bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-exposure treatment with whole inactivated H5N1 avian influenza virus protects against lethal homologous virus infection in mice
Authors: Hagan Mable , Ranadheera Charlene , Audet Jonathan , Morin Jocelyn , Leung Anders , Kobasa Darwyn 
Published: July 2016

AbstractConcerns with H5N1 influenza viruses include their prevalence in wild and domestic poultry, high mortality rate (~60%) in humans with some strains, lack of pre-existing immunity in humans and the possibility that these viruses acquire mutations that enable efficient transmission between humans. H5 subtype viruses of Eurasian origin have recently appeared in wild and domestic bird populations in North America and have led to the generation of new virus strains that are highly pathogenic in poultry. These new H5 HA containing viruses with their ability to evolve rapidly represent an unknown threat to humans in contact with infected poultry and vaccination with an off-the-shelf vaccine may be impractical to provide protection to at-risk individuals. Instead, we have evaluated the efficacy of a formalin-inactivated vaccine, which could be derived directly from a circulating virus, to provide post-exposure protection. This strategy was evaluated using a prototypic highly pathogenic avian H5N1 strain, A/Vietnam/1203/2004 and demonstrated rapid induction of adaptive immune responses providing protection in a mammalian model of lethal infection. Additionally, this post-exposure vaccine was highly efficacious when administered 24 hours after exposure. This study offers a platform for developing effective post-exposure vaccines for treatment of highly virulent influenza infections.
Exploration of acetanilide derivatives of 1-(ω-phenoxyalkyl)uracils as novel inhibitors of Hepatitis C Virus replication
Authors: Magri Andrea , Ozerov Alexander A. , Tunitskaya Vera L. , Valuev-Elliston Vladimir T. , Wahid Ahmed , Pirisi Mario , Simmonds Peter , Ivanov Alexander V. , Novikov Mikhail S. , Patel Arvind H. 
Published: July 2016

AbstractHepatitis C Virus (HCV) is a major public health problem worldwide. While highly efficacious directly-acting antiviral agents have been developed in recent years, their high costs and relative inaccessibility make their use limited. Here, we describe new 1-(ω-phenoxyalkyl)uracils bearing acetanilide fragment in 3 position of pyrimidine ring as potential antiviral drugs against HCV. Using a combination of various biochemical assays and in vitro virus infection and replication models, we show that our compounds are able to significantly reduce viral genomic replication, independently of virus genotype, with their IC50 values in the nanomolar range. We also demonstrate that our compounds can block de novo RNA synthesis and that effect is dependent on a chemical structure of the compounds. A detailed structure-activity relationship revealed that the most active compounds were the N3-substituted uracil derivatives containing 6-(4-bromophenoxy)hexyl or 8-(4-bromophenoxy)octyl fragment at N1 position.
Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL
Authors: Halliwell Diane E. , Morais Camilo L. M. , Lima Kássio M. G. , Trevisan Julio , Siggel-King Michele R. F. , Craig Tim , Ingham James , Martin David S. , Heys Kelly A. , Kyrgiou Maria , Mitra Anita , Paraskevaidis Evangelos , Theophilou Georgios , Martin-Hirsch Pierre L. , Cricenti Antonio , Luce Marco , Weightman Peter , Martin Francis L. 
Published: July 2016

AbstractCervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (≥0.2 μm). We compare these results with analyses following attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 μm to 30 μm due to the optical diffraction limit.
Therapeutic targeting of myeloid-derived suppressor cells involves a novel mechanism mediated by clusterin
Authors: Zhou Junmin , Donatelli Sarah S. , Gilvary Danielle L. , Tejera Melba M. , Eksioglu Erika A. , Chen Xianghong , Coppola Domenico , Wei Sheng , Djeu Julie Y. 
Published: July 2016

