bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myostatin inhibition therapy for insulin-deficient type 1 diabetes
Authors: Coleman Samantha K. , Rebalka Irena A. , D’Souza Donna M. , Deodhare Namita , Desjardins Eric M. , Hawke Thomas J. 
Published: September 2016

AbstractWhile Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with MyostatinLn/Ln mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management.
Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers
Authors: Iyire Affiong , Alaayedi Maryam , Mohammed Afzal R. 
Published: September 2016

AbstractThe aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 μg/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 μg/mL of lysine (p < 0.05) and 10 μg/mL histidine (p < 0.001), 100 μg/mL of glutamic acid (p < 0.05) and 200 μg/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin are the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism.
Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells
Authors: Ramirez Lisa , Herschkowitz Jason I. , Wang Jun 
Published: September 2016

AbstractCellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don’t have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force. Up to 10 proteins can be quantitated from each cell with hundreds of single-cell assays performed in parallel from one chip operation. We validated the technology and analyzed the oncogenic signatures of cancer stem cells by quantitating both aldehyde dehydrogenase (ALDH) activities and 5 signaling proteins in single MDA-MB-231 breast cancer cells. The technology has also been used to investigate the PI3K pathway activities of brain cancer cells expressing mutant epidermal growth factor receptor (EGFR) after drug intervention targeting EGFR signaling. Our portable single-cell system will potentially have broad application in the preclinical and clinical settings for cancer diagnosis in the future.
Transcriptional regulator PrqR plays a negative role in glucose metabolism and oxidative stress acclimation in Synechocystis sp. PCC 6803
Authors: Khan Rezaul Islam , Wang Yushu , Afrin Shajia , Wang Bing , Liu Yumin , Zhang Xiaoqing , Chen Lei , Zhang Weiwen , He Lin , Ma Gang 
Published: September 2016

AbstractPlant and cyanobacteria can perceive signals from soluble sugar and reactive oxygen species (ROS) and then coordinate gene expression under stress acclimation, but the underlying mechanism remains unclear. In this study, we found that the transcriptional factor PrqR (Slr0895) in Synechocystis can perceive signals from ROS generated after shifting from prolonged darkness with glucose into high-light. The deletion mutant (DprqR) showed increased growth rate and decreased ROS content, whereas the complementary strain (CprqR) restored the growth characteristics, phenotypes and ROS status of WT, thereby establishing PrqR as a negative regulator of ROS.LC/GC-MS-based metabolic profiling also showed active ROS mitigation in DprqR mutant. Further study by qRT-PCR, ChIP-PCR and deletion of both prqR and prqA (DprqR-DprqA mutant) revealed that PrqR exerts this negative regulation of ROS removal by controlling the expression of sodB and prqA (slr0896). Furthermore, PrqR also found to control glucose metabolism by regulating a positive regulator of glucose metabolism, sigE, and its regulons. Results suggest that PrqR was involved in perceiving signals from ROS under physiological condition, as well as in regulating stress removal and glucose metabolism.
New Insight into the Angle Insensitivity of Ultrathin Planar Optical Absorbers for Broadband Solar Energy Harvesting
Authors: Liu Dong , Yu Haitong , Duan Yuanyuan , Li Qiang , Xuan Yimin 
Published: September 2016

AbstractTwo challenging problems still remain for optical absorbers consisting of an ultrathin planar semiconductor film on top of an opaque metallic substrate. One is the angle-insensitive mechanism and the other is the system design needed for broadband solar energy harvesting. Here, first we theoretically demonstrates that the high refractive index, instead of the ultrathin feature as reported in previous studies, is the physical origin of the angle insensitivity for ultrathin planar optical absorbers. They exhibit omnidirectional resonance for TE polarization due to the high complex refractive index difference between the semiconductor and the air, while for TM polarization the angle insensitivity persists up to an incident angle related to the semiconductor refractive index. These findings were validated by fabricating and characterizing an 18 nm Ge/Ag absorber sample (representative of small band gap semiconductors for photovoltaic applications) and a 22 nm hematite/Ag sample (representative of large band gap semiconductors for photoelectrochemical applications). Then, we took advantage of angle insensitivity and designed a spectrum splitting configuration for broadband solar energy harvesting. The cascaded solar cell and unassisted solar water splitting systems have photovoltaic and photoelectrochemical cells that are also spectrum splitters, so an external spectrum splitting element is not needed.
Combination of TLR1/2 and TLR3 ligands enhances CD4+ T cell longevity and antibody responses by modulating type I IFN production
Authors: Lee Bo Ryeong , Jeong Soo Kyung , Ahn Byung Cheol , Lee Byeong-Jae , Shin Sung Jae , Yum Jung Sun , Ha Sang-Jun 
Published: September 2016

