bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood
Authors: Qi Ting , Wu Yang , Zeng Jian , Zhang Futao , Xue Angli , Jiang Longda , Zhu Zhihong , Kemper Kathryn , Yengo Loic , Zheng Zhili ,   eQTLGen Consortium, Agbessi Mawussé , Ahsan Habibul , Alves Isabel , Andiappan Anand , Awadalla Philip , Battle Alexis , Beutner Frank , Jan Bonder Marc , Boomsma Dorret , Christiansen Mark , Claringbould Annique , Deelen Patrick , Esko Tõnu , Favé Marie-Julie , Franke Lude , Frayling Timothy , Gharib Sina , Gibson Gregory , Hemani Gibran , Jansen Rick , Kähönen Mika , Kalnapenkis Anette , Kasela Silva , Kettunen Johannes , Kim Yungil , Kirsten Holger , Kovacs Peter , Krohn Knut , Kronberg-Guzman Jaanika , Kukushkina Viktorija , Kutalik Zoltan , Lee Bernett , Lehtimäki Terho , Loeffler Markus , Marigorta Urko M. , Metspalu Andres , Milani Lili , Müller-Nurasyid Martina , Nauck Matthias , Nivard Michel , Penninx Brenda , Perola Markus , Pervjakova Natalia , Pierce Brandon , Powell Joseph , Prokisch Holger , Psaty Bruce , Raitakari Olli , Ring Susan , Ripatti Samuli , Rotzschke Olaf , Ruëger Sina , Saha Ashis , Scholz Markus , Schramm Katharina , Seppälä Ilkka , Stumvoll Michael , Sullivan Patrick , Teumer Alexander , Thiery Joachim , Tong Lin , Tönjes Anke , van Dongen Jenny , van Meurs Joyce , Verlouw Joost , Völker Uwe , Võsa Urmo , Yaghootkar Hanieh , Zeng Biao , Marioni Riccardo E. , Montgomery Grant W. , Deary Ian J. , Wray Naomi R. , Visscher Peter M. , McRae Allan F. , Yang Jian 
Published: June 2018

AbstractUnderstanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r
b
). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples ($$\hat r_b = 0.70$$

r

^

b

=
0.70
for cis-eQTLs and $$\hat r_ b = 0.78$$

r

^

b

=
0.78
for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.
Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines
Authors: Porciani David , Cardwell Leah N. , Tawiah Kwaku D. , Alam Khalid K. , Lange Margaret J. , Daniels Mark A. , Burke Donald H. 
Published: June 2018

AbstractLarge RNAs and ribonucleoprotein complexes have powerful therapeutic potential, but effective cell-targeted delivery tools are limited. Aptamers that internalize into target cells can deliver siRNAs (<15 kDa, 19–21 nt/strand). We demonstrate a modular nanostructure for cellular delivery of large, functional RNA payloads (50–80 kDa, 175–250 nt) by aptamers that recognize multiple human B cell cancer lines and transferrin receptor-expressing cells. Fluorogenic RNA reporter payloads enable accelerated testing of platform designs and rapid evaluation of assembly and internalization. Modularity is demonstrated by swapping in different targeting and payload aptamers. Both modules internalize into leukemic B cell lines and remained colocalized within endosomes. Fluorescence from internalized RNA persists for ≥2 h, suggesting a sizable window for aptamer payloads to exert influence upon targeted cells. This demonstration of aptamer-mediated, cell-internalizing delivery of large RNAs with retention of functional structure raises the possibility of manipulating endosomes and cells by delivering large aptamers and regulatory RNAs.
Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition
Authors: Froese D. Sean , Kopec Jolanta , Rembeza Elzbieta , Bezerra Gustavo Arruda , Oberholzer Anselm Erich , Suormala Terttu , Lutz Seraina , Chalk Rod , Borkowska Oktawia , Baumgartner Matthias R. , Yue Wyatt W. 
Published: June 2018

