bluuebunny/crossref_metadata_2025_split huggingface dataset:
ITK signalling via the Ras/IRF4 pathway regulates the development and function of Tr1 cells
Authors: Huang Weishan , Solouki Sabrina , Koylass Nicholas , Zheng Song-Guo , August Avery 
Published: June 2017

AbstractType 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation. Tr1 cell development and suppressive function of Itk deficient cells can be restored by the expression of the transcription factor interferon regulatory factor 4 (IRF4). Downstream of ITK, Ras activity is responsible for Tr1 cell induction, as expression of constitutively active HRas rescues IRF4 expression and Tr1 cell differentiation in Itk−/− cells. We conclude that TCR/ITK signalling through the Ras/IRF4 pathway is required for functional development of Tr1 cells.
Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells
Authors: Kang Dong Hoon , Lee Doo Jae , Lee Sunmi , Lee So-Young , Jun Yukyung , Kim Yerin , Kim Youngeun , Lee Ju-Seog , Lee Dae-Kee , Lee Sanghyuk , Jho Eek-Hoon , Yu Dae-Yeul , Kang Sang Won 
Published: June 2017

AbstractMammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but their specific signaling role in cancer progression is poorly understood. Here we demonstrate that Prx type II (PrxII) plays a tumor-promoting role in colorectal cancer by interacting with a poly(ADP-ribose) polymerase (PARP) tankyrase. PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli (APC) gene reduces intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promotes survival. In human colorectal cancer cells with APC mutations, PrxII depletion consistently reduces the β-catenin levels and the expression of β-catenin target genes. Essentially, PrxII depletion hampers the PARP-dependent Axin1 degradation through tankyrase inactivation. Direct binding of PrxII to tankyrase ARC4/5 domains seems to be crucial for protecting tankyrase from oxidative inactivation. Furthermore, a chemical compound targeting PrxII inhibits the expansion of APC-mutant colorectal cancer cells in vitro and in vivo tumor xenografts. Collectively, this study reveals a redox mechanism for regulating tankyrase activity and implicates PrxII as a targetable antioxidant enzyme in APC-mutation-positive colorectal cancer.
fMRI Repetition Suppression During Generalized Social Categorization
Authors: Lau Tatiana , Cikara Mina 
Published: June 2017

AbstractCorrectly identifying friends and foes is integral to successful group living. Here, we use repetition suppression to examine the neural circuitry underlying generalized group categorization—the process of categorizing in-group and out-group members across multiple social categories. Participants assigned to an arbitrary team (i.e., Eagles or Rattlers) underwent fMRI while categorizing political and arbitrary in-group and out-group members. We found that frontoparietal control network exhibited repetition suppression in response to “identical in-group” (Democrat-Democrat or Eagles-Eagles) and “different in-group” (Eagles-Democrat or Democrat-Eagles) trials relative to “out-group/in-group trials” (Republican-Democrat or Rattler-Eagles). Specifically, the repetition suppression contrast map included bilateral superior parietal lobule, bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral middle temporal gyrus. Participants who reported an increased tendency to join and value their social groups exhibited decreased repetition suppression in bilateral DLPFC. Comparison of our whole-brain repetition suppression map with an independently identified map of frontoparietal control network revealed 34.3% overlap. Social categorization requires recognizing both a target’s group membership but also the target’s orientation toward one’s self. Fittingly, we find that generalized social categorization engages a network that acts as a functional bridge between dorsal attentional (exogenously-oriented) and default mode (internally-oriented) networks.
Proximal GATA-binding sites are essential for human HSD3B1 gene transcription in the placenta
Authors: Lai Tsai-Chun , Li Hsiao-Fang , Li Yu-Shian , Hung Pei-Yu , Shyu Ming-Kwang , Hu Meng-Chun 
Published: June 2017

