provides a robust, reproducible workflow that enables standardized global collection, storage and analysis of stool for microbiome studies.
Comb-referenced laser distance interferometer for industrial nanotechnology
Authors: Jang Yoon-Soo , Wang Guochao , Hyun Sangwon , Kang Hyun Jay , Chun Byung Jae , Kim Young-Jin , Kim Seung-Woo
Published: August 2016

A prototype laser distance interferometer is demonstrated by incorporating the frequency comb of a femtosecond laser for mass-production of optoelectronic devices such as flat panel displays and solar cell devices. This comb-referenced interferometer uses four different wavelengths simultaneously to enable absolute distance measurement with the capability of comprehensive evaluation of the measurement stability and uncertainty. The measurement result reveals that the stability reaches 3.4 nm for a 3.8 m distance at 1.0 s averaging, which further reduces to 0.57 nm at 100 s averaging with a fractional stability of 1.5 × 10−10. The uncertainty is estimated to be in a 10−8 level when distance is measured in air due to the inevitable ambiguity in estimating the refractive index, but it can be enhanced to a 10−10 level in vacuum.
Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy
Authors: Zhou Mengying , Zhang Xulang , Wen Xinyu , Wu Taihua , Wang Weidong , Yang Mingzhou , Wang Jing , Fang Ming , Lin Bingcheng , Lin Hongli
Published: August 2016

Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a “glomerulus-on-a-chip” (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing and create potential new personalized and accurate therapeutic platforms for glomerular disease.
Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity
Authors: Levin Albert M. , Sitarik Alexandra R. , Havstad Suzanne L. , Fujimura Kei E. , Wegienka Ganesa , Cassidy-Bushrow Andrea E. , Kim Haejin , Zoratti Edward M. , Lukacs Nicholas W. , Boushey Homer A. , Ownby Dennis R. , Lynch Susan V. , Johnson Christine C.
Published: August 2016

The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race-ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease.
Polycomb-group protein SlMSI1 represses the expression of fruit-ripening genes to prolong shelf life in tomato
Authors: Liu Dan-Dan , Zhou Li-Jie , Fang Mou-Jing , Dong Qing-Long , An Xiu-Hong , You Chun-Xiang , Hao Yu-Jin
Published: August 2016

Polycomb-group (PcG) protein MULTICOPY SUPPRESSOR OF IRA1 (MSI1) protein is an evolutionarily conserved developmental suppressor and plays a crucial role in regulating epigenetic modulations. However, the potential role and function of MSI1 in fleshy fruits remain unknown. In this study, SlMSI1 was cloned and transformed into tomato to explore its function. The quantitative real-time PCR results showed that SlMSI1 was highly expressed in flowers and fruits and that its transcript and protein levels were significantly decreased in fruits after the breaker stage. Additionally, SlMSI1-overexpressing transgenic tomatoes displayed abnormal non-ripening fruit formation, whereas its suppression promoted fruit ripening in transgenic tomatoes. Quantitative real-time PCR assays also showed that RIN and its regulons were decreased in SlMSI1 overexpression transgenic tomato fruits. Furthermore, RNA-seq analysis demonstrated that SlMSI1 inhibits fruit ripening by negatively regulating a large set of fruit-ripening genes in addition to RIN and its regulons. Finally, genetic manipulation of SlMSI1 and RIN successfully prolonged the fruit shelf life by regulating the fruit-ripening genes in tomato. Our findings reveal a novel regulatory function of SlMSI1 in fruit ripening and provide a new regulator that may be useful for genetic engineering and modification of fruit shelf life.
Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons
Authors: Hu Ganlu , Huang Kevin , Hu Youjin , Du Guizhen , Xue Zhigang , Zhu Xianmin , Fan Guoping
Published: August 2016

Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP) and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up-regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons.
Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine
Authors: Suman Shubhankar , Kumar Santosh , Fornace Albert J. , Datta Kamal
Published: August 2016

Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as56Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specificin vivomolecular data. We investigated long-term effects of56Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of56Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1 and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.
Pleiotropic action of CpG-ODN on endothelium and macrophages attenuates angiogenesis through distinct pathways
Authors: Wu Jiahui , Su Wenru , Powner Michael B. , Liu Jian , Copland David A. , Fruttiger Marcus , Madeddu Paolo , Dick Andrew D. , Liu Lei
Published: August 2016

