bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Initial Enhancement of Energetic Electrons and the Innermost Plasmapause Locations: Coronal Mass Ejection‐Driven Storm Periods
Authors: Khoo Leng Ying , Li Xinlin , Zhao Hong , Sarris Theodore E. , Xiang Zheng , Zhang Kun , Kellerman Adam C. , Blake J. Bernard
Published: October 2018

Using Van Allen Probes' observations and established plasmapause location (Lpp) models, we investigate the relationship between the location of the initial enhancement (IE) of energetic electrons and the innermost (among all magnetic local time sectors) Lpp over five intense storm periods. Our study reveals that the IE events for ~30‐keV to ~2‐MeV electrons always occurred outside of the innermost Lpp. On average, the inner extent of the IE events (LIE) for <800‐keV electrons was closer to the innermost Lpp when compared to the LIE for >800‐keV electrons that was found consistently at ~1.5 RE outside of the innermost Lpp. The IE of tens of kiloelectron volts electrons was observed before the IE of hundreds of kiloelectron volt electrons, and the IE of >800‐keV electrons was observed on average 12.6 ± 2.3 hr after the occurrence of the earliest IE event. In addition, we report an overall electron (~30 keV to ~2 MeV) flux increase outside the plasmasphere during the selected storm periods, in contrast to the little change of energy spectrum evolution inside the plasmasphere; this demonstrates the important role of the plasmasphere in shaping energetic electron dynamics. Our investigation of the LIE‐Lpp relationship also provides insights into the underlying physical processes responsible for the dynamics of ~30‐keV to ~2‐MeV electrons.
Partitioning Ocean Motions Into Balanced Motions and Internal Gravity Waves: A Modeling Study in Anticipation of Future Space Missions
Authors: Torres Hector S. , Klein Patrice , Menemenlis Dimitris , Qiu Bo , Su Zhan , Wang Jinbo , Chen Shuiming , Fu Lee‐Lueng
Published: October 2018

Internal gravity waves (IGWs) and balanced motions (BMs) with scales <100‐km capture most of the vertical velocity field in the upper ocean. They have, however, different impacts on the ocean energy budget, which explains the need to partition motions into BMs and IGWs. One way is to exploit the synergy of using different satellite observations, the only observations with global coverage, and a reasonable spatial and temporal resolution. But we need first to characterize and understand their signatures on the different surface oceanic fields. This study addresses this issue by using an ocean global numerical simulation with high‐resolution (1/48°). Our methodology is based on the analysis of the 12,000 frequency‐wave number spectra to discriminate these two classes of motions in the surface kinetic energy, sea surface height, sea surface temperature, sea surface salinity, relative vorticity, and divergence fields and for two seasons. Results reveal a complex picture worldwide of the partition of motions between IGWs and BMs in the different surface fields, depending on the season, the hemisphere, and low and high eddy kinetic energy regions. But they also highlight some generic properties on the impact of these two classes of motions on the different fields. This points to the synergy of using present and future satellite observations to assess the ocean kinetic energy on a global scale. The 12,000 frequency‐wave number spectra represent a World Ocean Atlas of the surface ocean dynamics not fully exploited in the present study. We hope the use of this World Ocean Atlas by other studies will lead to extend much these results.
Non-diagnostic symptoms in a mouse model of autism in relation to neuroanatomy: the BTBR strain reinvestigated
Authors: Faraji Jamshid , Karimi Mitra , Lawrence Cassandra , Mohajerani Majid H. , Metz Gerlinde A. S.
Published: October 2018

Several mouse models of autism spectrum disorder (ASD), including the BTBR T + tf/J (BTBR) inbred strain, display a diverse array of behavioral deficits with particular face validity. Here we propose that phenotyping these preclinical models of ASD should avoid excessive reliance on appearance validity of the behavioral observations. BTBR mice were examined in three non-diagnostic symptoms modalities, beside an anatomical investigation for construct validity. The BTBR strain displayed poor sensorimotor integration as reflected by shorter stride length and greater latency on the balance beam task (BBT) when compared with C57BL/6 (B6) controls. Also, locomotor indices in the open-field task (OFT) revealed that BTBR mice traveled longer distances with a remarkably faster exploration than the B6 group in favor of hyperactivity and impulsiveness. Furthermore, analysis of spatial performance including search strategies in the Morris water task (MWT) indicated spatial impairment in the BTBR strain due to failure to employ spatial strategies during navigation. Quantitative cytoarchitectonics and volumetric examinations also indicated abnormal cortical and subcortical morphology in the BTBR mice. The results are discussed in relation to the neuroanatomical correlates of motor and cognitive impairments in the BTBR strain. We conclude that non-diagnostic autistic-like symptoms in the BTBR mouse strain can be impacted by autism risk factors in a similar way than the traditional diagnostic signs.
Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma
Authors: Bernardo-Colón Alexandra , Vest Victoria , Clark Adrienne , Cooper Melissa L. , Calkins David J. , Harrison Fiona E. , Rex Tonia S.
Published: October 2018

