bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating
Authors: Exertier Cécile , Milazzo Lisa , Freda Ida , Montemiglio Linda Celeste , Scaglione Antonella , Cerutti Gabriele , Parisi Giacomo , Anselmi Massimiliano , Smulevich Giulietta , Savino Carmelinda , Vallone Beatrice 
Published: March 2019

AbstractNeuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant “Gly-loop”, the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs.
Temperature directly and indirectly influences food web structure
Authors: Gibert Jean P. 
Published: March 2019

AbstractUnderstanding whether and how environmental conditions may impact food web structure at a global scale is central to our ability to predict how food webs will respond to climate change. However, such an understanding is nascent. Using the best resolved available food webs to date, I address whether latitude, temperature, or both, explain the number of species and feeding interactions, the proportion of basal and top species, as well as the degree of omnivory, connectance and the number of trophic levels across food webs. I found that temperature is a more parsimonious predictor of food web structure than latitude. Temperature directly reduces the number of species, the proportion of basal species and the number of interactions while it indirectly increases omnivory levels, connectance and trophic level through its direct effects on the fraction and number of basal species. While direct impacts of temperature are routinely taken into account to predict how ecosystems may respond to global climate change, indirect effects have been largely overlooked. These results thus suggest that food webs may be affected by a combination of biotic and abiotic conditions, both directly and indirectly, in a changing world.
A novel 3-hydroxypropionic acid-inducible promoter regulated by the LysR-type transcriptional activator protein MmsR of Pseudomonas denitrificans
Authors: Nguyen Nam Hoai , Ainala Satish Kumar , Zhou Shengfang , Park Sunghoon 
Published: March 2019

AbstractMmsR (33.3 kDa) is a putative LysR-type transcriptional activator ofPseudomonas denitrificans. With the help of 3-hydroxypropionic acid (3-HP), an important platform chemical, MmsR positively regulates the expression ofmmsA, which encodes methylmalonylsemialdehyde dehydrogenase, the enzyme involved in valine degradation. In the present study, the cellular function of MmsR and its binding to the regulatory DNA sequence ofmmsAexpression were investigated bothin vivoandin vitro. Transcription of themmsAwas enhanced >140-fold in the presence of 3-HP. In the MmsR-responsive promoter region, two operators showing dyad symmetry, designated O1and O2and centered at the −79 and −28 positions, respectively, were present upstream of themmsAtranscription start site. An electrophoretic mobility shift assay indicated that MmsR binds to both operator sites for transcription activation, probably in cooperative manner. When either O1or O2or both regions were mutated, the inducibility by the MmsR-3-HP complex was significantly reduced or completely removed, indicating that both sites are required for transcription activation. A 3-HP sensor was developed by connecting the activation of MmsR to a green fluorescent readout. A more than 50-fold induction by 25 mM 3-HP was observed.
Mitochondrial DNA and genomic DNA ratio in embryo culture medium is not a reliable predictor for in vitro fertilization outcome
Authors: Zhang Xinyue , Sun Yue , Dong Xin , Zhou Jianming , Sun Fubo , Han Tingting , Lei Ping , Mao Rurong , Guo Xuzhou , Wang Qi , Li Penghao , Qu Ting , Huang Jihua , Li Lingxiao , Huang Tianhua , Zhong Ying , Gu Jiang 
Published: March 2019

AbstractTo investigate the ratio of mitochondrial DNA to genomic DNA (mt/gDNA) in embryo culture medium as a possible predictor for embryonic development and pregnancy outcome, we collected a total of 93 embryo biopsy specimens from 52 women at the corresponding Day 3 (D3) and Day 5 (D5) embryo culture medium of in vitro fertilization. With the multiple annealing and looping-based amplification cycles method of next-generation sequencing for whole genome amplification, we examined the karyotype of the biopsy samples and the mt/gDNA ratio in the culture medium. Results showed that the ratio of mt/gDNA had an upward trend with decreasing trophectoderm levels with no significant difference. At the same time, from D3 to D5, the mt/gDNA ratio in the medium of embryos that failed to become blastocysts showed an upward trend, and the mt/gDNA ratio of medium from embryos that reached blastulation with successful pregnancy showed a decreasing trend, but the differences were not statistically significant. We conclude that there is a certain correlation between mt/gDNA ratio and early embryonic development, but it does not reach a level that can be used as a clinical predictor.
Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components
Authors: Oh Ju Eun , Choi Ok Kyung , Park Ho Seon , Jung Hye Seung , Ryu Su Jeong , Lee Yong Deok , Lee Seung-Ah , Chung Sung Soo , Choi Eun Young , Lee Dong-Sup , Gho Yong Song , Lee Hakmo , Park Kyong Soo 
Published: March 2019

AbstractTransplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs.
Palaeoecology of Voulteryon parvulus (Eucrustacea, Polychelida) from the Middle Jurassic of La Voulte-sur-Rhône Fossil-Lagerstätte (France)
Authors: Audo Denis , Robin Ninon , Luque Javier , Krobicki Michal , Haug Joachim T. , Haug Carolin , Jauvion Clément , Charbonnier Sylvain 
Published: March 2019

AbstractExceptional and extremely rare preservation of soft parts, eyes, or syn-vivo associations provide crucial palaeoecological information on fossil-rich deposits. Here we present exceptionally preserved specimens of the polychelidan lobster Voulteryon parvulus, from the Jurassic of La Voulte-sur-Rhône Fossil-Lagerstätte, France, bearing eyes with hexagonal and square facets, ovaries, and a unique association with epibiont thecideoid brachiopods, giving insights onto the palaeoenvironment of this Lagerstätte. The eyes, mostly covered in hexagonal facets are interpreted as either apposition eyes (poorly adapted to low-light environment) or, less likely, as refractive or parabolic superposition eyes (compatible with dysphotic palaeoenvironments). The interpretation that V. parvulus had apposition eyes suggests an allochthonous, shallow water origin. However, the presence of thecideoid brachiopod ectosymbionts on its carapace, usually associated to dim-light paleoenvironments and/or rock crevices, suggests that V. parvulus lived in a dim-light setting. This would support the less parsimonious interpretation that V. parvulus had superposition eyes. If we accept the hypothesis that V. parvulus had apposition eyes, since the La Voulte palaeoenvironment is considered deep water and had a soft substrate, V. parvulus could have moved into the La Voulte Lagerstätte setting. If this is the case, La Voulte biota would record a combination of multiple palaeoenvironments.
Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts
Authors: Gillespie Zoe E. , Wang Chenxuan , Vadan Flaviu , Yu Topaza Y. , Ausió Juan , Kusalik Anthony , Eskiw Christopher H. 
Published: March 2019

AbstractMetformin is a widely-used treatment for type 2 diabetes and is reported to extend health and lifespan as a caloric restriction (CR) mimetic. Although the benefits of metformin are well documented, the impact of this compound on the function and organization of the genome in normal tissues is unclear. To explore this impact, primary human fibroblasts were treated in culture with metformin resulting in a significant decrease in cell proliferation without evidence of cell death. Furthermore, metformin induced repositioning of chromosomes 10 and 18 within the nuclear volume indicating altered genome organization. Transcriptome analyses from RNA sequencing datasets revealed that alteration in growth profiles and chromosome positioning occurred concomitantly with changes in gene expression profiles. We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments. Comparative analyses revealed that metformin induced divergent changes in the transcriptome than that of rapamycin, another proposed mimetic of CR. Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF). Therefore, we have demonstrated that metformin has significant impacts on genome organization and function in normal human fibroblasts, different from those of rapamycin, with FOXO3a likely playing a role in this response.
Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes
Authors: Jablonka Willy , Kim Il Hwan , Alvarenga Patricia H. , Valenzuela Jesus G. , Ribeiro Jose´ M. C. , Andersen John F. 
Published: March 2019

AbstractThe habit of blood feeding evolved independently in many insect orders of families. Sand flies and mosquitoes belong to separate lineages of blood-feeding Diptera and are thus considered to have evolved the trait independently. Because of this, sand fly salivary proteins differ structurally from those of mosquitoes, and orthologous groups are nearly impossible to define. An exception is the long-form D7-like proteins that show conservation with their mosquito counterparts of numerous residues associated with the N-terminal domain binding pocket. In mosquitoes, this pocket is responsible for the scavenging of proinflammatory cysteinyl leukotrienes and thromboxanes at the feeding site. Here we show that long-form D7 proteins AGE83092 and ABI15936 from the sand fly species, Phlebotomus papatasi and P. duboscqi, respectively, inhibit the activation of platelets by collagen and the thromboxane A2 analog U46619. Using isothermal titration calorimetry, we also demonstrate direct binding of U46619 and cysteinyl leukotrienes C4, D4 and E4 to the P. papatasi protein. The crystal structure of P. duboscqi ABI15936 was determined and found to contain two domains oriented similarly to those of the mosquito proteins. The N-terminal domain contains an apparent eicosanoid binding pocket. The C-terminal domain is smaller in overall size than in the mosquito D7s and is missing some helical elements. Consequently, it does not contain an obvious internal binding pocket for small-molecule ligands that bind to many mosquito D7s. Structural similarities indicate that mosquito and sand fly D7 proteins have evolved from similar progenitors, but phylogenetics and differences in intron/exon structure suggest that they may have acquired the ability to bind vertebrate eicosanoids independently, indicating a convergent evolution scenario.
Impaired hippocampal-cortical coupling but preserved local synchrony during sleep in APP/PS1 mice modeling Alzheimer’s disease
Authors: Zhurakovskaya E. , Ishchenko I. , Gureviciene I. , Aliev R. , Gröhn O. , Tanila H. 
Published: March 2019