AbstractThe folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 Å resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain of novel fold provides the predominant interface for MTHFR homo-dimerization, positioning the N-terminal serine-rich phosphorylation region near the C-terminal SAM-binding domain. This explains how MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition. Finally, we demonstrate that the 25-amino-acid inter-domain linker enables conformational plasticity and propose it to be a key mediator of SAM regulation. Together, these results provide insight into the molecular regulation of MTHFR.
Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation
Authors: Barrett Alan D. T. 
Published: June 2018

AbstractZika virus (ZIKV), a mosquito-borne flavivirus, was first identified in the 1940s in Uganda in Africa and emerged in the Americas in Brazil in May 2015. In the 30 months since ZIKV emerged as a major public health problem, spectacular progress has been made with vaccine development cumulating with the publication of three reports of phase 1 clinical trials in the 4th quarter of 2017. Clinical trials involving candidate DNA and purified inactivated virus vaccines showed all were safe and well-tolerated in the small number of volunteers and all induced neutralizing antibodies, although these varied by vaccine candidate and dosing regimen. These results suggest that a Zika vaccine can be developed and that phase 2 clinical trials are warranted. However, it is difficult to compare the results from the different phase 1 studies or with neutralizing antibodies induced by licensed flavivirus vaccines (Japanese encephalitis, tick-borne encephalitis, and yellow fever) as neutralizing antibody assays vary and, unfortunately, there are no standards for Zika virus neutralizing antibodies. In addition to clinical studies, substantial progress continues to be made in nonclinical development, particularly in terms of the ability of candidate vaccines to protect reproductive tissues, and the potential use of monoclonal antibodies for passive prophylaxis.
The Translational and Rotational Dynamics of a Colloid Moving Along the Air-Liquid Interface of a Thin Film
Authors: Das Subhabrata , Koplik Joel , Farinato Raymond , Nagaraj D. R. , Maldarelli Charles , Somasundaran Ponisseril 
Published: June 2018

AbstractThis study examines the translation and rotation of a spherical colloid straddling the (upper) air/liquid interface of a thin, planar, liquid film bounded from below by either a solid or a gas/liquid interface. The goal is to obtain numerical solutions for the hydrodynamic flow in order to understand the influence of the film thickness and the lower interface boundary condition. When the colloid translates on a film above a solid, the viscous resistance increases significantly as the film thickness decreases due to the fluid-solid interaction, while on a free lamella, the drag decreases due to the proximity to the free (gas/liquid) surface. When the colloid rotates, the contact line of the interface moves relative to the colloid surface. If no-slip is assumed, the stress becomes infinite and prevents the rotation. Here finite slip is used to resolve the singularity, and for small values of the slip coefficient, the rotational viscous resistance is dominated by the contact line stress and is surprisingly less dependent on the film thickness and the lower interface boundary condition. For a colloid rotating on a semi-infinite liquid layer, the rotational resistance is largest when the colloid just breaches the interface from the liquid side.
Association between oral health and general health indicators in older adults
Authors: Tran Trung Dung , Krausch-Hofmann Stefanie , Duyck Joke , de Almeida Mello Johanna , De Lepeleire Jan , Declerck Dominique , Declercq Anja , Lesaffre Emmanuel 
Published: June 2018

AbstractOral health (OH) and general health (GH) indicators are representations of the health status of the body. The OH indicators provide information about the oral health status while the GH indicators are used to assess the functional, cognitive, and mental conditions. OH is reported to be associated with GH. However, some specific associations, especially longitudinal relationships between OH and GH indicators, have not been fully explored. We examined the prediction ability from OH to GH and vice versa using a Belgian registry. We collected information from 8359 elderly participants, who were older than 65, lived at home, and received home care. The demographic and clinical information including three binary OH indicators and four ordinal GH indicators were collected. The participants were recorded at baseline and every six months afterwards. We opted for a generalization of a vector autoregressive model to ordinal responses. This model allows to estimate autocorrelations and cross-lagged correlations, addressing the prediction of GH from OH in a cross-sectional and longitudinal manner. We showed that individuals who had poorer OH had a higher risk of suffering from poor GH status. The percentages of correct or close prediction for GH indicators from OH indicators are high, being around 80% for all GH indicators. Additionally, having a poor OH (resp. GH) status was additionally predictive of a poor GH (resp. OH) status at following assessments. Our finding suggests using historical records of OH as well as GH indicators to draw better health care plan for geriatrics population.
Real-life speech production and perception have a shared premotor-cortical substrate
Authors: Glanz Olga , Derix Johanna , Kaur Rajbir , Schulze-Bonhage Andreas , Auer Peter , Aertsen Ad , Ball Tonio 
Published: June 2018