We investigated the role of oxidative stress and the inflammasome in trauma-induced axon degeneration and vision loss using a mouse model. The left eyes of male mice were exposed to over-pressure air waves. Wild-type C57Bl/6 mice were fed normal, high-vitamin-E (VitE), ketogenic or ketogenic-control diets. Mice lacking the ability to produce vitamin C (VitC) were maintained on a low-VitC diet. Visual evoked potentials (VEPs) and retinal superoxide levels were measured in vivo. Tissue was collected for biochemical and histological analysis. Injury increased retinal superoxide, decreased SOD2, and increased cleaved caspase-1, IL-1α, IL-1β, and IL-18 levels. Low-VitC exacerbated the changes and the high-VitE diet mitigated them, suggesting that oxidative stress led to the increase in IL-1α and activation of the inflammasome. The injury caused loss of nearly 50% of optic nerve axons at 2 weeks and astrocyte hypertrophy in mice on normal diet, both of which were prevented by the high-VitE diet. The VEP amplitude was decreased after injury in both control-diet and low-VitC mice, but not in the high-VitE-diet mice. The ketogenic diet also prevented the increase in superoxide levels and IL-1α, but had no effect on IL-1β. Despite this, the ketogenic diet preserved optic nerve axons, prevented astrocyte hypertrophy, and preserved the VEP amplitude. These data suggest that oxidative stress induces priming and activation of the inflammasome pathway after neurotrauma of the visual system. Further, blocking the activation of the inflammasome pathway may be an effective post-injury intervention.
Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels
Authors: Dobnikar Lina , Taylor Annabel L. , Chappell Joel , Oldach Phoebe , Harman Jennifer L. , Oerton Erin , Dzierzak Elaine , Bennett Martin R. , Spivakov Mikhail , Jørgensen Helle F.
Published: October 2018

Vascular smooth muscle cells (VSMCs) show pronounced heterogeneity across and within vascular beds, with direct implications for their function in injury response and atherosclerosis. Here we combine single-cell transcriptomics with lineage tracing to examine VSMC heterogeneity in healthy mouse vessels. The transcriptional profiles of single VSMCs consistently reflect their region-specific developmental history and show heterogeneous expression of vascular disease-associated genes involved in inflammation, adhesion and migration. We detect a rare population of VSMC-lineage cells that express the multipotent progenitor marker Sca1, progressively downregulate contractile VSMC genes and upregulate genes associated with VSMC response to inflammation and growth factors. We find that Sca1 upregulation is a hallmark of VSMCs undergoing phenotypic switching in vitro and in vivo, and reveal an equivalent population of Sca1-positive VSMC-lineage cells in atherosclerotic plaques. Together, our analyses identify disease-relevant transcriptional signatures in VSMC-lineage cells in healthy blood vessels, with implications for disease susceptibility, diagnosis and prevention.
Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA
Authors: Gudmundsson Julius , Sigurdsson Jon K. , Stefansdottir Lilja , Agnarsson Bjarni A. , Isaksson Helgi J. , Stefansson Olafur A. , Gudjonsson Sigurjon A. , Gudbjartsson Daniel F. , Masson Gisli , Frigge Michael L. , Stacey Simon N. , Sulem Patrick , Halldorsson Gisli H. , Tragante Vinicius , Holm Hilma , Eyjolfsson Gudmundur I. , Sigurdardottir Olof , Olafsson Isleifur , Jonsson Thorvaldur , Jonsson Eirikur , Barkardottir Rosa B. , Hilmarsson Rafn , Asselbergs Folkert W. , Geirsson Gudmundur , Thorsteinsdottir Unnur , Rafnar Thorunn , Thorleifsson Gudmar , Stefansson Kari
Published: October 2018

Benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) are common conditions affecting the majority of elderly males. Here we report the results of a genome-wide association study of symptomatic BPH/LUTS in 20,621 patients and 280,541 controls of European ancestry, from Iceland and the UK. We discovered 23 genome-wide significant variants, located at 14 loci. There is little or no overlap between the BPH/LUTS variants and published prostate cancer risk variants. However, 15 of the variants reported here also associate with serum levels of prostate specific antigen (PSA) (at a Bonferroni corrected P < 0.0022). Furthermore, there is a strong genetic correlation, rg = 0.77 (P = 2.6 × 10−11), between PSA and BPH/LUTS, and one standard deviation increase in a polygenic risk score (PRS) for BPH/LUTS increases PSA levels by 12.9% (P = 1.6×10−55). These results shed a light on the genetic background of BPH/LUTS and its substantial influence on PSA levels.
Stability and nature of the volume collapse of ε-Fe2O3 under extreme conditions
Authors: Sans J. A. , Monteseguro V. , Garbarino G. , Gich M. , Cerantola V. , Cuartero V. , Monte M. , Irifune T. , Muñoz A. , Popescu C.
Published: October 2018

Iron oxides are among the major constituents of the deep Earth’s interior. Among them, the epsilon phase of Fe2O3 is one of the less studied polymorphs and there is a lack of information about its structural, electronic and magnetic transformations at extreme conditions. Here we report the precise determination of its equation of state and a deep analysis of the evolution of the polyhedral units under compression, thanks to the agreement between our experiments and ab-initio simulations. Our results indicate that this material, with remarkable magnetic properties, is stable at pressures up to 27 GPa. Above 27 GPa, a volume collapse has been observed and ascribed to a change of the local environment of the tetrahedrally coordinated iron towards an octahedral coordination, finding evidence for a different iron oxide polymorph.
Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau
Authors: Freilich Rebecca , Betegon Miguel , Tse Eric , Mok Sue-Ann , Julien Olivier , Agard David A. , Southworth Daniel R. , Takeuchi Koh , Gestwicki Jason E.
Published: October 2018

