bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action video games improve reading abilities and visual-to-auditory attentional shifting in English-speaking children with dyslexia
Authors: Franceschini Sandro , Trevisan Piergiorgio , Ronconi Luca , Bertoni Sara , Colmar Susan , Double Kit , Facoetti Andrea , Gori Simone 
Published: July 2017

AbstractDyslexia is characterized by difficulties in learning to read and there is some evidence that action video games (AVG), without any direct phonological or orthographic stimulation, improve reading efficiency in Italian children with dyslexia. However, the cognitive mechanism underlying this improvement and the extent to which the benefits of AVG training would generalize to deep English orthography, remain two critical questions. During reading acquisition, children have to integrate written letters with speech sounds, rapidly shifting their attention from visual to auditory modality. In our study, we tested reading skills and phonological working memory, visuo-spatial attention, auditory, visual and audio-visual stimuli localization, and cross-sensory attentional shifting in two matched groups of English-speaking children with dyslexia before and after they played AVG or non-action video games. The speed of words recognition and phonological decoding increased after playing AVG, but not non-action video games. Furthermore, focused visuo-spatial attention and visual-to-auditory attentional shifting also improved only after AVG training. This unconventional reading remediation program also increased phonological short-term memory and phoneme blending skills. Our report shows that an enhancement of visuo-spatial attention and phonological working memory, and an acceleration of visual-to-auditory attentional shifting can directly translate into better reading in English-speaking children with dyslexia.
An engineered protein antagonist of K-Ras/B-Raf interaction
Authors: Kauke Monique J. , Traxlmayr Michael W. , Parker Jillian A. , Kiefer Jonathan D. , Knihtila Ryan , McGee John , Verdine Greg , Mattos Carla , Wittrup K. Dane 
Published: July 2017

AbstractRas is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction. R11.1.6 directly blocks interaction with Raf and reduces signaling through the Raf/MEK/ERK pathway. Our results support greater consideration of the state of switch I and provide a novel tool to study Ras biology. Most importantly, this work makes an unprecedented contribution to Ras research in inhibitor development strategy by revealing details of a targetable binding surface. Unlike the polar interfaces found for Ras/effector interactions, the K-Ras/R11.1.6 complex reveals an extensive hydrophobic interface that can serve as a template to advance the development of high affinity, non-covalent inhibitors of K-Ras oncogenic mutants.
Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
Authors: Dönertaş Handan Melike , İzgi Hamit , Kamacıoğlu Altuğ , He Zhisong , Khaitovich Philipp , Somel Mehmet 
Published: July 2017

AbstractIt was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an “up-down” pattern that was significant as determined by random permutations. In addition, 113 biological processes, including neuronal and synaptic functions, were consistently associated with genes showing an up-down tendency among all datasets. Genes up-regulated duringin vitroneuronal differentiation also displayed a tendency for up-down reversal, although at levels comparable to other genes. We argue that reversals may not represent aging-related neuronal loss. Instead, expression reversals may be associated with aging-related accumulation of stochastic effects that lead to loss of functional and structural identity in neurons.
Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
Authors: Chen Ying-Da , Fang Yi-Ting , Cheng Yi-Lin , Lin Chiou-Feng , Hsu Li-Jin , Wang Shu-Ying , Anderson Robert , Chang Chih-Peng , Lin Yee-Shin 
Published: July 2017

AbstractAnnexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells. Furthermore, knockdown of RAB8A and RAB27A, but not RAB27B, reduced IFN-γ-triggered ANXA2 secretion. Surface translocation of ANXA2 enhanced efferocytosis by epithelial cells, and inhibition of different exophagic steps, including autophagosome formation, fusion of autophagosomes with MVBs, and fusion of amphisomes with plasma membrane, reduced ANXA2-mediated efferocytosis. Our data reveal a novel route of IFN-γ-induced exophagy of ANXA2.
High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona
Authors: Honko Anna N. , Johnson Joshua C. , Marchand Jonathan S. , Huzella Louis , Adams Ricky D. , Oberlander Nicholas , Torzewski Lisa M. , Bennett Richard S. , Hensley Lisa E. , Jahrling Peter B. , Olinger Gene G. 
Published: July 2017

