bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly conductive fibre network enables centimetre-scale electron transport in multicellular cable bacteria
Authors: Meysman Filip J. R. , Cornelissen Rob , Trashin Stanislav , Bonné Robin , Martinez Silvia Hidalgo , van der Veen Jasper , Blom Carsten J. , Karman Cheryl , Hou Ji-Ling , Eachambadi Raghavendran Thiruvallur , Geelhoed Jeanine S. , Wael Karolien De , Beaumont Hubertus J. E. , Cleuren Bart , Valcke Roland , van der Zant Herre S. J. , Boschker Henricus T. S. , Manca Jean V. 
Published: September 2019

AbstractBiological electron transport is classically thought to occur over nanometre distances, yet recent studies suggest that electrical currents can run along centimetre-long cable bacteria. The phenomenon remains elusive, however, as currents have not been directly measured, nor have the conductive structures been identified. Here we demonstrate that cable bacteria conduct electrons over centimetre distances via highly conductive fibres embedded in the cell envelope. Direct electrode measurements reveal nanoampere currents in intact filaments up to 10.1 mm long (>2000 adjacent cells). A network of parallel periplasmic fibres displays a high conductivity (up to 79 S cm−1), explaining currents measured through intact filaments. Conductance rapidly declines upon exposure to air, but remains stable under vacuum, demonstrating that charge transfer is electronic rather than ionic. Our finding of a biological structure that efficiently guides electrical currents over long distances greatly expands the paradigm of biological charge transport and could enable new bio-electronic applications.
Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance
Authors: Ikeda Kazuhiro , Horie-Inoue Kuniko , Suzuki Takashi , Hobo Rutsuko , Nakasato Norie , Takeda Satoru , Inoue Satoshi 
Published: September 2019

AbstractRecent advance in cancer research sheds light on the contribution of mitochondrial respiration in tumorigenesis, as they efficiently produce ATP and oncogenic metabolites that will facilitate cancer cell growth. Here we show that a stabilizing factor for mitochondrial supercomplex assembly, COX7RP/COX7A2L/SCAF1, is abundantly expressed in clinical breast and endometrial cancers. Moreover, COX7RP overexpression associates with prognosis of breast cancer patients. We demonstrate that COX7RP overexpression in breast and endometrial cancer cells promotes in vitro and in vivo growth, stabilizes mitochondrial supercomplex assembly even in hypoxic states, and increases hypoxia tolerance. Metabolomic analyses reveal that COX7RP overexpression modulates the metabolic profile of cancer cells, particularly the steady-state levels of tricarboxylic acid cycle intermediates. Notably, silencing of each subunit of the 2-oxoglutarate dehydrogenase complex decreases the COX7RP-stimulated cancer cell growth. Our results indicate that COX7RP is a growth-regulatory factor for breast and endometrial cancer cells by regulating metabolic pathways and energy production.
Synchronous 500-year oscillations of monsoon climate and human activity in Northeast Asia
Authors: Xu Deke , Lu Houyuan , Chu Guoqiang , Liu Li , Shen Caiming , Li Fengjiang , Wang Can , Wu Naiqin 
Published: September 2019

AbstractPrehistoric human activities were likely influenced by cyclic monsoon climate changes in East Asia. Here we report a decadal-resolution Holocene pollen record from an annually-laminated Maar Lake in Northeast China, a proxy of monsoon climate, together with a compilation of 627 radiocarbon dates from archeological sites in Northeast China which is a proxy of human activity. The results reveal synchronous ~500-year quasi-periodic changes over the last 8000 years. The warm-humid/cold-dry phases of monsoon cycles correspond closely to the intensification/weakening of human activity and the flourishing/decline of prehistoric cultures. Six prosperous phases of prehistoric cultures, with one exception, correspond approximately to warm-humid phases caused by a strengthened monsoon. This ~500-year cyclicity in the monsoon and thus environmental change triggered the development of prehistoric cultures in Northeast China. The cyclicity is apparently linked to the El Niño-Southern Oscillation, against the background of long-term Holocene climatic evolution. These findings reveal a pronounced relationship between prehistoric human activity and cyclical climate change.
Heterogeneity in The Mechanical Properties of Integrins Determines Mechanotransduction Dynamics in Bone Osteoblasts
Authors: Shuaib Aban , Motan Daniyal , Bhattacharya Pinaki , McNabb Alex , Skerry Timothy M. , Lacroix Damien 
Published: September 2019