Small heat shock proteins (sHSPs) are a class of oligomeric molecular chaperones that limit protein aggregation. However, it is often not clear where sHSPs bind on their client proteins or how these protein-protein interactions (PPIs) are regulated. Here, we map the PPIs between human Hsp27 and the microtubule-associated protein tau (MAPT/tau). We find that Hsp27 selectively recognizes two aggregation-prone regions of tau, using the conserved β4-β8 cleft of its alpha-crystallin domain. The β4-β8 region is also the site of Hsp27–Hsp27 interactions, suggesting that competitive PPIs may be an important regulatory paradigm. Indeed, we find that each of the individual PPIs are relatively weak and that competition for shared sites seems to control both client binding and Hsp27 oligomerization. These findings highlight the importance of multiple, competitive PPIs in the function of Hsp27 and suggest that the β4-β8 groove acts as a tunable sensor for clients.
Publisher Correction: Engineered bidirectional promoters enable rapid multi-gene co-expression optimization
Authors: Vogl Thomas , Kickenweiz Thomas , Pitzer Julia , Sturmberger Lukas , Weninger Astrid , Biggs Bradley W. , Köhler Eva-Maria , Baumschlager Armin , Fischer Jasmin Elgin , Hyden Patrick , Wagner Marlies , Baumann Martina , Borth Nicole , Geier Martina , Ajikumar Parayil Kumaran , Glieder Anton
Published: October 2018

The original version of this Article was updated after publication to add the ORCID ID of the author Thomas Vogl, which was inadvertently omitted, and to include a corrected version of the ‘Description of Additional Supplementary Files’ which originally lacked legends for each file.
Quantum superiority for verifying NP-complete problems with linear optics
Authors: Arrazola Juan Miguel , Diamanti Eleni , Kerenidis Iordanis
Published: October 2018

Demonstrating quantum superiority for some computational task will be a milestone for quantum technologies and would show that computational advantages are possible not only with a universal quantum computer but with simpler physical devices. Linear optics is such a simpler but powerful platform where classically-hard information processing tasks, such as Boson Sampling, can be in principle implemented. In this work, we study a fundamentally different type of computational task to achieve quantum superiority using linear optics, namely the task of verifying NP-complete problems. We focus on a protocol by Aaronson et al. (2008) that uses quantum proofs for verification. We show that the proof states can be implemented in terms of a single photon in an equal superposition over many optical modes. Similarly, the tests can be performed using linear-optical transformations consisting of a few operations: a global permutation of all modes, simple interferometers acting on at most four modes, and measurement using single-photon detectors. We also show that the protocol can tolerate experimental imperfections.
Exploring brain functional connectivity in rest and sleep states: a fNIRS study
Authors: Nguyen Thien , Babawale Olajide , Kim Tae , Jo Hang Joon , Liu Hanli , Kim Jae Gwan
Published: October 2018

This study investigates the brain functional connectivity in the rest and sleep states. We collected EEG, EOG, and fNIRS signals simultaneously during rest and sleep phases. The rest phase was defined as a quiet wake-eyes open (w_o) state, while the sleep phase was separated into three states; quiet wake-eyes closed (w_c), non-rapid eye movement sleep stage 1 (N1), and non-rapid eye movement sleep stage 2 (N2) using the EEG and EOG signals. The fNIRS signals were used to calculate the cerebral hemodynamic responses (oxy-, deoxy-, and total hemoglobin). We grouped 133 fNIRS channels into five brain regions (frontal, motor, temporal, somatosensory, and visual areas). These five regions were then used to form fifteen brain networks. A network connectivity was computed by calculating the Pearson correlation coefficients of the hemodynamic responses between fNIRS channels belonging to the network. The fifteen networks were compared across the states using the connection ratio and connection strength calculated from the normalized correlation coefficients. Across all fifteen networks and three hemoglobin types, the connection ratio was high in the w_c and N1 states and low in the w_o and N2 states. In addition, the connection strength was similar between the w_c and N1 states and lower in the w_o and N2 states. Based on our experimental results, we believe that fNIRS has a high potential to be a main tool to study the brain connectivity in the rest and sleep states.
Ginsentides: Cysteine and Glycine-rich Peptides from the Ginseng Family with Unusual Disulfide Connectivity
Authors: Tam James P. , Nguyen Giang K. T. , Loo Shining , Wang Shujing , Yang Daiwen , Kam Antony
Published: October 2018

Ginseng, a popular and valuable traditional medicine, has been used for centuries to maintain health and treat disease. Here we report the discovery and characterization of ginsentides, a novel family of cysteine and glycine-rich peptides derived from the three most widely-used ginseng species: Panax ginseng, Panax quinquefolius, and Panax notoginseng. Using proteomic and transcriptomic methods, we identified 14 ginsentides, TP1-TP14 which consist of 31–33 amino acids and whose expression profiles are species- and tissues-dependent. Ginsentides have an eight-cysteine motif typical of the eight-cysteine-hevein-like peptides (8C-HLP) commonly found in medicinal herbs, but lack a chitin-binding domain. Transcriptomic analysis showed that the three-domain biosynthetic precursors of ginsentides differ from known 8C-HLP precursors in architecture and the absence of a C-terminal protein-cargo domain. A database search revealed an additional 50 ginsentide-like precursors from both gymnosperms and angiosperms. Disulfide mapping and structure determination of the ginsentide TP1 revealed a novel disulfide connectivity that differs from the 8C-HLPs. The structure of ginsentide TP1 is highly compact, with the N- and C-termini topologically fixed by disulfide bonds to form a pseudocyclic structure that confers resistance to heat, proteolysis, and acid and serum-mediated degradation. Together, our results expand the chemical space of natural products found in ginseng and highlight the occurrence, distribution, disulfide connectivity, and precursor architectures of cysteine- and glycine-rich ginsentides as a class of novel non-chitin-binding, non-cargo-carrying 8C-HLPs.
Reduction in nutritional quality and growing area suitability of common bean under climate change induced drought stress in Africa
Authors: Hummel Marijke , Hallahan Brendan F. , Brychkova Galina , Ramirez-Villegas Julian , Guwela Veronica , Chataika Bartholomew , Curley Edna , McKeown Peter C. , Morrison Liam , Talsma Elise F. , Beebe Steve , Jarvis Andy , Chirwa Rowland , Spillane Charles
Published: October 2018