AbstractThe recent epidemic of Ebola virus disease in West Africa resulted in an unprecedented number of cases and deaths. Due to the scope of the outbreak combined with the lack of available approved treatment options, there was strong motivation to investigate any potential drug which had existing data reporting anti-Ebola activity. Drugs with demonstrated antiviral activity in the nonhuman primate models already approved for another indication or for which there was existing safety data were considered to be priorities for evaluation by the World Health Organization. Sertraline hydrochloride was reported to have anti-Ebola activity in vitro alone and in combination with other approved drugs. Although the efficacy was less than 100% in the murine model, the established safety profile of this product, the potential benefit alone and in combination, as well as the lack of other available options prioritized this compound for testing in the Ebola virus intramuscular rhesus macaque challenge model. Using a blinded dosing strategy, we demonstrated that high dose sertraline monotherapy provided no benefit for the prevention of Ebola virus disease in rhesus macaques with regards to reduction of viral load, morbidity, or survival highlighting the challenges of translating results between in vitro and in vivo models.
Saliva and tooth biofilm bacterial microbiota in adolescents in a low caries community
Authors: Eriksson Linda , Lif Holgerson Pernilla , Johansson Ingegerd 
Published: July 2017

AbstractThe oral cavity harbours a complex microbiome that is linked to dental diseases and serves as a route to other parts of the body. Here, the aims were to characterize the oral microbiota by deep sequencing in a low-caries population with regular dental care since childhood and search for association with caries prevalence and incidence. Saliva and tooth biofilm from 17-year-olds and mock bacteria communities were analysed using 16S rDNA Illumina MiSeq (v3-v4) and PacBio SMRT (v1-v8) sequencing including validity and reliability estimates. Caries was scored at 17 and 19 years of age. Both sequencing platforms revealed that Firmicutes dominated in the saliva, whereas Firmicutes and Actinobacteria abundances were similar in tooth biofilm. Saliva microbiota discriminated caries-affected from caries-free adolescents, with enumeration of Scardovia wiggsiae, Streptococcus mutans, Bifidobacterium longum, Leptotrichia sp. HOT498, and Selenomonas spp. in caries-affected participants. Adolescents with B. longum in saliva had significantly higher 2-year caries increment. PacBio SMRT revealed Corynebacterium matruchotii as the most prevalent species in tooth biofilm. In conclusion, both sequencing methods were reliable and valid for oral samples, and saliva microbiota was associated with cross-sectional caries prevalence, especially S. wiggsiae, S. mutans, and B. longum; the latter also with the 2-year caries incidence.
Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam
Authors: Delabouglise Alexis , Choisy Marc , Phan Thang D. , Antoine-Moussiaux Nicolas , Peyre Marisa , Vu Ton D. , Pfeiffer Dirk U. , Fournié Guillaume 
Published: July 2017

AbstractWhile climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods – wavelet analysis, economic analysis, statistical and disease transmission modelling – we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens.
Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection
Authors: Wang Zhilong , Gao Yanhang , Zhang Chao , Hu Haiming , Guo Dongwei , Xu Yi , Xu Qiuping , Zhang Weihong , Deng Sisi , Lv Pingyun , Yang Yan , Ding Yanhua , Li Qingquan , Weng Changjiang , Chen Xinwen , Gong Sitang , Chen Hairong , Niu Junqi , Tang Hong 
Published: July 2017

AbstractHCV infection can decrease NAD+/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/OTg mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7.5.1 cells. Furthermore, QPRT enzymatic activity involved in suppression of HCV replication in cells. Activation of QPRT with clofibrate (CLO) or addition of QPRT catabolite NAD both inhibited HCV replication in cells, probably through NAD+-dependent Sirt1 inhibition of cellular lipogenesis. More importantly, administration of CLO, a hypolipidemic drug used in clinics, could significantly reduce the viral load in HCV infected C/OTg mice. Take together, these results suggested that HCV infection triggered proteasomal degradation of QPRT and consequently reduced de novo NAD synthesis and lipogenesis, in favor of HCV replication. Hepatic QPRT thus likely served as a cellular factor that dampened productive HCV replication.
Common shared genetic variation behind decreased risk of breast cancer in celiac disease
Authors: Ugalde-Morales Emilio , Li Jingmei , Humphreys Keith , Ludvigsson Jonas F. , Yang Haomin , Hall Per , Czene Kamila 
Published: July 2017

AbstractThere is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = −0.17, s.e. 0.05, P < 0.001) and overlap (Ppermuted < 0.001) between celiac disease and breast cancer. Using individual-level genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (PCD < 1.00E-05, PBC ≤ 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.
Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
Authors: Terada Daiki , Voet Arnout R. D. , Noguchi Hiroki , Kamata Kenichi , Ohki Mio , Addy Christine , Fujii Yuki , Yamamoto Daiki , Ozeki Yasuhiro , Tame Jeremy R. H. , Zhang Kam Y. J. 
Published: July 2017

