bluuebunny/crossref_metadata_2025 huggingface dataset:
CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection
Authors: Khairnar Vishal , Duhan Vikas , Patil Ashwini M. , Zhou Fan , Bhat Hilal , Thoens Christine , Sharma Piyush , Adomati Tom , Friendrich Sarah-Kim , Bezgovsek Judith , Dreesen Janine D. , Wennemuth Gunther , Westendorf Astrid M. , Zelinskyy Gennadiy , Dittmer Ulf , Hardt Cornelia , Timm Jörg , Göthert Joachim R. , Lang Philipp A. , Singer Bernhard B. , Lang Karl S.
Published: June 2018

Dysfunction of CD8+ T cells can lead to the development of chronic viral infection. Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection. Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. CEACAM1 is essential for activation of CD8+ T cells, and the absence of CEACAM1 on virus-specific CD8+ T cells limits the antiviral CD8+ T cell response. Treatment with anti-CEACAM1 antibody stabilizes Lck in the immunological synapse, prevents CD8+ T cell exhaustion, and improves control of virus infection in vivo. Treatment of human virus-specific CD8+ T cells with anti-CEACAM1 antibody similarly enhances their proliferation. We conclude that CEACAM1 is an important regulator of virus-specific CD8+ T cell functions in mice and humans and represents a promising therapeutic target for modulating CD8+ T cells.
Synthetic molecular evolution of hybrid cell penetrating peptides
Authors: Kauffman W. Berkeley , Guha Shantanu , Wimley William C.
Published: June 2018

Peptides and analogs such as peptide nucleic acids (PNA) are promising tools and therapeutics, but the cell membrane remains a barrier to intracellular targets. Conjugation to classical cell penetrating peptides (CPPs) such as pTat48–60 (tat) and pAntp43–68 (penetratin) facilitates delivery; however, efficiencies are low. Lack of explicit design principles hinders rational improvement. Here, we use synthetic molecular evolution (SME) to identify gain-of-function CPPs with dramatically improved ability to deliver cargoes to cells at low concentration. A CPP library containing 8192 tat/penetratin hybrid peptides coupled to an 18-residue PNA is screened using the HeLa pTRE-LucIVS2 splice correction reporter system. The daughter CPPs identified are one to two orders of magnitude more efficient than the parent sequences at delivery of PNA, and also deliver a dye cargo and an anionic peptide cargo. The significant increase in performance following a single iteration of SME demonstrates the power of this approach to peptide sequence optimization.
Immediate action is the best strategy when facing uncertain climate change
Authors: Abou Chakra Maria , Bumann Silke , Schenk Hanna , Oschlies Andreas , Traulsen Arne
Published: June 2018

Mitigating the detrimental effects of climate change is a collective problem that requires global cooperation. However, achieving cooperation is difficult since benefits are obtained in the future. The so-called collective-risk game, devised to capture dangerous climate change, showed that catastrophic economic losses promote cooperation when individuals know the timing of a single climatic event. In reality, the impact and timing of climate change is not certain; moreover, recurrent events are possible. Thus, we devise a game where the risk of a collective loss can recur across multiple rounds. We find that wait and see behavior is successful only if players know when they need to contribute to avoid danger and if contributions can eliminate the risks. In all other cases, act quickly is more successful, especially under uncertainty and the possibility of repeated losses. Furthermore, we incorporate influential factors such as wealth inequality and heterogeneity in risks. Even under inequality individuals should contribute early, as long as contributions have the potential to decrease risk. Most importantly, we find that catastrophic scenarios are not necessary to induce such immediate collective action.
Early Palaeozoic ocean anoxia and global warming driven by the evolution of shallow burrowing
Authors: van de Velde Sebastiaan , Mills Benjamin J. W. , Meysman Filip J. R. , Lenton Timothy M. , Poulton Simon W.
Published: June 2018

The evolution of burrowing animals forms a defining event in the history of the Earth. It has been hypothesised that the expansion of seafloor burrowing during the Palaeozoic altered the biogeochemistry of the oceans and atmosphere. However, whilst potential impacts of bioturbation on the individual phosphorus, oxygen and sulphur cycles have been considered, combined effects have not been investigated, leading to major uncertainty over the timing and magnitude of the Earth system response to the evolution of bioturbation. Here we integrate the evolution of bioturbation into the COPSE model of global biogeochemical cycling, and compare quantitative model predictions to multiple geochemical proxies. Our results suggest that the advent of shallow burrowing in the early Cambrian contributed to a global low-oxygen state, which prevailed for ~100 million years. This impact of bioturbation on global biogeochemistry likely affected animal evolution through expanded ocean anoxia, high atmospheric CO2 levels and global warming.
Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway
Authors: Tang-Huau Tsing-Lee , Gueguen Paul , Goudot Christel , Durand Mélanie , Bohec Mylène , Baulande Sylvain , Pasquier Benoit , Amigorena Sebastian , Segura Elodie
Published: June 2018