AbstractBone cells are exposed to dynamic mechanical stimulation that is transduced into cellular responses by mechanotransduction mechanisms. The extracellular matrix (ECM) provides a physical link between loading and bone cells, where mechanoreceptors, such as integrins, initiate mechanosensation. Though this relationship is well studied, the dynamic interplay between mechanosensation, mechanotransduction and cellular responses is unclear. A hybrid-multiscale model combining molecular, cellular and tissue interactions was developed to examine links between integrins’ mechanosensation and effects on mechanotransduction, ECM modulation and cell-ECM interaction. The model shows that altering integrin mechanosensitivity threshold (MT) increases mechanotransduction durations from hours to beyond 4 days, where bone formation starts. This is relevant to bone, where it is known that a brief stimulating period provides persistent influences for over 24 hours. Furthermore, the model forecasts that integrin heterogeneity, with respect to MT, would be able to induce sustained increase in pERK baseline > 15% beyond 4 days. This is analogous to the emergence of molecular mechanical memory signalling dynamics. Therefore, the model can provide a greater understanding of mechanical adaptation to differential mechanical responses at different times. Given reduction of bone sensitivity to mechanical stimulation with age, these findings may lead towards useful therapeutic targets for upregulation of bone mass.
Modular Protein Ligation: A New Paradigm as a Reagent Platform for Pre-Clinical Drug Discovery
Authors: Matico Rosalie , Szewczuk Lawrence M. , Pietrak Beth , Chen Stephanie , Dul Ed , Bonnette William G. , Meinhold Derrick W. , Quinque Geoffrey , Totoritis Rachel , Lewis Tia , Grimes Maggie , Fornwald Daniel , McCormick Patricia M. , Schaber Michael , Jiang Yong , Bledsoe Randy , Holbert Marc A. 
Published: September 2019

AbstractSignificant resource is spent by drug discovery project teams to generate numerous, yet unique target constructs for the multiple platforms used to drive drug discovery programs including: functional assays, biophysical studies, structural biology, and biochemical high throughput screening campaigns. To improve this process, we developed Modular Protein Ligation (MPL), a combinatorial reagent platform utilizing Expressed Protein Ligation to site-specifically label proteins at the C-terminus with a variety of cysteine-lysine dipeptide conjugates. Historically, such proteins have been chemically labeled non-specifically through surface amino acids. To demonstrate the feasibility of this approach, we first applied MPL to proteins of varying size in different target classes using different recombinant protein expression systems, which were then evaluated in several different downstream assays. A key advantage to the implementation of this paradigm is that one construct can generate multiple final products, significantly streamlining the reagent generation for multiple early drug discovery project teams.
Transport Properties and Finite Size Effects in β-Ga2O3 Thin Films
Authors: Ahrling Robin , Boy Johannes , Handwerg Martin , Chiatti Olivio , Mitdank Rüdiger , Wagner Günter , Galazka Zbigniew , Fischer Saskia F. 
Published: September 2019

AbstractThin films of the wide band gap semiconductor β-Ga2O3 have a high potential for applications in transparent electronics and high power devices. However, the role of interfaces remains to be explored. Here, we report on fundamental limits of transport properties in thin films. The conductivities, Hall densities and mobilities in thin homoepitaxially MOVPE grown (100)-orientated β-Ga2O3 films were measured as a function of temperature and film thickness. At room temperature, the electron mobilities ((115 ± 10) cm2/Vs) in thicker films (>150 nm) are comparable to the best of bulk. However, the mobility is strongly reduced by more than two orders of magnitude with decreasing film thickness ((5.5 ± 0.5) cm2/Vs for a 28 nm thin film). We find that the commonly applied classical Fuchs-Sondheimer model does not explain sufficiently the contribution of electron scattering at the film surfaces. Instead, by applying an electron wave model by Bergmann, a contribution to the mobility suppression due to the large de Broglie wavelength in β-Ga2O3 is proposed as a limiting quantum mechanical size effect.
Metabolomic and gene expression approaches reveal the developmental and environmental regulation of the secondary metabolism of yacón (Smallanthus sonchifolius, Asteraceae)
Authors: Padilla-González Guillermo F. , Frey Maximilian , Gómez-Zeledón Javier , Da Costa Fernando B. , Spring Otmar 
Published: September 2019