AbstractDespite the possibility of combining Toll-like receptor (TLR) ligands as adjuvants to improve vaccine efficacy, it remains unclear which combinations of TLR ligands are effective or what their underlying mechanisms may be. Here, we investigated the mechanism of action of L-pampo, a proprietary adjuvant composed of TLR1/2 and TLR3 ligands. L-pampo dramatically increased humoral immune responses against the tested target antigens, which was correlated with an increase in follicular helper T cells and the maintenance of antigen-specific CD4+ T cells. During the initial priming phase, in contrast to the induction of type I interferon (IFN) and pro-inflammatory cytokines stimulated by polyI:C, L-pampo showed a greatly diminished induction of type I IFN, but not of other cytokines, and remarkably attenuated IRF3 signaling, which appeared to be critical to L-pampo-mediated adjuvanticity. Collectively, our results demonstrate that the adjuvant L-pampo contributes to the promotion of antigen-specific antibodies and CD4+ T cell responses via a fine regulation of the TLR1/2 and TLR3 signaling pathways, which may be helpful in the design of improved vaccines.
Biosynthesis and characterization of silver nanoparticles prepared from two novel natural precursors by facile thermal decomposition methods
Authors: Goudarzi Mojgan , Mir Noshin , Mousavi-Kamazani Mehdi , Bagheri Samira , Salavati-Niasari Masoud 
Published: September 2016

AbstractIn this work, two natural sources, including pomegranate peel extract and cochineal dye were employed for the synthesis of silver nanoparticles. The natural silver complex from pomegranate peel extract resulted in nano-sized structures through solution-phase method, but this method was not efficient for cochineal dye-silver precursor and the as-formed products were highly agglomerated. Therefore, an alternative facile solid-state approach was investigated as for both natural precursors and the results showed successful production of well-dispersed nanoparticles with narrow size distribution for cochineal dye-silver precursor. The products were characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Energy dispersive X-ray microanalysis (EDX), and Transmission Electron Microscopy (TEM).
Time-dependent reversal of synaptic plasticity induced by physiological concentrations of oligomeric Aβ42: an early index of Alzheimer’s disease
Authors: Koppensteiner Peter , Trinchese Fabrizio , Fà Mauro , Puzzo Daniela , Gulisano Walter , Yan Shijun , Poussin Arthur , Liu Shumin , Orozco Ian , Dale Elena , Teich Andrew F. , Palmeri Agostino , Ninan Ipe , Boehm Stefan , Arancio Ottavio 
Published: September 2016

AbstractThe oligomeric amyloid-β (Aβ) peptide is thought to contribute to the subtle amnesic changes in Alzheimer’s disease (AD) by causing synaptic dysfunction. Here, we examined the time course of synaptic changes in mouse hippocampal neurons following exposure to Aβ42 at picomolar concentrations, mimicking its physiological levels in the brain. We found opposite effects of the peptide with short exposures in the range of minutes enhancing synaptic plasticity and longer exposures lasting several hours reducing it. The plasticity reduction was concomitant with an increase in the basal frequency of spontaneous neurotransmitter release, a higher basal number of functional presynaptic release sites and a redistribution of synaptic proteins including the vesicle-associated proteins synapsin I, synaptophysin and the post-synaptic glutamate receptor I. These synaptic alterations were mediated by cytoskeletal changes involving actin polymerization and p38 mitogen-activated protein kinase. These in vitro findings were confirmed in vivo with short hippocampal infusions of picomolar Aβ enhancing contextual memory and prolonged infusions impairing it. Our findings provide a model for initiation of synaptic dysfunction whereby exposure to physiologic levels of Aβ for a prolonged period of time causes microstructural changes at the synapse which result in increased transmitter release, failure of synaptic plasticity and memory loss.
Mapping the nicking efficiencies of nickase R.BbvCI for side-specific LNA-substituted substrates using rolling circle amplification
Authors: Wei Hua , Zhao Guojie , Hu Tianyu , Tang Suming , Jiang Jiquan , Hu Bo , Guan Yifu 
Published: September 2016