Presentation of exogenous antigens on MHC-I molecules, termed cross-presentation, is essential for cytotoxic CD8+T cell responses. In mice, dendritic cells (DCs) that arise from monocytes (mo-DCs) during inflammation have a key function in these responses by cross-presenting antigens locally in peripheral tissues. Whether human naturally-occurring mo-DCs can cross-present is unknown. Here, we use human mo-DCs and macrophages directly purified from ascites to address this question. Single-cell RNA-seq data show that ascites CD1c+DCs contain exclusively monocyte-derived cells. Both ascites mo-DCs and monocyte-derived macrophages cross-present efficiently, but are inefficient for transferring exogenous proteins into their cytosol. Inhibition of cysteine proteases, but not of proteasome, abolishes cross-presentation in these cells. We conclude that human monocyte-derived cells cross-present exclusively using a vacuolar pathway. Finally, only ascites mo-DCs provide co-stimulatory signals to induce effector cytotoxic CD8+T cells. Our findings thus provide important insights on how to harness cross-presentation for therapeutic purposes.
BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin
Authors: Wang Feng , He Qing , Yin Jia , Xu Sujuan , Hu Wei , Gu Lichuan
Published: June 2018

The virulence factor pyocyanin and the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP) play key roles in regulating biofilm formation and multi-drug efflux pump expression in Pseudomonas aeruginosa. However, the crosstalk between these two signaling pathways remains unclear. Here we show that BrlR (PA4878), previously identified as a c-di-GMP responsive transcriptional regulator, acts also as a receptor for pyocyanin. Crystal structures of free BrlR and c-di-GMP-bound BrlR reveal that the DNA-binding domain of BrlR contains two separate c-di-GMP binding sites, both of which are involved in promoting brlR expression. In addition, we identify a pyocyanin-binding site on the C-terminal multidrug-binding domain based on the structure of the BrlR-C domain in complex with a pyocyanin analog. Biochemical analysis indicates that pyocyanin enhances BrlR-DNA binding and brlR expression in a concentration-dependent manner.
Giant antidamping orbital torque originating from the orbital Rashba-Edelstein effect in ferromagnetic heterostructures
Authors: Chen Xi , Liu Yang , Yang Guang , Shi Hui , Hu Chen , Li Minghua , Zeng Haibo
Published: June 2018

Enhancing the in-plane current-induced torque efficiency in inversion-symmetry-breaking ferromagnetic heterostructures is of both fundamental and practical interests for emerging magnetic memory device applications. Here, we present an interface-originated magnetoelectric effect, the orbital Rashba–Edelstein effect, for realizing large torque efficiency in Pt/Co/SiO2/Pt films with strong perpendicular magnetic anisotropy (PMA). The key element is a pronounced Co 3d orbital splitting due to asymmetric orbital hybridization at the Pt/Co and Co/SiO2 interfaces, which not only stabilizes the PMA but also produces a large orbital torque upon the Co magnetization with current injection. The torque efficiency is found to be strongly magnetization direction- and temperature-dependent, and can reach up to 2.83 at room temperature, which is several times to one order of magnitude larger than those previously reported. This work highlights the active role of the orbital anisotropy for efficient torque generation and indicates a route for torque efficiency optimization through orbital engineering.
Impacts of warming on top-down and bottom-up controls of periphyton production
Authors: Kazanjian Garabet , Velthuis Mandy , Aben Ralf , Stephan Susanne , Peeters Edwin T. H. M. , Frenken Thijs , Touwen Jelle , Xue Fei , Kosten Sarian , Van de Waal Dedmer B. , de Senerpont Domis Lisette N. , van Donk Ellen , Hilt Sabine
Published: June 2018

Global warming profoundly impacts the functioning of aquatic ecosystems. Nonetheless, the effect of warming on primary producers is poorly understood, especially periphyton production, which is affected both directly and indirectly by temperature-sensitive top-down and bottom-up controls. Here, we study the impact of warming on gross primary production in experimental ecosystems with near-realistic foodwebs during spring and early summer. We used indoor mesocosms following a temperate temperature regime (control) and a warmed (+4 °C) treatment to measure biomass and production of phytoplankton and periphyton. The mesocosms’ primary production was dominated by periphyton (>82%) during the studied period (April-June). Until May, periphyton production and biomass were significantly higher in the warm treatment (up to 98% greater biomass compared to the control) due to direct temperature effects on growth and indirect effects resulting from higher sediment phosphorus release. Subsequently, enhanced grazer abundances seem to have counteracted the positive temperature effect causing a decline in periphyton biomass and production in June. We thus show, within our studied period, seasonally distinct effects of warming on periphyton, which can significantly affect overall ecosystem primary production and functioning.
A Canonical Biophysical Model of the CsrA Global Regulator Suggests Flexible Regulator-Target Interactions
Authors: Leistra A. N. , Gelderman G. , Sowa S. W. , Moon-Walker A. , Salis H. M. , Contreras L. M.
Published: June 2018