AbstractSleep, in addition to its brain restorative processes, plays an important role in memory transfer from its temporary store in the hippocampus to the more permanent storage in the neocortex. Alzheimer’s disease (AD) affects memory and sleep. The aim of this study was to explore disturbances in global and local synchrony patterns between brain regions in the APP/PS1 mouse model of the AD during natural sleep. We used 8 male APPswe/PS1dE9 mice and 6 wild-type littermates, aged 5–6 months, with multiple electrode bundles implanted into cortical regions, thalamus and hippocampus. We measured video-EEG in freely moving animals and analyzed synchrony during NREM vs REM sleep. Global synchrony between medial frontal cortex and hippocampus measured with magnitude-squared coherence was slightly decreased in delta range during NREM stage of sleep in APP/PS1 mice. In contrast, local hippocampal synchrony measured with cross-frequency coupling remained intact. Ripple structure or frequency did not differ between the genotypes. However, the coupling of the spindle-band power peak in the medial prefrontal cortex to hippocampal ripples was significantly decreased compared to wild-type animals. The delicate timing of hippocampal ripples, frontal delta, and corticothalamic spindle oscillations may be the first sign of impaired memory in amyloid plaque-forming transgenic mice.
Near-infrared tunable metalens based on phase change material Ge2Sb2Te5
Authors: Bai Wei , Yang Ping , Huang Jie , Chen Dingbo , Zhang Jingjing , Zhang Zhaojian , Yang Junbo , Xu Bing 
Published: March 2019

AbstractMetasurfaces draw everyone’s attention because they can precisely control the phase, amplitude and polarization of emergent light to achieve light field control in recent years. As one of the most practicable devices among the many applications of metasurface, metalens can extremely reduce the size as well as complexity of optical systems and realizes the higher optical quality compared with conventional lens. So it will be very potential to use metalens in integration systems to reaching higher integration and efficiency. In addition, dynamic control is always desirable in optical systems. In this work, we firstly design a near-infrared tunable metalens treating phase change materials as the meta-atoms which makes the tunable metalens become more compact. At designed wavelength of 1.55 μm, the focusing efficiency of our amorphous metalens is more than 16 times of the efficiency when it works at crystalline state, and its focal length can stay almost unchanged when the GST state is switched. The broadband performance of the metalens is also confirmed. This work may bring some good opportunities for the revolution of the next generation tunable integrated optics.
Transcriptomic analysis of the prothoracic gland from two lepidopteran insects, domesticated silkmoth Bombyx mori and wild silkmoth Antheraea pernyi
Authors: Bian Hai-Xu , Chen Dong-Bin , Zheng Xi-Xi , Ma Hong-Fang , Li Yu-Ping , Li Qun , Xia Run-Xi , Wang Huan , Jiang Yi-Ren , Liu Yan-Qun , Qin Li 
Published: March 2019

AbstractThe prothoracic gland (PG) is an important endocrine organ of synthesis and secretion of ecdysteroids that play critical roles in insects. Here, we used a comparative transcriptomic approach to characterize some common features of PGs from two lepidopteran speciesBombyx moriandAntheraea pernyi. Functional and pathway annotations revealed an overall similarity in gene profile between the two PG transcriptomes. As expected, almost all steroid hormone biosynthesis genes and the prothoracicitropic hormone receptor gene (Torso) were well represented in the two PGs. Impressively, two ecdysone receptor genes, eleven juvenile hormone related genes, more than 10 chemosensory protein genes, and a set of genes involved in circadian clock were also presented in the two PGs. Quantitative real time -PCR (qRT-PCR) validated the expression of 8 juvenile hormone and 12 clock related genes inB. moriPG, and revealed a different expression pattern during development in whole fifth larval instar. This contribution to insect PG transcriptome data will extend our understanding of the function and regulation of this important organ.
Quantitative relationships between SMAD dynamics and target gene activation kinetics in single live cells
Authors: Tidin Onur , Friman Elias T. , Naef Felix , Suter David M. 
Published: March 2019