AbstractWe used a novel asymmetric cleavage analysis method based on rolling circle amplification (RCA) to determine the effects of LNA modification of substrate on the two subunits of R.BbvCI cleavage. We designed two sets of cleavage circular substrates by using two different ligation strategies and analyzed the single strand cleavage efficiency affected by different modification positions both from the cleaved strands and the uncleaved strands. Results showed that the effects of LNA on cleavage rates of modified strands and unmodified strands were both site-dependent. The Nb.BbvCI and Nt.BbvCI were affected by LNA modification in different way. Most of the modification positions showed strong inhibition of both of these two nickases cleavage. However, the modification in T3 position of bottom strand hardly affected both of the two nickases activities. The results suggested an intimated interaction between the two subunits of R.BbvCI and the T3 position in bottom strand might be a less tight position which was hard to be disturbed.
Crystal structure of the two-subunit tRNA m1A58 methyltransferase TRM6-TRM61 from Saccharomyces cerevisiae
Authors: Wang Mingxing , Zhu Yuwei , Wang Chongyuan , Fan Xiaojiao , Jiang Xuguang , Ebrahimi Mohammad , Qiao Zhi , Niu Liwen , Teng Maikun , Li Xu 
Published: September 2016

AbstractThe N1 methylation of adenine at position 58 (m1A58) of tRNA is an important post-transcriptional modification, which is vital for maintaining the stability of the initiator methionine tRNAiMet. In eukaryotes, this modification is performed by the TRM6-TRM61 holoenzyme. To understand the molecular mechanism that underlies the cooperation of TRM6 and TRM61 in the methyl transfer reaction, we determined the crystal structure of TRM6-TRM61 holoenzyme from Saccharomyces cerevisiae in the presence and absence of its methyl donor S-Adenosyl-L-methionine (SAM). In the structures, two TRM6-TRM61 heterodimers assemble as a heterotetramer. Both TRM6 and TRM61 subunits comprise an N-terminal β-barrel domain linked to a C-terminal Rossmann-fold domain. TRM61 functions as the catalytic subunit, containing a methyl donor (SAM) binding pocket. TRM6 diverges from TRM61, lacking the conserved motifs used for binding SAM. However, TRM6 cooperates with TRM61 forming an L-shaped tRNA binding regions. Collectively, our results provide a structural basis for better understanding the m1A58 modification of tRNA occurred in Saccharomyces cerevisiae.
Discover the network mechanisms underlying the connections between aging and age-related diseases
Authors: Yang Jialiang , Huang Tao , Song Won-min , Petralia Francesca , Mobbs Charles V. , Zhang Bin , Zhao Yong , Schadt Eric E. , Zhu Jun , Tu Zhidong 
Published: September 2016

AbstractAlthough our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease.
Effects of Atmospheric-Pressure N2, He, Air, and O2 Microplasmas on Mung Bean Seed Germination and Seedling Growth
Authors: Zhou Renwu , Zhou Rusen , Zhang Xianhui , Zhuang Jinxing , Yang Size , Bazaka Kateryna , Ostrikov Kostya 
Published: September 2016

AbstractAtmospheric-pressure N2, He, air, and O2 microplasma arrays have been used to investigate the effects of plasma treatment on seed germination and seedling growth of mung bean in aqueous solution. Seed germination and growth of mung bean were found to strongly depend on the feed gases used to generate plasma and plasma treatment time. Compared to the treatment with atmospheric-pressure O2, N2 and He microplasma arrays, treatment with air microplasma arrays was shown to be more efficient in improving both the seed germination rate and seedling growth, the effect attributed to solution acidification and interactions with plasma-generated reactive oxygen and nitrogen species. Acidic environment caused by air discharge in water may promote leathering of seed chaps, thus enhancing the germination rate of mung bean, and stimulating the growth of hypocotyl and radicle. The interactions between plasma-generated reactive species, such as hydrogen peroxide (H2O2) and nitrogen compounds, and seeds led to a significant acceleration of seed germination and an increase in seedling length of mung bean. Electrolyte leakage rate of mung bean seeds soaked in solution activated using air microplasma was the lowest, while the catalase activity of thus-treated mung bean seeds was the highest compared to other types of microplasma.
Catastrophic Cervical Spine Injuries in Contact Sports
Authors: Hutton Michael James , McGuire Robert A. , Dunn Robert , Williams Richard , Robertson Peter , Twaddle Bruce , Kiely Patrick , Clarke Andrew , Mazda Keyvan , Davies Paul , Pagarigan Krystle T. , Dettori Joseph R. 
Published: September 2016

