bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome
Authors: Arrondel Christelle , Missoury Sophia , Snoek Rozemarijn , Patat Julie , Menara Giulia , Collinet Bruno , Liger Dominique , Durand Dominique , Gribouval Olivier , Boyer Olivia , Buscara Laurine , Martin Gaëlle , Machuca Eduardo , Nevo Fabien , Lescop Ewen , Braun Daniela A. , Boschat Anne-Claire , Sanquer Sylvia , Guerrera Ida Chiara , Revy Patrick , Parisot Mélanie , Masson Cécile , Boddaert Nathalie , Charbit Marina , Decramer Stéphane , Novo Robert , Macher Marie-Alice , Ranchin Bruno , Bacchetta Justine , Laurent Audrey , Collardeau-Frachon Sophie , van Eerde Albertien M. , Hildebrandt Friedhelm , Magen Daniella , Antignac Corinne , van Tilbeurgh Herman , Mollet Géraldine 
Published: September 2019

AbstractN6-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t6A) is a universal modification essential for translational accuracy and efficiency. The t6A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.
Prediction of ferroelectricity-driven Berry curvature enabling charge- and spin-controllable photocurrent in tin telluride monolayers
Authors: Kim Jeongwoo , Kim Kyoung-Whan , Shin Dongbin , Lee Sang-Hoon , Sinova Jairo , Park Noejung , Jin Hosub 
Published: September 2019

AbstractIn symmetry-broken crystalline solids, pole structures of Berry curvature (BC) can emerge, and they have been utilized as a versatile tool for controlling transport properties. For example, the monopole component of the BC is induced by the time-reversal symmetry breaking, and the BC dipole arises from a lack of inversion symmetry, leading to the anomalous Hall and nonlinear Hall effects, respectively. Based on first-principles calculations, we show that the ferroelectricity in a tin telluride monolayer produces a unique BC distribution, which offers charge- and spin-controllable photocurrents. Even with the sizable band gap, the ferroelectrically driven BC dipole is comparable to those of small-gap topological materials. By manipulating the photon handedness and the ferroelectric polarization, charge and spin circular photogalvanic currents are generated in a controllable manner. The ferroelectricity in group-IV monochalcogenide monolayers can be a useful tool to control the BC dipole and the nonlinear optoelectronic responses.
Exploration of stem endophytic communities revealed developmental stage as one of the drivers of fungal endophytic community assemblages in two Amazonian hardwood genera
Authors: Skaltsas Demetra N. , Badotti Fernanda , Vaz Aline Bruna Martins , Silva Felipe Ferreira da , Gazis Romina , Wurdack Kenneth , Castlebury Lisa , Góes-Neto Aristóteles , Chaverri Priscila 
Published: September 2019

AbstractMany aspects of the dynamics of tropical fungal endophyte communities are poorly known, including the influence of host taxonomy, host life stage, host defence, and host geographical distance on community assembly and composition. Recent fungal endophyte research has focused on Hevea brasiliensis due to its global importance as the main source of natural rubber. However, almost no data exist on the fungal community harboured within other Hevea species or its sister genus Micrandra. In this study, we expanded sampling to include four additional Hevea spp. and two Micrandra spp., as well as two host developmental stages. Through culture-dependent and -independent (metagenomic) approaches, a total of 381 seedlings and 144 adults distributed across three remote areas within the Peruvian Amazon were sampled. Results from both sampling methodologies indicate that host developmental stage had a greater influence in community assemblage than host taxonomy or locality. Based on FunGuild ecological guild assignments, saprotrophic and mycotrophic endophytes were more frequent in adults, while plant pathogens were dominant in seedlings. Trichoderma was the most abundant genus recovered from adult trees while Diaporthe prevailed in seedlings. Potential explanations for that disparity of abundance are discussed in relation to plant physiological traits and community ecology hypotheses.
Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysfunction in women with common genetic variants in SLC30A2
Authors: Kelleher Shannon L. , Gagnon Annie , Rivera Olivia C. , Hicks Steven D. , Carney Molly C. , Alam Samina 
Published: September 2019

