bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A
Authors: Mahesh Guruswamy , Rivas Gustavo B. S. , Caster Courtney , Ost Evan B. , Amunugama Ravi , Jones Richard , Allen David L. , Hardin Paul E. 
Published: October 2020

AbstractCircadian clocks keep time via ~ 24 h transcriptional feedback loops. In Drosophila, CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors are feedback loop components whose transcriptional status varies over a circadian cycle. Although changes in the state of activators and repressors has been characterized, how their status is translated to transcriptional activity is not understood. We used mass spectrometry to identify proteins that interact with GFP-tagged CLK (GFP-CLK) in fly heads at different times of day. Many expected and novel interacting proteins were detected, of which several interacted rhythmically and were potential regulators of protein levels, activity or transcriptional output. Genes encoding these proteins were tested to determine if they altered circadian behavior via RNAi knockdown in clock cells. The NIPPED-A protein, a scaffold for the SAGA and Tip60 histone modifying complexes, interacts with GFP-CLK as transcription is activated, and reducing Nipped-A expression lengthens circadian period. RNAi analysis of other SAGA complex components shows that the SAGA histone deubiquitination (DUB) module lengthened period similarly to Nipped-A RNAi knockdown and weakened rhythmicity, whereas reducing Tip60 HAT expression drastically weakened rhythmicity. These results suggest that CLK-CYC binds NIPPED-A early in the day to promote transcription through SAGA DUB and Tip60 HAT activity.
Microstructural degeneration and cerebrovascular risk burden underlying executive dysfunction after stroke
Authors: Veldsman Michele , Werden Emilio , Egorova Natalia , Khlif Mohamed Salah , Brodtmann Amy 
Published: October 2020

AbstractExecutive dysfunction affects 40% of stroke patients, but is poorly predicted by characteristics of the stroke itself. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We used structural equation modelling to investigate whether measures of white matter microstructural integrity (fractional anisotropy and mean diffusivity) and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity.
126 stroke patients (mean age 68.4 years) were scanned three months post-stroke and compared to 40 age- and sex-matched control participants on neuropsychological measures of executive function. Executive function was below what would be expected for age and education level in stroke patients as measured by the organizational components of the Rey Complex Figure Test, F(3,155) = 17, R2 = 0.25, p < 0.001 (group significant predictor at p < 0.001) and the Trail-Making Test (B), F(3,157) = 3.70, R2 = 0.07, p < 0.01 (group significant predictor at p < 0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk (root mean square error of approximation = 0.02).
Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity (r = − 0.74, p < 0.001), than executive dysfunction and stroke severity (r = 0.22, p < 0.01). The relationship between executive function and white matter integrity is mediated by cerebrovascular burden. White matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity. Executive dysfunction and incident stroke can be both considered manifestations of cerebrovascular risk factors.
Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma
Authors: Peviani Marco , Spano Giorgia , Pagani Antonella , Brugnara Gianluca , Covino Cesare , Galli Rossella , Biffi Alessandra , Politi Letterio S. 
Published: October 2020

AbstractIn this work we optimized a novel approach for combining in vivo MRI and ex vivo high-resolution fluorescence microscopy that involves: (i) a method for slicing rat brain tissue into sections with the same thickness and spatial orientation as in in vivo MRI, to better correlate in vivo MRI analyses with ex-vivo imaging via scanning confocal microscope and (ii) an improved clearing protocol compatible with lipophilic dyes that highlight the neurovascular network, to obtain high tissue transparency while preserving tissue staining and morphology with no significant tissue shrinkage or expansion. We applied this methodology in two rat models of glioblastoma (GBM; U87 human glioma cells and patient-derived human glioblastoma cancer stem cells) to demonstrate how vital the information retrieved from the correlation between MRI and confocal images is and to highlight how the increased invasiveness of xenografts derived from cancer stem cells may not be clearly detected by standard in vivo MRI approaches. The protocol studied in this work could be implemented in pre-clinical GBM research to further the development and validation of more predictive and translatable MR imaging protocols that can be used as critical diagnostic and prognostic tools. The development of this protocol is part of the quest for more efficacious treatment approaches for this devastating and still uncurable disease. In particular, this approach could be instrumental in validating novel MRI-based techniques to assess cellular infiltration beyond the macroscopic tumor margins and to quantify neo-angiogenesis.
Cep55 overexpression promotes genomic instability and tumorigenesis in mice
Authors: Sinha Debottam , Nag Purba , Nanayakkara Devathri , Duijf Pascal H. G. , Burgess Andrew , Raninga Prahlad , Smits Veronique A. J. , Bain Amanda L. , Subramanian Goutham , Wall Meaghan , Finnie John. W. , Kalimutho Murugan , Khanna Kum Kum 
Published: October 2020