AbstractComputational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificialβ-trefoil lectin that recognises Burkitt’s lymphoma cells, and which was designed with the intention of finding a basis for novel cancer treatments or diagnostics. The new protein, called “Mitsuba”, is based on the structure of the natural shellfish lectin MytiLec-1, a member of a small lectin family that uses unique sequence motifs to bindα-D-galactose. The three subdomains of MytiLec-1 each carry one galactose binding site, and the 149-residue protein forms a tight dimer in solution. Mitsuba (meaning “three-leaf” in Japanese) was created by symmetry constraining the structure of a MytiLec-1 subunit, resulting in a 150-residue sequence that contains three identical tandem repeats. Mitsuba-1 was expressed and crystallised to confirm the X-ray structure matches the predicted model. Mitsuba-1 recognises cancer cells that express globotriose (Galα(1,4)Galβ(1,4)Glc) on the surface, but the cytotoxicity is abolished.
Surface Energy Driven Cubic-to-Hexagonal Grain Growth of Ge2Sb2Te5 Thin Film
Authors: Zheng Yonghui , Cheng Yan , Huang Rong , Qi Ruijuan , Rao Feng , Ding Keyuan , Yin Weijun , Song Sannian , Liu Weili , Song Zhitang , Feng Songlin 
Published: July 2017

AbstractPhase change memory (PCM) is a promising nonvolatile memory to reform current commercial computing system. Inhibiting face-centered cubic (f-) to hexagonal (h-) phase transition of Ge2Sb2Te5 (GST) thin film is essential for realizing high-density, high-speed, and low-power PCM. Although the atomic configurations of f- and h-lattices of GST alloy and the transition mechanisms have been extensively studied, the real transition process should be more complex than previous explanations, e.g. vacancy-ordering model for f-to-h transition. In this study, dynamic crystallization procedure of GST thin film was directly characterized by in situ heating transmission electron microscopy. We reveal that the equilibrium to h-phase is more like an abnormal grain growth process driven by surface energy anisotropy. More specifically, [0001]-oriented h-grains with the lowest surface energy grow much faster by consuming surrounding small grains, no matter what the crystallographic reconfigurations would be on the frontier grain-growth boundaries. We argue the widely accepted vacancy-ordering mechanism may not be indispensable for the large-scale f-to-h grain growth procedure. The real-time observations in this work contribute to a more comprehensive understanding of the crystallization behavior of GST thin film and can be essential for guiding its optimization to achieve high-performance PCM applications.
Identification of a Flavonoid Glucosyltransferase Involved in 7-OH Site Glycosylation in Tea plants (Camellia sinensis)
Authors: Dai Xinlong , Zhuang Juhua , Wu Yingling , Wang Peiqiang , Zhao Guifu , Liu Yajun , Jiang Xiaolan , Gao Liping , Xia Tao 
Published: July 2017

AbstractFlavonol glycosides, which are often converted from aglycones in a process catalyzed by UDP-glycosyltransferases (UGTs), play an important role for the health of plants and animals. In the present study, a gene encoding a flavonoid 7-O-glycosyltransferase (CsUGT75L12) was identified in tea plants. Recombinant CsUGT75L12 protein displayed glycosyltransferase activity on the 7-OH position of multiple phenolic compounds. In relative comparison to wild-type seeds, the levels of flavonol-glucosides increased in Arabidopsis seeds overexpressing CsUGT75L12. In order to determine the key amino acid residues responsible for the catalytic activity of the protein, a series of site-directed mutagenesis and enzymatic assays were performed based on the 3D structural modeling and docking analyses. These results suggested that residue Q54 is a double binding site that functions as both a sugar receptor and donor. Residues H56 and T151, corresponding to the basic active residues H20 and D119 of VvGT1, were not irreplaceable for CsUGT75L12. In addition, residues Y182, S223, P238, T239, and F240 were demonstrated to be responsible for a ‘reversed’ sugar receptor binding model. The results of single and triple substitutions confirmed that the function of residues P238, T239, and F240 may substitute or compensate with each other for the flavonoid 7-O-glycosyltransferase activity.
Patients' Perception of Bone and Tissue Excision, and the Size and Weight of Prostheses at Total Knee Arthroplasty
Authors: Rossi Benjamin , Jayasekera Narlaka , Kelly Fionnuala , Eyres Keith 
Published: July 2017