Bacterial global post-transcriptional regulators execute hundreds of interactions with targets that display varying molecular features while retaining specificity. Herein, we develop, validate, and apply a biophysical, statistical thermodynamic model of canonical target mRNA interactions with the CsrA global post-transcriptional regulator to understand the molecular features that contribute to target regulation. Altogether, we model interactions of CsrA with a pool of 236 mRNA: 107 are experimentally regulated by CsrA and 129 are suspected interaction partners. Guided by current understanding of CsrA-mRNA interactions, we incorporate (i) mRNA nucleotide sequence, (ii) cooperativity of CsrA-mRNA binding, and (iii) minimization of mRNA structural changes to identify an ensemble of likely binding sites and their free energies. The regulatory impact of bound CsrA on mRNA translation is determined with the RBS calculator. Predicted regulation of 66 experimentally regulated mRNAs adheres to the principles of canonical CsrA-mRNA interactions; the remainder implies that other, diverse mechanisms may underlie CsrA-mRNA interaction and regulation. Importantly, results suggest that this global regulator may bind targets in multiple conformations, via flexible stretches of overlapping predicted binding sites. This novel observation expands the notion that CsrA always binds to its targets at specific consensus sequences.
Dexmedetomidine Added to Sufentanil Patient-Controlled Intravenous Analgesia Relieves the Postoperative Pain after Cesarean Delivery: A Prospective Randomized Controlled Multicenter Study
Authors: Nie Yuyan , Tu Weifeng , Shen Xiaofeng , Yu Weifeng , Yu Yonghao , Song Xingrong , Wang Shiduan , Luo Ailin , Cao Minghui , Wu Xinmin , Huang Shaoqiang
Published: June 2018

This study evaluated the efficacy and safety of dexmedetomidine in intravenous patient-controlled analgesia (PCA) after cesarean delivery. This multicenter study enrolled 208 subjects who were scheduled for selective cesarean delivery from 9 research centers. Patients received 0.5 ug/kg dexmedetomidine (study group) or normal saline (control group) after delivery and an intravenous PCA pump after surgery (100 μg sufentanil +300 μg dexmedetomidine for the study group, 100 μg sufentanil for the control group, background infusion: 1 ml/h, bolus dose: 2 ml and lock time: 8 min). The sufentanil consumption, pain scores, rescue analgesia, sedation scores, analgesic satisfaction, the incidence of postoperative nausea and vomiting (PONV) and the first passage of flatus were recorded within 24 h after surgery. The sufentanil consumption in the study group was significantly lower than that in the control group (p = 0.004). Compared with the control group, the study group had lower pain scores (p < 0.01), higher analgesic satisfaction degree [p < 0.001, odd ratio 4.28 and 95% CI (2.46, 7.46)], less requirement of rescue analgesia (p = 0.003), lower incidence of PONV (p = 0.005 and p < 0.001, respectively), and shorter time to first passage of flatus (p = 0.007). Dexmedetomidine added to sufentanil intravenous PCA significantly enhanced the analgesic effects, improved analgesic satisfaction, and had the potential benefits of reducing PONV and the recovery of intestinal functions after cesarean section.
Mesenchymal Stem Cells in Combination with Hyaluronic Acid for Articular Cartilage Defects
Authors: Li Lang , Duan Xin , Fan Zhaoxin , Chen Long , Xing Fei , Xu Zhao , Chen Qiang , Xiang Zhou
Published: June 2018

Mesenchymal stem cells (MSCs) and hyaluronic acid (HA) have been found in previous studies to have great potential for medical use. This study aimed to investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) combined with HA on articular cartilage repair in canines. Twenty-four healthy canines (48 knee-joints), male or female with weight ranging from 5 to 6 kg, were operated on to induce cartilage defect model and divided into 3 groups randomly which received different treatments: BMSCs plus HA (BMSCs-HA), HA alone, and saline. Twenty-eight weeks after treatment, all canines were sacrificed and analyzed by gross appearance, magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining, Masson staining, toluidine blue staining, type II collagen immunohistochemistry, gross grading scale and histological scores. MSCs plus HA regenerated more cartilage-like tissue than did HA alone or saline. According to the macroscopic evaluation and histological assessment score, treatment with MSCs plus HA also lead to significant improvement in cartilage defects compared to those in the other 2 treatment groups (P < 0.05). These findings suggested that allogeneic BMSCs plus HA rather than HA alone was effective in promoting the formation of cartilage-like tissue for repairing cartilage defect in canines.
Increased activin A levels in prediabetes and association with carotid intima-media thickness: a cross-sectional analysis from I-Lan Longitudinal Aging Study
Authors: Kuo Chin-Sung , Lu Ya-Wen , Hsu Chien-Yi , Chang Chun-Chin , Chou Ruey-Hsing , Liu Li-Kuo , Chen Liang-Kung , Huang Po-Hsun , Chen Jaw-Wen , Lin Shing-Jong
Published: June 2018

Activin A and its binding protein follistatin may be crucial in glucose homeostasis, as multifunctional proteins mediating inflammatory and anti-inflammatory effects. However, clinical data on the activin A level in prediabetes, and the association between the circulating activin A level and carotid intima-media thickness (cIMT), are lacking. We aimed to investigate activin A and follistatin levels and their associations with cIMT. In total, 470 inhabitants of I-Lan county (235 men; mean age 69 ± 9 years) with measurements of serum activin A and follistatin levels were included. Patients with prediabetes and diabetes had significantly increased activin A concentrations compared with those in the normal glycemic group (both p < 0.001). A multivariable logistic regression model demonstrated that the circulating activin A level was associated with prediabetes and diabetes independently of other risk factors. Moreover, the circulating activin A levels were associated positively with cIMT in prediabetes (rs = 0.264, p = 0.001). In conclusion, activin A level, but not follistatin, was elevated independent of demographic variables with borderline significance and was correlated positively with cIMT in prediabetes. Activin A and follistatin levels were elevated in diabetes. In addition, elevated activin A was an independent risk factor for prediabetes and diabetes.
Lithium-ion conducting oxide single crystal as solid electrolyte for advanced lithium battery application
Authors: Kataoka Kunimitsu , Nagata Hiroshi , Akimoto Junji
Published: June 2018