AbstractThe enzyme 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) is involved in the synthesis of active steroid hormones. Two human 3β-HSD isoforms are expressed in a tissue-specific pattern. HSD3B1 (type I) expression is essential to produce progesterone for pregnancy maintenance. To understand the mechanisms of human HSD3B1 activation in the placenta, 2.2 kb of 5′-flanking sequence and 5′-deletions were fused to the luciferase reporter gene and transfected into human JEG-3 cells. The proximal −238/+337 sequence had the highest promoter activity. Two GATA elements were identified at −106/−99 and −52/−45. Mutations of either sites greatly reduced promoter activity in JEG-3 cells, demonstrating the importance of GATA sites. EMSA revealed the specific binding of GATA2 and GATA3 to the GATA sequences at −106/−99 and −52/−45. ChIP assays demonstrated the association of GATA2 but not GATA3 with the GATA-binding regions of the HSD3B1 promoter in JEG-3 cells. GATA2 knockdown significantly reduced HSD3B1 expression in JEG-3 cells; however, GATA3 knockdown increased HSD3B1 expression. Western blot analysis revealed high levels of GATA2 but not GATA3 in human placental tissues. This study identified GATA motifs as essential control elements for HSD3B1 transcription and GATA2 as a novel transcriptional regulator of HSD3B1 expression in the human placenta.
Moving and unsinkable graphene sheets immobilized enzyme for microfluidic biocatalysis
Authors: Gong An , Zhu Chang-Tong , Xu Yan , Wang Fang-Qin , Tsabing D’assise Kinfack , Wu Fu-An , Wang Jun 
Published: June 2017

AbstractEnzymatic catalysis in microreactors has attracted growing scientific interest because of high specific surface enabling heat and mass transfer and easier control of reaction parameters in microreactors. However, two major challenges that limit their application are fast inactivation and the inability to the biocatalysts in microchannel reactors. A fluid and unsinkable immobilized enzyme were firstly applied in a microchannel reactor for biocatalysis in this study. Functionalized forms of graphene-immobilized naringinase flowing in microchannels have yielded excellent results for isoquercitrin production. A maximum yield of 92.24 ± 3.26% was obtained after 20 min in a microchannel reactor. Ten cycles of enzymatic hydrolysis reaction were successively completed and an enzyme activity above 85.51 ± 2.76% was maintained. The kinetic parameter Vm/Km increased to 1.9-fold and reaction time was decreased to 1/3 compared with that in a batch reactor. These results indicated that the moving and unsinkable graphene sheets immobilized enzyme with a high persistent specificity and a mild catalytic characteristic enabled the repetitive use of enzyme and significant cost saving for the application of enzyme catalysis. Thus, the developed method has provided an efficient and simple approach for the productive and repeatable microfluidic biocatalysis.
Galactosylsphingamides: new α-GalCer analogues to probe the F’-pocket of CD1d
Authors: Guillaume Joren , Wang Jing , Janssens Jonas , Remesh Soumya G. , Risseeuw Martijn D. P. , Decruy Tine , Froeyen Mathy , Elewaut Dirk , Zajonc Dirk M. , Calenbergh Serge Van 
Published: June 2017

AbstractInvariant Natural Killer T-cells (iNKT-cells) are an attractive target for immune response modulation, as upon CD1d-mediated stimulation with KRN7000, a synthetic α-galactosylceramide, they produce a vast amount of cytokines. Here we present a synthesis that allows swift modification of the phytosphingosine side chain by amidation of an advanced methyl ester precursor. The resulting KRN7000 derivatives, termed α-galactosylsphingamides, were evaluated for their capacity to stimulate iNKT-cells. While introduction of the amide-motif in the phytosphingosine chain is tolerated for CD1d binding and TCR recognition, the studied α-galactosylsphingamides showed compromised antigenic properties.
Synergistic effect of human Bone Morphogenic Protein-2 and Mesenchymal Stromal Cells on chronic wounds through hypoxia-inducible factor-1 α induction
Authors: François Sabine , Eder Véronique , Belmokhtar Karim , Machet Marie-Christine , Douay Luc , Gorin Norbert-Claude , Benderitter Marc , Chapel Alain 
Published: June 2017