Climate change impacts on food security will involve negative impacts on crop yields, and potentially on the nutritional quality of staple crops. Common bean is the most important grain legume staple crop for human diets and nutrition worldwide. We demonstrate by crop modeling that the majority of current common bean growing areas in southeastern Africa will become unsuitable for bean cultivation by the year 2050. We further demonstrate reductions in yields of available common bean varieties in a field trial that is a climate analogue site for future predicted drought conditions. Little is known regarding the impact of climate change induced abiotic stresses on the nutritional quality of common beans. Our analysis of nutritional and antinutritional compounds reveals that iron levels in common bean grains are reduced under future climate-scenario relevant drought stress conditions. In contrast, the levels of protein, zinc, lead and phytic acid increase in the beans under such drought stress conditions. This indicates that under climate-change induced drought scenarios, future bean servings by 2050 will likely have lower nutritional quality, posing challenges for ongoing climate-proofing of bean production for yields, nutritional quality, human health, and food security.
Efficacy and Resistance Management Potential of a Modified Vip3C Protein for Control of Spodoptera frugiperda in Maize
Authors: Kahn Theodore W. , Chakroun Maissa , Williams Jayme , Walsh Tom , James Bill , Monserrate Jessica , Ferré Juan
Published: October 2018

A modified Vip3C protein has been developed that has a spectrum of activity that has the potential to be commercially useful for pest control, and shows good efficacy against Spodoptera frugiperda in insect bioassays and field trials. For the first time Vip3A and Vip3C proteins have been compared to Cry1 and Cry2 proteins in a complete set of experiments from insect bioassays to competition binding assays to field trials, and the results of these complementary experiments are in agreement with each other. Binding assays with radiolabelled toxins and brush border membrane vesicles from S. frugiperda and Helicoverpa armigera show that the modified Vip3C protein shares binding sites with Vip3A, and does not share sites with Cry1F or Cry2A. In agreement with the resulting binding site model, Vip3A-resistant insects were also cross-resistant to the modified Vip3C protein. Furthermore, maize plants expressing the modified Vip3C protein, but not those expressing Cry1F protein, were protected against Cry1F-resistant S. frugiperda in field trials.
Genome-wide patterns of local adaptation in Western European Drosophila melanogaster natural populations
Authors: Mateo Lidia , Rech Gabriel E. , González Josefa
Published: October 2018

Signatures of spatially varying selection have been investigated both at the genomic and transcriptomic level in several organisms. In Drosophila melanogaster, the majority of these studies have analyzed North American and Australian populations, leading to the identification of several loci and traits under selection. However, several studies based mainly in North American populations showed evidence of admixture that likely contributed to the observed population differentiation patterns. Thus, disentangling demography from selection might be challenging when analyzing these populations. European populations could help identify loci under spatially varying selection provided that no recent admixture from African populations would have occurred. In this work, we individually sequence the genome of 42 European strains collected in populations from contrasting environments: Stockholm (Sweden) and Castellana Grotte (Southern Italy). We found low levels of population structure and no evidence of recent African admixture in these two populations. We thus look for patterns of spatially varying selection affecting individual genes and gene sets. Besides single nucleotide polymorphisms, we also investigated the role of transposable elements in local adaptation. We concluded that European populations are a good dataset to identify candidate loci under spatially varying selection. The analysis of the two populations sequenced in this work in the context of all the available D. melanogaster data allowed us to pinpoint genes and biological processes likely to be relevant for local adaptation. Identifying and analyzing populations with low levels of population structure and admixture should help to disentangle selective from non-selective forces underlying patterns of population differentiation in other species as well.
The effect of LTP- and LTD-like visual stimulation on modulation of human orientation discrimination
Authors: Marzoll Andreas , Saygi Tan , Dinse Hubert R.
Published: October 2018

Studies showing that repetitive visual stimulation protocols alter perception and induce cortical reorganization, as well-reported for the tactile domain, have been sparse. In this study, we investigated how “long-term potentiation [LTP]-like” and “long-term depression [LTD]-like” repetitive visual stimulation affects orientation discrimination ability in human observers. LTP-like stimulation with features most closely resembling the stimuli used during behavioral assessment evoked the largest improvement, while the effects were smaller in protocols that differed in shape or orientation features. This gradient suggests lower learning specificity than classical perceptual learning experiments, possibly because of an interplay of task- and feature-based factors. All modulatory effects of repetitive stimulation were superimposed on top of spontaneous task learning. Moreover, blockwise analysis revealed that LTP-like stimulation, in contrast to LTD-like or sham stimulation, prevented a loss of practice-related gain of orientation discrimination thresholds. This observation highlights a critical role of LTP-like stimulation for consolidation, typically observed during sleep.
Strategic allocation of working memory resource
Authors: Yoo Aspen H. , Klyszejko Zuzanna , Curtis Clayton E. , Ma Wei Ji
Published: October 2018