Today, all-solid-state secondary lithium-ion batteries have attracted attention in research and development all over the world as a next-generation energy storage device. A key material for the all-solid-state lithium batteries is inorganic solid electrolyte, including oxide and sulfide materials. Among the oxide electrolytes, garnet-type oxide exhibits the highest lithium-ion conductivity and a wide electrochemical potential window. However, they have major problems for practical realization. One of the major problems is an internal short-circuit in charging and discharging. In the polycrystalline garnet-type oxide electrolyte, dendrites of lithium metal easily grow through the void or impurity in grain boundaries of the sintered body, which causes serious internal short-circuits in the battery system. To solve these problems, we present an all-solid-state battery system using a single-crystal oxide electrolyte. We are the first to successfully grow centimeter-sized single crystals of garnet-type by the floating zone method. The single-crystal solid electrolyte exhibits an extremely high lithium-ion conductivity of 10−3 S cm−1 at 298 K. The garnet-type single-crystal electrolyte has an advantageous bulk nature to realize the bulk conductivity without grain boundaries such as in a sintered polycrystalline body, and will be a game-changing technology for achieving highly safe advanced battery systems.
Elevated CO2 and O3 alter the feeding efficiency of Acyrthosiphon pisum and Aphis craccivora via changes in foliar secondary metabolites
Authors: Yan Hongyu , Guo Honggang , Yuan Erliang , Sun Yucheng , Ge Feng
Published: June 2018

Elevated CO2and O3can affect aphid performance via altering plant nutrients, however, little is known about the role of plant secondary metabolites in this process, especially for aphids feeding behaviors. We determined the effects of elevated CO2and O3on the growth and phenolics of alfalfa (Medicago sativa) and feeding behaviors of the pea aphids (Acyrthosiphon pisum) and cowpea aphids (Aphis craccivora). Elevated CO2improved plant growth, but could not completely offset the negative effects of elevated O3. Elevated O3increased foliar genistin content at the vegetative stage, increased ferulic acid at the reproductive stage, and elevated CO2increased those at both stages. Simultaneously elevated CO2and O3increased foliar ferulic acid content at the reproductive stage and increased genistin content at both stages. For pea aphids, feeding efficiency was reduced under elevated CO2at the reproductive stage and decreased under elevated O3at the vegetative stage. For cowpea aphids, feeding efficiency was increased under elevated CO2at the vegetative stage and decreased under elevated O3at both stages. Simultaneously elevated CO2and O3decreased both aphids feeding efficiency. We concluded that CO2and O3independently or interactively had different effects on two aphids feeding behaviors through altering foliar ferulic acid and genistin contents.
Harnessing Free Energy From Nature For Efficient Operation of Compressed Air Energy Storage System and Unlocking the Potential of Renewable Power Generation
Authors: Venkataramani Gayathri , Ramalingam Velraj , Viswanathan Kishore
Published: June 2018

Energy storage technologies have gained considerable momentum in the recent years owing to the rising tide of renewables. The deployment of energy storage is a trend set to continue into 2018 and beyond. In the near future, compressed air energy storage (CAES) will serve as an integral component of several energy intensive sectors. However, the major drawback in promoting CAES system in both large and small scale is owing to its minimum turn around efficiency. In the present work the major drawbacks associated with various existing configurations of CAES system are analysed. Interesting results of Isothermal CAES system are obtained through the present analysis to generate additional output energy compared to the supplied input by harnessing the free energy from the natural water bodies/ocean to enhance the overall turnaround efficiency of the system. The optimum operational characteristics of charging and discharging cycles are also addressed. In the present energy scenario, increasing the percentage of renewable energy (RE) share in the power generation is quite challenging since RE based power generation is intermittent in nature. The integration of energy storage technologies with RE source is imperative as it mitigates the intermittency of available energy. However, the development of efficient energy storage systems is one of the prime challenges in the promotion of renewable energy in a large scale. Among the various storage systems, electrochemical battery storage and pumped hydro storage (PHS) have attracted the commercial market. However, the shorter cycle life makes the battery storage more expensive and the PHS systems involves certain geographical and site constraints. Beyond the said storage systems, compressed air energy storage system which is one of the technically proven system has not been targeted the commercial market owing to its lower turnaround efficiency. Hence, the motivation behind the present research is towards developing efficient CAES configuration with higher turnaround efficiency thereby attaining economic feasibility and sustainability.
Algae explosive growth mechanism enabling weather-like forecast of harmful algal blooms
Authors: Tian Rongxiang , Chen Jianfang , Sun Xiangwei , Li Dewang , Liu Chongxuan , Weng Huanxin
Published: June 2018