AbstractStudies in humans and pre-clinical animal models show milk-derived miRNAs reflect mammary gland function during lactation. The zinc transporter SLC30A2/ZnT2 plays a critical role in mammary gland function; ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and secretion, resulting in sub-optimal lactation. Non-synonymous genetic variation in SLC30A2 is common in humans, and several common ZnT2 variants are associated with changes in milk components that suggest breast dysfunction in women. To identify novel mechanisms through which dysfunction might occur, milk-derived miRNA profiles were characterized in women harboring three common genetic variants in SLC30A2 (D103E, T288S, and Exon 7). Expression of ten miRNAs differed between genotypes, and contributed to distinct spatial separation. Studies in breast milk and cultured MECs confirmed expression of ZnT2 variants alters abundance of protein levels of several predicted mRNA targets critical for breast function (PRLR, VAMP7, and SOX4). Moreover, bioinformatic analysis identified two novel gene networks that may underlie normal MEC function. Thus, we propose that genetic variation in genes critical for normal breast function such as SLC30A2 has important implications for lactation performance in women, and that milk-derived miRNAs can be used to identify novel mechanisms and for diagnostic potential.
Mathematical modeling of drug-induced receptor internalization in the HER2-positive SKBR3 breast cancer cell-line
Authors: Fehling-Kaschek Mirjam , Peckys Diana B. , Kaschek Daniel , Timmer Jens , Jonge Niels de 
Published: September 2019

AbstractAbout 20% of breast cancer tumors over-express the HER2 receptor. Trastuzumab, an approved drug to treat this type of breast cancer, is a monoclonal antibody directly binding at the HER2 receptor and ultimately inhibiting cancer cell growth. The goal of our study was to understand the early impact of trastuzumab on HER2 internalization and recycling in the HER2-overexpressing breast cancer cell line SKBR3. To this end, fluorescence microscopy, monitoring the amount of HER2 expression in the plasma membrane, was combined with mathematical modeling to derive the flux of HER2 receptors from and to the membrane. We constructed a dynamic multi-compartment model based on ordinary differential equations. To account for cancer cell heterogeneity, a first, dynamic model was expanded to a second model including two distinct cell phenotypes, with implications for different conformational states of HER2, i.e. monomeric or homodimeric. Our mathematical model shows that the hypothesis of fast constitutive HER2 recycling back to the plasma membrane does not match the experimental data. It conclusively describes the experimental observation that trastuzumab induces sustained receptor internalization in cells with membrane ruffles. It is also concluded that for rare, non-ruffled (flat) cells, HER2 internalization occurs three orders of magnitude slower than for the bulk, ruffled cell population.
High-throughput-compatible assays using a genetically-encoded calcium indicator
Authors: Wu Nyantsz , Nishioka Walter K. , Derecki Noël C. , Maher Michael P. 
Published: September 2019

AbstractMeasurement of intracellular calcium in live cells is a key component of a wide range of basic life science research, and crucial for many high-throughput assays used in modern drug discovery. Synthetic calcium indicators have become the industry standard, due their ease of use, high reliability, wide dynamic range, and availability of a large variety of spectral and chemical properties. Genetically-encoded calcium indicators (GECIs) have been optimized to the point where their performance rivals that of synthetic calcium indicators in many applications. Stable expression of a GECI has distinct advantages over synthetic calcium indicators in terms of reagent cost and simplification of the assay process. We generated a clonal cell line constitutively expressing GCaMP6s; high expression of the GECI was driven by coupling to a blasticidin resistance gene with a self-cleaving cis-acting hydrolase element (CHYSEL) 2A peptide. Here, we compared the performance of the GECI GCaMP6s to the synthetic calcium indicator fluo-4 in a variety of assay formats. We demonstrate that the pharmacology of ion channel and GPCR ligands as determined using the two indicators is highly similar, and that GCaMP6s is viable as a direct replacement for a synthetic calcium indicator.
Expression of immune regulatory genes correlate with the abundance of specific Clostridiales and Verrucomicrobia species in the equine ileum and cecum
Authors: Lindenberg F. , Krych L. , Fielden J. , Kot W. , Frøkiær H. , van Galen G. , Nielsen D. S. , Hansen A. K. 
Published: September 2019

