bluuebunny/crossref_metadata_2025 huggingface dataset:
Aufnahme und Entlassung von Menschen mit Demenz – Kommunikation aus Sicht von Experten der Kurzzeitpflege
Authors: Kuske Silke , Bartholomeyczik Sabine
Published: August 2015

Zusammenfassung. Hintergrund: Über die Prozesse und den Informationsaustausch versorgungsrelevanter Informationen von Menschen mit Demenz (MmD) zwischen den Settings Häuslichkeit und Kurzzeitpflege ist bislang wenig bekannt. Vor diesem Hintergrund wurden die Prozesse und der Informationsaustausch unter Berücksichtigung der beteiligten Akteure rekonstruiert sowie qualitätsrelevante Faktoren identifiziert. Methoden: Leitfadengestützte Telefoninterviews mit 16 Experten aus 15 Einrichtungen mit Kurzzeitpflege wurden durchgeführt. Ergebnisse: Die Qualität des Informationsaustauschs zwischen den beteiligten Personen divergiert je nach Einrichtung. Dies betraf den Zeitpunkt und die Häufigkeit von Aufnahmegesprächen, Vollständigkeitsprüfungen von Informationen sowie die Beschaffung benötigter Informationen. Den Einrichtungen war gemeinsam, dass nach der Entlassung gewöhnlich keine weiteren koordinierten Schritte vorgesehen waren. Für die Koordination und die Durchführung von Überleitungsevaluationen ergab sich ein Handlungsbedarf. Schlussfolgerung: Für MmD ist eine rechtzeitige Beschaffung kurzzeitpflegerelevanter Informationen von Bedeutung. Ebenso spielen die Koordination aller an der Versorgung beteiligten Personen, eine verbindliche Regelung der Informationswege und eine Entlastung der versorgenden Angehörigen eine wichtige Rolle beim Informationsaustausch. Ein bedarfsgerechtes, settingübergreifendes Case Management, ein Überleitungsstandard und die Evaluation der Überleitungsqualität könnten im Hinblick auf die Qualitätssicherung in der Versorgung von MmD einen wichtigen Beitrag leisten.
To Go or Not to Go for the Sell
Authors: Hamstra Melvyn R. W. , Rietzschel Eric F. , Groeneveld Denise M.
Published: August 2015

Selling products and services is a central function in organizations. Although explaining sales success has mainly been approached from broad trait perspectives, tactical decision-making potentially explains additional variance in this crucial outcome. We propose and find that promotion focus positively predicts sales agents’ success, while prevention focus negatively predicts sales success. These relations were significant while controlling for five-factor traits. Predictors were measured before participants started on the job; outcome was the total number of sales participants made. As such, results evidence incremental validity of regulatory focus in predicting objective sales performance.
Noninvasive Cerebral Oximetry during Endovascular Therapy for Acute Ischemic Stroke: An Observational Study
Authors: Hametner Christian , Stanarcevic Predrag , Stampfl Sibylle , Rohde Stefan , Veltkamp Roland , Bösel Julian
Published: August 2015

Implementing endovascular stroke care often impedes neurologic assessment in patients who need sedation or general anesthesia. Cerebral near-infrared spectroscopy (NIRS) may help physicians monitor cerebral tissue viability, but data in hyperacute stroke patients receiving endovascular treatment are sparse. In this observational study, the NIRS index regional oxygen saturation (rSO2) was measured noninvasively before, during, and after endovascular therapy via bilateral forehead NIRS optodes. During the study period, 63 patients were monitored with NIRS; 43 qualified for analysis. Before recanalization, 10 distinct rSO2 decreases occurred in 11 patients with respect to time to intubation. During recanalization, two kinds of unilateral rSO2 changes occurred in the affected hemisphere: small peaks throughout the treatment ( n = 14, 32.6%) and sustained increases immediately after recanalization ( n = 2, 4.7%). Lower area under the curve 10% below baseline was associated with better reperfusion status (thrombolysis in cerebral infarction ≥ 2b, P = 0.009). At the end of the intervention, lower interhemispheric rSO2 difference predicted death within 90 days ( P = 0.037). After the intervention, higher rSO2 variability predicted poor outcome (modified Rankin scale > 3, P = 0.032). Our findings suggest that bi-channel rSO2-NIRS has potential for guiding neuroanesthesia and predicting outcome. To better monitor local revascularization, an improved stroke-specific set-up in future studies is necessary.
Multicohort analysis of the maternal age effect on recombination
Authors: Martin Hilary C. , Christ Ryan , Hussin Julie G. , O’Connell Jared , Gordon Scott , Mbarek Hamdi , Hottenga Jouke-Jan , McAloney Kerrie , Willemsen Gonnecke , Gasparini Paolo , Pirastu Nicola , Montgomery Grant W. , Navarro Pau , Soranzo Nicole , Toniolo Daniela , Vitart Veronique , Wilson James F. , Marchini Jonathan , Boomsma Dorret I. , Martin Nicholas G. , Donnelly Peter
Published: August 2015