As a global problem in coastal environments, harmful algal blooms (HABs) have seriously affected the health of coastal ecosystems and regional economies. Here we report an aerosol-trigger mechanism for the occurrence of HABs based on long-term field data and laboratory experiments. The occurrence times of HABs and aerosol events had a significant correlation from 2005 to 2013 in the East China Sea, indicating that aerosol transport was probably an alternative trigger of HABs. HABs mostly occur in the transition time between winter and summer, during which northwest monsoon transport substantial aerosol (rich in phosphate, iron and other trace metals) to coastal waters, as revealed by chemical measurements, transmission electron microscope and electron microprober results. Such nutrients can stimulate algal growth in our incubation experiments, suggesting that such aerosol transport can be important nutrient sources for the East China Sea where phytoplankton growth is relatively phosphate limited. Air-borne nutrients are available for algal growth by rapid downward air flow, which additional results a clear weather condition, and thus adequate light intensity for algal growth. At last, the transition from northwest monsoon to warm southwest monsoon establishes favorable seawater temperature for algal blooms. Such weather-related aerosol-trigger mechanism suggests possibly forecast of HABs.
Generalized Empirical Bayes Modeling via Frequentist Goodness of Fit
Authors: Mukhopadhyay Subhadeep , Fletcher Douglas
Published: June 2018

The two key issues of modern Bayesian statistics are: (i) establishing principled approach fordistillingstatistical prior that isconsistentwith the given data from an initial believable scientific prior; and (ii) development of aconsolidatedBayes-frequentist data analysis workflow that is more effective than either of the two separately. In this paper, we propose the idea of “Bayesviagoodness-of-fit” as a framework for exploring these fundamental questions, in a way that is general enough to embrace almost all of the familiar probability models. Several examples, spanning application areas such as clinical trials, metrology, insurance, medicine, and ecology show the unique benefit of this new point of view as a practical data science tool.
Vasodilator-stimulated phosphoprotein (VASP) is not a major mediator of platelet aggregation, thrombogenesis, haemostasis, and antiplatelet effect of prasugrel in rats
Authors: Ito Yusuke , Ohno Kousaku , Morikawa Yuka , Tomizawa Atsuyuki , Mizuno Makoto , Sugidachi Atsuhiro
Published: June 2018

Vasodilator-stimulated phosphoprotein (VASP) is a member of actin regulatory proteins implicated in platelet adhesion. In addition, phosphorylation of VASP is utilised for the assessment of platelet reactivity in patients treated with P2Y12 receptor antagonists, a class of antiplatelet agents. However, the role of VASP in platelet aggregation, thrombogenesis, haemostasis, and the antiplatelet effect of P2Y12 receptor antagonists remains unclear. We investigated these effects using heterozygous and homozygous VASP knockout rats generated with a CRISPR/Cas9 system. Baseline characteristics, such as haematology and other biochemical parameters, were comparable among the genotypes. In vitro platelet aggregation stimulated by adenosine diphosphate (ADP) or collagen, P-selectin expression of rat platelets treated with ADP, and in vivo thrombocytopenia induced by collagen were also comparable among the genotypes. In addition, in vivo thrombogenesis in a ferric chloride-induced arterial thrombosis model and bleeding time were also comparable among the genotypes. Furthermore, the in vitro antiplatelet effect of prasugrel, a third-generation P2Y12 receptor antagonist, was unaffected by VASP knockout. Although phosphorylated VASP is still an important surrogate marker specific for P2Y12 antagonists, our findings demonstrate that VASP is not a major mediator of platelet aggregation, thrombogenesis, haemostasis, and the antiplatelet effect of prasugrel in rats.
Somatosensory innervation of the oral mucosa of adult and aging mice
Authors: Moayedi Yalda , Duenas-Bianchi Lucia F. , Lumpkin Ellen A.
Published: June 2018

Oral mechanoreception is implicated in fundamental functions including speech, food intake and swallowing; yet, the neuroanatomical substrates that encode mechanical stimuli are not well understood. Tactile perception is initiated by intricate mechanosensitive machinery involving dedicated cells and neurons. This signal transduction setup is coupled with the topology and mechanical properties of surrounding epithelium, thereby providing a sensitive and accurate system to detect stress fluctuations from the external environment. We mapped the distribution of anatomically distinct neuronal endings in mouse oral cavity using transgenic reporters, molecular markers and quantitative histomorphometry. We found that the tongue is equipped with an array of putative mechanoreceptors that express the principal mechanosensory channel Piezo2, including end bulbs of Krause innervating individual filiform papillae and a novel class of neuronal fibers innervating the epithelium surrounding taste buds. The hard palate and gums are densely populated with three classes of sensory afferents organized in discrete patterns including Merkel cell-neurite complexes, Meissner’s corpuscles and glomerular corpuscles. In aged mice, we find that palatal Merkel cells reduce in number at key time-points that correlate with impaired oral abilities, such as swallowing and mastication. Collectively, this work identifies the mechanosensory architecture of oral tissues involved in feeding.
Optimization of neural networks via finite-value quantum fluctuations
Authors: Ohzeki Masayuki , Okada Shuntaro , Terabe Masayoshi , Taguchi Shinichiro
Published: June 2018