Visual working memory (VWM), the brief retention of past visual information, supports a range of cognitive functions. One of the defining, and largely studied, characteristics of VWM is how resource-limited it is, raising questions about how this resource is shared or split across memoranda. Since objects are rarely equally important in the real world, we ask how people split this resource in settings where objects have different levels of importance. In a psychophysical experiment, participants remembered the location of four targets with different probabilities of being tested after a delay. We then measured their memory accuracy of one of the targets. We found that participants allocated more resource to memoranda with higher priority, but underallocated resource to high- and overallocated to low-priority targets relative to the true probability of being tested. These results are well explained by a computational model in which resource is allocated to minimize expected estimation error. We replicated this finding in a second experiment in which participants bet on their memory fidelity after making the location estimate. The results of this experiment show that people have access to and utilize the quality of their memory when making decisions. Furthermore, people again allocate resource in a way that minimizes memory errors, even in a context in which an alternative strategy was incentivized. Our study not only shows that people are allocating resource according to behavioral relevance, but suggests that they are doing so with the aim of maximizing memory accuracy.
Incorporation of Hydroxyethylcellulose-Functionalized Halloysite as a Means of Decreasing the Thermal Conductivity of Oilwell Cement
Authors: Cho Junsang , Waetzig Gregory R. , Udayakantha Malsha , Hong Claire Y. , Banerjee Sarbajit
Published: October 2018

The significant heat loss and severe thermal fluctuations inherent in steam-assisted gravity drainage (SAGD) and cyclic steam stimulation (CSS) impose considerable constraints on well cementing. In order to obtain better energy efficiency and mechanical robustness, there is considerable interest in the development of low-thermal-conductivity cement that can provide a combination of enhanced thermal insulation and mechanical resilience upon thermal cycling. However, the current palette of thermal cements is exceedingly sparse. In this article, we illustrate a method for decreasing the thermal conductivity of cement by inclusion of hydroxyethylcellulose-functionalized halloysite nanotubes. Halloysite/hydroxyethylcellulose inclusions offer an abundance of disparate interfaces and void space that can effectively scatter phonons, thereby bringing about a pronounced reduction of thermal conductivity. The microstructure of the nanocomposite cementitious matrix is strongly modified even as the compositional profile remains essentially unaltered. Modified cement nanocomposites incorporating halloysite nanotubes along with hydroxyethylcellulose in a 8:1 ratio with an overall loading of 2 wt.% exhibit the lowest measured thermal conductivity of 0.212 ± 0.003 W/m.K, which is substantially reduced from the thermal conductivity of unmodified cement (1.252 W/m.K). The ability to substantially decrease thermal conductivity without deleterious modification of mechanical properties through alteration of microstructure, inclusion of encapsulated void spaces, and introduction of multiple phonon-scattering interfaces suggests an entirely new approach to oilwell cementing based on the design of tailored nanocomposites.
The synthesis, crystal, hydrogen sulfide detection and cell assement of novel chemsensors based on coumarin derivatives
Authors: Chen Yanmei , Shang Xuefang , Li Congshu , Xue Zhenzhen , Chen Hongli , Wu Hongwei , Wang Tianyun
Published: October 2018

A series of chemsensors (1–4) containing fluorobenzene group based on coumarin derivatives have been developed for the selective and sensitive detection of H2S. The advantages of the synthesized fluorescent probe (compound 1) were the low detection limit (4 × 10−6 mol·L−1), good selectivity and high sensitivity which had been demonstrated through UV-vis, fluorescent titration experiments. Besides cytotoxicity test of compounds (1 and 2) was studied and the results indicated that compounds (1 and 2) showed almost no cytotoxicityat at a concentration of 150 μg·mL−1. The interacted mechanism was the thiolysis reaction of dinitrophenyl ether which had been confirmed by fluorescence and HRMS titration experiment. In addition, probe 1 can also detect HS− selectively by naked eye in pure DMSO solvent.
Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of FOXP1
Authors: Johnson Tyler B. , Mechels Keegan , Anderson Ruthellen H. , Cain Jacob T. , Sturdevant David A. , Braddock Stephen , Pinz Hailey , Wilson Mark A. , Landsverk Megan , Roux Kyle J. , Weimer Jill M.
Published: October 2018

Haploinsufficiency of Forkhead box protein P1 (FOXP1), a highly conserved transcription factor, leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. Most of the reported FOXP1 mutations occur on the C-terminus of the protein and cluster around to the forkhead domain. All reported FOXP1 pathogenic variants result in abnormal cellular localization and loss of transcriptional repression activity of the protein product. Here we present three patients with the same FOXP1 mutation, c.1574G>A (p.R525Q), that results in the characteristic loss of transcription repression activity. This mutation, however, represents the first reported FOXP1 mutation that does not result in cytoplasmic or nuclear aggregation of the protein but maintains normal nuclear localization.
RETRACTED ARTICLE: TET2 inhibits tumorigenesis of breast cancer cells by regulating caspase-4
Authors: Zhu Xuguo , Li Shuangqi
Published: October 2018