Study Design Systematic review. Objectives To determine the incidence of catastrophic cervical spine injuries (CCSIs) among elite athletes participating in contact team sports and whether the incidence varies depending on the use of protective gear or by player position. Methods Electronic databases and reference lists of key articles published from January 1, 2000, to January 29, 2016, were searched. Results Fourteen studies were included that reported CCSI in rugby ( n = 10), American football ( n = 3), and Irish hurling ( n = 1). Among Rugby Union players, incidence of CCSI was 4.1 per 100,000 player-hours. Among National Football League players, the CCSI rate was 0.6 per 100,000 player-exposures. At the collegiate level, the CCSI rate ranged from 1.1 to 4.7 per 100,000 player-years. Mixed populations of elite and recreational rugby players in four studies report a CCSI rate of 1.4 to 7.2 per 100,000 player-years. In this same population, the scrum accounted for 30 to 51% of total reported CCSIs in Rugby Union versus 0 to 4% in Rugby League. The tackle accounted for 29 to 39% of injuries in Rugby Union and 78 to 100% of injuries in Rugby League. Making a tackle was responsible for 29 to 80% of injuries in American football. Conclusion CCSIs are infrequent among elite athletes. There is insufficient evidence to determine the effect of protective gear (e.g., helmets, padding) on CCSI incidence. Scrum and tackle in rugby and tackling in American football account for the majority of CCSIs in each respective sport.
Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression
Authors: Nishitsuji Hironori , Ujino Saneyuki , Yoshio Sachiyo , Sugiyama Masaya , Mizokami Masashi , Kanto Tatsuya , Shimotohno Kunitada 
Published: September 2016

Significance
Here, we describe a key feature of the long noncoding RNA (lncRNA) involved in innate immunity. We identified 182 lncRNAs that were highly modulated in poly(I:C)-treated hepatocyte cells. Of these, lncRNA#32 regulated the level of IFN-stimulated genes under both unstimulated and type I IFN-stimulated conditions through interactions with hnRNPU and ATF2, and therefore plays an important role in antiviral immunity.
Parent-of-origin effects of A1CF and AGO2 on testicular germ-cell tumors, testicular abnormalities, and fertilization bias
Authors: Carouge Delphine , Blanc Valerie , Knoblaugh Sue E. , Hunter Robert J. , Davidson Nicholas O. , Nadeau Joseph H. 
Published: September 2016

Significance
Usually diagnosed in young men, testicular germ cell tumors (TGCTs) originate from abnormalities in germ cells during fetal development. Testicular cancer is a complex disease combining multiple genetic variants and environmental factors. The discovery of unconventional inheritance for TGCT risk both in humans and mice highlighted the major contribution of epigenetic mechanisms. The current work identifies two TGCT modifiers, the RNA-binding proteins apolipoprotein B mRNA-editing enzyme complex 1 (APOBEC1) complementation factor (A1CF) and Argonaute 2 (AGO2), respectively involved in RNA editing and RNA silencing. These results help us better understand the epigenetic control of germ-cell fate, urogenital development, and gamete functions.
A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders
Authors: Inoue Ryo , Sakaue Yuko , Sawai Chihiro , Sawai Toshihiro , Ozeki Motoyuki , Romero-Pérez Gustavo A , Tsukahara Takamitsu 
Published: September 2016

Abstract
Fecal and blood samples of infants with autism spectrum disorders (ASD) and healthy infants were analyzed to investigate the association of altered gut microbiota and ASD development. 16S rRNA gene-based sequencing found that, unlike those of healthy infants, feces of ASD infants had significantly higher and lower abundance of genera Faecalibacterium and Blautia, respectively. Moreover, DNA microarray analysis of peripheral blood mononuclear cells (PBMC) detected more highly than low expressed genes in ASD infants than in healthy infants. Gene Ontology analysis revealed that differentially expressed genes between ASD and healthy infants were involved in interferon (IFN)-γ and type-I IFN signaling pathways. Finally, strong positive correlations between expression of IFN signaling-associated genes in PBMC and fecal abundance of Faecalibacterium were found. Our results strongly suggested that altered gut microbiota in infants resulted from ASD development and was associated with systemic immunity dysregulation, especially chronic inflammation.
Direct Alloying of Steel with Nickel Concentrate
Authors: Nokhrina O I , Rozhikhina I D , Proshunin I E 
Published: September 2016

Abstract
A technology of alloying steel with nickel reduced from nickel concentrate is analysed and developed. Limits of reduction concentration areas are defined. An optimal composition of nickel concentrate pellets and a method of feeding them into the furnace are deduced from experiments. It is proved that when pellets made of nickel concentrate and coke are added into the charge during steel smelting by the technology of alloyed scrap remelting, nickel recovery achieves 92-95%. The technology was tested by smelting DSP-40 steel.