AbstractMyeloid-derived suppressor cells (MDSCs) constitute a key checkpoint that impedes tumor immunity against cancer. Chemotherapeutic intervention of MDSCs has gained ground as a strategy for cancer therapy but its mechanism remains obscure.We report here a unique mechanism by which monocytic (M)-MDSCs are spared, allowing them to polarize towards M1 macrophages for reactivation of immunity against breast cancer. We first demonstrated that curcumin, like docetaxel (DTX), can selectively target CD11b+Ly6G+Ly6Clow granulocytic (G)-MDSCs, sparing CD11b+Ly6G−Ly6Chigh M-MDSCs, with reduced tumor burden in 4T1-Neu tumor-bearing mice. Curcumin treatment polarized surviving M-MDSCs toward CCR7+ Dectin-1−M1 cells, accompanied by IFN-γ production and cytolytic function in T cells. Selective M-MDSC chemoresistence to curcumin and DTX was mediated by secretory/cytoplasmic clusterin (sCLU). sCLU functions by trapping Bax from mitochondrial translocation, preventing the apoptotic cascade. Importantly, sCLU was only found in M-MDSCs but not in G-MDSCs. Knockdown of sCLU in M-MDSCs and RAW264.7 macrophages was found to reverse their natural chemoresistance. Clinically, breast cancer patients possess sCLU expression only in mature CD68+ macrophages but not in immature CD33+ immunosuppressive myeloid cells infiltrating the tumors. We thus made the seminal discovery that sCLU expression in M-MDSCs accounts for positive immunomodulation by chemotherapeutic agents.
Functional conservation and diversification of the soybean maturity gene E1 and its homologs in legumes
Authors: Zhang Xingzheng , Zhai Hong , Wang Yaying , Tian Xiaojie , Zhang Yupeng , Wu Hongyan , Lü Shixiang , Yang Guang , Li Yuqiu , Wang Lu , Hu Bo , Bu Qingyun , Xia Zhengjun 
Published: July 2016

AbstractGene regulatory networks involved in flowering time and photoperiodic responses in legumes remain unknown. Although the major maturity gene E1 has been successfully deciphered in soybean, knowledge on the functional conservation of this gene is limited to a certain extent to E1 homologs in legumes. The ectopic expression of Phvul.009G204600 (PvE1L), an E1 homolog from common bean, delayed the onset of flowering in soybean. By contrast, the ectopic expression of Medtr2g058520 (MtE1L) from Medicago truncatula did not affect the flowering of soybean. Characterization of the late-flowering mte1l mutant indicated that MtE1L promoted flowering in Medicago truncatula. Moreover, all transgenic E1, PvE1L and MtE1L soybean lines exhibited phenotypic changes in terms of plant height. Transgenic E1 or PvE1L plants were taller than the wild-type, whereas transgenic MtE1L plants produced dwarf phenotype with few nodes and short internode. Thus, functional conservation and diversification of E1 family genes from legumes in the regulation of flowering and plant growth may be associated with lineage specification and genomic duplication.
Breast reconstruction with single-pedicle TRAM flap in breast cancer patients with low midline abdominal scar
Authors: Wu Jun-Dong , Huang Wen-He , Qiu Si-Qi , He Li-Fang , Guo Cui-Ping , Zhang Yong-Qu , Zhang Fan , Zhang Guo-Jun 
Published: July 2016

AbstractBreast reconstruction with transverse rectus abdominis myocutaneous (TRAM) flap is challenging in patients with low midline abdominal scar. In this study, we aimed to investigate the clinical feasibility of immediate breast reconstruction using single-pedicle TRAM (SP-TRAM) flaps in patients with low midline abdominal scar. There were 4 strict selection criteria: 1) presence at least 3 perforators on the pedicle side; 2) perforators with regional average flow velocity of >20 cm/s; 3) upper edge of the abdominal scar at least 4 cm from the umbilicus; and 4) scar age >1 year. Eight breast cancer patients with low midline abdominal scar (scar group) and 20 without (control group) underwent immediate breast reconstruction with SP-TRAM flaps consisting of zone I and III and zone II tissues. Flap complications, donor-site complications, and cosmetic results were compared between the two groups. All flaps survived and both groups presented similar flap and donor site complications, including fat necrosis, seroma, hematoma, infection, delayed wound healing, and abdominal hernia, and patients in both groups had similar aesthetic results (p > 0.05). Thus, the study demonstrated that breast reconstruction using SP-TRAM flap was a safe approach in carefully selected patients with low midline abdominal scar.
Advances in mapping malaria for elimination: fine resolution modelling of Plasmodium falciparum incidence
Authors: Alegana Victor A. , Atkinson Peter M. , Lourenço Christopher , Ruktanonchai Nick W. , Bosco Claudio , Erbach-Schoenberg Elisabeth zu , Didier Bradley , Pindolia Deepa , Le Menach Arnaud , Katokele Stark , Uusiku Petrina , Tatem Andrew J. 
Published: July 2016