AbstractThe transduction of extracellular signals through signaling pathways that culminate in a transcriptional response is central to many biological processes. However, quantitative relationships between activities of signaling pathway components and transcriptional output of target genes remain poorly explored. Here we developed a dual bioluminescence imaging strategy allowing simultaneous monitoring of nuclear translocation of the SMAD4 and SMAD2 transcriptional activators upon TGF-β stimulation, and the transcriptional response of the endogenous connective tissue growth factor (ctgf) gene. Using cell lines allowing to vary exogenous SMAD4/2 expression levels, we performed quantitative measurements of the temporal profiles of SMAD4/2 translocation and ctgf transcription kinetics in hundreds of individual cells at high temporal resolution. We found that while nuclear translocation efficiency had little impact on initial ctgf transcriptional activation, high total cellular SMAD4 but not SMAD2 levels increased the probability of cells to exhibit a sustained ctgf transcriptional response. The approach we present here allows time-resolved single cell quantification of transcription factor dynamics and transcriptional responses and thereby sheds light on the quantitative relationship between SMADs and target gene responses.
High Incidence of a Novel Rickettsia Genotype in Parasitic Haemaphysalis longicornis from China-North Korea Border
Authors: Xu Heling , Zhang Qi , Guan Hao , Zhong Yuening , Jiang Fenghua , Chen Zeliang , Han Xiaohu 
Published: March 2019

AbstractTicks are notorious vectors for various pathogens that cause infections in animals and humans worldwide. Rickettsia spp., a zoonotic tick-borne pathogen that could be used as a weapon agent, is widely spread in China. In the present study, ticks were collected for species identification and Rickettsia screening. PCR amplification targeting the tick 18s rRNA gene was first conducted for species validation, and then, amplification was conducted for the Rickettsia housekeeping gene for the infection rate and phylogenetic analysis. The collected ticks were identified as Haemaphysalis longicornis, 7.36% of which were Rickettsia-positive. The phylogenetic analysis showed that the Rickettsia in the parasitic ticks belonged to a novel genotype, whose closest genetic relationship was with Rickettsia heilongjiangenesis. The samples were collected in Dandong, a city on the border between China and North Korea. Considering the geographical and biological situations of the sampling sites, more extensive surveillance and risk evaluation of the tick species and tick-borne diseases are required.
Robust mouse tracking in complex environments using neural networks
Authors: Geuther Brian Q. , Deats Sean P. , Fox Kai J. , Murray Steve A. , Braun Robert E. , White Jacqueline K. , Chesler Elissa J. , Lutz Cathleen M. , Kumar Vivek 
Published: March 2019

AbstractThe ability to track animals accurately is critical for behavioral experiments. For video-based assays, this is often accomplished by manipulating environmental conditions to increase contrast between the animal and the background in order to achieve proper foreground/background detection (segmentation). Modifying environmental conditions for experimental scalability opposes ethological relevance. The biobehavioral research community needs methods to monitor behaviors over long periods of time, under dynamic environmental conditions, and in animals that are genetically and behaviorally heterogeneous. To address this need, we applied a state-of-the-art neural network-based tracker for single mice. We compare three different neural network architectures across visually diverse mice and different environmental conditions. We find that an encoder-decoder segmentation neural network achieves high accuracy and speed with minimal training data. Furthermore, we provide a labeling interface, labeled training data, tuned hyperparameters, and a pretrained network for the behavior and neuroscience communities.
Allosteric effects in cyclophilin mutants may be explained by changes in nano-microsecond time scale motions
Authors: Wapeesittipan Pattama , Mey Antonia S. J. S. , Walkinshaw Malcolm D. , Michel Julien 
Published: March 2019

AbstractThis work investigates the connection between stochastic protein dynamics and function for the enzyme cyclophilin A (CypA) in wild-type form, and three variants that feature several mutations distal from the active site. Previous biophysical studies have suggested that conformational exchange between a ‘major’ active and a ‘minor’ inactive state on millisecond timescales plays a key role in catalysis for CypA. Here this hypothesis is addressed by a variety of molecular dynamics simulation techniques. Strikingly we show that exchange between major and minor active site conformations occurs at a rate that is 5 to 6 orders of magnitude faster than previously proposed. The minor active site conformation is found to be catalytically impaired, and decreased catalytic activity of the mutants is caused by changes in Phe113 motions on a ns-μs timescale. Therefore millisecond timescale motions may not be necessary to explain allosteric effects in cyclophilins.