AbstractMotor-cognitive accounts assume that the articulatory cortex is involved in language comprehension, but previous studies may have observed such an involvement as an artefact of experimental procedures. Here, we employed electrocorticography (ECoG) during natural, non-experimental behavior combined with electrocortical stimulation mapping to study the neural basis of real-life human verbal communication. We took advantage of ECoG’s ability to capture high-gamma activity (70–350 Hz) as a spatially and temporally precise index of cortical activation during unconstrained, naturalistic speech production and perception conditions. Our findings show that an electrostimulation-defined mouth motor region located in the superior ventral premotor cortex is consistently activated during both conditions. This region became active early relative to the onset of speech production and was recruited during speech perception regardless of acoustic background noise. Our study thus pinpoints a shared ventral premotor substrate for real-life speech production and perception with its basic properties.
Airway brushing as a new experimental methodology to detect airway gene expression signatures in mouse lung squamous cell carcinoma
Authors: Pan Jing , Xiong Donghai , Zhang Qi , Szabo Eva , Miller Mark Steven , Lubet Ronald A. , Wang Yian , You Ming 
Published: June 2018

AbstractAs a consequence of exposure to environmental toxicants, a “field cancerization” effect occurs in the lung, resulting in the development of a field of initiated, but morphologically normal appearing cells within a damaged epithelium containing mutations in oncogene or tumor suppressor genes. Unlike humans, whose airway field of injury associated with lung cancer has long been investigated with airway brushings obtained via bronchoscopy, no methods are available for similar studies in the mouse due to the small size of the murine airways. In this protocol, we describe a detailed method for performing airway brushing from a live mouse, which enables repeated sampling from the same mouse and thus, mimicking the bronchoscopy protocol used in humans. Using this approach in the N-nitroso-tris-chloroethylurea (NTCU)-induced mouse lung squamous cell carcinoma (SCC) model, we isolated airway epithelial cells with intact cell membrane structure and then performed transcriptome sequencing (RNA-Seq). We found activation of the PI3K signaling network to be the most significant in cytologically normal bronchial airway epithelial cells of mice with preneoplastic lung SCC lesions. Prolonged exposure to NTCU also induced activation of NF-kappaB (NFƙB), the downstream pathway of PI3K; this NTCU-induced lung SCC progression can be reversed by blocking the NFƙB pathway.
PQQ ameliorates D-galactose induced cognitive impairments by reducing glutamate neurotoxicity via the GSK-3β/Akt signaling pathway in mouse
Authors: Zhou Xing-qin , Yao Zhi-wen , Peng Ying , Mao Shi-shi , Xu Dong , Qin Xiao-feng , Zhang Rong-jun 
Published: June 2018