There is an integral relationship between vascular cells and leukocytes in supporting healthy tissue homeostasis. Furthermore, activation of these two cellular components is key for tissue repair following injury. Toll-like receptors (TLRs) play a role in innate immunity defending the organism against infection, but their contribution to angiogenesis remains unclear. Here we used synthetic TLR9 agonists, cytosine-phosphate-guanosine oligodeoxynucleotides (CpG-ODN), to investigate the role of TLR9 in vascular pathophysiology and identify potential therapeutic translation. We demonstrate that CpG-ODN stimulates inflammation yet inhibits angiogenesis. Regulation of angiogenesis by CpG-ODN is pervasive and tissue non-specific. Further, we noted that synthetic CpG-ODN requires backbone phosphorothioate but not TLR9 activation to render and maintain endothelial stalk cells quiescent. CpG-ODN pre-treated endothelial cells enhance macrophage migration but restrain pericyte mobilisation. CpG-ODN attenuation of angiogenesis, however, remains TLR9-dependent, as inhibition is lost in TLR9 deficient mice. Additionally, CpG-ODNs induce an M1 macrophage phenotype that restricts angiogenesis. The effects mediated by CpG-ODNs can therefore modulate both endothelial cells and macrophages through distinct pathways, providing potential therapeutic application in ocular vascular disease.
Multilayer Network Analysis of Nuclear Reactions
Authors: Zhu Liang , Ma Yu-Gang , Chen Qu , Han Ding-Ding
Published: August 2016

The nuclear reaction network is usually studied via precise calculation of differential equation sets and much research interest has been focused on the characteristics of nuclides, such as half-life and size limit. In this paper, however, we adopt the methods from both multilayer and reaction networks and obtain a distinctive view by mapping all the nuclear reactions in JINA REACLIB database into a directed network with 4 layers: neutron, proton, 4He and the remainder. The layer names correspond to reaction types decided by the currency particles consumed. This combined approach reveals that, in the remainder layer, the β-stability has high correlation with node degree difference and overlapping coefficient. Moreover, when reaction rates are considered as node strength, we find that, at lower temperatures, nuclide half-life scales reciprocally with its out-strength. The connection between physical properties and topological characteristics may help to explore the boundary of the nuclide chart.
Hypomineralized Second Primary Molars as Predictor of Molar Incisor Hypomineralization
Authors: Negre-Barber A. , Montiel-Company J. M. , Boronat-Catalá M. , Catalá-Pizarro M. , Almerich-Silla J. M.
Published: August 2016

Molar incisor hypomineralization (MIH) is a developmental defect of dental enamel that shares features with hypomineralized second primary molars (HSPM). Prior to permanent tooth eruption, second primary molars could have predictive value for permanent molar and incisor hypomineralization. To assess this possible relationship, a cross-sectional study was conducted in a sample of 414 children aged 8 and 9 years from the INMA cohort in Valencia (Spain). A calibrated examiner (linear-weighted Kappa 0.83) performed the intraoral examinations at the University of Valencia between November 2013 and 2014, applying the diagnostic criteria for MIH and HSPM adopted by the European Academy of Paediatric Dentistry. 100 children (24.2%) presented MIH and 60 (14.5%) presented HSPM. Co-occurrence of the two defects was observed in 11.1% of the children examined. The positive predictive value was 76.7% (63.9–86.6) and the negative predictive value 84.7% (80.6–88.3). The positive likelihood ratio (S/1-E) was 10.3 (5.9–17.9) and the negative likelihood ratio (1-S/E) 0.57 (0.47–0.68). The odds ratio was 18.2 (9.39–35.48). It was concluded that while the presence of HSPM can be considered a predictor of MIH, indicating the need for monitoring and control, the absence of this defect in primary dentition does not rule out the appearance of MIH.
Molecular hydrogen suppresses activated Wnt/β-catenin signaling
Authors: Lin Yingni , Ohkawara Bisei , Ito Mikako , Misawa Nobuaki , Miyamoto Kentaro , Takegami Yasuhiko , Masuda Akio , Toyokuni Shinya , Ohno Kinji
Published: August 2016

Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC and Axin1. We additionally found that H2 reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases.
Epsin1 modulates synaptic vesicle retrieval capacity at CNS synapses
Authors: Kyung Jae Won , Bae Jae Ryul , Kim Dae-Hwan , Song Woo Keun , Kim Sung Hyun
Published: August 2016