We numerically test an optimization method for deep neural networks (DNNs) using quantum fluctuations inspired by quantum annealing. For efficient optimization, our method utilizes the quantum tunneling effect beyond the potential barriers. The path integral formulation of the DNN optimization generates an attracting force to simulate the quantum tunneling effect. In the standard quantum annealing method, the quantum fluctuations will vanish at the last stage of optimization. In this study, we propose a learning protocol that utilizes a finite value for quantum fluctuations strength to obtain higher generalization performance, which is a type of robustness. We demonstrate the performance of our method using two well-known open datasets: the MNIST dataset and the Olivetti face dataset. Although computational costs prevent us from testing our method on large datasets with high-dimensional data, results show that our method can enhance generalization performance by induction of the finite value for quantum fluctuations.
Analysis of atomic beam collimation by laser cooling
Authors: Li Shangyan , Zhou Min , Xu Xinye
Published: June 2018

The collimation of a thermal atomic ytterbium beam utilizing a two-dimensional optical molasses is analysed by employing the Monte Carlo simulation. The dependencies of the collimation efficiency on power, frequency detuning and beam size of the laser are studied for various conditions, especially for the case of an imbalanced laser intensity and an impure laser polarization. The influences of these imperfect factors are discussed, and the lowest transverse temperature by the collimation in the experiment is evaluated.
Supraphysiological Levels of Oxygen Exposure During the Neonatal Period Impairs Signaling Pathways Required for Learning and Memory
Authors: Ramani Manimaran , Kumar Ranjit , Halloran Brian , Lal Charitharth Vivek , Ambalavanan Namasivayam , McMahon Lori L.
Published: June 2018

Preterm infants often require prolonged oxygen supplementation and are at high risk of neurodevelopmental impairment. We recently reported that adult mice exposed to neonatal hyperoxia (postnatal day [P] 2 to 14) had spatial navigation memory deficits associated with hippocampal shrinkage. The mechanisms by which early oxidative stress impair neurodevelopment are not known. Our objective was to identify early hyperoxia-induced alterations in hippocampal receptors and signaling pathways necessary for memory formation. We evaluated C57BL/6 mouse pups at P14, exposed to either 85% oxygen or air from P2 to 14. We performed targeted analysis of hippocampal ligand-gated ion channels and proteins necessary for memory formation, and global bioinformatic analysis of differentially expressed hippocampal genes and proteins. Hyperoxia decreased hippocampal mGLU7, TrkB, AKT, ERK2, mTORC1, RPS6, and EIF4E and increased α3, α5, and ɤ2 subunits of GABAA receptor and PTEN proteins, although changes in gene expression were not always concordant. Bioinformatic analysis indicated dysfunction in mitochondria and global protein synthesis and translational processes. In conclusion, supraphysiological oxygen exposure reduced proteins necessary for hippocampus-dependent memory formation and may adversely impact hippocampal mitochondrial function and global protein synthesis. These early hippocampal changes may account for memory deficits seen in preterm survivors following prolonged oxygen supplementation.
The Role of PET-Based Radiomic Features in Predicting Local Control of Esophageal Cancer Treated with Concurrent Chemoradiotherapy
Authors: Xiong Junfeng , Yu Wen , Ma Jingchen , Ren Yacheng , Fu Xiaolong , Zhao Jun
Published: June 2018

This study was designed to evaluate the predictive performance of 18F-fluorodeoxyglucose positron emission tomography (PET)-based radiomic features for local control of esophageal cancer treated with concurrent chemoradiotherapy (CRT). For each of the 30 patients enrolled, 440 radiomic features were extracted from both pre-CRT and mid-CRT PET images. The top 25 features with the highest areas under the receiver operating characteristic curve for identifying local control status were selected as discriminative features. Four machine-learning methods, random forest (RF), support vector machine, logistic regression, and extreme learning machine, were used to build predictive models with clinical features, radiomic features or a combination of both. An RF model incorporating both clinical and radiomic features achieved the best predictive performance, with an accuracy of 93.3%, a specificity of 95.7%, and a sensitivity of 85.7%. Based on risk scores of local failure predicted by this model, the 2-year local control rate and PFS rate were 100.0% (95% CI 100.0–100.0%) and 52.2% (31.8–72.6%) in the low-risk group and 14.3% (0.0–40.2%) and 0.0% (0.0–40.2%) in the high-risk group, respectively. This model may have the potential to stratify patients with different risks of local failure after CRT for esophageal cancer, which may facilitate the delivery of personalized treatment.
Introduction of a new repair technique in bony avulsion of the FDP tendon: A biomechanical study
Authors: Halát Gabriel , Negrin Lukas L. , Unger Ewald , Koch Thomas , Streicher Johannes , Erhart Jochen , Platzer Patrick , Hajdu Stefan
Published: June 2018

The purpose of this study was to determine the biomechanical characteristics of an innovative surgical technique based on a tension banding principle using a suture anchor in the repair of bony avulsions of the flexor digitorum profundus tendon. After injury simulation in 45 fresh frozen distal phalanges from human cadavers, repair was performed with minifragment screws, interosseous sutures and the innovative technique (15 per group). All repairs were loaded for a total of 500 cycles. Subsequently the specimens were loaded to failure. Load at failure, load at first noteworthy displacement (>2 mm), elongation of the system, gap formation at the avulsion site, and the mechanism of failure were assessed. The new techniques’ superior performance in load at failure (mean: 100.5 N), load at first noteworthy displacement (mean 77.4 N), and gap formation (median 0 mm) was statistically significant, which implies a preferable rigidity of the repair. No implant extrusion or suture rupture during cyclic loading were recorded when the new technique was applied. This innovative repair technique is superior biomechanically to other commonly used surgical tendon reattachment methods, particularly with respect to an early passive mobilisation protocol. Further, due to its subcutaneous position, reduction of complications may be achieved.
Cotranslational protein targeting to the membrane: Nascent-chain transfer in a quaternary complex formed at the translocon
Authors: Draycheva Albena , Lee Sejeong , Wintermeyer Wolfgang
Published: June 2018