AbstractOxidative stress is known to be associated with various age-related diseases. D-galactose (D-gal) has been considered a senescent model which induces oxidative stress response resulting in memory dysfunction. Pyrroloquinoline quinone (PQQ) is a redox cofactor which is found in various foods. In our previous study, we found that PQQ may be converted into a derivative by binding with amino acid, which is beneficial to several pathological processes. In this study, we found a beneficial glutamate mixture which may diminish neurotoxicity by oxidative stress in D-gal induced mouse. Our results showed that PQQ may influence the generation of proinflammatory mediators, including cytokines and prostaglandins during aging process. D-gal-induced mouse showed increased MDA and ROS levels, and decreased T-AOC activities in the hippocampus, these changes were reversed by PQQ supplementation. Furthermore, PQQ statistically enhanced Superoxide Dismutase SOD2 mRNA expression. PQQ could ameliorate the memory deficits and neurotoxicity induced by D-gal via binding with excess glutamate, which provide a link between glutamate-mediated neurotoxicity, inflammation and oxidative stress. In addition, PQQ reduced the up-regulated expression of p-Akt by D-gal and maintained the activity of GSK-3β, resulting in a down-regulation of p-Tau level in hippocampus. PQQ modulated memory ability partly via Akt/GSK-3β pathway.
Impact of nicotine replacement therapy as an adjunct to anti-tuberculosis treatment and behaviour change counselling in newly diagnosed pulmonary tuberculosis patients: an open-label, randomised controlled trial
Authors: Sharma Surendra Kumar , Mohan Alladi , Singh Achintya Dinesh , Mishra Hridesh , Jhanjee Sonali , Pandey Ravindra Mohan , Singh Binit Kumar , Sharma Rohini , Pallipamu Prakash Babu , Pai Madhukar , Dheda Keertan 
Published: June 2018

AbstractWe evaluated the impact of intensive smoking cessation activities as an adjunct to anti-tuberculosis treatment on patient-related treatment outcomes. In this open-label, randomised controlled trial, self-reporting smokers with pulmonary tuberculosis who initiated standard anti-tuberculosis treatment were randomised to either nicotine replacement therapy and behaviour change counselling (n = 400) or counselling alone (n = 400) provided at baseline and two follow-up visits. The primary outcomes were change in TBscore at 24-weeks and culture conversion at 8-weeks. Biochemical smoking quit rates defined as serum cotinine levels <10 ng/mL and/or exhaled carbon monoxide levels <6 ppm (47·8% vs 32·4%, p-value =< 0·001) and self-reported quit rates (69.3% vs 38·7%, p-value =< 0·001) were significantly higher in the intervention arm at 24-weeks. Though the TBscores at 24 weeks (95% CI) were lower in the intervention arm [2·07 (1·98, 2·17) versus 2.12 (2·02, 2·21)], the difference was not clinically meaningful. Patients in the control arm required treatment extension more often than intervention arm (6·4% vs 2·6%, p-value = 0·02). Combining nicotine replacement therapy with behaviour change counselling resulted in significantly higher quit rates and lower cotinine levels, however, impact on patient-related (TBscore) or microbiological outcomes (culture conversion) were not seen.
Water Vapor Transfer and Near-Surface Salinity Contrasts in the North Atlantic Ocean
Authors: Reagan James , Seidov Dan , Boyer Tim 
Published: June 2018

AbstractMaintaining North Atlantic (NA) intra-basin near-surface salinity (NSS) contrast between the high NSS (>37.0) in the subtropical NA (STNA) and low NSS (<35.0) in the subpolar NA (SPNA) has been shown to be important in sustaining the strength of the Atlantic Meridional Overturning Circulation. Evaporation (E) exceeding precipitation (P) in the STNA is primarily responsible for the high NSS there, whereas P dominating E in the SPNA contributes to its low NSS. With a basic understanding of NA intra-basin moisture transport, a correlation analysis was conducted between E-P/NSS over the NA subpolar gyre (SPG) and E-P across the rest of the NA over the 1985–2012 time period. Significant anti-correlations exist between E-P/NSS over the NA SPG and E-P over the central/northern STNA. This suggests that during times of high E over the central/northern STNA there is high (low) precipitation (NSS) over the SPG demonstrating a relationship likely exists between E over the STNA and NSS over the SPG. The maximum anti-correlated area is poleward of the maximum E-P location in the STNA, which is examined. These results provide a first step to ultimately utilizing NSS in the NA as a proxy for estimating changes in the hydrological cycle.
Confirmation of high-throughput screening data and novel mechanistic insights into VDR-xenobiotic interactions by orthogonal assays
Authors: Mahapatra Debabrata , Franzosa Jill A. , Roell Kyle , Kuenemann Melaine Agnes , Houck Keith A. , Reif David M. , Fourches Denis , Kullman Seth W. 
Published: June 2018