AbstractBillions of bacteria inhabit the gastrointestinal tract. Immune-microbial cross talk is responsible for immunological homeostasis, and symbiotic microbial species induce regulatory immunity, which helps to control the inflammation levels. In this study we aimed to identify species within the equine intestinal microbiota with the potential to induce regulatory immunity. These could be future targets for preventing or treating low-grade chronic inflammation occurring as a result of intestinal microbial changes and disruption of the homeostasis. 16S rRNA gene amplicon sequencing was performed on samples of intestinal microbial content from ileum, cecum, and colon of 24 healthy horses obtained from an abattoir. Expression of genes coding for IL-6, IL-10, IL-12, IL-17, 18 s, TNFα, TGFβ, and Foxp3 in the ileum and mesenteric lymph nodes was measured by qPCR. Intestinal microbiota composition was significantly different in the cecum and colon compared to the ileum, which contains large abundances of Proteobacteria. Especially members of the Clostridiales order correlated positively with the regulatory T-cell transcription factor Foxp3 and so did the phylum Verrucomicrobia. We conclude that Clostridiales and Verrucomicrobia have the potential to induce regulatory immunity and are possible targets for intestinal microbial interventions aiming at regulatory immunity improvement.
Muscle transcriptome analysis reveals genes and metabolic pathways related to mineral concentration in Bos indicus
Authors: Afonso Juliana , Coutinho Luiz Lehmann , Tizioto Polyana Cristine , da Silva Diniz Wellison Jarles , de Lima Andressa Oliveira , Rocha Marina Ibelli Pereira , Buss Carlos Eduardo , Andrade Bruno Gabriel Nascimento , Piaya Otávio , da Silva Juliana Virginio , Lins Laura Albuquerque , Gromboni Caio Fernando , Nogueira Ana Rita Araújo , Fortes Marina Rufino Salinas , Mourao Gerson Barreto , de Almeida Regitano Luciana Correia 
Published: September 2019

AbstractMineral content affects the biological processes underlying beef quality. Muscle mineral concentration depends not only on intake-outtake balance and muscle type, but also on age, environment, breed, and genetic factors. To unveil the genetic factors involved in muscle mineral concentration, we applied a pairwise differential gene expression analysis in groups of Nelore steers genetically divergent for nine different mineral concentrations. Here, based on significant expression differences between contrasting groups, we presented candidate genes for the genetic regulation of mineral concentration in muscle. Functional enrichment and protein-protein interaction network analyses were carried out to search for gene regulatory processes concerning each mineral. The core genetic regulation for all minerals studied, except Zn, seems to rest on interactions between components of the extracellular matrix. Regulation of adipogenesis-related pathways was also significant in our results. Antagonistic patterns of gene expression for fatty acid metabolism-related genes may explain the Cu and Zn antagonistic effect on fatty acid accumulation. Our results shed light on the role of these minerals on cell function.
Engineered Carbonic Anhydrase VI-Mimic Enzyme Switched the Structure and Affinities of Inhibitors
Authors: Kazokaitė Justina , Kairys Visvaldas , Smirnovienė Joana , Smirnov Alexey , Manakova Elena , Tolvanen Martti , Parkkila Seppo , Matulis Daumantas 
Published: September 2019

AbstractSecretory human carbonic anhydrase VI (CA VI) has emerged as a potential drug target due to its role in pathological states, such as excess acidity-caused dental caries and injuries of gastric epithelium. Currently, there are no available CA VI-selective inhibitors or crystallographic structures of inhibitors bound to CA VI. The present study focuses on the site-directed CA II mutant mimicking the active site of CA VI for inhibitor screening. The interactions between CA VI-mimic and a series of benzenesulfonamides were evaluated by fluorescent thermal shift assay, stopped-flow CO2 hydration assay, isothermal titration calorimetry, and X-ray crystallography. Kinetic parameters showed that A65T, N67Q, F130Y, V134Q, L203T mutations did not influence catalytic properties of CA II, but inhibitor affinities resembled CA VI, exhibiting up to 0.16 nM intrinsic affinity for CA VI-mimic. Structurally, binding site of CA VI-mimic was found to be similar to CA VI. The ligand interactions with mutated side chains observed in three crystallographic structures allowed to rationalize observed variation of binding modes and experimental binding affinities to CA VI. This integrative set of kinetic, thermodynamic, and structural data revealed CA VI-mimic as a useful model to design CA VI-specific inhibitors which could be beneficial for novel therapeutic applications.
Sound symbolic congruency detection in humans but not in great apes
Authors: Margiotoudi Konstantina , Allritz Matthias , Bohn Manuel , Pulvermüller Friedemann 
Published: September 2019