Epigenetic regulators have been shown to influence breast cancer progression. However, the detailed mechanism by which TET2 plays the suppressive role in tumorigenesis remains not completely understood. We employed RT-qPCR and westernblot to examine genes expression. Next, the bisulphite sequencing PCR was used to determine the methylation level at CASP4 promoter in the cells. Phenotypically, we utilized growth curve analysis, colony formation in soft agar and xenograft tumor assay to assess tumorigenesis of MCF-7 cell. We found that TET2 knockout enhanced colony formation ability and in vivo tumor formation ability of MCF-7 cell, whereas TET2 depletion not affected the growth rate of MCF-7 cell in the culture. Mechanistically, TET2 loss led to a significant decrease in caspase-4 expression possibly via increasing DNA methylation of CASP4 promoter in MCF-7 cell. To validate, TET2 overexpression led to higher level of caspase-4 in MDA-MB-231 and 293T cells, which was dependent on TET2 enzymatic activity. Finally, we observed that caspase-4 could revert, at least partially, TET2 deletion-induced tumorigenesis of MCF-7. In summary, we reveal a novel mechanism that TET2 suppresses tumorigenesis of breast cancer cells through caspase-4. Our findings will facilitate development of new diagnostic markers or therapeutical therapies for breast cancer.
Impact of Escherichia coli K12 and O18:K1 on human platelets: Differential effects on platelet activation, RNAs and proteins
Authors: Fejes A. V. , Best M. G. , van der Heijden W. A. , Vancura A. , Verschueren H. , de Mast Q. , Wurdinger T. , Mannhalter C.
Published: October 2018

Blood platelets can interact with bacteria, possibly leading to platelet activation, cytokine and microparticle release and immune signalling. Besides, bacteria can also affect the platelet RNA content. We investigated the impact of non-pathogenic K12 and pathogenic O18:K1Escherichia (E.) colistrains on platelet activation, RNA expression patterns, and selected proteins. Depending on bacteria concentration, contact of platelets withE. coliK12 lead to an increase of P-selectin (24–51.3%), CD63 (15.9–24.3%), PAC-1 (3.8–14.9%) and bound fibrinogen (22.4–39%) on the surface.E. coliO18:K1 did not affect these markers. Sequencing analysis of total RNA showed thatE. coliK12 caused a significant concentration change of 103 spliced mRNAs, of which 74 decreased. For the RNAs ofHMBS(logFC = +5.73),ATP2C1(logFC = −3.13) andLRCH4(logFC = −4.07) changes were detectable by thromboSeq and Tuxedo pipelines. By Western blot we observed the conversion of HMBS protein from a 47 kDA to 40 kDa product byE. coliK12, O18:K1 and by purified lipopolysaccharide. While ATP2C1 protein was released from platelets,E. colieither reduced the secretion or broke down the released protein making it undetectable by antibodies. Our results demonstrate that differentE. colistrains influence activation, RNA and protein levels differently which may affect platelet-bacteria crosstalk.
Overexpression of CD98 in intestinal epithelium dysregulates miRNAs and their targeted proteins along the ileal villus-crypt axis
Authors: Han Moon K. , Baker Mark , Zhang Yuchen , Yang Chunhua , Zhang Mingzhen , Garg Pallavi , Viennois Emilie , Merlin Didier
Published: October 2018

CD98 has been implicated in the experimental model of inflammatory bowel disease. We have previously shown that IEC-specific overexpression of CD98 mediates intestinal inflammation and intestinal epithelial barrier dysfunction. Mice overexpressing CD98 exhibited severe colitis and a greater susceptibility to CAC. Here we demonstrated CD98 overexpression to dysregulate homeostatic gradient profile of miRNA and protein expression along the ileal villus-crypt axis. Using miRNA-target gene prediction module, we observed differentially expressed miRNAs to target proteins of villus and crypt profoundly affected by CD98 overexpression. We have utilized online bioinformatics as methods to further scrutinize the biological meanings of miRNA-target data. We identified significant interactions among the differentially regulated proteins targeted by altered miRNAs in Tg mice. The biological processes affected by the predicted targets of miRNAs deviate from the homeostatic functions of the miRNA-gene-protein axis of the wildtype mice. Our results emphasize a dynamic perturbation of miRNA and protein expression in villus-crypt axis contributing to potential biological consequences of altering CD98 expression. Our findings also suggest the need for a consideration of arrays of interacting biological entities (i.e. miRNAs-mRNAs, protein-protein interaction) or a combination comparison for a better understanding of the disease pathology which is necessary for an effective therapeutic target development.
Ophirina amphinema n. gen., n. sp., a New Deeply Branching Discobid with Phylogenetic Affinity to Jakobids
Authors: Yabuki Akinori , Gyaltshen Yangtsho , Heiss Aaron A. , Fujikura Katsunori , Kim Eunsoo
Published: October 2018

We report a novel nanoflagellate, Ophirina amphinema n. gen. n. sp., isolated from a lagoon of the Solomon Islands. The flagellate displays ‘typical excavate’ morphological characteristics, such as the presence of a ventral feeding groove with vanes on the posterior flagellum. The cell is ca. 4 µm in length, bears two flagella, and has a single mitochondrion with flat to discoid cristae. The flagellate exists in two morphotypes: a suspension-feeder, which bears flagella that are about the length of the cell, and a swimmer, which has longer flagella. In a tree based on the analysis of 156 proteins, Ophirina is sister to jakobids, with moderate bootstrap support. Ophirina has some ultrastructural (e.g. B-fibre associated with the posterior basal body) and mtDNA (e.g. rpoA–D) features in common with jakobids. Yet, other morphological features, including the crista morphology and presence of two flagellar vanes, rather connect Ophirina to non-jakobid or non-discobid excavates. Ophirina amphinema has some unique features, such as an unusual segmented core structure within the basal bodies and a rightward-oriented dorsal fan. Thus, Ophirina represents a new deeply-branching member of Discoba, and its mosaic morphological characteristics may illuminate aspects of the ancestral eukaryotic cellular body plan.
Systems pharmacology reveals the unique mechanism features of Shenzhu Capsule for treatment of ulcerative colitis in comparison with synthetic drugs
Authors: Feng Wuwen , Ao Hui , Yue Shijun , Peng Cheng
Published: October 2018

