bluuebunny/crossref_metadata_2025_split huggingface dataset:
Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes
Authors: Kojo Satoshi , Tanaka Hirokazu , Endo Takaho A. , Muroi Sawako , Liu Ye , Seo Wooseok , Tenno Mari , Kakugawa Kiyokazu , Naoe Yoshinori , Nair Krutula , Moro Kazuyo , Katsuragi Yoshinori , Kanai Akinori , Inaba Toshiya , Egawa Takeshi , Venkatesh Byrappa , Minoda Aki , Kominami Ryo , Taniuchi Ichiro 
Published: September 2017

AbstractT-lineage committed precursor thymocytes are screened by a fate-determination process mediated via T cell receptor (TCR) signals for differentiation into distinct lineages. However, it remains unclear whether any antecedent event is required to couple TCR signals with the transcriptional program governing lineage decisions. Here we show that Bcl11b, known as a T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3, central regulators for the CD4-helper/CD8-cytotoxic lineage choice. Loss of Bcl11b results in random expression of these factors and, thereby, lineage scrambling that is disconnected from TCR restriction by MHC. Initial Thpok repression by Bcl11b prior to the pre-selection stage is independent of a known silencer for Thpok, and requires the last zinc-finger motif in Bcl11b protein, which by contrast is dispensable for T-lineage commitment. Collectively, our findings shed new light on the function of Bcl11b in priming lineage-specifying genes to integrate TCR signals into subsequent transcriptional regulatory mechanisms.
Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity
Authors: Flaherty Erin , Deranieh Rania M. , Artimovich Elena , Lee Inkyu S. , Siegel Arthur J. , Levy Deborah L. , Nestor Michael W. , Brennand Kristen J. 
Published: September 2017

AbstractVariants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio. Here, we report the effect of this heterozygous intragenic deletion in CNTNAP2 on global gene expression and neuronal activity in the same cohort. Our findings suggest that heterozygous CNTNAP2 deletions affect genes involved in neuronal development and neuronal activity; however, these data reflect only one family trio and therefore more deletion carriers, with a variety of genetic backgrounds, will be needed to understand the molecular mechanisms underlying CNTNAP2 deletions.
MicroRNA regulation of CYP 1A2, CYP3A4 and CYP2E1 expression in acetaminophen toxicity
Authors: Gill Pritmohinder , Bhattacharyya Sudeepa , McCullough Sandra , Letzig Lynda , Mishra Prasun J. , Luo Chunqiao , Dweep Harsh , James Laura 
Published: September 2017

AbstractMicroRNAs (miRNAs) that regulate the cytochrome P-450 isoforms involved in acetaminophen (APAP) toxicity were examined in HepaRG cells treated with APAP (20 mM). In-vitro studies found that APAP protein adducts were increased at 1 h, followed by ALT increases at 12 and 24 h. CYP1A2, CYP3A4 and CYP2E1 mRNA levels were decreased, while miRNAs were increased for miR-122-5p, miR-378a-5p, miR-27b-3p at 6 h and miR-125b-5p at 12 h and miR-27b-3p at 24 h. Putative miRNA binding sites on the 3′UTRs of the CYPs were identified in-silico. Overexpression of miR-122-5p and miR-378a-5p in cells suppressed protein expression of CYP1A2, CYP3A4 and CYP2E1. Luciferase reporter assays confirmed the interaction between miR-122 and the 3′UTR of the CYP1A2 and CYP3A4. Thus, the in-vitro experiments showed that miR-122-5p and miR-378a-5p upregulation were associated with translational repression of CYPs. Serum samples of children with APAP overdose had significant elevation of miR-122-5p, miR-378a-5p, miR-125b-5p and miR-27b-3p, compared to healthy controls and receiver operator curves of the miRNAs had AUCs of 91 to 100%. Collectively, the data suggest that miRNA elevations in APAP toxicity represent a regulatory response to modify CYP1A2, CYP3A4 and CYP2E1 translation due to cellular stress and injury.
Determining the biomechanics of touch sensation in C. elegans
Authors: Elmi Muna , Pawar Vijay M. , Shaw Michael , Wong David , Zhan Haoyun , Srinivasan Mandayam A. 
Published: September 2017

