bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostik von Autismus- Spektrum-Störungen im Kindes-, Jugend- und Erwachsenenalter: Überblick zu den wesentlichen Fragestellungen und Ergebnissen des ersten Teils der S3-Leitlinie
Authors: Vllasaliu Leonora , Jensen Katrin , Dose Matthias , Hagenah Ulrich , Hollmann Helmut , Kamp-Becker Inge , Lechmann Claus , Poustka Luise , Sinzig Judith , Spitzcok von Brisinski Ingo , van Elst Ludger Tebartz , Will Diana , Vogeley Kai , Freitag Christine M.
Published: October 2018

Zusammenfassung. Hintergrund: Autismus-Spektrum-Störungen (ASS) umfassen die ICD-10-Diagnosen (International Statistical Classification of Diseases and Related Health Problems) frühkindlicher Autismus, Asperger-Syndrom und atypischer Autismus und zeigen eine Lebenszeitprävalenz von bis zu 1 %. Die S3-Leitlinie der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. hat zum Ziel, evidenzbasierte Diagnostik und Therapie für professionelle Akteure im Gesundheits- und Sozialsystem systematisch zusammenzufassen und klinische Empfehlungen zu konsentieren. Der vorliegende Artikel fasst die wesentlichen Ergebnisse zum Teil Diagnostik zusammen. Methodik: Die Leitliniengruppe besteht aus 14 klinischen und wissenschaftlichen Fachgesellschaften sowie Patienten-/Angehörigen-Vertretern. Die Empfehlungen basieren dabei auf den Ergebnissen systematischer Literatursuche, Datenextraktion, Studienqualitäts-Bewertung sowie metaanalytischer Datenaggregation in Kombination mit der klinischen Expertise der jeweiligen Vertreter. Die Empfehlungen wurden anhand eines nominalen Gruppenprozesses abgestimmt. Ergebnisse: Der aktuelle Forschungsstand zur Diagnostik wird zusammengefasst. Dabei liegt ein besonderer Schwerpunkt auf der Frage der Notwendigkeit und Entbehrlichkeit verschiedener Bestandteile des diagnostischen Prozesses. Nach einer allgemeinen Einführung zum Krankheitsbild werden insbesondere die wesentlichen Aspekte der Anamnese, die sinnvolle Verwendung von Screening- und Diagnostikinstrumenten, die internistisch-neurologische Untersuchung, apparative Diagnostik, testpsychologische Untersuchung, Aufklärung und Beratung sowie sinnvolle Verlaufsdiagnostik detailliert dargestellt. Schlussfolgerung: Die ASS-Leitlinie gibt evidenzbasierte, klinisch konsentierte Empfehlungen zum Prozess der Diagnostik von ASS im Kindes-, Jugend- und Erwachsenenalter. Sie bietet Anwendern zudem die Möglichkeit, sich in kurzer Zeit über die Hintergründe der Störung sowie verschiedene diagnostische Instrumente zu informieren.
Ist Sauerstoffmangel immer nur schädlich?
Authors: Schläpfer Martin
Published: October 2018

Zusammenfassung. Die Aufgabe des Kreislaufs ist die Versorgung von Gewebe mit Sauerstoff und Nährstoffen. Zustände des Sauerstoffmangels (Hypoxie) werden als bedrohlich erachtet, da abhängig vom Ausprägungsgrad Zellen absterben, sei es durch apoptotische oder nekrotische Vorgänge. Dem versucht das Gewebe durch evolutionär erhaltene Signalwege entgegenzuwirken, z.B. über den nukleären Hypoxie-induzierbaren Faktor, der das Gewebe schützen soll, indem er das Überleben der Zellen fördert und gleichzeitig in Angiogenese, Hämatogenese und Stoffwechselprozesse eingreift. Neuere Erkenntnisse weisen darauf hin, dass gerade diese konservierten Signalwege auch therapeutische Ansätze in der Wundheilung von Knochen und Haut sowie in der Regeneration von Geweben, z.B. der Leber, und dem hämatopoetischen System, bedeuten können.
Narkolepsie und andere «zentrale Hypersomnolenzen»
Authors: Mathis Johannes
Published: October 2018

Zusammenfassung. «Tagesschläfrigkeit», «Hypersomnie» im Sinne eines verlängerten Schlafbedürfnisses, «Müdigkeit» oder «Erschöpfung» (Fatigue) sind häufige Symptome in der Praxis jedes Arztes, die eine möglichst gute Differenzierung und genaue Diagnostik erfordern, bevor eine gezielte Therapie möglich ist. Nach dem Ausschluss diverser internistischer und neurologischer Ursachen und einem polysomnografischen Ausschluss eines Schlaf-Apnoe-Syndroms oder anderen Ursachen eines nichterholsamen Schlafes bleibt schlussendlich die differenzialdiagnostisch schwierige Gruppe der sogenannten «zentralen Hypersomnolenzen» (Central Disorders of Hypersomnolence), zu denen neben der Narkolepsie mit und ohne Kataplexie, die idiopathische Hypersomnie und die nichtorganische Hypersomnie gehören. Wegen der therapeutischen Konsequenzen müssen diese Ursachen so gut wie möglich unterschieden, und auch vom banalen Schlafmanko und vom chronischen Erschöpfungssyndrom abgegrenzt werden, wozu oft eine interdisziplinäre Abklärung mit objektiven Messungen der beklagten Symptome erforderlich ist.
Seasonal Wetness, Soil Organic Carbon, and Fire Influence Soil Hydrological Properties and Water Repellency in a Sagebrush‐Steppe Ecosystem
Authors: Chandler David G. , Cheng Yang , Seyfried Mark S. , Madsen Matthew D. , Johnson Chris E. , Williams C. Jason
Published: October 2018