Membrane proteins in bacteria are cotranslationally inserted into the plasma membrane through the SecYEG translocon. Ribosomes exposing the signal-anchor sequence (SAS) of a membrane protein are targeted to the translocon by the signal recognition particle (SRP) pathway. SRP scans translating ribosomes and forms high-affinity targeting complexes with those exposing a SAS. Recognition of the SAS activates SRP for binding to its receptor, FtsY, which, in turn, is primed for SRP binding by complex formation with SecYEG, resulting in a quaternary targeting complex. Here we examine the effect of SecYEG docking to ribosome-nascent-chain complexes (RNCs) on SRP binding and SAS transfer, using SecYEG embedded in phospholipid-containing nanodiscs and monitoring FRET between fluorescence-labeled constituents of the targeting complex. SecYEG–FtsY binding to RNC–SRP complexes lowers the affinity of SRP to both ribosome and FtsY, indicating a general weakening of the complex due to partial binding competition near the ribosomal peptide exit. The rearrangement of the quaternary targeting complex to the pre-transfer complex requires an at least partially exposed SAS. The presence of SecYEG-bound FtsY and the length of the nascent chain strongly influence nascent-chain transfer from SRP to the translocon and repositioning of SRP in the post-transfer complex.
Open monitoring meditation reduces the involvement of brain regions related to memory function
Authors: Fujino Masahiro , Ueda Yoshiyuki , Mizuhara Hiroaki , Saiki Jun , Nomura Michio
Published: June 2018

Mindfulness meditation consists of focused attention meditation (FAM) and open monitoring meditation (OMM), both of which reduce activation of the default mode network (DMN) and mind-wandering. Although it is known that FAM requires intentional focused attention, the mechanisms of OMM remain largely unknown. To investigate this, we examined striatal functional connectivity in 17 experienced meditators (mean total practice hours = 920.6) during pre-resting, meditation, and post-resting states comparing OMM with FAM, using functional magnetic resonance imaging. Both FAM and OMM reduced functional connectivity between the striatum and posterior cingulate cortex, which is a core hub region of the DMN. Furthermore, OMM reduced functional connectivity of the ventral striatum with both the visual cortex related to intentional focused attention in the attentional network and retrosplenial cortex related to memory function in the DMN. In contrast, FAM increased functional connectivity in these regions. Our findings suggest that OMM reduces intentional focused attention and increases detachment from autobiographical memory. This detachment may play an important role in non-judgmental and non-reactive attitude during OMM. These findings provide new insights into the mechanisms underlying the contribution of OMM to well-being and happiness.
Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America
Authors: Cano Luis , Cerapio Juan Pablo , Ruiz Eloy , Marchio Agnès , Turlin Bruno , Casavilca Sandro , Taxa Luis , Marti Guillaume , Deharo Eric , Pineau Pascal , Bertani Stéphane
Published: June 2018

We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.
Parrots have evolved a primate-like telencephalic-midbrain-cerebellar circuit
Authors: Gutiérrez-Ibáñez Cristián , Iwaniuk Andrew N. , Wylie Douglas R.
Published: June 2018

It is widely accepted that parrots show remarkable cognitive abilities. In mammals, the evolution of complex cognitive abilities is associated with increases in the size of the telencephalon and cerebellum as well as the pontine nuclei, which connect these two regions. Parrots have relatively large telencephalons that rival those of primates, but whether there are also evolutionary changes in their telencephalon-cerebellar relay nuclei is unknown. Like mammals, birds have two brainstem pontine nuclei that project to the cerebellum and receive projections from the telencephalon. Unlike mammals, birds also have a pretectal nucleus that connects the telencephalon with the cerebellum: the medial spiriform nucleus (SpM). We found that SpM, but not the pontine nuclei, is greatly enlarged in parrots and its relative size significantly correlated with the relative size of the telencephalon across all birds. This suggests that the telencephalon-SpM-cerebellar pathway of birds may play an analogous role to cortico-ponto-cerebellar pathways of mammals in controlling fine motor skills and complex cognitive processes. We conclude that SpM is key to understanding the role of telencephalon-cerebellar pathways in the evolution of complex cognitive abilities in birds.
Widespread distribution of prophage-encoded virulence factors in marine Vibrio communities
Authors: Castillo Daniel , Kauffman Kathryn , Hussain Fatima , Kalatzis Panos , Rørbo Nanna , Polz Martin F. , Middelboe Mathias
Published: June 2018