AbstractActing as chemical defense or signaling compounds, secondary metabolites (SMs) play an essential role in the evolutionary success of many angiosperm plant families. However, the adaptive advantages that SMs confer, and the influence of environmental and developmental factors on SMs expression, remains poorly understood. A study of taxa endemic to the variable Andean climate, using a metabolomics approach, may provide further insight. By analyzing gene expression patterns and metabolic fingerprints, we report herein the developmental and environmental regulation of the secondary metabolism ofSmallanthus sonchifolius(yacón), a medicinal Andean plant. Our results demonstrate a clear developmental stage dependent regulation of the secondary metabolism of yacón leaves wherein the metabolic diversity increases with plant age. However, environmental factors seem to regulate biosynthetic pathways, creating differences in the expression of chemical classes, pointing to an association between transcription levels of relevant genes and the relative amounts of more than 40 different metabolites. This study suggests that the secondary metabolism of yacón is regulated by a complex interplay between environmental factors and developmental stage and provides insight into the regulatory factors and adaptive roles of SMs in Andean taxa.
Light-inducible carotenoid production controlled by a MarR-type regulator in Corynebacterium glutamicum
Authors: Sumi Satoru , Suzuki Yuto , Matsuki Tetsuro , Yamamoto Takahiro , Tsuruta Yudai , Mise Kou , Kawamura Takuya , Ito Yusuke , Shimada Yuka , Watanabe Erika , Watanabe Shoko , Toriyabe Minami , Takano Hatsumi , Ueda Kenji , Takano Hideaki 
Published: September 2019

AbstractCarotenoid production in some non-phototropic bacteria occurs in a light-dependent manner to protect cells from photo-oxidants. Knowledge regarding the transcriptional regulator involved in the light-dependent production of carotenoids of non-phototrophic bacteria has been mainly confined to coenzyme B12-based photo-sensitive regulator CarH/LitR family proteins belonging to a MerR family transcriptional regulator. In this study, we found that bacteria belonging to Micrococcales and Corynebacteriales exhibit light-dependent carotenoid-like pigment production including an amino acid-producer Corynebacterium glutamicum AJ1511. CrtR is a putative MarR family transcriptional regulator located in the divergent region of a carotenoid biosynthesis gene cluster in the genome of those bacteria. A null mutant for crtR of C. glutamicum AJ1511 exhibited constitutive production of carotenoids independent of light. A complemented strain of the crtR mutant produced carotenoids in a light-dependent manner. Transcriptional analysis revealed that the expression of carotenoid biosynthesis genes is regulated in a light-dependent manner in the wild type, while the transcription was upregulated in the crtR mutant irrespective of light. In vitro experiments demonstrated that a recombinant CrtR protein binds to the specific sequences within the intergenic region of crtR and crtE, which corresponds to −58 to −7 for crtE, and +26 to −28 for crtR with respect to the transcriptional start site, and serves as a repressor for crtE transcription directed by RNA polymerase containing SigA. Taken together, the results indicate that CrtR light-dependently controls the expression of the carotenoid gene cluster in C. glutamicum and probably closely related Actinobacteria.
Computational chemoproteomics to understand the role of selected psychoactives in treating mental health indications
Authors: Fine Jonathan , Lackner Rachel , Samudrala Ram , Chopra Gaurav 
Published: September 2019

AbstractWe have developed the Computational Analysis of Novel Drug Opportunities (CANDO) platform to infer homology of drug behaviour at a proteomic level by constructing and analysing structural compound-proteome interaction signatures of 3,733 compounds with 48,278 proteins in a shotgun manner. We applied the CANDO platform to predict putative therapeutic properties of 428 psychoactive compounds that belong to the phenylethylamine, tryptamine, and cannabinoid chemical classes for treating mental health indications. Our findings indicate that these 428 psychoactives are among the top-ranked predictions for a significant fraction of mental health indications, demonstrating a significant preference for treating such indications over non-mental health indications, relative to randomized controls. Also, we analysed the use of specific tryptamines for the treatment of sleeping disorders, bupropion for substance abuse disorders, and cannabinoids for epilepsy. Our innovative use of the CANDO platform may guide the identification and development of novel therapies for mental health indications and provide an understanding of their causal basis on a detailed mechanistic level. These predictions can be used to provide new leads for preclinical drug development for mental health and other neurological disorders.
Ixodes scapularis salivary gland microRNAs are differentially expressed during Powassan virus transmission
Authors: Hermance Meghan E. , Widen Steven G. , Wood Thomas G. , Thangamani Saravanan 
Published: September 2019