Prescribed fire is an important tool for rangeland management in sage‐steppe ecosystems, yet the long‐term effects of this practice on soil hydraulic properties are not well known. We explore interactions among site geomorphology, soil organic carbon (SOC) soil N, soil water repellency (SWR), and plant community type on infiltration properties before fire and 8 years thereafter in a semiarid research watershed. The objective was to assess the sustainability of rangeland burning in sage‐steppe ecosystems. Many types of measurements were made in three plant communities to identify how differences in soil hydraulic properties are related to differences in plant cover and soil texture and to determine relationships among SOC, SWR, soil water contact angle, and infiltration properties. Measurements were made on transects in burned and unburned catchments. We found that severity and occurrence of surface SWR were substantially reduced 8 years after a fire within the area originally covered with mountain big sagebrush, where the fire intensity was greatest. Surface SWR was lowest in the sparsely vegetated low sagebrush, where SOC was also lowest. Unsaturated hydraulic conductivity (Kh) increased in each vegetation type over the 8‐year period after burning and was not directly related to SWR. Spatial variability in Kh was primarily controlled by soil texture, whereas differences in sorptivity (S) were controlled by SWR and aridity. SOC is not well correlated to soil surface SWR. The decadal scale changes in Kh and associations between S and site characteristics indicate forms of resilience to fire across a moisture gradient.
Can You Express Your Science in 17 Syllables?
Authors: Duncombe Jenessa
Published: October 2018

Researchers are taking to Twitter to tell the world about their research through the lines of haiku. Now it’s your turn!
Infrared Characterization of Jupiter's Equatorial Disturbance Cycle
Authors: Antuñano Arrate , Fletcher Leigh N. , Orton Glenn S. , Melin Henrik , Rogers John H. , Harrington Joseph , Donnelly Padraig T. , Rowe‐Gurney Naomi , Blake James S. D.
Published: October 2018

We use an infrared data set captured between 1984 and 2017 using several instruments and observatories to report five rare equatorial disturbances that completely altered the appearance of Jupiter's equatorial zone (EZ): the clearance of tropospheric clouds revealed a new 5‐μm‐bright band encircling the planet at the equator, accompanied by large 5‐μm‐bright filaments. Three events were observed in ground‐based images in 1973, 1979, and 1992. We report and characterize for the first time the entire evolution of two new episodes of this unusual EZ state that presented their maximum 5‐μm‐brightness in December 1999 and February 2007, coinciding with a brown coloration south of the equator and with large bluish filaments and white plumes in the northern EZ at visible wavelengths. We characterize their typical infrared‐bright lifetimes of 12–18 months, with possible periodicities of 6–8 or 13–14 years. We predict that a full‐scale equatorial disturbance could occur in 2019–2021.
High‐Frequency Thermal Fluctuations and Instabilities in the Radiation Belt Environment
Authors: Hwang Junga , Yoon Peter H.
Published: October 2018

This paper overviews the electrostatic and electromagnetic theories of spontaneous emission in magnetized plasma as they relate to measured electric and magnetic field fluctuations in quiet time radiation belt and ring current region. The pervasively detected high‐frequency fluctuations in the upper‐hybrid frequency range as well as the background low‐frequency range spectral profile in the whistler mode range are explained within the context of the spontaneous emission theory. The quasilinear calculation of loss cone instability is also carried out in order to validate the assumption of spontaneous emission model. It is shown that the saturated wave amplitudes associated with the upper‐hybrid and multiple‐harmonic cyclotron instability are quite low, indicating that the theoretical explanation based upon the assumption of spontaneous emission theory may be adequate for understanding the observed background fluctuations during quiet times.
Ion Dynamics and the Shock Profile of a Low‐Mach Number Shock
Authors: Gedalin Michael , Zhou Xiaoyan , Russell Christopher T. , Drozdov Alexander , Liu Terry Z
Published: October 2018

The directly measured magnetic field fluctuates even at low‐Mach number shocks. Separation of the essential shock profile from features superimposed onto it is one of the basic problems of shock physics. The essential structure is one which affects the ion motion and is shaped by the produced ion distributions: the macroscopic fields which are built self‐consistently and together with the ion dynamics. The advanced test particle analysis is used to derive the magnetic profile which is consistent with the collisionless ion motion in the macroscopic fields of the shock front. The downstream side of the derived profile is in good agreement with the observed profile of a low‐Mach number interplanetary shock. The analysis allows us to improve the determination of the Mach number and provides an approximate value of the cross‐shock potential, which is not measured. It is shown that α‐particles cause nonperiodicity of the downstream magnetic oscillations. The performed hybrid simulations support the conclusion that the macroscopic fields of the shock play the main role in the formation of downstream ion distributions. The role of fluctuations is to enhance smoothing of the distributions and speed up relaxation to gyrotropy. The measured ion distributions well agree with the theoretically predicted onset of the anisotropy at the shock crossing and its persistence well into the downstream region.
Physically Constrained Stochastic Shallow Convection in Realistic Kilometer‐Scale Simulations
Authors: Sakradzija Mirjana , Klocke Daniel
Published: October 2018