AbstractChronic skin ulcers and burns require advanced treatments. Mesenchymal Stromal Cells (MSCs) are effective in treating these pathologies. Bone Morphogenic Protein-2 (BMP-2) is known to enhance angiogenesis. We investigated whether recombinant human hBMP-2 potentiates the effect of MSCs on wound healing. Severe ulceration was induced in rats by irradiation and treated by co-infusion of MSCs with hBMP-2 into the ulcerated area which accelerated wound healing. Potentiation of the effect of MSCs by hBMP-2 on endothelial repair improved skin healing. HBMP-2 and MSCs synergistically, in a supra additive or enhanced manner, renewed tissue structures, resulting in normalization of the epidermis, hair follicles, sebaceous glands, collagen fibre density, and blood vessels. Co-localization of MSCs with CD31 + cells suggests recruitment of endothelial cells at the site of injection. HBMP-2 and MSCs enhanced angiogenesis and induced micro-vessel formation in the dermis where hair follicles were regenerated. HBMP-2 acts by causing hypoxia-inducible factor-1 α (HIF-1α) expression which impacts endothelial tube formation and skin repair. This effect is abolished by siRNA. These results propose that new strategies adding cytokines to MSCs should be evaluated for treating radiation-induced dermatitis, burns, and chronic ulcers in humans.
Inter-Model Warming Projection Spread: Inherited Traits from Control Climate Diversity
Authors: Hu Xiaoming , Taylor Patrick C. , Cai Ming , Yang Song , Deng Yi , Sejas Sergio 
Published: June 2017

AbstractSince Chaney’s report, the range of global warming projections in response to a doubling of CO2—from 1.5 °C to 4.5 °C or greater —remains largely unscathed by the onslaught of new scientific insights. Conventional thinking regards inter-model differences in climate feedbacks as the sole cause of the warming projection spread (WPS). Our findings shed new light on this issue indicating that climate feedbacks inherit diversity from the model control climate, besides the models’ intrinsic climate feedback diversity that is independent of the control climate state. Regulated by the control climate ice coverage, models with greater (lesser) ice coverage generally possess a colder (warmer) and drier (moister) climate, exhibit a stronger (weaker) ice-albedo feedback, and experience greater (weaker) warming. The water vapor feedback also inherits diversity from the control climate but in an opposite way: a colder (warmer) climate generally possesses a weaker (stronger) water vapor feedback, yielding a weaker (stronger) warming. These inherited traits influence the warming response in opposing manners, resulting in a weaker correlation between the WPS and control climate diversity. Our study indicates that a better understanding of the diversity amongst climate model mean states may help to narrow down the range of global warming projections.
Ultra‐low power frequency‐shift keying demodulator based on injection‐locking ring oscillator without using phase locked loop for wireless body area networks
Authors: Sattari R. , Safarian A. 
Published: June 2017

An ultra‐low power frequency‐shift keying (FSK) demodulator based on injection‐locking ring oscillator for wireless body area networks is presented. The proposed system uses the power‐efficient injection‐locking ring oscillator (ILRO) to replace the LC oscillator which occupies much more area on chip with higher power consumption. In addition, through the ILRO, the frequency modulated input signal is converted to a full swing rectangular signal, which can be directly demodulated by a chain of down‐conversion passive mixers, lowpass filters and a comparator. Power efficiency and simplicity of the proposed structure eliminate conventional FSK demodulator based on power‐hungry phase locked loops, which needs to be calibrated by auto‐frequency calibrator to periodically compensate the free running frequency deviations due to temperature variations and charge pump leakage current. The proposed FSK demodulator is designed and simulated in 180 nm CMOS technology while consuming only 23.37 µW from a 0.7 V supply.
Multifetal Pregnancy Reduction of Trichorionic Triplet Gestations: What is the Benefit?
Authors: Herlihy Nola , Naqvi Mariam , Romero Julie , Gupta Simi , Monteagudo Ana , Rebarber Andrei , Fox Nathan 
Published: June 2017

Objective This study aims to determine the efficacy of multifetal pregnancy reduction (MFPR) in improving obstetrical outcomes for trichorionic triplet gestations.
Study Design Retrospective cohort study of patients with multiple gestations delivered by a single maternal-fetal medicine practice from 2005 to 2016. We compared patients with trichorionic triamniotic triplet gestations who underwent MFPR to those with an ongoing triplet pregnancy (TT), as well as primary dichorionic diamniotic twin gestations (DD). Logistic regression analysis was used to control for any differences at baseline.
Results There were 42 patients in the MFPR group, 43 women in the TT group, and 693 women in the DD group. Comparing MFPR to TT, the likelihood of preterm birth < 34 weeks was similar (31.0 vs. 39.5%, adjusted odds ratio [aOR]: 0.63, 95% confidence interval [CI]: 0.21, 1.87). There were no differences in gestational age at delivery, pregnancy loss < 24 weeks, or the likelihood of all, none, or at least two babies surviving to discharge. Mean birth weights were significantly higher and cesarean delivery rates lower for MFPR (2,128 vs. 1,836 g, p = 0.028 and 69 vs. 86%, aOR: 0.25, 95% CI: 0.06, 0.94) as compared with the TT group. MFPR had significantly worse outcomes than DD.
Conclusion In trichorionic triamniotic triplet pregnancies, our study suggests that obstetrical outcomes may not be as dramatically improved with MFPR as seen in older studies.
Komplementäre und alternative Methoden bei Krebs einordnen und bewerten
Authors: Ernst Anke , Klein Stefanie 
Published: June 2017