AbstractHigh expression of centrosomal protein CEP55 has been correlated with clinico-pathological parameters across multiple human cancers. Despite significant in vitro studies and association of aberrantly overexpressed CEP55 with worse prognosis, its causal role in vivo tumorigenesis remains elusive. Here, using a ubiquitously overexpressing transgenic mouse model, we show that Cep55 overexpression causes spontaneous tumorigenesis and accelerates Trp53+/− induced tumours in vivo. At the cellular level, using mouse embryonic fibroblasts (MEFs), we demonstrate that Cep55 overexpression induces proliferation advantage by modulating multiple cellular signalling networks including the hyperactivation of the Pi3k/Akt pathway. Notably, Cep55 overexpressing MEFs have a compromised Chk1-dependent S-phase checkpoint, causing increased replication speed and DNA damage, resulting in a prolonged aberrant mitotic division. Importantly, this phenotype was rescued by pharmacological inhibition of Pi3k/Akt or expression of mutant Chk1 (S280A) protein, which is insensitive to regulation by active Akt, in Cep55 overexpressing MEFs. Moreover, we report that Cep55 overexpression causes stabilized microtubules. Collectively, our data demonstrates causative effects of deregulated Cep55 on genome stability and tumorigenesis which have potential implications for tumour initiation and therapy development.
Subjective value and decision entropy are jointly encoded by aligned gradients across the human brain
Authors: Bobadilla-Suarez Sebastian , Guest Olivia , Love Bradley C. 
Published: October 2020

AbstractRecent work has considered the relationship between value and confidence in both behavioural and neural representation. Here we evaluated whether the brain organises value and confidence signals in a systematic fashion that reflects the overall desirability of options. If so, regions that respond to either increases or decreases in both value and confidence should be widespread. We strongly confirmed these predictions through a model-based fMRI analysis of a mixed gambles task that assessed subjective value (SV) and inverse decision entropy (iDE), which is related to confidence. Purported value areas more strongly signalled iDE than SV, underscoring how intertwined value and confidence are. A gradient tied to the desirability of actions transitioned from positive SV and iDE in ventromedial prefrontal cortex to negative SV and iDE in dorsal medial prefrontal cortex. This alignment of SV and iDE signals could support retrospective evaluation to guide learning and subsequent decisions.
Inclusion crystals of V-shaped host molecules having trialkoxybenzene moieties with a carborane or benzoquinone derivative
Authors: Kawahata Masatoshi , Tominaga Masahide , Komatsu Ryota , Hyodo Tadashi , Yamaguchi Kentaro 
Published: October 2020

Crystallization of an o-carborane or benzoquinone derivative with adamantane-based molecules possessing pyrogallol derivatives resulted in the formation of inclusion crystals through CH⋯O or lone pair⋯π interactions.
Identification and characterisation of the Volvox carteri Moco carrier protein
Authors: Hercher Thomas W. , Krausze Joern , Yang Jing , Kirk Martin L. , Kruse Tobias 
Published: October 2020

Abstract
The molybdenum cofactor (Moco) is a redox active prosthetic group found in the active site of Moco-dependent enzymes (Mo-enzymes). As Moco and its intermediates are highly sensitive towards oxidative damage, these are believed to be permanently protein bound during synthesis and upon maturation. As a major component of the plant Moco transfer and storage system, proteins have been identified that are capable of Moco binding and release but do not possess Moco-dependent enzymatic activities. The first protein found to possess these properties was the Moco carrier protein (MCP) from the green alga Chlamydomonas reinhardtii. Here, we describe the identification and biochemical characterisation of the Volvox carteri (V. carteri) MCP and, for the first time, employ a comparative analysis to elucidate the principles behind MCP Moco binding. Doing so identified a sequence region of low homology amongst the existing MCPs, which we showed to be essential for Moco binding to V. carteri MCP.
Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases
Authors: Blokland Kaj E.C. , Pouwels Simon D. , Schuliga Michael , Knight Darryl A. , Burgess Janette K. 
Published: October 2020