AbstractThe sense of touch is a fundamental mechanism that nearly all organisms use to interact with their surroundings. However, the process of mechanotransduction whereby a mechanical stimulus gives rise to a neuronal response is not well understood. In this paper we present an investigation of the biomechanics of touch using the model organism C. elegans. By developing a custom micromanipulation and force sensing system around a high resolution optical microscope, we measured the spatial deformation of the organism’s cuticle and force response to controlled uniaxial indentations. We combined these experimental results with anatomical data to create a multilayer computational biomechanical model of the organism and accurately derive its material properties such as the elastic modulus and poisson’s ratio. We demonstrate the utility of this model by combining it with previously published electrophysiological data to provide quantitative insights into different biomechanical states for mechanotransduction, including the first estimate of the sensitivity of an individual mechanoreceptor to an applied stimulus (parameterised as strain energy density). We also interpret empirical behavioural data to estimate the minimum number of mechanoreceptors which must be activated to elicit a behavioural response.
Adaptation trajectories during adhesion and spreading affect future cell states
Authors: Bruekers Stéphanie M. C. , Bao Min , Hendriks José M. A. , Mulder Klaas W. , Huck Wilhelm T. S. 
Published: September 2017

AbstractCells are complex systems in which dynamic gene expression and protein-interaction networks adapt to changes in the environment. Seeding and subsequent spreading of cells on substrates represents an example of adaptation to a major perturbation. The formation of adhesive interactions and self-organisation of the cytoskeleton during initial spreading might prime future cell behaviour. To elucidate the role of these events on later cellular behaviour, we mapped the trajectories by which cells respond to seeding on substrates with different physical properties. Our experiments on cell spreading dynamics on collagen- or fibrin-coated polyacrylamide gels and collagen or fibrin hydrogels show that on each substrate, cells follow distinct trajectories of morphological changes, culminating in fundamentally different cell states as quantified by RNA-expression levels, YAP/TAZ localisation, proliferation and differentiation propensities. The continuous adaptation of the cell to environmental cues leaves traces due to differential cellular organisation and gene expression profiles, blurring correlations between a particular physical property and cellular phenotype.
Prolonged seizure activity causes caspase dependent cleavage and dysfunction of G-protein activated inwardly rectifying potassium channels
Authors: Baculis Brian C. , Weiss Amanda C. , Pang Weilun , Jeong Han Gil , Lee Jun Hee , Liu Dai-Chi , Tsai Nien-Pei , Chung Hee Jung 
Published: September 2017

AbstractRecurrent high-frequency epileptic seizures cause progressive hippocampal sclerosis, which is associated with caspase-3 activation and NMDA receptor-dependent excitotoxicity. However, the identity of caspase-3 substrates that contribute to seizure-induced hippocampal atrophy remains largely unknown. Here, we show that prolonged high-frequency epileptiform discharges in cultured hippocampal neurons leads to caspase-dependent cleavage of GIRK1 and GIRK2, the major subunits of neuronal G protein-activated inwardly rectifying potassium (GIRK) channels that mediate membrane hyperpolarization and synaptic inhibition in the brain. We have identified caspase-3 cleavage sites in GIRK1 (387ECLD390) and GIRK2 (349YEVD352). The YEVD motif is highly conserved in GIRK2-4, and located within their C-terminal binding sites for Gβγ proteins that mediate membrane-delimited GIRK activation. Indeed, the cleaved GIRK2 displays reduced binding to Gβγ and cannot coassemble with GIRK1. Loss of an ER export motif upon cleavage of GIRK2 abolishes surface and current expression of GIRK2 homotetramic channels. Lastly, kainate-induced status epilepticus causes GIRK1 and GIRK2 cleavage in the hippocampus in vivo. Our findings are the first to show direct cleavage of GIRK1 and GIRK2 subunits by caspase-3, and suggest the possible role of caspase-3 mediated down-regulation of GIRK channel function and expression in hippocampal neuronal injury during prolonged epileptic seizures.
Explorability and the origin of network sparsity in living systems
Authors: Busiello Daniel M. , Suweis Samir , Hidalgo Jorge , Maritan Amos 
Published: September 2017

AbstractThe increasing volume of ecologically and biologically relevant data has revealed a wide collection of emergent patterns in living systems. Analysing different data sets, ranging from metabolic gene-regulatory to species interaction networks, we find that these networks are sparse, i.e. the percentage of the active interactions scales inversely proportional to the system size. To explain the origin of this puzzling common characteristic, we introduce the new concept of explorability: a measure of the ability of an interacting system to adapt to newly intervening changes. We show that sparsity is an emergent property resulting from optimising both explorability and dynamical robustness, i.e. the capacity of the system to remain stable after perturbations of the underlying dynamics. Networks with higher connectivities lead to an incremental difficulty to find better values for both the explorability and dynamical robustness, associated with the fine-tuning of the newly added interactions. A relevant characteristic of our solution is its scale invariance, i.e., it remains optimal when several communities are assembled together. Connectivity is also a key ingredient in determining ecosystem stability and our proposed solution contributes to solving May’s celebrated complexity-stability paradox.
The Role of Cortisol/ACTH Ratio for Screening of Subclinical Hypercortisolism in Patients with Adrenal Incidentalomas
Authors: Li Lele , Yang Guoqing , Dou Jingtao , Gu Weijun , Lv Zhaohui , Lu Juming , Mu Yiming 
Published: September 2017