Several studies have reported that the number of crossovers increases with maternal age in humans, but others have found the opposite. Resolving the true effect has implications for understanding the maternal age effect on aneuploidies. Here, we revisit this question in the largest sample to date using single nucleotide polymorphism (SNP)-chip data, comprising over 6,000 meioses from nine cohorts. We develop and fit a hierarchical model to allow for differences between cohorts and between mothers. We estimate that over 10 years, the expected number of maternal crossovers increases by 2.1% (95% credible interval (0.98%, 3.3%)). Our results are not consistent with the larger positive and negative effects previously reported in smaller cohorts. We see heterogeneity between cohorts that is likely due to chance effects in smaller samples, or possibly to confounders, emphasizing that care should be taken when interpreting results from any specific cohort about the effect of maternal age on recombination.
Unlocking the energy capabilities of micron-sized LiFePO4
Authors: Guo Limin , Zhang Yelong , Wang Jiawei , Ma Lipo , Ma Shunchao , Zhang Yantao , Wang Erkang , Bi Yujing , Wang Deyu , McKee William C. , Xu Ye , Chen Jitao , Zhang Qinghua , Nan Cewen , Gu Lin , Bruce Peter G. , Peng Zhangquan
Published: August 2015

Utilization of LiFePO4 as a cathode material for Li-ion batteries often requires size nanonization coupled with calcination-based carbon coating to improve its electrochemical performance, which, however, is usually at the expense of tap density and may be environmentally problematic. Here we report the utilization of micron-sized LiFePO4, which has a higher tap density than its nano-sized siblings, by forming a conducting polymer coating on its surface with a greener diazonium chemistry. Specifically, micron-sized LiFePO4 particles have been uniformly coated with a thin polyphenylene film via the spontaneous reaction between LiFePO4 and an aromatic diazonium salt of benzenediazonium tetrafluoroborate. The coated micron-sized LiFePO4, compared with its pristine counterpart, has shown improved electrical conductivity, high rate capability and excellent cyclability when used as a ‘carbon additive free’ cathode material for rechargeable Li-ion batteries. The bonding mechanism of polyphenylene to LiFePO4/FePO4 has been understood with density functional theory calculations.
Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex
Authors: Fisher Oriana S. , Deng Hanqiang , Liu Dou , Zhang Ya , Wei Rong , Deng Yong , Zhang Fan , Louvi Angeliki , Turk Benjamin E. , Boggon Titus J. , Su Bing
Published: August 2015

Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.
Drosophila germ granules are structured and contain homotypic mRNA clusters
Authors: Trcek Tatjana , Grosch Markus , York Andrew , Shroff Hari , Lionnet Timothée , Lehmann Ruth
Published: August 2015

Germ granules, specialized ribonucleoprotein particles, are a hallmark of all germ cells. In Drosophila, an estimated 200 mRNAs are enriched in the germ plasm, and some of these have important, often conserved roles in germ cell formation, specification, survival and migration. How mRNAs are spatially distributed within a germ granule and whether their position defines functional properties is unclear. Here we show, using single-molecule FISH and structured illumination microscopy, a super-resolution approach, that mRNAs are spatially organized within the granule whereas core germ plasm proteins are distributed evenly throughout the granule. Multiple copies of single mRNAs organize into ‘homotypic clusters’ that occupy defined positions within the center or periphery of the granule. This organization, which is maintained during embryogenesis and independent of the translational or degradation activity of mRNAs, reveals new regulatory mechanisms for germ plasm mRNAs that may be applicable to other mRNA granules.
RNA-seq reveals the critical role of OtpR in regulating Brucella melitensis metabolism and virulence under acidic stress
Authors: Liu Wenxiao , Dong Hao , Li Jing , Ou Qixing , Lv Yujin , Wang Xiaolei , Xiang Zuoshuang , He Yongqun , Wu Qingmin
Published: August 2015