A new configuration of a parameterization for shallow convection in the Icosahedral Nonhydrostatic Model (ICON) is described and tested on a single realistic test case. As a test case, a shallow convective day over Germany is simulated using four different configurations of ICON. These configurations differ by the choice of the shallow convection parameterization, which can be deterministic, stochastic, or completely switched off. As the fourth configuration, the ICON large eddy simulation setup is used as a reference against which the three other ICON model configurations are tested and compared at resolutions from 1 to 10 km. It is demonstrated that a deterministic mass flux closure combined with the stochastic sampling of the cloud base mass fluxes corrects the spatial and temporal distribution of cloudiness. The mean vertical structure of the cloud layer and vertical profiles of the thermodynamic variables in the boundary layer are also improved. The stochastic parameterization adapts to the model resolution by its formulation, while a limited scale‐aware behavior is present in the outcome of the simulations. This limitation stems from the resolution dependence of the resolved dynamics, which produces incorrect distributions of cloudiness, and scale‐dependence opposite of what is expected based on the reference large eddy simulation results. The deterministic version of the convection scheme cannot correct the behavior of the resolved dynamics, while the stochastic version corrects the resolved dynamics to some extent and improves the overall behavior across resolutions.
Sunspot Observations on 10 and 11 February 1917: A Case Study in Collating Known and Previously Undocumented Records
Authors: Willis D. M. , Wilkinson J. , Scott C. J. , Wild M. N. , Stephenson F. R. , Hayakawa H. , Brugge R. , Macdonald L. T.
Published: October 2018

An extensive investigation of ships' logs, as part of the Old Weather citizen‐science project, identified a sunspot observation made from HMS Hilary on 10 February 1917. This sunspot record was accompanied by detailed meteorological records that have enabled a reconstruction of the conditions under which the observation was made (overcast with detached clouds). Although there is no incontrovertible evidence that this was an unaided‐eye observation, comparison with an unaided‐eye observation recorded on the 11 February 1917 in a local treatise from Hénán province in China confirms that this sunspot group was visible to the unaided eye. White‐light photographs from the Dehra Dun Observatory confirm the detailed description of the sunspot group provided by the naval observer. Moreover, comparisons with tabular data published by the Royal Observatory, Greenwich, confirm the statement that this was an unusually large sunspot group. Indeed, on 11 February 1917 the area of the sunspot group was greater than the area of any sunspot group recorded previously at the Royal Observatory, Greenwich. A comparison with a modern unaided‐eye observation confirms that it is possible to observe sunspots under meteorological conditions similar to those experienced on‐board HMS Hilary.
Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness
Authors: Kim Hee Yeon , Kim Dong Keon , Bae Seung-Hyun , Gwak HyeRan , Jeon Ji Hoon , Kim Jong Kwang , Lee Byung Il , You Hye Jin , Shin Dong Hoon , Kim Young-Ho , Kim Soo Youl , Han Sung-Sik , Shim Jin-Kyoung , Lee Ji-Hyun , Kang Seok-Gu , Jang Hyonchol
Published: October 2018

Glioblastoma is a highly malignant tumor that easily acquires resistance to treatment. The stem-cell-like character (stemness) has been thought to be closely associated with the treatment resistance of glioblastoma cells. In this study, we determined that farnesyl diphosphate synthase (FDPS), a key enzyme in isoprenoid biosynthesis, plays an important role in maintaining glioblastoma stemness. A comparison of the mRNA expression in patient-derived glioblastoma sphere cells, which maintain stemness, and their differentiated counterparts, which lose stemness, via RNA sequencing showed that most of the altered genes were networked in the cholesterol biosynthesis pathway. We screened Federal Drug Administration (FDA)-approved drugs targeting specific enzymes in the cholesterol biosynthesis pathway for their ability to inhibit glioblastoma sphere formation. Inhibitors of FDPS, such as alendronate and zoledronate, significantly reduced the formation of glioblastoma spheres, and alendronate was effective at a lower molar concentration than zoledronate. Knockdown of FDPS using short hairpin RNA also completely inhibited the formation of secondary spheres. FDPS mRNA in patients with glioblastoma was associated with malignancy in three independent microarray data sets. RNA sequencing showed that alendronate treatment reduced the embryonic stem cell signature and activated development- and necrosis-related pathways in glioblastoma spheres. These results suggest that FDPS is important for the maintenance of glioblastoma stemness and that alendronate, a drug widely used to treat osteoporosis, can be repositioned to treat glioblastoma.
Trends in Chronic Liver Disease-Related Hospitalizations: A Population-Based Study
Authors: Asrani Sumeet K. , Hall Lauren , Hagan Michael , Sharma Sushma , Yeramaneni Samrat , Trotter James , Talwalkar Jayant , Kanwal Fasiha
Published: October 2018

OBJECTIVES:

In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex.