Synaptic vesicle retrieval is an essential process for continuous maintenance of neural information flow after synaptic transmission. Epsin1, originally identified as an EPS15-interacting protein, is a major component of clathrin-mediated endocytosis. However, the role of Epsin1 in synaptic vesicle endocytosis at CNS synapses remains elusive. Here, we showed significantly altered synaptic vesicle endocytosis in neurons transfected with shRNA targeting Epsin1 during/after neural activity. Endocytosis was effectively restored by introducing shRNA-insensitive Epsin1 into Epsin1-depleted neurons. Domain studies performed on neurons in which domain deletion mutants of Epsin1 were introduced after Epsin1 knockdown revealed that ENTH, CLAP, and NPFs are essential for synaptic vesicle endocytosis, whereas UIMs are not. Strikingly, the efficacy of the rate of synaptic vesicle retrieval (the “endocytic capacity”) was significantly decreased in the absence of Epsin1. Thus, Epsin1 is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles.
Investigation of mechanism: spoof SPPs on periodically textured metal surface with pyramidal grooves
Authors: Tian Lili , Liu Jianlong , Zhou Keya , Gao Yang , Liu Shutian
Published: August 2016

In microwave and terahertz frequency band, a textured metal surface can support spoof surface plasmon polaritons (SSPPs). In this paper, we explore a SSPPs waveguide composed of a metal block with pyramidal grooves. Under the deep subwavelength condition, theoretical formulas for calculation of dispersion relations are derived based on the modal expansion method (MEM). Using the obtained formulas, a general analysis is given about the properties of the SSPPs in the waveguides with upright and downward pyramidal grooves. It is demonstrated that the SSPPs waveguides with upright pyramidal grooves give better field-confinement. Numerical simulations are used to check the theoretical analysis and show good agreement with the analytical results. In addition, the group velocity of the SSPPs propagating along the waveguide is explored and two structures are designed to show how to trap the SSPPs on the metal surface. The calculation methodology provided in this paper can also be used to deal with the SSPPs waveguides with irregular grooves.
Frobenius-norm-based measures of quantum coherence and asymmetry
Authors: Yao Yao , Dong G. H. , Xiao Xing , Sun C. P.
Published: August 2016

We formulate the Frobenius-norm-based measures for quantum coherence and asymmetry respectively. In contrast to the resource theory of coherence and asymmetry, we construct a natural measure of quantum coherence inspired from optical coherence theory while the group theoretical approach is employed to quantify the asymmetry of quantum states. Besides their simple structures and explicit physical meanings, we observe that these quantities are intimately related to the purity (or linear entropy) of the corresponding quantum states. Remarkably, we demonstrate that the proposed coherence quantifier is not only a measure of mixedness, but also an intrinsic (basis-independent) quantification of quantum coherence contained in quantum states, which can also be viewed as a normalized version of Brukner-Zeilinger invariant information. In our context, the asymmetry of N-qubit quantum systems is considered under local independent and collective"Equation missing" transformations. In- triguingly, it is illustrated that the collective effect has a significant impact on the asymmetry measure and quantum correlation between subsystems plays a non-negligible role in this circumstance.
The emergence of superstructural order in insulin amyloid fibrils upon multiple rounds of self-seeding
Authors: Surmacz-Chwedoruk Weronika , Babenko Viktoria , Dec Robert , Szymczak Piotr , Dzwolak Wojciech
Published: August 2016

Typically, elongation of an amyloid fibril entails passing conformational details of the mother seed to daughter generations of fibrils with high fidelity. There are, however, several factors that can potentially prevent such transgenerational structural imprinting from perpetuating, for example heterogeneity of mother seeds or so-calledconformational switching. Here, we examine phenotypic persistence of bovine insulin amyloid ([BI]) upon multiple rounds of self-seeding under quiescent conditions. According to infrared spectroscopy, with the following passages of homologous seeding, daughter fibrils gradually depart from the mother seed’s spectral characteristics. We note that this transgenerational structural drift in [BI] amyloid leads toward fibrils with infrared, chiroptical and morphological traits similar to those of the superstructural variant of fibrils which normally forms upon strong agitation of insulin solutions. However, in contrast to agitation-induced insulin amyloid, the superstructural assemblies of daughter fibrils isolated through self-seeding are sonication-resistant. Our results suggest that formation of single amyloid fibrils is not a dead-end of the amyloidogenic self-assembly. Instead, the process appears to continue toward the self-assembly of higher-order structures although on longer time-scales. From this perspective, the fast agitation-induced aggregation of insulin appears to be a shortcut to amyloid superstructures whose formation under quiescent conditions is slow.
Understanding music with cochlear implants
Authors: Bruns Lisa , Mürbe Dirk , Hahne Anja
Published: August 2016