In clinic, both synthetic drugs and Shenzhu Capsule (SZC), one kind of traditional Chinese medicines (TCMs), are used to treat ulcerative colitis (UC). In our study, a systems pharmacology approach was employed to elucidate the chemical and mechanism differences between SZC and synthetic drugs in treating UC. First, the compound databases were constructed for SZC and synthetic drugs. Then, the targets of SZC were predicted with on-line tools and validated using molecular docking method. Finally, chemical space, targets, and pathways of SZC and synthetic drugs were compared. Results showed that atractylenolide I, atractylone, kaempferol, etc., were bioactive compounds of SZC. Comparison of SZC and synthetic drugs showed that (1) in chemical space, the area of SZC encompasses the area of synthetic drugs; (2) SZC can act on more targets and pathways than synthetic drugs; (3) SZC can not only regulate immune and inflammatory reactions but also act on ulcerative colitis complications (bloody diarrhea) and prevent UC to develop into colorectal cancer whereas synthetic drugs mainly regulate immune and inflammatory reactions. Our study could help us to understand the compound and mechanism differences between TCM and synthetic drugs.
Magnetocardiography on an isolated animal heart with a room-temperature optically pumped magnetometer
Authors: Jensen Kasper , Skarsfeldt Mark Alexander , Stærkind Hans , Arnbak Jens , Balabas Mikhail V. , Olesen Søren-Peter , Bentzen Bo Hjorth , Polzik Eugene S.
Published: October 2018

Optically pumped magnetometers are becoming a promising alternative to cryogenically-cooled superconducting magnetometers for detecting and imaging biomagnetic fields. Magnetic field detection is a completely non-invasive method, which allows one to study the function of excitable human organs with a sensor placed outside the human body. For instance, magnetometers can be used to detect brain activity or to study the activity of the heart. We have developed a highly sensitive miniature optically pumped magnetometer based on cesium atomic vapor kept in a paraffin-coated glass container. The magnetometer is optimized for detection of biological signals and has high temporal and spatial resolution. It is operated at room- or human body temperature and can be placed in contact with or at a mm-distance from a biological object. With this magnetometer, we detected the heartbeat of an isolated guinea-pig heart, which is an animal widely used in biomedical studies. In our recordings of the magnetocardiogram, we can detect the P-wave, QRS-complex and T-wave associated with the cardiac cycle in real time. We also demonstrate that our device is capable of measuring the cardiac electrographic intervals, such as the RR- and QT-interval, and detecting drug-induced prolongation of the QT-interval, which is important for medical diagnostics.
Enhanced pharmacological efficacy of sumatriptan due to modification of its physicochemical properties by inclusion in selected cyclodextrins
Authors: Paczkowska Magdalena , Mizera Mikołaj , Sałat Kinga , Furgała Anna , Popik Piotr , Knapik-Kowalczuk Justyna , Krause Anna , Szymanowska-Powałowska Daria , Fojud Zbigniew , Kozak Maciej , Paluch Marian , Cielecka-Piontek Judyta
Published: October 2018

The study focused on the pharmacological action of sumatriptan, in particular its antiallodynic and antihyperalgesic properties, as an effect of cyclodextrinic inclusion of sumatriptan, resulting in changes of its physicochemical qualities such as dissolution and permeability through artificial biological membranes, which had previously been examinedin vitroin a gastro-intestinal model. The inclusion of sumatriptan into β-cyclodextrin and 2-hydroxylpropylo-β-cyclodextrin by kneading was confirmed with the use of spectral (fourier-transform infrared spectroscopy (FT-IR); solid state nuclear magnetic resonance spectroscopy with magic angle spinning condition,1H and13C MAS NMR) and thermal (differential scanning calorimetry (DSC)) methods. A precise indication of the domains of sumatriptan responsible for its interaction with cyclodextrin cavities was possible due to a theoretical approach to the analysis of experimental spectra. A high-performance liquid chromatography with a diode-array detector method (HPLC-DAD) was employed to determine changes in the concentration of sumatriptan during dissolution and permeability experiments. The inclusion of sumatriptan in complex with cyclodextrins was found to significantly modify its dissolution profiles by increasing the concentration of sumatriptan in complexed form in an acceptor solution compared to in its free form. Following complexation, sumatriptan manifested an enhanced ability to permeate through artificial biological membranes in a gastro-intestinal model for both cyclodextrins at all pH values. As a consequence of the greater permeability of sumatriptan and its increased dissolution from the complexes, an improved pharmacological response was observed when cyclodextrin complexes were applied.
Planarians as models to investigate the bioactivity of gold(I) complexes in vivo
Authors: Tunes Luiza G. , Allen John M. , Zayas Ricardo M. , do Monte-Neto Rubens L.
Published: October 2018