Abstract
Introduction The cortisol/ACTH ratio was supposed to be helpful in the screening of subclinical hypercortisolism (SHC) in the published literatures. This study assessed the cortisol/ACTH ratio in patients with adrenal incidentaloma (AI) confirmed to have SHC and investigated its role for screening SCS in patients with AI.
Methods This descriptive retrospective study included 183 patients with AIs [45 with SHC and 138 with non-functional adenoma (NFA)]. Cortisol and ACTH levels were measured at 8:00, 16:00, and 0:00, and the cortisol/ACTH ratio was calculated. ROC curve was used to evaluate efficacy of the cortisol/ACTH ratio, explore the best cut-off value and its corresponding sensitivity and specificity.
Results The cortisol/ACTH ratios at all time points were significantly higher in the SHC group than the NFA group (P<0.05) and were significantly correlated with serum cortisol levels after the 1-mg dexamethasone suppression test (DST). Area Under the Curve (AUC) of the cortisol/ACTH ratio at 0:00 and midnight serum cortisol levels were 0.893 (0.843–0.943) and 0.831 (0.765–0.806), respectively. A cortisol/ACTH ratio at 0:00 cut-off of 32.18 nM/pM showed a sensitivity of 100% and specificity of 39.1%. The optimal cut-off was 68.83 nM/pM (sensitivity 86.7%, specificity 75.4%).
Conclusions Patients with SHC have a higher cortisol/ACTH ratio than those with NFAs. The cortisol/ACTH ratio is significantly correlated with serum cortisol after the 1-mg DST. The diagnostic performance of the cortisol/ACTH ratio at 0:00 is superior to midnight serum cortisol. Therefore, the cortisol/ACTH ratio at 0:00 may be a reliable parameter for SHC screening in patient with AI.
Optimising health economic evaluations for geriatric cancer
patients
Authors: Goettler Andrea , Kessel Tanja-Maria , Sonntag Diana 
Published: September 2017

Abstract
Aim Despite the growing number of elderly cancer patients, health economic
evaluations have not put enough attention on this patient group. We reflect on
the current state of health economic evaluations for geriatric patients and
present suggestions for improvements.
Method We reviewed the scientific literature on health economic
evaluations for geriatric patients in Germany and internationally. Additionally,
we conducted a scoping review on cost-utility analyses on cancer treatment for
older patients (> 60 years).
Results The literature review resulted in eight relevant studies. Besides
the paucity of economic evaluations for elderly patients, we also present
quality limitations. From the literature, we identify four recommendations
regarding cost calculation, geriatric assessment, patient decision-making and
quality of life on how to design better economic evaluations for geriatric
cancer treatment.
Conclusion The demographic change requires more attention regarding
elderly patients in health economics. Including patients above 70 years of age
in health economic evaluations and improving cost-utility analyses will help to
improve resource allocations and effective healthcare for the elderly.
Modernes interdisziplinäres Management einer uretero-iliakalen Fistel (Fallbericht)
Authors: Benedix D. , Meyer F. , Fischbach F. , Janitzky A. , Halloul Z. 
Published: September 2017