AbstractSuccessful tick feeding is facilitated by an assortment of pharmacologically-active factors in tick saliva that create an immunologically privileged micro-environment in the host’s skin. Through a process known as saliva-assisted transmission, bioactive tick salivary factors modulate the host environment, promoting transmission and establishment of a tick-borne pathogen. This phenomenon was previously demonstrated for Powassan virus (POWV), a North American tick-borne flavivirus that is the causative agent of a severe neuroinvasive disease in humans. Here, we sought to characterize the Ixodes scapularis salivary gland microRNAs (miRNAs) expressed during the earliest period of POWV transmission to a mammalian host. POWV-infected and uninfected I. scapularis females were fed on naïve mice for 1, 3, and 6 hours, and Illumina next generation sequencing was used to characterize the salivary gland miRNA expression profiles of POWV-infected versus uninfected ticks. 379 salivary miRNAs were detected, of which 338 are reported here as putative novel I. scapularis miRNAs. 35 salivary gland miRNAs were significantly up-regulated and 17 miRNAs were significantly down-regulated in response to POWV infection. To investigate the potential role of salivary gland miRNAs in POWV replication in-vitro, we transfected miRNA inhibitors into VeroE6 cells to profile temporal POWV replication in mammalian cells. Together, the small RNA sequencing data and the in vitro miRNA inhibition assay suggest that the differentially expressed tick salivary miRNAs could act in regulating POWV replication in host tissues.
Association of Anti-Mullerian Hormone with C-Reactive Protein in Men
Authors: Kadariya Dinesh , Kurbanova Nargiza , Qayyum Rehan 
Published: September 2019

AbstractWhile serum anti-mullerian hormone (AMH) levels are inversely associated with all-cause mortality in men, the underlying mechanisms are unclear. Elevated levels of inflammation, also associated with all-cause mortality, and may be the link between AMH and mortality. Hence, we examined the association of AMH with serum c-reactive protein (CRP), a biomarker of inflammation, in men. We included men ≥20 years from the National Health and Nutrition Examination Survey (1999–2004). We used survey weight-adjusted linear regression to examine the association between AMH and CRP without and with adjustment for age, race, body mass index (BMI), smoking, hypertension, diabetes, cholesterol, glomerular filtration rate (GFR), testosterone, androstenedione, and sex hormone binding globulin. Of the 949 men, 212 (22%) were elderly, 493 (52%) Caucasian, 254 (27%) current smokers, 100 (10%) diabetics, and 312 (33%) had hypertension. Mean (SD) AMH was 8.4 (7.2) ng/mL and median (IQR) CRP level was 0.17 (3) mg/L. Using linear regression, each 10 ng/mL rise in AMH was associated with 0.09 mg/dL (95%CI = −0.14 to −0.03; p = 0.002) decrease before and 0.08 mg/dL (95%CI = −0.13 to −0.02; p = 0.004) decrease in CRP after adjusting for potential confounders. Similarly, men in the highest quartile of AMH had significantly lower CRP compared to those in the lowest quartile (unadjusted difference = −0.19 mg/dL; 95%CI = −0.31 to −0.06; p = 0.006, adjusted difference = −0.16 mg/dL; 95%CI = −0.3 to −0.01; p = 0.035). We found an independent, robust, and inverse association between CRP and AMH in men. Effect of AMH on mortality may be through amelioration of inflammation.
Time-Spectral based Polarization-Encoding for Spatial-Temporal Super-Resolved NSOM Readout
Authors: Karelits Matityahu , Mandelbaum Yaakov , Zalevsky Zeev , Karsenty Avi 
Published: September 2019

AbstractDetection of evanescent waves through Near-field Scanning Optical Microscopy (NSOM) has been simulated in the past, using Finite Elements Method (FEM) and 2D advanced simulations of a silicon Schottky diode, shaped as a truncated trapezoid photodetector, and sharing a subwavelength pin hole aperture. Towards enhanced resolution and next applications, the study of polarization’s influence was added to the scanning. The detector has been horizontally shifted across a vertically oriented Gaussian beam while several E-field modes, are projected on the top of the device. Both electrical and electro-optical simulations have been conducted. These results are promising towards the fabrication of a new generation of photodetector devices which can serve for Time-Spectral based Polarization-Encoding for Spatial-Temporal Super-Resolved NSOM Readout, as developed in the study.
Concentration and pollution assessment of heavy metals within surface sediments of the Raohe Basin, China
Authors: Wei Jin , Duan Maoqing , Li Yiping , Nwankwegu Amechi S. , Ji Yong , Zhang Jie 
Published: September 2019