The response regulator OtpR is critical for the growth, morphology and virulence ofBrucella melitensis. Compared to its wild type strain 16 M,B. melitensis16 MΔotpRmutant has decreased tolerance to acid stress. To analyze the genes regulated by OtpR under acid stress, we performed RNA-seq whole transcriptome analysis of 16 MΔotpRand 16 M. In total, 501 differentially expressed genes were identified, including 390 down-regulated and 111 up-regulated genes. Among these genes, 209 were associated with bacterial metabolism, including 54 genes involving carbohydrate metabolism, 13 genes associated with nitrogen metabolism and seven genes associated with iron metabolism. The 16 MΔotpRalso decreased capacity to utilize different carbon sources and to tolerate iron limitation in culture experiments. Notably, OtpR regulated manyBrucellavirulence factors essential forB. melitensisintracellular survival. For instance, thevirBoperon encoding type IV secretion system was significantly down-regulated and 36 known transcriptional regulators (e.g., vjbRandblxR) were differentially expressed in 16 MΔotpR.Selected RNA-seq results were experimentally confirmed by RT-PCR and RT-qPCR. Overall, these results deciphered differential phenomena associated with virulence, environmental stresses and cell morphology in 16 MΔotpRand 16 M, which provided important information for understanding the detailed OtpR-regulated interaction networks andBrucellapathogenesis.
Inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation
Authors: Han Ruijun , Wang Xinying , Bachovchin William , Zukowska Zofia , Osborn John W.
Published: August 2015

Adipocytes are the primary cells in adipose tissue and adipocyte dysfunction causes lipodystrophy, obesity and diabetes. The dipeptidyl peptidase (DPP) 4 family includes four enzymes, DPP4, DPP8, DPP9 and fibroblast activation protein (FAP). DPP4 family inhibitors have been used for the treatment of type 2 diabetes patients, but their role in adipocyte formation are poorly understood. Here we demonstrate that the DPP8/9 selective inhibitor 1G244 blocks adipogenesis in preadipocyte 3T3-L1 and 3T3-F422A, while DPP4 and FAP inhibitors have no effect. In addition, knockdown of DPP8 or DPP9 significantly impairs adipocyte differentiation in preadipocytes. We further uncovered that blocking the expression or activities of DPP8 and DPP9 attenuates PPARγ2 induction during preadipocyte differentiation. Addition of PPARγ agonist thiazolidinediones (TZDs), or ectopic expression of PPARγ2, is able to rescue the adipogenic defect caused by DPP8/9 inhibition in preadipocytes. These results indicate the importance of DPP8 and DPP9 on adipogenesis.
Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers
Authors: Anand Prachi , O’Neil Alison , Lin Emily , Douglas Trevor , Holford Mandë
Published: August 2015

The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.
YIP1 family member 4 (YIPF4) is a novel cellular binding partner of the papillomavirus E5 proteins
Authors: Müller Marietta , Wasson Christopher W. , Bhatia Ramya , Boxall Sally , Millan David , Goh Grace Y.S. , Haas Jürgen , Stonehouse Nicola J. , Macdonald Andrew
Published: August 2015

E5 proteins are amongst the least understood of the Human Papillomavirus (HPV) encoded gene products. They are small, membrane-integrated proteins known to modulate a number of critical host pathways associated with pathogenesis including growth factor receptor signaling and immune evasion. Their role in the virus life cycle is less clear, indicating a role in the productive stages of the life cycle. However, a mechanism for this is currently lacking. Here we describe the identification of a novel binding partner of E5, YIPF4 using yeast two-hybrid analysis. YIPF4 is also a poorly characterized membrane spanning protein. Mutagenesis studies implicated the transmembrane regions of each protein as important for their interaction. Binding to YIPF4 was found for all E5 proteins tested suggesting that this interaction may mediate a conserved E5 function. In normal human keratinocytes YIPF4 expression was down-regulated upon differentiation and this reduction was partially rescued in cells harbouring HPV. Despite the conserved nature of the interaction with E5, siRNA mediated depletion of YIPF4 failed to impede two well-characterized functions of E5, namely EGFR trafficking or HLA class I presentation. Continued studies of YIPF4 are warranted to determine its role in the PV life cycle.
Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling
Authors: Szebényi Kornélia , Füredi András , Kolacsek Orsolya , Pergel Enikő , Bősze Zsuzsanna , Bender Balázs , Vajdovich Péter , Tóvári József , Homolya László , Szakács Gergely , Héja László , Enyedi Ágnes , Sarkadi Balázs , Apáti Ágota , Orbán Tamás I.
Published: August 2015