AbstractThe extracellular matrix (ECM) is a complex network of macromolecules surrounding cells providing structural support and stability to tissues. The understanding of the ECM and the diverse roles it plays in development, homoeostasis and injury have greatly advanced in the last three decades. The ECM is crucial for maintaining tissue homoeostasis but also many pathological conditions arise from aberrant matrix remodelling during ageing. Ageing is characterised as functional decline of tissue over time ultimately leading to tissue dysfunction, and is a risk factor in many diseases including cardiovascular disease, diabetes, cancer, dementia, glaucoma, chronic obstructive pulmonary disease (COPD) and fibrosis. ECM changes are recognised as a major driver of aberrant cell responses. Mesenchymal cells in aged tissue show signs of growth arrest and resistance to apoptosis, which are indicative of cellular senescence. It was recently postulated that cellular senescence contributes to the pathogenesis of chronic fibrotic diseases in the heart, kidney, liver and lung. Senescent cells negatively impact tissue regeneration while creating a pro-inflammatory environment as part of the senescence-associated secretory phenotype (SASP) favouring disease progression. In this review, we explore and summarise the current knowledge around how aberrant ECM potentially influences the senescent phenotype in chronic fibrotic diseases. Lastly, we will explore the possibility for interventions in the ECM–senescence regulatory pathways for therapeutic potential in chronic fibrotic diseases.
A new trigger mechanism for coronal mass ejections
Authors: James A. W. , Green L. M. , van Driel-Gesztelyi L. , Valori G. 
Published: October 2020

Context. Many previous studies have shown that the magnetic precursor of a coronal mass ejection (CME) takes the form of a magnetic flux rope, and a subset of them have become known as “hot flux ropes” due to their emission signatures in ∼10 MK plasma.
Aims. We seek to identify the processes by which these hot flux ropes form, with a view of developing our understanding of CMEs and thereby improving space weather forecasts.
Methods. Extreme-ultraviolet observations were used to identify five pre-eruptive hot flux ropes in the solar corona and study how they evolved. Confined flares were observed in the hours and days before each flux rope erupted, and these were used as indicators of episodic bursts of magnetic reconnection by which each flux rope formed. The evolution of the photospheric magnetic field was observed during each formation period to identify the process(es) that enabled magnetic reconnection to occur in the β <  1 corona and form the flux ropes.
Results. The confined flares were found to be homologous events and suggest flux rope formation times that range from 18 hours to 5 days. Throughout these periods, fragments of photospheric magnetic flux were observed to orbit around each other in sunspots where the flux ropes had a footpoint. Active regions with right-handed (left-handed) twisted magnetic flux exhibited clockwise (anticlockwise) orbiting motions, and right-handed (left-handed) flux ropes formed.
Conclusions. We infer that the orbital motions of photospheric magnetic flux fragments about each other bring magnetic flux tubes together in the corona, enabling component reconnection that forms a magnetic flux rope above a flaring arcade. This represents a novel trigger mechanism for solar eruptions and should be considered when predicting solar magnetic activity.
Probabilistic interpretation of a system of coupled Hamilton-Jacobi-Bellman-Isaacs equations
Authors: Li Juan , Li Wenqiang , Wei Qingmeng 
Published: October 2020

By introducing a stochastic differential game whose dynamics and multi-dimensional cost functionals form a multi-dimensional coupled forward-backward stochastic differential equation with jumps, we give a probabilistic interpretation to a system of coupled Hamilton-Jacobi-Bellman-Isaacs equations. For this, we generalize the definition of the lower value function initially defined only for deterministic times t and states x to stopping times τ and random variables η ∈ L2(Ω, 𝓕τ, P; ℝ). The generalization plays a key role in the proof of a strong dynamic programming principle. This strong dynamic programming principle allows us to show that the lower value function is a viscosity solution of our system of multi-dimensional coupled Hamilton-Jacobi-Bellman-Isaacs equations. The uniqueness is obtained for a particular but important case.
Test performance and predictors of accuracy of endoscopic ultrasound-guided fine-needle aspiration for diagnosing biliary strictures or masses
Authors: Raine Tim , Thomas John P. , Brais Rebecca , Godfrey Edmund , Carroll Nicholas R. , Metz Andrew J. 
Published: October 2020