AbstractThe aim of this study is to ascertain patients' perception of the amount of bone and tissue excision and size and weight of their implanted prostheses at total knee arthroplasty (TKA). To our knowledge, no prior study in the English orthopaedic literature has analyzed these parameters against patient perception of TKA. In a prospective study of eight consecutive TKA (six primary and two single-stage revision TKA procedures) by a single surgeon, patients estimated the weight of their implanted knee. We assessed actual weights of their implants and bone cement. Patients estimated the size of their prostheses by sketching the tibial and femoral bone cuts upon a printout of an anteroposterior and lateral radiographs of their preoperative knee. We utilized an articulated plastic model knee for patient reference. Our study shows almost half a kilogram of weight is added postoperatively to the surgical site as a result of tissue excision, explanted material, and implanted prosthesis and cement. All patients overestimated the weight of their implanted prostheses and extent of bone excision. Thus, even ‘well-informed’ patients overestimate their bone resection and weight of implanted prosthesis at TKA. We postulate such misconceptions among TKA patients are common, and may impact negatively upon patient perception of TKA, their postoperative recovery and outcome.
Comparison of HbA1c Measurements using 3 Methods in 75 Patients Referred to One Outpatient Department
Authors: Roth Johannes , Müller Nicolle , Lehmann Thomas , Böer Klas , Löbel Sven , Pum Joachim , Müller Ulrich 
Published: July 2017

Abstract
Objective HbA1c is the most important surrogate parameter to assess the quality of diabetes care and is also used for the diagnosis of diabetes mellitus (DM) since 2010. We investigated the comparability of 3 HbA1c methods in the city of Jena (Germany).
Methods The HbA1c determination was carried out in 50 healthy subjects and 24 people with DM (age 51.2±16.3 years, HbA1c 6.8±2.2%) with 3 different hemoglobin A1c testing methods at 4 locations in one city. Our laboratory (HPLC method) served as a reference for comparing the results. All methods are IFCC standardized and all devices are certified by the interlaboratory test.
Results The mean HbA1c of people without diabetes was: laboratory A (TOSOH G8, HPLC) 5.7±0.3%; laboratory B (TOSOH G8, HPLC) 5.5±0.3%, laboratory C (VARIANT II) 5.2±0.3%; laboratory D (COBAS INT.) 5.6±0.3%. All differences are significant (p=0.001).The mean HbA1c of patients with mild to moderate elevated HbA1c was: Laboratory A 7.5±0.9%; B 7.3±1.0%; C 7.0±0.9%; D 7.5±1.1%. Differences are significant (p=0.001) except between laboratory A and D (p=0.8).The mean HbA1c of patients with massively increased HbA1c was: laboratory A 11.5±1.8%; laboratory B 11.4±1.8%; laboratory C 10.8±1.6%; laboratory D 11.5±1.5%. Differences between laboratory A and C, as well as between C and D were significant (p=0.001).
Conclusion The mean IFCC standardized HbA1c from 75 people differs by up to 0.5% absolute between 4 laboratories. This difference is clinically significant and may lead to misdiagnosis and wrong treatment decisions, while HbA1c value from one patient were analyzed in different laboratories within a short time.
100-jährige Tradition – Die Dermatologische Klinik USZ steter Fokus: Innovative Klinik und translationale Foschung
Authors: Geiges M. 
Published: July 2017

ZusammenfassungSeit das Fach „Dermatologie und Venerologie“ von der Universität in Zürich 1916 den ersten Lehrstuhl erhielt, prägten hervorragende Kliniker, welche in der Forschung Pionierarbeit leisteten, die Geschichte der Dermatologischen Klinik des UniversitätsSpitals in Zürich.Mit dem ersten Ordinarius Bruno Bloch nahm die beeindruckende Entwicklung der Klinik ihren Lauf. Von Beginn an stand eine umfassende und innovative Patientenversorgung im Zentrum – dies gepaart mit hoch professioneller, intensiver und international ausgerichteter Forschung. Über mittlerweile mehr als 100 Jahre steht diese unter dem Credo der translationalen Forschung, damit die Patienten so rasch als möglich von neuesten Forschungserkenntnissen in der klinischen Behandlung profitieren können. Die heutige breite und gleichzeitig hochspezialisierte Ausrichtung der Klinik ist historisch durch die Schwerpunkte der Klinikdirektoren gewachsen, welche von den jeweiligen Nachfolgern weitergeführt und ergänzt wurden: funktionelle Immunbiologie unter Bloch, Radiotherapie unter Guido Miescher, Allergologie unter Hans Storck, Genetik und Ekzemforschung unter Urs Walter Schnyder und Onkologie (Melanom, Lymphome) unter Günter Burg. Unter der Leitung von Lars French liegen die heutigen Schwerpunkte der Klinik bei den „schweren entzündlichen Hautkrankheiten“ und der „Dermatoonkologie“.