AbstractHigh throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays. Transient transactivation assay (TT) using a human VDR plasmid and Cyp24 luciferase reporter construct revealed 20/21 active VDR agonists and 18/19 active VDR antagonists. Mammalian-2-hybrid assay (M2H) was then used to evaluate VDR interactions with co-activators and co-regulators. With the exception of a select few compounds, VDR agonists exhibited significant recruitment of co-regulators and co-activators whereas antagonists exhibited considerable attenuation of recruitment by VDR. A unique set of compounds exhibiting synergistic activity in antagonist mode and no activity in agonist mode was identified. Cheminformatics modeling of VDR-ligand interactions were conducted and revealed selective ligand VDR interaction. Overall, data emphasizes the molecular complexity of ligand-mediated interactions with VDR and suggest that VDR transactivation may be a target site of action for diverse xenobiotics.
Scaling photonic lanterns for space-division multiplexing
Authors: Velázquez-Benítez Amado M. , Antonio-López J. Enrique , Alvarado-Zacarías Juan C. , Fontaine Nicolas K. , Ryf Roland , Chen Haoshuo , Hernández-Cordero Juan , Sillard Pierre , Okonkwo Chigo , Leon-Saval Sergio G. , Amezcua-Correa Rodrigo 
Published: June 2018

AbstractWe present a new technique allowing the fabrication of large modal count photonic lanterns for space-division multiplexing applications. We demonstrate mode-selective photonic lanterns supporting 10 and 15 spatial channels by using graded-index fibres and microstructured templates. These templates are a versatile approach to position the graded-index fibres in the required geometry for efficient mode sampling and conversion. Thus, providing an effective scalable method for large number of spatial modes in a repeatable manner. Further, we demonstrate the efficiency and functionality of our photonic lanterns for optical communications. Our results show low insertion and mode dependent losses, as well as enhanced mode selectivity when spliced to few mode transmission fibres. These photonic lantern mode multiplexers are an enabling technology for future ultra-high capacity optical transmission systems.
The guanine nucleotide exchange factor Arhgef7/βPix promotes axon formation upstream of TC10
Authors: López Tobón Alejandro , Suresh Megalakshmi , Jin Jing , Vitriolo Alessandro , Pietralla Thorben , Tedford Kerry , Bossenz Michael , Mahnken Kristina , Kiefer Friedemann , Testa Giuseppe , Fischer Klaus-Dieter , Püschel Andreas W. 
Published: June 2018

AbstractThe characteristic six layers of the mammalian neocortex develop sequentially as neurons are generated by neural progenitors and subsequently migrate past older neurons to their final position in the cortical plate. One of the earliest steps of neuronal differentiation is the formation of an axon. Small GTPases play essential roles during this process by regulating cytoskeletal dynamics and intracellular trafficking. While the function of GTPases has been studied extensively in cultured neurons andin vivomuch less is known about their upstream regulators. Here we show that Arhgef7 (also called βPix or Cool1) is essential for axon formation during cortical development. The loss of Arhgef7 results in an extensive loss of axons in cultured neurons and in the developing cortex. Arhgef7 is a guanine-nucleotide exchange factor (GEF) for Cdc42, a GTPase that has a central role in directing the formation of axons during brain development. However, active Cdc42 was not able to rescue the knockdown of Arhgef7. We show that Arhgef7 interacts with the GTPase TC10 that is closely related to Cdc42. Expression of active TC10 can restore the ability to extend axons in Arhgef7-deficient neurons. Our results identify an essential role of Arhgef7 during neuronal development that promotes axon formation upstream of TC10.