METHODS:

We examined all CLD-related inpatient encounters (2000–2015) in Dallas–Fort Worth (DFW) using data from the DFW council collaborative that captures claims data from 97% of all hospitalizations in DFW (10.7 million regional patients).

RESULTS:

There were 83,539 CLD-related hospitalizations in 48,580 unique patients across 84 hospitals. The age and gender standardized annual rate of CLD-related hospitalization increased from 48.9 per 100,000 in 2000 to 125.7 per 100,000 in 2014. Mean age at hospitalization increased from 54.0 (14.1) to 58.5 (13.5) years; the proportion of CLD patients above 65 years increased from 24.2% to 33.1%. HCV-related hospitalizations plateaued, whereas an increase was seen in hospitalizations related to alcohol (9.1 to 22.7 per 100,000) or fatty liver (1.4 per 100,000 to 19.5 per 100,000). The prevalence of medical comorbidities increased for CLD patients: coronary artery disease (4.8% to 14.3%), obesity (2.8% to 14.6%), chronic kidney disease (2.8% to 18.2%), and diabetes (18.0% to 33.2%). Overall hospitalizations with traditional complications of portal hypertension (ascites, varices, and peritonitis) remained stable over time. However, hospitalization with complications related to infection increased from 54.7% to 66.4%, and renal failure increased by sevenfold (2.7% to 19.5%).

CONCLUSIONS:

CLD-related hospitalizations have increased twofold over the last decade. Hospitalized CLD patients are older and sicker with multiple chronic conditions. Traditional complications of portal hypertension have been superseded by infection and renal failure, warranting a need to redefine what it means to have decompensated CLD.
BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair
Authors: Guo Yuxing , Yuan Yuan , Wu Ling , Ho Thach-Vu , Jing Junjun , Sugii Hideki , Li Jingyuan , Han Xia , Feng Jifan , Guo Chuanbin , Chai Yang
Published: October 2018

Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells (MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein (BMP) signalling and depend on BMP-mediated Indian hedgehog (IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand (RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog (Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMP-mediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.
Tumor suppressive miR-6775-3p inhibits ESCC progression through forming a positive feedback loop with p53 via MAGE-A family proteins
Authors: Meng Lingjiao , Liu Fei , Ju Yingchao , Ding Pingan , Liu Sihua , Chang Sheng , Liu Shina , Zhang Yi , Lian Yishui , Gu Lina , Zhang Xiaochong , Sang Meixiang
Published: October 2018

Accumulating evidences indicate that microRNAs (miRNAs) play vital roles in multiple diseases, including cancer. In the present study, we showed that miR-6775-3p plays a tumor suppressive role in esophageal squamous cell carcinoma (ESCC). High expression miR-6775-3p is associated with good clinical outcomes of ESCC patients. Over-expression of miR-6775-3p inhibited tumor growth and liver metastasis of ESCC xenograft tumors. Enforced expression of miR-6775-3p inhibited ESCC cell proliferation, migration, and invasion. KEGG pathway analysis revealed that miR-6775-3p was associated with the genes on “pathway in cancer”. Mechanically, miR-6775-3p inhibited the expression of tumor antigens MAGE-A family through direct binding the 3′UTR region of MAGE-A mRNAs, and attenuated MAGE-A-inhibited transcriptional activity of tumor suppressor p53. In addition, miR-6775-3p also directly inhibits its host gene SLC7A5 which has been reported to play oncogenic roles in cancer progression. Interestingly, miR-6775-3p and its host gene SLC7A5 were directly transcriptionally induced by p53. Thus, for the first time, our study proposed a novel positive feedback regulation between miR-6775-3p and p53 via MAGE-A family, which plays crucial role in ESCC progression.
Estrogen nuclear receptors affect cell migration by altering sublocalization of AQP2 in glioma cell lines
Authors: Wan Shu , Jiang Juanjuan , Zheng Chuanming , Wang Ning , Zhai Xia , Fei Xiangwei , Wu Ruijin , Jiang Xiuxiu
Published: October 2018

Glioblastomas are capable of infiltrating into neighboring brain tissues. The prognosis of a male patient is worse than that of women. Here, we demonstrate the effects of estrogen on invasion of glioma cells via regulating estrogen nuclear receptors (ERα and ERβ) combined with aquaporin 2 (AQP2). In our study, we conclude that AQP2 was located mainly in the nuclei of the glioma cell lines and is capable of inhibiting cell invasion. According to the gene ontology analysis, out of 138 screened genes, three genes of ankyrin repeat and FYVE domain containing 1 (ANKFY1), lymphocyte transmembrane adaptor 1 (LAX1), and latent transforming growth factor beta-binding protein 1 (LTBP1) were found to be regulating the ERα and ERβ. The expression of ERα was found to be high, whereas the expression of both ERβ and AQP2 was low in glioma cells from patient tissues and glioblastoma cell lines. The expression levels of AQP2, ANKFY1, LAX1, and LTBP1 were upregulated by both ERα small interfering RNA (siRNA) and overexpression of ERβ. AQP2 inhibition of cell invasion was inversely influenced by LAX1siRNA. The luciferase report system indicated that AQP2 promoted the transcriptional activity of LAX1 and inhibited cell invasion. These data suggest that ERβ may function as AQP promoter in the nucleus to sustain cells' stability by promoting AQP production, while ERα acts as an antagonist of AQP2. The ratio between ERα and ERβ is likely to affect the distribution of AQP2 in the nucleus. Low level of ERβ reduces the inhibition of invasion of glioma cells influenced by high level of LAX1 expression, leading to an increase in the invasion ability of glioma cells.
A reference haplotype panel for genome-wide imputation of short tandem repeats
Authors: Saini Shubham , Mitra Ileena , Mousavi Nima , Fotsing Stephanie Feupe , Gymrek Melissa
Published: October 2018