Direct stimulation of the auditory nerve via a Cochlear Implant (CI) enables profoundly hearing-impaired people to perceive sounds. Many CI users find language comprehension satisfactory, but music perception is generally considered difficult. However, music contains different dimensions which might be accessible in different ways. We aimed to highlight three main dimensions of music processing in CI users which rely on different processing mechanisms: (1) musical discrimination abilities, (2) access to meaning in music and (3) subjective music appreciation. All three dimensions were investigated in two CI user groups (post- and prelingually deafened CI users, all implanted as adults) and a matched normal hearing control group. The meaning of music was studied by using event-related potentials (with the N400 component as marker) during a music-word priming task while music appreciation was gathered by a questionnaire. The results reveal a double dissociation between the three dimensions of music processing. Despite impaired discrimination abilities of both CI user groups compared to the control group, appreciation was reduced only in postlingual CI users. While musical meaning processing was restorable in postlingual CI users, as shown by a N400 effect, data of prelingual CI users lack the N400 effect and indicate previous dysfunctional concept building.
Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis
Authors: Xu Wen-long , Ling Ying-chun , Wang Zhi-kai , Deng Fang
Published: August 2016

An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78–90%; the pooled specificity was 93% with a 95% CI of 90–95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD.
Werner syndrome through the lens of tissue and tumour genomics
Authors: Tokita Mari , Kennedy Scott R. , Risques Rosa Ana , Chun Stephen G. , Pritchard Colin , Oshima Junko , Liu Yan , Bryant-Greenwood Peter K. , Welcsh Piri , Monnat Raymond J.
Published: August 2016

Werner syndrome (WS) is the canonical adult human progeroid (‘premature aging’) syndrome. Patients with this autosomal recessive Mendelian disorder display constitutional genomic instability and an elevated risk of important age-associated diseases including cancer. Remarkably few analyses of WS patient tissue and tumors have been performed to provide insight into WS disease pathogenesis or the high risk of neoplasia. We used autopsy tissue from four mutation-typed WS patients to characterize pathologic and genomic features of WS, and to determine genomic features of three neoplasms arising in two of these patients. The results of these analyses provide new information on WS pathology and genomics; provide a first genomic characterization of neoplasms arising in WS; and provide new histopathologic and genomic data to test several popular models of WS disease pathogenesis.
One-step Solution Processing of Ag, Au and Pd@MXene Hybrids for SERS
Authors: Satheeshkumar Elumalai , Makaryan Taron , Melikyan Armen , Minassian Hayk , Gogotsi Yury , Yoshimura Masahiro
Published: August 2016

We report on one-step hybridization of silver, gold and palladium nanoparticles from solution onto exfoliated two-dimensional (2D) Ti3C2 titanium carbide (MXene) nanosheets. The produced hybrid materials can be used as substrates for surface-enhanced Raman spectroscopy (SERS). An approximate analytical approach is also developed for the calculation of the surface plasmon resonance (SPR) frequency of nanoparticles immersed in a medium, near the interface of two dielectric media with different dielectric constants. We obtained a good match with the experimental data for SPR wavelengths, 440 nm and 558 nm, respectively for silver and gold nanoparticles. In the case of palladium, our calculated SPR wavelength for the planar geometry was 160 nm, demonstrating that non-spherical palladium nanoparticles coupled with 2D MXene yield a broad, significanlty red-shifted SPR band with a peak at 230 nm. We propose a possible mechanism of the plasmonic hybridization of nanoparticles with MXene. The as-prepared noble metal nanoparticles on MXene show a highly sensitive SERS detection of methylene blue (MB) with calculated enhancement factors on the order of 105. These findings open a pathway for extending visible-range SERS applications of novel 2D hybrid materials in sensors, catalysis, and biomedical applications.