AbstractThe long-term goal of the global effort to tackle malaria is national and regional elimination and eventually eradication. Fine scale multi-temporal mapping in low malaria transmission settings remains a challenge and the World Health Organisation propose use of surveillance in elimination settings. Here, we show how malaria incidence can be modelled at a fine spatial and temporal resolution from health facility data to help focus surveillance and control to population not attending health facilities. Using Namibia as a case study, we predicted the incidence of malaria, via a Bayesian spatio-temporal model, at a fine spatial resolution from parasitologically confirmed malaria cases and incorporated metrics on healthcare use as well as measures of uncertainty associated with incidence predictions. We then combined the incidence estimates with population maps to estimate clinical burdens and show the benefits of such mapping to identifying areas and seasons that can be targeted for improved surveillance and interventions. Fine spatial resolution maps produced using this approach were then used to target resources to specific local populations, and to specific months of the season. This remote targeting can be especially effective where the population distribution is sparse and further surveillance can be limited to specific local areas.
Targeting cellular mRNAs translation by CRISPR-Cas9
Authors: Liu Yuchen , Chen Zhicong , He Anbang , Zhan Yonghao , Li Jianfa , Liu Li , Wu Hanwei , Zhuang Chengle , Lin Junhao , Zhang Qiaoxia , Huang Weiren 
Published: July 2016

AbstractRecently CRISPR-Cas9 system has been reported to be capable of targeting a viral RNA and this phenomenon thus raises an interesting question of whether Cas9 can also influence translation of cellular mRNAs. Here, we show that both natural and catalytically dead Cas9 can repress mRNA translation of cellular genes and that only the first 14 nt in the 5′ end of sgRNA is essential for this process. CRISPR-Cas9 can suppress the protein expression of an unintended target gene without affecting its DNA sequence and causes unexpected phenotypic changes. Using the designed RNA aptamer-ligand complexes which physically obstruct translation machinery, we indicate that roadblock mechanism is responsible for this phenomenon. Our work suggests that studies on Cas9 should avoid the potential off-target effects by detecting the alteration of genes at both the DNA and protein levels.
Orchestration of gene expression across the seasons: Hypothalamic gene expression in natural photoperiod throughout the year in the Siberian hamster
Authors: Petri Ines , Diedrich Victoria , Wilson Dana , Fernández-Calleja José , Herwig Annika , Steinlechner Stephan , Barrett Perry 
Published: July 2016

AbstractIn nature Siberian hamsters utilize the decrement in day length following the summer solstice to implement physiological adaptations in anticipation of the forthcoming winter, but also exploit an intrinsic interval timer to initiate physiological recrudescence following the winter solstice. However, information is lacking on the temporal dynamics in natural photoperiod of photoperiodically regulated genes and their relationship to physiological adaptations. To address this, male Siberian hamsters born and maintained outdoors were sampled every month over the course of one year. As key elements of the response to photoperiod, thyroid hormone signalling components were assessed in the hypothalamus. From maximum around the summer solstice (late-June), Dio2 expression rapidly declined in advance of physiological adaptations. This was followed by a rapid increase in Mct8 expression (T3/T4 transport), peaking early-September before gradually declining to minimum expression by the following June. Dio3 showed a transient peak of expression beginning late-August. A recrudescence of testes and body mass occurred from mid-February, but Dio2 expression remained low until late-April of the following year, converging with the time of year when responsiveness to short-day length is re-established. Other photoperiodically regulated genes show temporal regulation, but of note is a transient peak in Gpr50 around late-July.
An investigation of BMP-7 mediated alterations to BMP signalling components in human tenocyte-like cells
Authors: Klatte-Schulz Franka , Giese Gerry , Differ Christopher , Minkwitz Susann , Ruschke Karen , Puts Regina , Knaus Petra , Wildemann Britt 
Published: July 2016