Short tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in complex traits. However, genotyping arrays used in genome-wide association studies focus on single nucleotide polymorphisms (SNPs) and do not readily allow identification of STR associations. We leverage next-generation sequencing (NGS) from 479 families to create a SNP + STR reference haplotype panel. Our panel enables imputing STR genotypes into SNP array data when NGS is not available for directly genotyping STRs. Imputed genotypes achieve mean concordance of 97% with observed genotypes in an external dataset compared to 71% expected under a naive model. Performance varies widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic repeats. Imputation increases power over individual SNPs to detect STR associations with gene expression. Imputing STRs into existing SNP datasets will enable the first large-scale STR association studies across a range of complex traits.
Design of Peptoid-peptide Macrocycles to Inhibit the β-catenin TCF Interaction in Prostate Cancer
Authors: Schneider Jeffrey A. , Craven Timothy W. , Kasper Amanda C. , Yun Chi , Haugbro Michael , Briggs Erica M. , Svetlov Vladimir , Nudler Evgeny , Knaut Holger , Bonneau Richard , Garabedian Michael J. , Kirshenbaum Kent , Logan Susan K.
Published: October 2018

New chemical inhibitors of protein–protein interactions are needed to propel advances in molecular pharmacology. Peptoids are peptidomimetic oligomers with the capability to inhibit protein-protein interactions by mimicking protein secondary structure motifs. Here we report the in silico design of a macrocycle primarily composed of peptoid subunits that targets the β-catenin:TCF interaction. The β-catenin:TCF interaction plays a critical role in the Wnt signaling pathway which is over-activated in multiple cancers, including prostate cancer. Using the Rosetta suite of protein design algorithms, we evaluate how different macrocycle structures can bind a pocket on β-catenin that associates with TCF. The in silico designed macrocycles are screened in vitro using luciferase reporters to identify promising compounds. The most active macrocycle inhibits both Wnt and AR-signaling in prostate cancer cell lines, and markedly diminishes their proliferation. In vivo potential is demonstrated through a zebrafish model, in which Wnt signaling is potently inhibited.
Appreciation of different styles of humor: An fMRI study
Authors: Chan Yu-Chen , Hsu Wei-Chin , Liao Yi-Jun , Chen Hsueh-Chih , Tu Cheng-Hao , Wu Ching-Lin
Published: October 2018

Humor styles are important in facilitating social relationships. Following humor styles theory, this functional magnetic resonance imaging (fMRI) study is the first to use “one-liner” humor to investigate the neural correlates involved in appreciating humor styles that differ in terms of target (self or other) and motivation (benign or detrimental). Interestingly, we observed greater activation in response to humor that facilitates relationships with others (self-defeating and affiliative humor) than to humor that enhances the self (self-enhancing and aggressive humor). Self-defeating humor may play an important role in Chinese culture in facilitating social relationships at one’s own expense. Psychophysiological interaction (PPI) analysis revealed temporal pole (TP)-frontal functional connectivity underlying the appreciation of self-directed humor, and temporo-parietal junction (TPJ)-frontal connectivity underlying the appreciation of other-directed humor. Amygdala-frontal coupling was observed during the appreciation of detrimental humor, while nucleus accumbens (NAc)-temporal coupling and midbrain-frontal coupling appear to play a role in the affective experience of amusement in response to benign humor. This study contributes to our understanding of the neural correlates of appreciating different humor styles, including humor that facilitates social relationships.
Genome-wide identification of AP2/ERF superfamily genes and their expression during fruit ripening of Chinese jujube
Authors: Zhang Zhong , Li Xingang
Published: October 2018

The Ethylene response factor (ERF) belongs to the APETALA2/ethylene response factor (AP2/ERF) superfamily, located at the end of the ethylene signalling pathway, and has important roles in regulating the ethylene-related response genes. Thus, identifying and charactering this transcription factor would be helpful to elucidate ethylene related fruit ripening regulation in Chinese jujube (Ziziphus jujuba Mill.). In the present study, 119 AP2/ERF genes, including 5 Related to ABI3/VPs (RAV), 17 AP2s, 57 ERFs, 39 dehydration-responsive element-binding (DREB) factors and 1 soloist gene, were identified from the jujube genome sequences. Genome localization, gene duplication, phylogenetic relationships and conserved motifs were simultaneously analysed. Using available transcriptomic data, 85 genes with differential transcripts in the flower, leaf and fruit were detected, suggesting a broad regulation of AP2/ERF genes in the growth and development of jujube. Among them, 44 genes were expressed in the fruit. As assessed by quantitative PCR, 15 up- and 23 downregulated genes corresponding to fruit full maturity were found, while in response to 100 μl l−1 ethylene, 6 up- and 16 downregulated genes were generated. By comparing the output, ZjERF54 and DREB39 were found to be the best candidate genes that positively participated in jujube fruit ripening, while ZjERF25 and ZjERF36, which had an ERF-associated amphiphilic repression (EAR) motif, were ripening repressors. These findings help to gain insights into AP2/ERF gene evolution and provide a useful resource to further understand the ethylene regulatory mechanisms underlying Chinese jujube fruit ripening.
Characterization of the miRNA regulators of the human ovulatory cascade
Authors: Yerushalmi G. M. , Salmon-Divon M. , Ophir L. , Yung Y. , Baum M. , Coticchio G. , Fadini R. , Mignini-Renzini M. , Dal Canto M. , Machtinger R. , Maman E. , Hourvitz A.
Published: October 2018