Gold(I)-containing complexes are used in drug discovery research for rheumatoid arthritis, cancer, and parasitic infections. In this study, we tested the bioactivity of gold(I) complexesin vivousing planarians. The planarianSchmidtea mediterraneapossesses orthologues of tumor suppressor genes, such asp53, that, when silenced, cause deregulation of cell proliferation and apoptosis. In this context, we tested two triethylphosphine-gold(I) complexes (AdO and AdT) to determine if they can attenuate phenotypes that result fromp53inhibition. First, we identified the drug concentration that did not affect survival or regeneration and evaluated the drug’s effect on cell division and apoptosis. We found that AdT treatment decreased the number of mitotic cells and that all drug treatments increased the number of apoptotic cells. We then performedp53(RNAi)and drug treatments concomitantly and observed the phenotype progression. Drug treatment increased survival three-fold and decreased apoptosis, which resulted in an attenuated phenotype. Our results indicate that planarians can be treated with gold(I) complexes, and that this treatment can diminish thep53(RNAi)phenotype and extend survival. In this work we show that planarians can be used as a model to study thein vivoeffect of gold(I) complexes and to further investigate their mechanisms of action.
Microearthquakes preceding a M4.2 Earthquake Offshore Istanbul
Authors: Malin Peter E. , Bohnhoff Marco , Blümle Felix , Dresen Georg , Martínez-Garzón Patricia , Nurlu Murat , Ceken Ulubey , Kadirioglu Filiz Tuba , Kartal Recai Feyiz , Kilic Tugbay , Yanik Kenan
Published: October 2018

A primary hurdle in observing small foreshocks is the detection-limit of most seismic networks, which is typically about magnitude M1-1.5. We show that a start-up test of a borehole-based seismic network with a much lower detection limit overcame this problem for an Mw4.2 earthquake. This earthquake occurred offshore of Istanbul, Turkey, on a fault system that is likely to rupture in an M > 7 event in the coming decades. In the three days before and two after, a total of 62 or more earthquakes, including at least 18 foreshocks, came from the mainshock source area. The signal similarity of the foreshocks shows a clear increase during the hours before the Mw4.2 mainshock. Similar foreshock sequences have recently been reported for a few well monitored M > 7 plate-boundary earthquakes. The sequence surrounding the Mw4.2 gives the impression of stochastic failures that ended up interactively unloading stress concentrations. The Mw4.2 mainshock then resulted from the accumulated release of significantly smaller events, as suggested by other field and laboratory studies.
Effect of coffee or coffee components on gut microbiome and short-chain fatty acids in a mouse model of metabolic syndrome
Authors: Nishitsuji Kazuchika , Watanabe Syunsuke , Xiao Jinzhong , Nagatomo Ryosuke , Ogawa Hirohisa , Tsunematsu Takaaki , Umemoto Hitomi , Morimoto Yuki , Akatsu Hiroyasu , Inoue Koichi , Tsuneyama Koichi
Published: October 2018

We previously showed that male Tsumura Suzuki obese diabetes (TSOD) mice, a spontaneous mouse model of metabolic syndrome, manifested gut dysbiosis and subsequent disruption of the type and quantity of plasma short-chain fatty acids (SCFAs), and daily coffee intake prevented nonalcoholic steatohepatitis in this mouse model. Here, we present a preliminary study on whether coffee and its major components, caffeine and chlorogenic acid, would affect the gut dysbiosis and the disrupted plasma SCFA profile of TSOD mice, which could lead to improvement in the liver pathology of these mice. Three mice per group were used. Daily intake of coffee or its components for 16 wk prevented liver lobular inflammation without improving obesity in TSOD mice. Coffee and its components did not repair the altered levels of Gram-positive and Gram-negative bacteria and an increased abundance of Firmicutes in TSOD mice but rather caused additional changes in bacteria in six genera. However, caffeine and chlorogenic acid partially improved the disrupted plasma SCFA profile in TSOD mice, although coffee had no effects. Whether these alterations in the gut microbiome and the plasma SCFA profile might affect the liver pathology of TSOD mice may deserve further investigation.
Uranium (VI) detection in groundwater using a gold nanoparticle/paper-based lateral flow device
Authors: Quesada-González Daniel , Jairo Grace A. , Blake Robert C. , Blake Diane A. , Merkoçi Arben
Published: October 2018

The contamination in groundwater due to the presence of uranium is nowadays a subject of concern due to the severe health problems associated with renal failure, genotoxicity and cancer. The standard methods to detect uranium require time-consuming processes and expensive non-portable equipment, so these measurements are rarely performed in-field, which increases the time until water samples are analysed. Furthermore, the few portable methods available do not allow quantitative analysis and the detection limit is often not low enough to reach the recommendations for drinking water (30 ppb or 126 nM of uranium). For the first time, we propose a portable, fast, inexpensive and sensitive paper-based biosensor able to detect in situ U(VI) in water samples: U(VI) selective gold nanoparticle-based lateral flow strips. Antibody-coated gold nanoparticles are used as labels in the proposed lateral flow system because of their biocompatibility; in addition, these nanoparticles provide high sensitivity due to their intense plasmonic effect. The antibody used in the assay recognizes soluble U(VI) complexed to the chelator, 2,9-dicarboxyl-1,10-phenanthroline (DCP). Because of the small size of the U(VI)-DCP complex, this assay employs a competitive format that reaches a limit of detection of 36.38 nM, lower than the action level (126 nM) established by the World Health Organization and the U.S. Environmental Protection Agency for drinking waters.