AbstractThere are a vast number of complementary and alternative medicines (CAM) in oncology. Also patients' needs for information on these methods are growing. Helping patients to classify and evaluate CAM methods is a challenge. The Cancer Information Service at the German Cancer Research Center has developed a benefit-risk-assessment based on evidence-based medicine and individual patient traits: To rate a CAM’s benefit, the scientific evidence and the patient’s therapeutic goals have to be taken into account. To estimate its risks, both, the method itself and the patient’s status of health must be considered.
Update: Kardiovaskuläre Schlafmedizin
Authors: Linz Benedikt , Böhm Michael , Linz Dominik 
Published: June 2017

AbstractThe prevalence of sleep-disordered breathing (SDB) is high in patients with cardiovascular diseases. Typical symptoms like daytime sleepiness can be absent and those patients may report unspecific, therapy-resistant symptoms related to their underlying disease. Particularly sleep-related symptoms like nocturia, nocturnal dyspnea and pectangina can be present. Based on the results of recently published studies, the treatment of central sleep apnea in patients with symptomatic, systolic heart failure by adaptive servo-ventilation is no longer recommended. Although the treatment of obstructive sleep apnea did not prevent cardiovascular events, it improved snoring, daytime sleepiness and health-related quality of life. Furthermore, studies imply that treatment of SDB should be considered as an adjunct treatment modality in patients with hypertension and atrial fibrillation. Due to the high prevalence, screening for SDB can help to identify patients at high cardiovascular risk.
Urosepsis bei Kindern und Jugendlichen – konservative und operative Therapie
Authors: Oswald Josef 
Published: June 2017

ZusammenfassungFieberhafte Harnwegsinfekte (HWI) sind die häufigsten Infektionen im Kindesalter, die Urosepsis, wenngleich selten, stellt die schwerste Komplikation der kindlichen Infektion des Urogenitaltraktes dar. Die korrekte Diagnose, insbesondere die Mitbeteiligung der Nieren im Säuglings- und Kleinkindesalter kann aufgrund der unspezifischen Symptome schwierig sein, neben Harn und Labor sowie nicht invasiver Diagnostik (Ultraschall) kann eine weitere spezifische Diagnostik (DMSA Szintigrafie) notwendig sein. Die Akuttherapie besteht aus der gezielten parenteralen Antibiose wie der qualifizierten pädiatrischen Sepsistherapie, selten ist eine chirurgisch-interventionelle Desobstruktion nötig. Hier kommen neben der Katheterdrainage des unteren und oberen Harntraktes offene Operationstechniken – situations- und kindgerecht – zum Einsatz. Im weiteren Verlauf ist es entscheidend, kausale Faktoren wie angeborene Fehlbildungen mit negativem Einfluss auf den Harntransport (vesikoureteraler Reflux, Fehlbildungen mit postrenaler Obstruktion) zu identifizieren und zu behandeln.
qSVA framework for RNA quality correction in differential expression analysis
Authors: Jaffe Andrew E. , Tao Ran , Norris Alexis L. , Kealhofer Marc , Nellore Abhinav , Shin Joo Heon , Kim Dewey , Jia Yankai , Hyde Thomas M. , Kleinman Joel E. , Straub Richard E. , Leek Jeffrey T. , Weinberger Daniel R. 
Published: June 2017

Significance
Many studies use measurements of gene expression in human postmortem and ex vivo tissues like brain and blood to characterize genomic correlates of illness. However, molecular analyses of these tissues can be susceptible to a wide range of confounders that may be difficult to measure and remove. In this article, we describe an analysis framework for identifying and removing previously uncharacterized quality biases in measurements of RNA. Our paper critically highlights the shortcomings of standard RNA quality correction approaches, such as statistically adjusting for RNA integrity numbers. We show that the our framework removes residual confounding by RNA quality and greatly improves replication of significant differentially expressed genes across independent datasets by more than threefold compared with previous approaches.
Sex-specific early survival drives adult sex ratio bias in snowy plovers and impacts mating system and population growth
Authors: Eberhart-Phillips Luke J. , Küpper Clemens , Miller Tom E. X. , Cruz-López Medardo , Maher Kathryn H. , dos Remedios Natalie , Stoffel Martin A. , Hoffman Joseph I. , Krüger Oliver , Székely Tamás 
Published: June 2017