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver and blood cells. No pathological alterations were found in these animals and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects and provide evidence for the role of Na+/Ca2+exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies.
Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach
Authors: Dong Yan , Zhao Qun , Ma Xiaoyan , Ma Guowu , Liu Caiyun , Chen Zhuwen , Yu Liyuan , Liu Xuefeng , Zhang Yanguang , Shao Shujuan , Xiao Jing , Li Jia , Zhang Weimin , Fu Ming , Dong Lijia , Yang Xiandong , Guo Xu , Xue Liyan , Fang Fei , Zhan Qimin , Zhang Lihua
Published: August 2015

Oral squamous cell carcinoma (OSCC) is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. B(a)P and DMBA are key carcinogens in tobacco smoke. In the present study, for the first time we established the cancerous cell line OSCC-BD induced by B(a)P/DMBA mixture and transformed from dysplastic oral leukoplakia cell line DOK. Cell morphology, proliferation ability, migration ability, colony formation and tumorigenicity were studied and confirmed the malignant characteristics of OSCC-BD cells. We further identified the differential proteins between DOK and OSCC-BD cells by stable isotope dimethyl labeling based quantitative proteomic method, which showed 18 proteins up-regulated and 16 proteins down-regulated with RSD < 8%. Differential proteins are mainly related to cell cycle, cell proliferation, DNA replication, RNA splicing and apoptosis. Abberant binding function, catalysis activity and transportor activity of differential proteins might contribute to the malignant transformation of OLK. Of the 34 identified differential proteins with RSD < 8%, 13 novel cancer-related proteins were reported in the present study. This study might provide a new insight into the mechanism of OLK malignant transformation and the potent biomarkers for early diagnosis, meanwhile further facilitate the application of the quantification proteomics to carcinogenesis research.
Two Novel NYX Gene Mutations in the Chinese Families with X-linked Congenital Stationary Night Blindness
Authors: Dai Shuzhen , Ying Ming , Wang Kai , Wang Liming , Han Ruifang , Hao Peng , Li Ningdong
Published: August 2015

Mutations in NYX and CACNA1F gene are responsible for the X-linked congenital stationary night blindness (CSNB). In this study, we described the clinical characters of the two Chinese families with X-linked CSNB and detected two novel mutations of c. 371_377delGCTACCT and c.214A>C in the NYX gene by direct sequencing. These two mutations would expand the mutation spectrum of NYX. Our study would be helpful for further studying molecular pathogenesis of CSNB.
Eyes on words: A fixation-related fMRI study of the left occipito-temporal cortex during self-paced silent reading of words and pseudowords
Authors: Schuster Sarah , Hawelka Stefan , Richlan Fabio , Ludersdorfer Philipp , Hutzler Florian
Published: August 2015

The predominant finding of studies assessing the response of the left ventral occipito-temporal cortex (vOT) to familiar words and to unfamiliar, but pronounceable letter strings (pseudowords) is higher activation for pseudowords. One explanation for this finding is that readersautomaticallygenerate predictions about a letter string’s identity – pseudowords mismatch these predictions and the higher vOT activation is interpreted as reflecting the resultantprediction errors. The majority of studies, however, administered tasks which imposed demands above and beyond the intrinsic requirements of visual word recognition. The present study assessed the response of the left vOT to words and pseudowords by using the onset of the first fixation on a stimulus as time point for modeling the BOLD signal (fixation-related fMRI). This method allowed us to assess the neural correlates of self-paced silent reading with minimal task demands and natural exposure durations. In contrast to the predominantly reported higher vOT activation for pseudowords, we found higher activation for words. This finding is at odds with the expectation of higher vOT activation for pseudowords due to automatically generated predictions and the accompanying elevation of prediction errors. Our finding conforms to an alternative explanation which considers such top-down processing to be non-automatic and task-dependent.
Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3α
Authors: Fala Angela M. , Oliveira Juliana F. , Adamoski Douglas , Aricetti Juliana A. , Dias Marilia M. , Dias Marcio V. B. , Sforça Maurício L. , Lopes-de-Oliveira Paulo S. , Rocco Silvana A. , Caldana Camila , Dias Sandra M. G. , Ambrosio Andre L. B.
Published: August 2015

Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.
A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells
Authors: Yeon Kwon Doo , Seon Kwon Jin , Hun Park Seung , Hun Park Ji , Hee Jang So , Yun Yin Xiang , Yun Jeong-Ho , Ho Kim Jae , Hyun Min Byoung , Hee Lee Jun , Kim Wan-Doo , Suk Kim Moon
Published: August 2015

A computer-designed, solvent-free scaffold offer several potential advantages such as ease of customized manufacture andin vivosafety. In this work, we firstly used a computer-designed, solvent-free scaffold and human dental pulp stem cells (hDPSCs) to regenerate neo-bone within cranial bone defects. The hDPSCs expressed mesenchymal stem cell markers and served as an abundant source of stem cells with a high proliferation rate. In addition, hDPSCs showed a phenotype of differentiated osteoblasts in the presence of osteogenic factors (OF). We used solid freeform fabrication (SFF) with biodegradable polyesters (MPEG-(PLLA-co-PGA-co-PCL) (PLGC)) to fabricate a computer-designed scaffold. The SFF technology gave quick and reproducible results. To assess bone tissue engineeringin vivo, the computer-designed, circular PLGC scaffold was implanted into a full-thickness cranial bone defect and monitored by micro-computed tomography (CT) and histology of thein vivotissue-engineered bone. Neo-bone formation of more than 50% in both micro-CT and histology tests was observed at only PLGC scaffold with hDPSCs/OF. Furthermore, the PLGC scaffold gradually degraded, as evidenced by the fluorescent-labeled PLGC scaffold, which provides information to tract biodegradation of implanted PLGC scaffold. In conclusion, we confirmed neo-bone formation within a cranial bone defect using hDPSCs and a computer-designed PLGC scaffold.
Csk-Induced Phosphorylation of Src at Tyrosine 530 is Essential for H2O2-Mediated Suppression of ERK1/2 in Human Umbilical Vein Endothelial Cells
Authors: Jeon Bo Kyung , Kwon Kihwan , Kang Jihee Lee , Choi Youn-Hee
Published: August 2015

Mitogen-activated protein kinases (MAPKs) are key signal transducers involved in various cellular events such as growth, proliferation and differentiation. Previous studies have reported that H2O2 leads to phosphorylation of extracellular signal-regulated kinase (ERK), one of the MAPKs in endothelial cells. The current study shows that H2O2 suppressed ERK1/2 activation and phosphorylation at specific concentrations and times in human umbilical vein endothelial cells but not in immortalized mouse aortic endothelial cells or human astrocytoma cell line CRT-MG. Phosphorylation of other MAPK family members (i.e., p38 and JNK) was not suppressed by H2O2. The decrease in ERK1/2 phosphorylation induced by H2O2 was inversely correlated with the level of phosphorylation of Src tyrosine 530. Using siRNA, it was found that H2O2-induced suppression of ERK1/2 was dependent on Csk. Physiological laminar flow abrogated, but oscillatory flow did not affect, the H2O2-induced suppression of ERK1/2 phosphorylation. In conclusion, H2O2-induced Csk translocation to the plasma membrane leads to phosphorylation of Src at the tyrosine 530 residue resulting in a reduction of ERK1/2 phosphorylation. Physiological laminar flow abrogates this effect of H2O2 by inducing phosphorylation of Src tyrosine 419. These findings broaden our understanding of signal transduction mechanisms in the endothelial cells against oxidative stress.
Performance comparison of four commercial human whole-exome capture platforms
Authors: Shigemizu Daichi , Momozawa Yukihide , Abe Testuo , Morizono Takashi , Boroevich Keith A. , Takata Sadaaki , Ashikawa Kyota , Kubo Michiaki , Tsunoda Tatsuhiko
Published: August 2015