Ovarian follicular development and ovulation are complex and tightly regulated processes that involve regulation by microRNAs (miRNAs). We previously identified differentially expressed mRNAs between human cumulus granulosa cells (CGCs) from immature early antral follicles (germinal vesicle - GV) and mature preovulatory follicles (metaphase II - M2). In this study, we performed an integrated analysis of the transcriptome and miRNome in CGCs obtained from the GV cumulus-oocyte complex (COC) obtained from IVM and M2 COC obtained from IVF. A total of 43 differentially expressed miRNAs were identified. Using Ingenuity IPA analysis, we identified 7288 potential miRNA-regulated target genes. Two hundred thirty-four of these target genes were also found in our previously generated ovulatory gene library while exhibiting anti-correlated expression to the identified miRNAs. IPA pathway analysis suggested that miR-21 and FOXM1 cooperatively inhibit CDC25A, TOP2A and PRC1. We identified a mechanism for the temporary inhibition of VEGF during ovulation by TGFB1, miR-16-5p and miR-34a-5p. The linkage bioinformatics analysis between the libraries of the coding genes from our preliminary study with the newly generated library of regulatory miRNAs provides us a comprehensive, integrated overview of the miRNA-mRNA co-regulatory networks that may play a key role in controlling post-transcriptomic regulation of the ovulatory process.
Task-irrelevant spatial dividers facilitate counting and numerosity estimation
Authors: Li Qi , Nakashima Ryoichi , Yokosawa Kazuhiko
Published: October 2018

Counting is characterized as a slow and error-prone action relying heavily on serial allocation of focused attention. However, quick and accurate counting is required for many real-world tasks (e.g., counting heads to ensure everyone is evacuated to a safe place in an emergency). Previous research suggests that task-irrelevant spatial dividers, which segment visual displays into small areas, facilitate focused attention and improve serial search. The present study investigated whether counting, which is also closely related to focused attention, can be facilitated by spatial dividers. Furthermore, the effect of spatial dividers on numerosity estimation, putatively dependent upon distributed attention, was also examined to provide insights into different types of number systems and different modes of visual attention. The results showed profound performance improvement by task-irrelevant spatial dividers in both counting and numerosity estimation tasks, indicating that spatial dividers may activate interaction between number and visual attention systems. Our findings provide the first evidence that task-irrelevant spatial dividers can be used to facilitate various types of numerical cognition.
Identification of Differentially Expressed Non-coding RNA in Porcine Alveolar Macrophages from Tongcheng and Large White Pigs Responded to PRRSV
Authors: Zhen Yueran , Wang Fengqing , Liang Wan , Liu Jianjian , Gao Guoli , Wang Yan , Xu Xuewen , Su Qiuju , Zhang Qingde , Liu Bang
Published: October 2018

Porcine reproductive and respiratory syndrome (PRRS) is one of the most ruinous diseases in pig production. Our previous work showed that Tongcheng pigs (TC) were less susceptible to PRRS virus (PRRSV) than Large White (LW) pigs. To elucidate the difference in PRRSV resistance between the two breeds, small RNA-seq and ribo-zero RNA-seq were used to identify differentially expressed non-coding RNAs (including miRNAs and lincRNAs) responded to PRRSV in porcine alveolar macrophages (PAMs) from TC and LW pigs. Totally, 250 known mature miRNAs were detected. For LW pigs, there were 44 down-regulated and 67 up-regulated miRNAs in infection group; while for TC pigs, 12 down-regulated and 23 up-regulated miRNAs in TC infection group were identified. The target genes of the common differentially expressed miRNAs (DEmiRNAs) in these two breeds were enriched in immune-related processes, including apoptosis process, inflammatory response, T cell receptor signaling pathway and so on. In addition, 5 shared DEmiRNAs (miR-181, miR-1343, miR-296-3p, miR-199a-3p and miR-34c) were predicted to target PRRSV receptors, of which miR-199a-3p was validated to inhibit the expression of CD151. Interestingly, miR-378 and miR-10a-5p, which could inhibit PRRSV replication, displayed higher expression level in TC control group than that in LW control group. Contrarily, miR-145-5p and miR-328, which were specifically down-regulated in LW pigs, could target inhibitory immunoreceptors and may involve in immunosuppression caused by PRRSV. This indicates that DEmiRNAs are involved in the regulation of the immunosuppression and immune escape of the two breeds. Furthermore, we identified 616 lincRNA transcripts, of which 48 and 30 lincRNAs were differentially expressed in LW and TC pigs, respectively. LincRNATCONS_00125566may play an important role in the entire regulatory network, and was predicted to regulate the expression of immune-related genes through binding with miR-1343 competitively. In conclusion, this study provides an important resource for further revealing the interaction between host and virus, which will specify a new direction for anti-PRRSV research.
Vision facilitates tactile perception when grasping an object
Authors: Juravle Georgiana , Colino Francisco L. , Meleqi Xhino , Binsted Gordon , Farnè Alessandro
Published: October 2018