AbstractSurface sediment samples were collected from four areas (the Jingdezhen Industrialized Area (JDZ), Upstream (UP), the Dexing Mining Area (DX), and Downstream (DM)) to investigate the concentration and chemical composition of heavy metals. The sediments were analysed for Cu, Zn, Pb, Cd, Cr, As, and Ni using a sequential extraction scheme according to the improved BCR (European Community Bureau of Reference) method. The obtained results show that the maximum values of Cu (793.52 μg·g−1), Zn (72.09 μg·g−1), Pb (222.19 μg·g−1), and Cd (1.60 μg·g−1) were collected from the DX sampling area, while the JDZ area had the highest concentrations of Cr (97.09 μg·g−1), As (318.05 μg·g−1), and Ni (66.35 μg·g−1). The majority of metal values far exceeded their corresponding background values. The risk analysis of geo-accumulation index (Igeo) indicated that the heavy metals Cu and As were the main pollution factors and each element of the pollution degree followed the order of: Cu > As > Pb > Cd > Cr > Zn. Metal partitioning characteristics were also considered and more than 80% of metals show potential bioavailability and toxic effects.
Core set construction and association analysis of Pinus massoniana from Guangdong province in southern China using SLAF-seq
Authors: Bai Qingsong , Cai Yanling , He Boxiang , Liu Wanchuan , Pan Qingyou , Zhang Qian 
Published: September 2019

AbstractGermplasm resource collection and utilization are important in forestry species breeding. High-through sequencing technologies have been playing increasing roles in forestry breeding. In this study, specific-locus amplified fragment sequencing (SLAF-seq) was employed to analyze 149 masson pine (Pinus massoniana) accessions collected from Guangdong in China. A large number of 471,660 SNPs in the total collection were identified from 599,164 polymorphic SLAF tags. Population structure analysis showed that 149 masson pines could not be obviously divided into subpopulations. Two core sets, containing 29 masson pine accessions for increasing resin and wood yield respectively, were obtained from the total collection. Phenotypic analyses of five traits showed abundant variations, 25 suggestive and 9 significant SNPs were associated with the resin-yielding capacity (RYC’) and volume of wood (VW) using EMMAX and FaST-LMM; 22 suggestive and 11 significant SNPs were associated with RYC’ and VW using mrMLM and FASTmrMLM. Moreover, a large number of associated SNPs were detected in trait HT, DBH, RW and RYC using mrMLM, FASTmrMLM, FASTmrEMMA and ISIS EM-BLASSO. The core germplasm sets would be a valuable resource for masson pine improvement and breeding. In addition, the associated SNP markers would be meaningful for masson pine resource selection.
Detection of Gram-negative bacterial outer membrane vesicles using DNA aptamers
Authors: Shin Hye-Su , Gedi Vinayakumar , Kim Joon-Ki , Lee Dong-ki 
Published: September 2019

AbstractInfection of various pathogenic bacteria causes severe illness to human beings. Despite the research advances, current identification tools still exhibit limitations in detecting Gram-negative bacteria with high accuracy. In this study, we isolated single-stranded DNA aptamers against multiple Gram-negative bacterial species using Toggle-cell-SELEX (systemic evolution of ligands by exponential enrichment) and constructed an aptamer-based detection tool towards bacterial secretory cargo released from outer membranes of Gram-negative bacteria. Three Gram-negative bacteria, Escherichia coli DH5α, E. coli K12, and Serratia marcescens, were sequentially incubated with the pool of random DNA sequences at each SELEX loop. Two aptamers selected, GN6 and GN12, were 4.2-times and 3.6-times higher binding to 108 cells of Gram-negative bacteria than to Gram-positive bacteria tested, respectively. Using GN6 aptamer, we constructed an Enzyme-linked aptamer assay (ELAA) to detect bacterial outer membrane vesicles (OMVs) of Gram-negative bacteria, which contain several outer membrane proteins with potent immunostimulatory effects. The GN6-ELAA showed high sensitivity to detect as low as 25 ng/mL bacterial OMVs. Aptamers developed in this study show a great potential to facilitate medical diagnosis and early detection of bacterial terrorism, based on the ability to detect bacterial OMVs of multiple Gram-negative bacteria.