Zusammenfassung
Einleitung Pathologische Fistelungen des arteriellen Systems zu luminalen Organsystemen stellen eine Herausforderung in ihrem adäquaten Management dar.
Ziel Wissenschaftlicher Fallbericht zur kombiniert gefäßchirurgisch und interventionell-radiologischen Versorgung einer seltenen rechtsseitigen uretero-iliakalen Fistel unter Diskussion des Vorgehens und Zusammenfassung gewonnener klinischer Erfahrungen.
Fallkonstellation Stationäre Aufnahme eines 79-jährigen Patienten mit Hämaturie und Blasentamponade bei aktinisch bedingten Ureterstrikturen beidseits infolge neoadjuvanter Radiochemotherapie (im Rahmen der Vorbereitung einer abdominoperinealen Rektumexstirpation wegen suprasphinktären Karzinoms [ypT3ypN0M0]). Das Labor erbrachte eine Anämie, die transabdominale Sonografie eine Harnstauung bds. Die CT wies keine manifeste Blutung infolge wechselnder Hämorrhagieepisoden nach.
Interventionelle Maßnahmen Zunächst erfolgten Blasenspülung und Katheterwechsel in den Ureteren. Aufgrund der ausgelösten rechtsseitigen endoluminalen Blutung in den rechten Ureter wurde die kombiniert gefäßchirurgische/interventionell-radiologische Versorgung mit i) Amplatzer-Insertion (AMPLATZER™Vascular Plug II; St. Jude Medical, Saint Paul, Minnesota, U.S.A.) in die A. iliaca interna dextra und ii) rechts-iliacalem Stenting durch „cross-over“-Manöver von links-femoral vorgenommen.
Verlauf Infolge einer Dissektion am arteriellen Zugang rechts-femoral erfolgte eine Gefäßdesobliteration und Intimarefixation in der A. femoralis superficialis dextra. Der Patient stabilisierte sich zeitgerecht (u. a. periinterventionelle ITS-Betreuung) bei Entlassung am 15. postinterventionellen Tag ohne Anhalt für lokales Rektumkarzinomrezidiv. Eine Re-Blutung war nicht aufgetreten. Weiterhin waren Doppel-J-Katheterwechsel erforderlich.
Zusammenfassung Die zügige Hybrid-Operation ist im präsentierten Fall als absolut indizierte und prognostisch aussichtsreiche Vorgehensweise für die rezidivierende arterielle Blutung einer uretero-iliakalen Fistel anzusehen.
Schlussfolgerung Das minimal-invasive Herangehen mittels Stenting ist die Methode der Wahl im stufenweisen und zeitgerechten Management der potenziell lebensbedrohlichen uretero-iliakalen Fistel bei arterieller endoluminaler Blutung und drohendem hämorrhagischen Schock.
Evaluation of the Interference of Hemoglobin Variant J-Bangkok on Glycated Hemoglobin (HbA1c) Measurement by Five Different Methods
Authors: Wen Dong-Mei , Xu Sheng-Nan , Wang Wei-Jia , Zhang Xiu-Ming , Suo Ming-Huan , Zhang De-Cai 
Published: September 2017

Abstract
Objective The interference of the hemoglobin variant (Hb J-Bangkok) was evaluated on 4 different glycated hemoglobin assays and compared with a reference immuno assay.
Methods An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of Hb J-Bangkok caused a statistically significant difference in HbA1c results compared with a reference immuno assay. Statistical analysis was performed on the difference of the estimated average glucose calculated from HbA1c values and fasting plasma glucose in the Hb J-Bangkok variant group using the different detection systems. Deming regression analysis was used to determinate whether Hb J-Bangkok had a significant interference on HbA1c results using an HbA1c±10% relative bias at 6% and 9% HbA1c as evaluation limits.
Results Turbidimetric inhibition immunoassay method, and enzymatic methods were not affected by Hb J-Bangkok. However, Hb J-Bangkok showed statistically significant interference to the two ion-exchange high-performance liquid chromatography methods.
Conclusion When performing HbA1c tests, clinical laboratory personnel should identify the Hb variant and select the appropriate methods or use alternative indicators.
Organerhaltende Verfahren zur Therapie des Nierenzellkarzinoms
Authors: Wülfing Christian 
Published: September 2017

ZusammenfassungDie organerhaltende Therapie von Nierentumoren ist in den letzten Jahren zunehmend zur Standardtherapie erklärt worden. Internationale
Leitlinien empfehlen die operative Nierenteilresektion vor der radikalen Tumornephrektomie wann immer technisch möglich. Neben den
operativen Techniken, die zunehmend auch minimalinvasiv erfolgen, ergänzen die sogenannten ablativen Therapien, zu denen vor allem die
Radiofrequenzablation (RFA) und die Kryotherapie gezählt werden, das Therapiespektrum. Die ablativen Therapien sollen derzeit noch Patienten
hohen Alters oder Patienten mit erhöhter Komorbidität vorbehalten sein, weil die Datenlage noch keine gleichwertige evidenzbasierte
Empfehlung wie für die operative Nierenteilresektion zulässt. Schließlich ist auch die aktive Überwachung („Active Surveillance“) eine
wichtige Therapieoption, die insbesondere für Patienten mit kleinen Tumoren, langsamer Wachstumsgeschwindigkeit und erhöhtem Alter bzw.
erhöhter Komorbidität infrage kommt.
Primäre Offenwinkelglaukome
Authors: Hoffmann Esther , Prokosch-Willing Verena 
Published: September 2017