AbstractTheories on the evolution of language highlight iconicity as one of the unique features of human language. One important manifestation of iconicity is sound symbolism, the intrinsic relationship between meaningless speech sounds and visual shapes, as exemplified by the famous correspondences between the pseudowords ‘maluma’ vs. ‘takete’ and abstract curved and angular shapes. Although sound symbolism has been studied extensively in humans including young children and infants, it has never been investigated in non-human primates lacking language. In the present study, we administered the classic “takete-maluma” paradigm in both humans (N = 24 and N = 31) and great apes (N = 8). In a forced choice matching task, humans but not great apes, showed crossmodal sound symbolic congruency effects, whereby effects were more pronounced for shape selections following round-sounding primes than following edgy-sounding primes. These results suggest that the ability to detect sound symbolic correspondences is the outcome of a phylogenetic process, whose underlying emerging mechanism may be relevant to symbolic ability more generally.
Ultrathin acoustic cloaking by a conformal hybrid metasurface
Authors: Wang Yihe , Cheng Ying , Liu Xiaojun 
Published: September 2019

AbstractUltrathin acoustic cloaking of obstacles with arbitrary shape is achieved by a conformal hybrid metasurface, which is composed of an outer layer of phase-control metasurface (PCM) and an inner layer of near-zero-index metasurface (NZIM). Here, the PCM and NZIM are discretized into two types of labyrinth elements. The NZIM is functionally equivalent to an equiphase area and can guide the waves around the obstacle, while the PCM can perpendicularly transfer the incident waves to the NZIM and then control the emergent waves from NZIM to propagate along the original incident direction. The efficient cloaking by hybrid metasurface tightly covered on the edges of the square and circular obstacles is demonstrated, with a total thickness only 0.62 times of operating wavelength.
Human cardiac myosin light chain 4 (MYL4) mosaic expression patterns vary by sex
Authors: Wang Tony Y. , Arking Dan E. , Maleszewski Joseph J. , Fox-Talbot Karen , Nieuwenhuis Tim O. , Santhanam Lakshmi , Virmani Renu , Rosenberg Avi Z. , Halushka Marc K. 
Published: September 2019

AbstractSex disparities modulate cardiac function, although the proteins and mechanisms remain to be elucidated. We recently demonstrated a mosaic pattern of protein expression in the heart for over 100 proteins. Here we investigate one of these proteins, myosin light chain 4 (MYL4), which is important for contractile functions by increasing force production. We assayed the expression pattern of MYL4 across 756 ventricular myocardial samples from 668 individuals utilizing a semi-automated Cell Profiler method on five tissue microarrays (TMAs) of cardiac tissues across a diverse set of diseases. The percentage of MYL4 positive cells was significantly higher in male subjects independently across all five TMAs, regardless of disease state (p = 8.66e-15). Higher MYL4 expression was also modestly associated with hypertrophic cardiomyopathy (p = 6.3e-04). MYL4 expression did not associate with sudden cardiac death or other cardiomyopathies. This study demonstrates a new mosaic pattern of protein expression that underlies sex disparities in the human heart.
A protocol integrating remote patient monitoring patient reported outcomes and cardiovascular biomarkers
Authors: Shufelt Chrisandra , Dzubur Eldin , Joung Sandy , Fuller Garth , Mouapi Kelly N. , Van Den Broek Irene , Lopez Mayra , Dhawan Shivani , Arnold Corey W. , Speier William , Mastali Mitra , Fu Qin , Van Eyk Jennifer E. , Spiegel Brennan , Merz C. Noel Bairey 
Published: September 2019