Significance
Sex biases are widespread in nature and represent a fundamental component of sexual selection and population biology—but at which point in life history do these biases emerge? We report a detailed individual-based demographic analysis of an intensively studied wild bird population to evaluate origins of sex biases and their consequences on mating strategies and population dynamics. We document a strongly male-biased adult sex ratio, which is consistent with behavioral observations of female-biased polygamy. Notably, sex-biased juvenile rather than adult survival contributed most to the adult sex ratio. Sex biases also strongly influenced population viability, which was significantly overestimated when sex ratio and mating system were ignored. Our study, therefore, has implications for both sexual selection theory and biodiversity conservation.
Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States
Authors: Aloe Carlin , Kulldorff Martin , Bloom Barry R. 
Published: June 2017

Significance
Pertussis has been on the rise in the United States, and, in 2012, the United States had the highest number of reported pertussis (whooping cough) cases since 1955. This study provides evidence of spatial clustering of nonmedical vaccine exemptions in kindergarteners and spatial clustering of pertussis cases in children age groups 5 years and younger and 10 to 14 years at the community level. The results suggest that states should reconsider allowing nonmedical vaccine exemptions. The data also suggest a need for the creation of a longer-acting pertussis vaccine or improved regimen and a revised vaccination schedule for the current acellular pertussis vaccine.
Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells
Authors: Bailis Julie M. , Weidmann Alyson G. , Mariano Natalie F. , Barton Jacqueline K. 
Published: June 2017

Significance
We have developed a family of rhodium compounds that bind DNA mismatches and are cytotoxic to mismatch repair (MMR)-deficient cancer cells. This study describes the cellular mechanism of action of the compounds that enables this selective cytotoxicity. The compound binding mode, metalloinsertion, displaces the mismatched base pairs from the DNA helix and creates a DNA lesion that activates the DNA damage response. This lesion is unable to be repaired in MMR-deficient cells. This mechanism is distinct from other compounds that target DNA and provides a therapeutic strategy for treatment of cancers with MMR deficiency.
Treatment of Incomplete Jones Fractures With Low-Intensity Pulsed Ultrasound (LIPUS)
Authors: Tomohiko Tateishi , Nagase Tsuyoshi , Nakagawa Teruhiko , Masamitsu Tsuchiya 
Published: June 2017

Objective:
Stress fractures of the proximal epiphysis of the fifth metatarsal bone (termed Jones fracture) frequently occur in both senior high-school-age and older contestant-level soccer players, and its incidence in Japanese soccer players is higher than that in European players. Surgery is most commonly indicated for a complete fracture, and about 3 months are required before the patient is able to return to the sport. We have performed a “Jones fracture screening” to reduce the incidence of these fractures. While surveying its frequency and promoting education on its prevalence and symptoms, we tried to discover incomplete fractures early and treat them using LIPUS without limiting their soccer practice.

Subjects and Methods:
The subjects were 341 students (682 feet) from 3 senior high schools and university soccer clubs. Primary screening for tenderness and by diagnostic ultrasound imaging was performed as a Jones fracture screening. Fifty subjects (50 feet) were positive on the ultrasonic diagnosis, and secondary screening was recommended. Forty subjects underwent radiography (secondary screening rate: 80%), and 5 subjects (5 feet) were diagnosed with incomplete Jones fractures. Conservative treatment centering on LIPUS was performed in these 5 players who still continued to participate in all soccer practices.

Results:
Bone union was achieved in 2 subjects (2 feet) after about 6 months without taking a break from soccer practice. The other 3 subjects (3 feet) are at 2 months after the diagnosis and are being followed without taking a break from soccer practice.

Discussion:
Incomplete Jones fractures that are discovered early by an ultrasonic check-up for bone expansion with subsequent early treatment with LIPUS may heal without taking a break from practice. No preventive method has been established for Jones fractures. This check-up may serve as a useful preventative approach, and we will make an effort to suggest it as a common practice.