AbstractThe incidence of tendon re-tears post-surgery is an ever present complication. It is suggested that the application of biological factors, such as bone morphogenetic protein 7 (BMP-7), can reduce complication rates by promoting tenogenic characteristics in in vitro studies. However, there remains a dearth of information in regards to the mechanisms of BMP-7 signalling in tenocytes. Using primary human tenocyte-like cells (hTLCs) from the supraspinatus tendon the BMP-7 signalling pathway was investigated: induction of the BMP associated Smad pathway and non-Smad pathways (AKT, p38, ERK1/2 and JNK); alterations in gene expression of BMP-7 associated receptors, Smad pathway components, Smad target gene (ID1) and tenogenic marker scleraxis. BMP-7 increases the expression of specific BMP associated receptors, BMPR-Ib and BMPR-II and Smad8. Additionally, BMP-7 activates significantly Smad1/5/8 and slightly p38 pathways as indicated by an increase in phosphorylation and proven by inhibition experiments, where p-ERK1/2 and p-JNK pathways remain mainly unresponsive. Furthermore, BMP-7 increases the expression of the Smad target gene ID1 and the tendon specific transcription factor scleraxis. The study shows that tenocyte-like cells undergo primarily Smad8 and p38 signalling after BMP-7 stimulation. The up-regulation of tendon related marker genes and matrix proteins such as Smad8/9, scleraxis and collagen I might lead to positive effects of BMP-7 treatment for rotator cuff repair, without significant induction of osteogenic and chondrogenic markers.
Comprehensive design of omnidirectional high-performance perovskite solar cells
Authors: Zhang Yutao , Xuan Yimin 
Published: July 2016

AbstractThe comprehensive design approach is established with coupled optical-electrical simulation for perovskite-based solar cell, which emerged as one of the most promising competitors to silicon solar cell for its low-cost fabrication and high PCE. The selection of structured surface, effect of geometry parameters, incident angle-dependence and polarization-sensitivity are considered in the simulation. The optical modeling is performed via the finite-difference time-domain method whilst the electrical properties are obtained by solving the coupled nonlinear equations of Poisson, continuity and drift-diffusion equations. The optical and electrical performances of five different structured surfaces are compared to select a best structured surface for perovskite solar cell. The effects of the geometry parameters on the optical and electrical properties of the perovskite cell are analyzed. The results indicate that the light harvesting is obviously enhanced by the structured surface. The electrical performance can be remarkably improved due to the enhanced light harvesting of the designed best structured surface. The angle-dependence for s- and p-polarizations is investigated. The structured surface exhibits omnidirectional behavior and favorable polarization-insensitive feature within a wide incident angle range. Such a comprehensive design approach can highlight the potential of perovskite cell for power conversion in the full daylight.
Parametric instability of optical non-Hermitian systems near the exceptional point
Authors: Zyablovsky A. A. , Andrianov E. S. , Pukhov A. A. 
Published: July 2016

AbstractIn contrast to Hermitian systems, the modes of non-Hermitian systems are generally nonorthogonal. As a result, the power of the system signal depends not only on the mode amplitudes but also on the phase shift between them. In this work, we show that it is possible to increase the mode amplitudes without increasing the power of the signal. Moreover, we demonstrate that when the system is at the exceptional point, any infinitesimally small change in the system parameters increases the mode amplitudes. As a result, the system becomes unstable with respect to such perturbation. We show such instability by using the example of two coupled waveguides in which loss prevails over gain and all modes are decaying. This phenomenon enables compensation for losses in dissipative systems and opens a wide range of applications in optics, plasmonics and optoelectronics, in which loss is an inevitable problem and plays a crucial role.
Receptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells
Authors: Beuter Simone , Ardi Ziv , Horovitz Omer , Wuchter Jennifer , Keller Stefanie , Saha Rinki , Tripathi Kuldeep , Anunu Rachel , Kehat Orli , Kriebel Martin , Richter-Levin Gal , Volkmer Hansjürgen 
Published: July 2016