AbstractWe describe the protocol, design, and methodology of the Prediction, Risk, and Evaluation of Major Adverse Cardiac Events (PRE-MACE) study as a multicomponent remote patient monitoring in cardiology. Using biosensor, biomarkers, and patient-reported outcomes in participants with stable ischemic heart disease, the PRE-MACE study is designed to measure cross-sectional correlations and establish the ability of remote monitoring to predict major adverse cardiovascular event (MACE) biomarkers and incident MACE at baseline and 12-month follow-up. It will further assess the adherence and cost-effectiveness of remote monitoring and blood sampling over the initial months. Despite medication and lifestyle changes, patients with cardiovascular disease can experience MACE due to undertreatment, poor adherence, or failure to recognize clinical or biochemical changes that presage MACE. Identifying patients using remote monitoring to detect MACE forerunners has potential to improve outcomes, avoid MACE, and reduce resource utilization. Data collection will include: (1) continuous remote monitoring using wearable biosensors; (2) biomarker measurements using plasma and at-home micro-sampling blood collection; and (3) patient-reported outcomes to monitor perceived stress, anxiety, depression, and health-related quality of life. Two hundred participants will be followed for 90 days with a subset (n = 80) monitored for 180 days. All participants will be followed up for MACE at 12 months.The PRE-MACE study will utilize remote monitoring with biosensors, biomarkers, and patient-reported outcomes to identify intermediate biomarkers of MACE in patients with stable ischemic heart disease. If shown to be effective, this intervention can be utilized between health visits to predict MACE and reduce financial impact of MACE.
Effects of Encouraging the Use of Gestures on Speech
Authors: Cravotta Alice , Busà M. Grazia , Prieto Pilar 
Published: September 2019

Purpose
Previous studies have investigated the effects of the inability to produce hand gestures on speakers' prosodic features of speech; however, the potential effects of encouraging speakers to gesture have received less attention, especially in naturalistic settings. This study aims at investigating the effects of encouraging the production of hand gestures on the following speech correlates: speech discourse length (number of words and discourse length in seconds), disfluencies (filled pauses, self-corrections, repetitions, insertions, interruptions, speech rate), and prosodic properties (measures of fundamental frequency [F0] and intensity).

Method
Twenty native Italian speakers took part in a narration task in which they had to describe the content of short comic strips to a confederate listener in 1 of the following 2 conditions: (a) nonencouraging condition (N), that is, no instructions about gesturing were given, and (b) encouraging condition (E), that is, the participants were instructed to gesture while telling the story.

Results
Instructing speakers to gesture led effectively to higher gesture rate and salience. Significant differences were found for (a) discourse length (e.g., the narratives had more words in E than in N) and (b) acoustic measures (F0 maximum, maximum intensity, and mean intensity metrics were higher in E than in N).

Conclusion
The study shows that asking speakers to use their hands while describing a story can have an effect on narration length and can also impact on F0 and intensity metrics. By showing that enhancing the gesture stream could affect speech prosody, this study provides further evidence that gestures and prosody interact in the process of speech production.
Die Feinnadelpunktion der Schilddrüse: Praktische Durchführung und Fallbeispiele
Authors: Schäfer Wolfgang 
Published: September 2019

ZusammenfassungDie Feinnadelpunktion der Schilddrüse ist ein etabliertes Verfahren, um Schilddrüsenknoten artdiagnostisch einordnen zu können. Die FNP ist dabei ein wenig belastendes, nebenwirkungsarmes Verfahren, welches eine wichtige Säule in der Schilddrüsenknotendiagnostik darstellt. In der Hand des erfahrenen Punkteurs in Kombination mit einem versierten Pathologen ist die diagnostische Aussagekraft hoch, sodass mittels der FNP eine relevante Anzahl diagnostischer Schilddrüsenoperationen vermieden werden können. In dieser Übersichtsarbeit wird auf die Anforderungen des Robert Koch-Instituts an die Hygiene bei der Feinnadelpunktion der Schilddrüse eingegangen. Sonografiegesteuerte effektive Punktionstechniken werden vorgestellt. Die Befundungskategorien des Pathologen und ihre Auswirkungen auf das klinische Vorgehen werden aufgezeigt. Fallbeispiele illustrieren die Korrelation der klinischen Befunde mit den zytologischen und den makroskopischen Befunden sowie den folgenden histologischen Präparaten.