Abstract
Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as an important method for obtaining a preoperative tissue diagnosis for suspected cholangiocarcinoma. However, doubts remain about test sensitivity. This study assessed the value and limitations of EUS-FNA in clinical practice.
Patients and methods Patients undergoing EUS-FNA for biliary strictures/masses at a UK tertiary referral center from 2005 to 2014 were prospectively enrolled. Data on EUS-FNA findings, histology, and endoscopy and patient outcomes were collected to evaluate test performance and identify factors predictive of an inaccurate diagnostic result.
Results Ninety-seven patients underwent a total of 112 EUS-FNA procedures. Overall test sensitivity for an initial EUS-FNA for suspected cholangiocarcinoma was 75 % (95 % CI 64 %–84 %), with specificity 100 % (95 % CI 85 %–100 %) and negative predictive value 0.62 (95 % CI 0.47–0.75). Hilar lesions, the presence of a biliary stent, and a diagnosis of PSC were significantly independently associated with an inaccurate result. For the most difficult cases, repeat sampling and use of the Papanicolaou cytopathology grading scale led to an increase in test sensitivity from 17 % to 100 % (P = 0.015) with no loss of specificity.
Conclusions EUS-FNA was found to be a useful method for obtaining a preoperative tissue diagnosis for patients with suspected cholangiocarcinoma. This study identified markers that can reduce test accuracy and measures that can improve test performance of EUS-FNA.
CT imaging features of the normal parathyroid gland in the dog
Authors: Lautscham Esther , von Klopmann Clea , Schaub Sebastian , Stengel Christiane , Hartmann Antje 
Published: October 2020

ZusammenfassungGegenstand und Ziel Ziel dieser prospektiven Pilotstudie war zu beurteilen, ob die physiologische Glandula parathyroidea beim Hund computertomografisch dargestellt werden kann, und eine Beschreibung ihres CT-Erscheinungsbildes zu geben.Material und Methoden In die Studie wurden 25 Hunde aufgenommen, bei denen aufgrund von Erkrankungen im Halsbereich ohne Bezug zu Schild- oder Nebenschilddrüse ein CT-Scan erfolgte. Einschlusskriterium waren unauffällige Befunde bei der allgemeinen klinischen Untersuchung und der Blutuntersuchung (Blutbild und blutchemische Analyse). CT-Bilder vor und nach Kontrastmittelapplikation (30–45 Sekunden nach der Kontrastmittelinjektion, frühe venöse Phase) wurden mit einem 16-Schichten-Spiral-CT unter Verwendung eines Field of View von 18 cm, einer Schichtdicke von 1 mm und einer Matrix von 512 × 512 angefertigt. Zwei Radiologen begutachteten die CT-Aufnahmen unabhängig voneinander. Die Sichtbarkeit der Parathyreoidea wurde erfasst und die Interobserver-Reliabilität ermittelt. Bei den darstellbaren Nebenschilddrüsen wurden folgende Parameter bestimmt: Größe, Dichte (in Hounsfield Units [HU], vor und nach Kontrastmittelgabe), Dichte der Schilddrüse, Abgrenzung (exzellent, mäßig, schlecht).Ergebnisse Nur 20 bzw. 25 Nebenschilddrüsen waren durch die beiden Untersucher erkennbar. Die Anzahl differierte zwischen Nativaufnahmen und Bildern nach Kontrastmittelgabe nicht. Die Interobserver-Reliabilität hinsichtlich der Erkennbarkeit war moderat (κ = 0,40). Für Länge, Breite und Höhe der Nebenschilddrüsen (Mittelwert ± Standardabweichung) ergaben sich 4,2 × 2,5 × 2,9 mm ± 1,3 × 0,8 × 1,0 mm. Die Dichte betrug 39,7 ± 20,6 HU vor und 103,1 ± 47,1 HU nach Kontrastmittelgabe. Damit stellten sich die Nebenschilddrüsen im Vergleich zur Schilddrüse (vor und nach Kontrastmittelgabe 166,7 ± 34,3 HU bzw. 234,0 ± 60,1 HU) hypoattenuierend dar.Schlussfolgerung Diese Studie liefert die erste Beschreibung des CT-Erscheinungsbilds der angenommen physiologischen Nebenschilddrüse beim Hund. Die Sichtbarkeit des Organs war jedoch schlecht.Klinische Relevanz Trotz der schlechten Visualisierung der Nebenschilddrüse im CT ist sie gelegentlich wahrnehmbar. Die ermittelten Dimensionen waren teilweise größer als bisher für sonografische Darstellung beschrieben, ohne dass die untersuchten Hunde erkennbare Symptome eines Hyperparathyreodismus aufwiesen. Eine computertomografisch sichtbare Nebenschilddrüse impliziert daher möglicherweise nicht unbedingt eine Erkrankung. Weitere Studien dazu sind notwendig.
Ulzerative granulomatöse Kolitis durch Prototheca spp. bei einem Rhodesian Ridgeback in Deutschland
Authors: Geisen Vera , Mayer Christian , Harrer Julia , Hartmann Katrin , Ulrich Sebastian , Unterer Stefan 
Published: October 2020