Tactile sensitivity measured on the hand is significantly decreased for a moving (MH), as opposed to a resting hand (RH). This process (i.e., tactile suppression) is affected by the availability of visual information during goal-directed action. However, the timing of the contribution of visual information is currently unclear for reach-to-grasp movements, especially in the period before the digits land on the object to grasp it. Here participants reached for, grasped, and lifted an object placed in front of them in conditions of full/limited vision. Tactile perception was assessed by measures of signal detection theory (d’ & c’). Electro-cutaneous stimulation could be delivered/not at the MH/RH, either during movement preparation, execution, before grasping, or while lifting the object. Results confirm tactile gating at the MH. This result is accompanied by a significant conservative criterion shift at the MH for the latter movement stages. Importantly, visual information enhances MH sensitivity just before grasping the object, but also improves RH sensitivity, during object lift. These findings reveal that tactile suppression is shaped by visual inputs at critical action stages. Further, they indicate that such a time-dependent modulation from vision to touch extends beyond the MH, suggesting a dynamic monitoring of the grasp space.
Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II–III colorectal cancer
Authors: Huang Chih-Yang , Chiang Shu-Fen , Ke Tao-Wei , Chen Tsung-Wei , You Ying-Shu , Chen William Tzu-Liang , Chao K. S. Clifford
Published: October 2018

Programmed cell death-1 (PDCD1/PD-1) and its ligand programmed cell death 1 ligand 1 (CD274/PD-L1) have been reported to suppress anti-tumor T cell-mediated immune responses. However, the clinical significance of CD274 in colorectal cancer were still elusive. We aim to clarify the relationships between CD8+ intratumor-infiltrating lymphocytes (TILs) and CD274 as well as their prognostic values in stage II-III colon carcinoma. Tumor differentiation, perineural invasion (PNI), pN stage and DNA mismatch repair (MMR)-deficient were clearly correlated with CD8+ TILs counts within the tumor microenvironment (p < 0.0001). Furthermore, tumor differentiation and PNI were suggestively correlated with tumor CD274 expression (p = 0.02 and p = 0.0195). Tumor CD274 level was significantly correlated with higher CD8+ TILs (p < 0.0001) but was not associated with MMR-deficient status (p = 0.14). High tumor CD274 expression [hazard ratio (HR) = 2.16, 95% CI = 1.63–2.86, p < 0.0001] and CD8+ TILs [HR = 1.51, 95% CI = 1.19–1.91, p = 0.0007] were associated with improved disease-free survival and overall survival. Additionally, the subgroup of patients who had a high CD8+ TILs/tumor CD274 have better survival outcomes compared with other subgroups (71% vs 53%; p < 0.0001). Therefore, the CD8+ TILs counts and tumor CD274 may be prognostic factors to predict survival and therapeutic responses in stage II–III colon carcinoma patients.
A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area
Authors: Jenkins Timothy P. , Formenti Fabio , Castro Cecilia , Piubelli Chiara , Perandin Francesca , Buonfrate Dora , Otranto Domenico , Griffin Julian L. , Krause Lutz , Bisoffi Zeno , Cantacessi Cinzia
Published: October 2018

Data from recent studies support the hypothesis that infections by human gastrointestinal (GI) helminths impact, directly and/or indirectly, on the composition of the host gut microbial flora. However, to the best of our knowledge, these studies have been conducted in helminth-endemic areas with multi-helminth infections and/or in volunteers with underlying gut disorders. Therefore, in this study, we explore the impact of natural mono-infections by the human parasite Strongyloides stercoralis on the faecal microbiota and metabolic profiles of a cohort of human volunteers from a non-endemic area of northern Italy (S+), pre- and post-anthelmintic treatment, and compare the findings with data obtained from a cohort of uninfected controls from the same geographical area (S−). Analyses of bacterial 16S rRNA high-throughput sequencing data revealed increased microbial alpha diversity and decreased beta diversity in the faecal microbial profiles of S+ subjects compared to S−. Furthermore, significant differences in the abundance of several bacterial taxa were observed between samples from S+ and S− subjects, and between S+ samples collected pre- and post-anthelmintic treatment. Faecal metabolite analysis detected marked increases in the abundance of selected amino acids in S+ subjects, and of short chain fatty acids in S− subjects. Overall, our work adds valuable knowledge to current understanding of parasite-microbiota associations and will assist future mechanistic studies aimed to unravel the causality of these relationships.
Using insects to detect, monitor and predict the distribution of Xylella fastidiosa: a case study in Corsica
Authors: Cruaud Astrid , Gonzalez Anne-Alicia , Godefroid Martin , Nidelet Sabine , Streito Jean-Claude , Thuillier Jean-Marc , Rossi Jean-Pierre , Santoni Sylvain , Rasplus Jean-Yves
Published: October 2018