ZusammenfassungDas Glaukom gehört zu den häufigsten irreversiblen Erblindungsursachen weltweit und die alternde Gesellschaft in den westlichen Industrieländern impliziert ein hohes Risiko einer weiteren Zunahme. Das primäre Offenwinkelglaukom stellt den bei Weitem häufigsten Glaukomtyp des Erwachsenenalters dar. Die Therapie erfolgt zunächst konservativ mit einer Monotherapie, bei unzureichender Einstellung des Zieldruckbereichs sollte jedoch frühzeitig eine Glaukomoperation durchgeführt werden.
Ist Diabetes heilbar durch bariatrische Chirurgie? – Mechanismen der Verbesserung der diabetischen Stoffwechsellage durch chirurgische Adipositastherapie –
Authors: Weck Matthias 
Published: September 2017

In den letzten Jahren wurden die Ergebnisse randomisierter kontrollierter Studien publiziert, die im 5-Jahres-Verlauf die metabolischen Effekte der bariatrischen Chirurgie mit konventionellen Formen der Gewichtsreduktion vergleichen. Diese Studien zeigen unisono, dass die bariatrische Chirurgie hinsichtlich der Besserung der diabetischen Stoffwechsellage den konventionellen Behandlungsformen signifikant überlegen ist. Die Diabetesremissionsraten variieren abhängig von Ausgangsparametern, Operationsmethode und Follow-up-Dauer zwischen 95 und 23 %.Ist Diabetes heilbar durch bariatrische Chirurgie? Die klare Antwort muss lauten: Nein, aberInsofern ist die bariatrische Chirurgie in Form von Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) und den neueren Verfahren wie Omega Loop Bypass („Mini-Bypass“) oder biliopankreatische Diversion (BPD) eine wirkungsvolle therapeutische Option in der Behandlung des Diabetes mellitus Typ 2 und verringert offenbar auch das Risiko des Auftretens von mikrovaskulären Diabetesfolgekomplikationen. Je früher im Krankheitsverlauf die bariatrische Chirurgie SSherangezogen wird, desto effektiver scheinen diese Verfahren zu sein.Welche der Operationen für Patienten mit Typ-2-Diabetes am besten geeignet ist, ist derzeit nicht definitiv entschieden. Der RYGB scheint etwas effektiver zu sein. Die Verfahren der bariatrischen Chirurgie gehören in das Spektrum der differenzialtherapeutischen Überlegungen insbesondere bei adipösen Patienten mit Typ-2-Diabetes mit einem BMI > 35 kg/m².Die Mechanismen der Verbesserung der diabetischen Stoffwechsellage durch bariatrische Operationen werden anhand der aktuellen Literatur detailliert beschrieben. Die Indikationen, Kontraindikationen, Komplikationen und Therapiealgorithmen der bariatrischen Chirurgie bei Typ-2-Diabetes sind in den entsprechenden Leitlinien ausführlich dargestellt und nicht Gegenstand dieser Publikation.
Ant-inspired density estimation via random walks
Authors: Musco Cameron , Su Hsin-Hao , Lynch Nancy A. 
Published: September 2017

SignificanceHighly complex distributed algorithms are ubiquitous in nature: from the behavior of social insect colonies and bird flocks, to cellular differentiation in embryonic development, to neural information processing. In our research, we study biological computation theoretically, combining a scientific perspective, which seeks to better understand the systems being studied, with an engineering perspective, which takes inspiration from these systems to improve algorithm design. In this work, we focus on the problem of population density estimation in ant colonies, demonstrating that extremely simple algorithms, similar to those used by ants, solve the problem with strong theoretical guarantees and have a number of interesting computational applications.
Muon capture on light isotopes in Double Chooz
Authors: Strait M 
Published: September 2017

Abstract
Using the Double Chooz reactor neutrino detector, we have measured the products of µ
− capture on 12C, 13C, 14N and 16O. Over a period of 490 days, we collected 2.3 × 106 stopping cosmic µ
−, of which 1.8 × 105 captured on these nuclei in the inner detector. The resulting isotopes were tagged using prompt neutron emission (when applicable), the subsequent beta decays, and, in some cases, β-delayed neutrons. Production of these βn isotopes, primarily 9Li, which are

ν
¯

e

backgrounds, was found at a significance of 5.5σ. The probability of 9Li production per capture on natC is (2.4 ± 0.9(stat) ± 0.1(syst)) × 10−4. We have made the most precise measurement of the rate of 12C(µ
−, ν)12B to date,

6.57

−
0.21

+
0.11

×

10

3

s

−
1

,

or

(

17.35

−
0.59

+
0.35

)

%

of nuclear captures. By tagging excited states emitting gammas, the ground state transition rate to 12B is found to be

5.68

−
0.23

+
0.14

×

10

3

s

−
1

.