ZusammenfassungEin 10 Monate alter, männlich intakter Rhodesian Ridgeback wurde wegen chronischen Dickdarmdurchfalls und Hämatochezie vorgestellt. Der Hund stammte aus Deutschland und hatte das Land nie verlassen. Die Laboruntersuchung des vorbehandelnden Tierarztes ergab neben einer Neutrophilie eine Hyperkaliämie und eine Hyponatriämie. Mit einem Serumbasalkortisolwert von 4,3 µg/dl konnte ein Hypoadrenokortizismus weitgehend ausgeschlossen werden. Eine vom Tierarzt durch geführte antibiotische Behandlung hatte keine Besserung bewirkt. Daher war der Hund mit Prednisolon behandelt worden. Unter 2-wöchiger Prednisolongabe kam es zu einer deutlichen Verstärkung des Durchfalls sowie einem Gewichtsverlust von 6 kg. Bei Vorstellung an der Medizinischen Kleintierklinik der LMU München war der Hund im Allgemeinbefinden mittelgradig reduziert, deutlich abgemagert, dehydriert, hypovolämisch und hatte eine rektale Körpertemperatur von 39,6 °C. Bei der sonografischen Untersuchung zeigte sich eine generalisiert verdickte Dickdarmwand und koloskopisch eine hochgradig ulzerativ veränderte Dickdarmschleimhaut. Histologischer Befund war eine ulzerative granulomatöse Kolitis. Durch die Periodic-Acid-Schiff-Reaktion ließen sich in den Schnitten der Dickdarmbioptate mikrobielle Strukturen darstellen, die für eine Algeninfektion diagnostisch waren. Die bei der mikrobiellen Untersuchung anzüchtbaren Prototheken wurden mittels MALDI-TOF-MS als Prototheca zopfii identifiziert. Zum Nachweis einer möglichen Immundefizienz wurden die Immunglobuline im Serum bestimmt. Die IgM-Konzentration war erniedrigt, während sich IgG- und IgA-Konzentration im Referenzbereich befanden. Aufgrund der Verschlechterung des Allgemeinbefindens, der vorsichtigen Prognose und der hohen Kosten eines Therapieversuchs wurde der Hund eine Woche später euthanasiert und der Tierkörper pathologisch untersucht. Histopathologisch wurden Prototheken auch in den abdominalen Lymphknoten, jedoch nicht in den Augen oder im zentralen Nervensystem identifiziert. Der Fall zeigt, dass eine Prototheken-Infektion auch bei Hunden aus Deutschland als Differenzialdiagnose für chronischen Dickdarmdurchfall in Betracht gezogen werden sollte, insbesondere bei Patienten mit ulzerativer granulomatöser Kolitis. Sie kann bei der histologischen Untersuchung ohne Spezialfärbung leicht übersehen werden.