We sampledca2500 specimens ofPhilaenus spumarius(Hemiptera: Aphrophoridae) throughout Corsica withouta prioriknowledge on the presence of symptoms on plants. We screened 448 specimens for the presence ofXylella fastidiosa (Xf)using qPCR and a custom nested PCR. qPCR appeared versatile and under-estimated the prevalence ofXf. Nested PCR showed thatXfwas present in all populations. Molecular results were validated by prediction on the distribution ofXfmade from tests conducted on plants, which shows the pertinence of using vectors in risk assessment studies.Xfwas detected in tenerals and adults. Thus,P.spumariuscould acquireXffrom its host plant, mostlyCistus monspeliensisin Corsica, which may act as reservoir for the next season. This contrasts with other observations and suggests that management strategies may have to be adapted on a case-by-case basis. At least two genetic entities and several variants ofXfnot yet identified on plants were present in the insects, which suggests ancient introductions ofXfand a probable underestimation of the current diversity of the strains present in Corsica. Interestingly 6% of the specimens carried two subspecies ofXf. Studies are required to better characterize the strains present in Corsica and to determine how the disease was introduced, spread and why no sign of a potential epidemic was detected earlier. This study shows that, when sensitive enough methods are implemented, spittlebugs (and more specificallyP.spumariusfor which species distribution modelling shows it could be a good sentinel for Europe) can be used to predict and better assess the exact distribution ofXf. Furthermore,Xfmultiply only in their foregut and does not become circulative, which facilitates its detection.
Differences in the fecal microbiota of neonates born at home or in the hospital
Authors: Combellick Joan L. , Shin Hakdong , Shin Dongjae , Cai Yi , Hagan Holly , Lacher Corey , Lin Din L. , McCauley Kathryn , Lynch Susan V. , Dominguez-Bello Maria Gloria
Published: October 2018

Research on the neonatal microbiome has been performed mostly on hospital-born infants, who often undergo multiple birth-related interventions. Both the hospital environment and interventions around the time of birth may affect the neonate microbiome. In this study, we determine the structure of the microbiota in feces from babies born in the hospital or at home, and from vaginal samples of their mothers. We included 35 vaginally-born, breast-fed neonates, 14 of whom delivered at home (4 in water), and 21 who delivered in the hospital. Feces from babies and mothers and maternal vaginal swab samples were collected at enrollment, the day of birth, followed by days 1, 2, 7, 14, 21, and 28. At the time of birth, the diversity of the vaginal microbiota of mothers delivering in the hospital was lower than in mothers delivering at home, and showed higher proportion of Lactobacillus. Among 20 infants not exposed to perinatal maternal antibiotics or water birth, fecal beta diversity differed significantly by birth site, with hospital-born infants having lower Bacteroides, Bifidobacterium, Streptococcus, and Lactobacillus, and higher Clostridium and Enterobacteriaceae family (LDA > 3.0), than babies born at home. At 1 month of age, feces from infants born in the hospital also induced greater pro-inflammatory gene expression (TLR4, IL-8, occludin and TGFβ) in human colon epithelial HT-29 cells. The results of this work suggest that hospitalization (perinatal interventions or the hospital environment) may affect the microbiota of the vaginal source and the initial colonization during labor and birth, with effects that could persist in the intestinal microbiota of infants 1 month after birth. More research is needed to determine specific factors that alter bacterial transmission between mother and baby and the long-term health implications of these differences for the developing infant.
Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases
Authors: Hammitzsch Ariane , Chen Liye , de Wit Jelle , Al-Mossawi M. Hussein , Ridley Anna , Sekine Takuya , Simone Davide , Doig Karen , Skapenko Alla , Bowness Paul
Published: October 2018

Treatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, culturedin-vitrounder Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFNγ were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow.In-vitroinhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing ofJAK1-3andTyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS.
A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
Authors: Saengwimol Duangporn , Rojanaporn Duangnate , Chaitankar Vijender , Chittavanich Pamorn , Aroonroch Rangsima , Boontawon Tatpong , Thammachote Weerin , Jinawath Natini , Hongeng Suradej , Kaewkhaw Rossukon
Published: October 2018

Persistent or recurrent retinoblastoma (RB) is associated with the presence of vitreous or/and subretinal seeds in advanced RB and represents a major cause of therapeutic failure. This necessitates the development of novel therapies and thus requires a model of advanced RB for testing candidate therapeutics. To this aim, we established and characterized a three-dimensional, self-organizing organoid model derived from chemotherapy-naïve tumors. The responses of organoids to drugs were determined and compared to relate organoid model to advanced RB, in terms of drug sensitivities. We found that organoids had histological features resembling retinal tumors and seeds and retained DNA copy-number alterations as well as gene and protein expression of the parental tissue. Cone signal circuitry (M/L+ cells) and glial tumor microenvironment (GFAP+ cells) were primarily present in organoids. Topotecan alone or the combined drug regimen of topotecan and melphalan effectively targeted proliferative tumor cones (RXRγ+ Ki67+) in organoids after 24-h drug exposure, blocking mitotic entry. In contrast, methotrexate showed the least efficacy against tumor cells. The drug responses of organoids were consistent with those of tumor cells in advanced disease. Patient-derived organoids enable the creation of a faithful model to use in examining novel therapeutics for RB.