Prophages are known to encode important virulence factors in the human pathogen Vibrio cholerae. However, little is known about the occurrence and composition of prophage-encoded traits in environmental vibrios. A database of 5,674 prophage-like elements constructed from 1,874 Vibrio genome sequences, covering sixty-four species, revealed that prophage-like elements encoding possible properties such as virulence and antibiotic resistance are widely distributed among environmental vibrios, including strains classified as non-pathogenic. Moreover, we found that 45% of Vibrio species harbored a complete prophage-like element belonging to the Inoviridae family, which encode the zonula occludens toxin (Zot) previously described in the V. cholerae. Interestingly, these zot-encoding prophages were found in a variety of Vibrio strains covering both clinical and marine isolates, including strains from deep sea hydrothermal vents and deep subseafloor sediments. In addition, the observation that a spacer from the CRISPR locus in the marine fish pathogen V. anguillarum strain PF7 had 95% sequence identity with a zot gene from the Inoviridae prophage found in V. anguillarum strain PF4, suggests acquired resistance to inoviruses in this species. Altogether, our results contribute to the understanding of the role of prophages as drivers of evolution and virulence in the marine Vibrio bacteria.
Engineered Hsp70 chaperones prevent Aβ42-induced memory impairments in a Drosophila model of Alzheimer’s disease
Authors: Martín-Peña Alfonso , Rincón-Limas Diego E. , Fernandez-Fúnez Pedro
Published: June 2018

Proteinopathies constitute a group of diseases in which certain proteins are abnormally folded leading to aggregation and eventual cell failure. Most neurodegenerative diseases belong to protein misfolding disorders and, among them, Alzheimer’s disease (AD) is the most prevalent. AD is characterized by accumulation of the amyloid-β42 (Aβ42) peptide in the extracellular space. Hence, we genetically engineered a molecular chaperone that was selectively delivered to this cellular location. It has been reported that the heat shock protein 70 (Hsp70) binds Aβ42 preventing self-aggregation. Here, we employed two isoforms of the Hsp70, cytosolic and extracellular, to evaluate their potential protective effect against the memory decline triggered by extracellular deposition of Aβ42. Both Hsp70 isoforms significantly improved memory performance of flies expressing Aβ42, irrespective of their age or the level of Aβ42 load. Using olfactory classical conditioning, we established a Drosophila model of AD based on Aβ42 neurotoxicity and monitored memory decline through aging. The onset of the memory impairment observed was proportional to the cumulative level of Aβ42 in the Drosophila brain. These data support the use of this Drosophila model of AD to further investigate molecules with a protective activity against Aβ42-induced memory loss, contributing to the development of palliative therapies for AD.
The epidemiological characteristics and molecular phylogeny of the dengue virus in Guangdong, China, 2015
Authors: Sun Jiufeng , Zhang Huan , Tan Qiqi , Zhou Huiqiong , Guan Dawei , Zhang Xin , Duan Jinhua , Cai Songwu , Peng Zhiqiang , He Jianfeng , Ke Changwen , Lin Jinyan , Liu Tao , Ma Wenjun , Wu De
Published: June 2018

In 2015, an unexpected multiple outbreak of dengue occurred in Guangdong, China. In total, 1,699 cases were reported, of which 1,627 cases were verified to have DENV infections by nucleic acid or NS1 protein, including 44 DENV-1, 1126 DENV-2, 18 DENV-3 and 6 DENV-4, and the other cases were confirmed by NS1 ELISA. Phylogenetic analyses of DENV-1 isolates identified two genotypes (I and V). The predominant DENV-2 outbreak isolates were the Cosmopolitan genotypes, which likely originated from Malaysia. The DENV-3 isolates were assigned into genotype I and genotype III. All 6 DENV-4 isolates from imported cases were likely originally from Cambodia, Thailand and the Philippines. The entomological surveillance showed a moderate risk for the BI index in Chaozhou and Foshan and a low risk in Guangzhou. The imported cases were mostly detected in Guangzhou and Foshan. Surprisingly, the most serious outbreak occurred in Chaozhou, but not in Guangzhou or Foshan. A combined analyses demonstrated the multiple geographical origins of this outbreak, and highlight the detection of suspected cases after the alerting of imported cases, early implementation of control policies and reinforce the vector surveillance strategies were the key points in the chain of prevention and control of dengue epidemics.
Ramifications of Atmospheric Humidity on Monsoon Depressions over the Indian Subcontinent
Authors: Baisya Himadri , Pattnaik Sandeep , Hazra Vivekananda , Sisodiya Anshul , Rai Deepika
Published: June 2018

In this study, a comprehensive investigation is carried out to examine the sensitivity of tropospheric relative humidity (RH) on monsoon depressions (MDs) under a changing climate regime through surrogate climate change approach over the Indian region. Composite analysis of four MDs show a persistent warming (RH2+) and cooling (RH2−) throughout the troposphere in the sensitivity experiments. In-depth analysis of a MD over the Arabian Sea (AS) exhibits sustained warming for RH2+, which is accredited to 2.6% increase in stratiform clouds accounting for 13% increment in heating, whereas 5% increment in convective clouds hardly contribute to total heating. Frozen hydrometeors (graupel and snow) are speculated to be the major contributors to this heating. Stratiform clouds showed greater sensitivity to RH perturbations in the lower troposphere (1000–750 hPa), albeit very less sensitivity for convective clouds, both in the lower and mid-troposphere (700–500 hPa). Precipitation is enhanced in a moist situation (RH2+) owing to positive feedbacks induced by moisture influx and precipitation efficiency, while negative feedbacks suppressed precipitation in a dry troposphere (RH2−). In a nutshell, it is inferred that under moist (dry) situations, it is highly likely that intense (weak) MDs will occur in the near future over the Indian region.