AbstractNeuronal transmission is regulated by the local circuitry which is composed of principal neurons targeted at different subcellular compartments by a variety of interneurons. However, mechanisms that contribute to the subcellular localisation and maintenance of GABAergic interneuron terminals are poorly understood. Stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin and its interaction with the guanine nucleotide exchange factor collybistin. Lentiviral knockdown experiments in adult rats indicated that the receptor tyrosine kinase EphA7 is required for the stabilisation of basket cell terminals on proximal dendritic and somatic compartments of granular cells of the dentate gyrus. EphA7 deficiency and concomitant destabilisation of GABAergic synapses correlated with impaired long-term potentiation and reduced hippocampal learning. Reduced GABAergic innervation may be explained by an impact of EphA7 on gephyrin clustering. Overexpression or ephrin stimulation of EphA7 induced gephyrin clustering dependent on the mechanistic target of rapamycin (mTOR) which is an interaction partner of gephyrin. Gephyrin interactions with mTOR become released after mTOR activation while enhanced interaction with the guanine nucleotide exchange factor collybistin was observed in parallel. In conclusion, EphA7 regulates gephyrin clustering and the maintenance of inhibitory synaptic connectivity via mTOR signalling.
Radicalization and Radical Catalysis of Biomass Sugars: Insights from First-principles Studies
Authors: Yang Gang , Zhu Chang , Zou Xianli , Zhou Lijun 
Published: July 2016

AbstractAb initio and density functional calculations are conducted to investigate the radicalization processes and radical catalysis of biomass sugars. Structural alterations due to radicalization generally focus on the radicalized sites and radicalization affects H-bonds in D-fructofuranose more than in D-glucopyranose, potentially with outcome of new H-bonds. Performances of different functionals and basis sets are evaluated for all radicalization processes and enthalpy changes and Gibbs free energies for these processes are presented with high accuracy, which can be referenced for subsequent experimental and theoretical studies. It shows that radicalization can be utilized for direct transformation of biomass sugars and for each sugar, C rather than O sites are always preferred for radicalization, thus suggesting the possibility to activate C-H bonds of biomass sugars. Radical catalysis is further combined with Brønsted acids and it clearly states that functionalization fundamentally regulates the catalytic effects of biomass sugars. In presence of explicit water molecules, functionalization significantly affects the activation barriers and reaction energies of protonation rather than dehydration steps. Tertiary butyl and phenyl groups with large steric hindrances or hydroxyl and amino groups resulting in high stabilities for protonation products drive the protonation steps to occur facilely at ambient conditions.
Benzothiazinethione is a potent preclinical candidate for the treatment of drug-resistant tuberculosis
Authors: Gao Chao , Peng Cuiting , Shi Yaojie , You Xinyu , Ran Kai , Xiong Lu , Ye Ting-hong , Zhang Lidan , Wang Ningyu , Zhu Yongxia , Liu Kun , Zuo Weiqiong , Yu Luoting , Wei Yuquan 
Published: July 2016

AbstractNew chemotherapeutic compounds are needed to combat multidrug-resistant Mycobacterium tuberculosis (Mtb), which remains a serious public-health challenge. Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1 enzyme) has been characterized as an attractive therapeutic target to address this urgent demand. Herein, we have identified a new class of DprE1 inhibitors benzothiazinethiones as antitubercular agents. Benzothiazinethione analogue SKLB-TB1001 exhibited excellent activity against Mtb in the Microplate Alamar blue assay and intracellular model, meanwhile SKLB-TB1001 was also highly potent against multi-drug resistant extensively and drug resistant clinical isolates. Importantly, no antagonism interaction was found with any two-drug combinations tested in the present study and the combination of SKLB-TB1001 with rifampicin (RMP) was proved to be synergistic. Furthermore, benzothiazinethione showed superb in vivo antitubercular efficacy in an acute Mtb infection mouse model, significantly better than that of BTZ043. These data combined with the bioavailability and safety profiles of benzothiazinethione indicates SKLB-TB1001 is a promising preclinical candidate for the treatment of drug-resistant tuberculosis.