Whole exome sequencing (WXS) is widely used to identify causative genetic mutations of diseases. However, not only have several commercial human exome capture platforms been developed, but substantial updates have been released in the past few years. We report a performance comparison for the latest release of four commercial platforms, Roche/NimbleGen’s SeqCap EZ Human Exome Library v3.0, Illumina’s Nextera Rapid Capture Exome (v1.2), Agilent’s SureSelect XT Human All Exon v5 and Agilent’s SureSelect QXT, using the same DNA samples. Agilent XT showed the highest target enrichment efficiency and the best SNV and short indel detection sensitivity in coding regions with the least amount of sequencing. Agilent QXT had slightly inferior target enrichment than Agilent XT. Illumina, with additional sequencing, detected SNVs and short indels at the same quality as Agilent XT and showed the best performance in coverage of medically interesting mutations. NimbleGen detected more SNVs and indels in untranslated regions than the others. We also found that the platforms, which enzymatically fragment the genomic DNA (gDNA), detected more homozygous SNVs than those using sonicated gDNA. We believe that our analysis will help investigators when selecting a suitable exome capture platform for their particular research.
Label-free single-cell protein quantification using a drop-based mix-and-read system
Authors: Abbaspourrad Alireza , Zhang Huidan , Tao Ye , Cui Naiwen , Asahara Haruichi , Zhou Ying , Yue Dongxian , Koehler Stephan A. , Ung Lloyd W. , Heyman John , Ren Yukun , Ziblat Roy , Chong Shaorong , Weitz David A.
Published: August 2015

Quantitative protein analysis of single cells is rarely achieved due to technical difficulties of detecting minute amounts of proteins present in one cell. We develop a mix-and-read assay for drop-based label-free protein analysis of single cells. This high-throughput method quantifies absolute, rather than relative, amounts of proteins and does not involve antibody labeling or mass spectrometry.
Akt2 knock-down reveals its contribution to human lung cancer cell proliferation, growth, motility, invasion and endothelial cell tube formation
Authors: Attoub Samir , Arafat Kholoud , Kamel Hammadi Nasseredine , Mester Jan , Gaben Anne-Marie
Published: August 2015

The Akt/PKB serine/threonine protein kinase consists of three isoforms: Akt-1, −2 and −3. Their overexpression has been detected in human cancers, but their roles in cancer progression are unclear. We investigated the impact of specific silencing of Akt1 and Akt2 on human lung cancer cell proliferation, colony growth, motility and invasion in vitro as well as tumor growth in vivo using human Non-Small Cell Lung Cancer cells LNM35 and on the vascular tube formation using HUVEC cells. Although silencing of Akt1 decreased cellular invasion at least in part via COX-2 inhibition, it had almost no effect on cell motility, proliferation, colony formation and angiogenesis. Transient as well as stable silencing of Akt2 resulted in a strong inhibition of Rb phosphorylation associated with a decrease in cellular proliferation and colony formation, leading to the inhibition of tumor growth in the xenograft model. Silencing of Akt2 also reduced cellular motility and invasion in vitro, presumably via COX-2 inhibition. Moreover, silencing of Akt2 in the HUVEC cells resulted in the inhibition of their spontaneous angiogenic phenotype. Altogether, these results indicate that Akt2 plays an important role in lung cancer progression and can be a promising target for lung cancer therapy.
Advances in nowcasting influenza-like illness rates using search query logs
Authors: Lampos Vasileios , Miller Andrew C. , Crossan Steve , Stefansen Christian
Published: August 2015

User-generated content can assist epidemiological surveillance in the early detection and prevalence estimation of infectious diseases, such as influenza. Google Flu Trends embodies the first public platform for transforming search queries to indications about the current state of flu in various places all over the world. However, the original model significantly mispredicted influenza-like illness rates in the US during the 2012–13 flu season. In this work, we build on the previous modeling attempt, proposing substantial improvements. Firstly, we investigate the performance of a widely used linear regularized regression solver, known as the Elastic Net. Then, we expand on this model by incorporating the queries selected by the Elastic Net into a nonlinear regression framework, based on a composite Gaussian Process. Finally, we augment the query-only predictions with an autoregressive model, injecting prior knowledge about the disease. We assess predictive performance using five consecutive flu seasons spanning from 2008 to 2013 and qualitatively explain certain shortcomings of the previous approach. Our results indicate that a nonlinear query modeling approach delivers the lowest cumulative nowcasting error and also suggest that query information significantly improves autoregressive inferences, obtaining state-of-the-art performance.
Quasi-Static Magnetic Field Shielding Using Longitudinal Mu-Near-Zero Metamaterials
Authors: Lipworth Guy , Ensworth Joshua , Seetharam Kushal , Lee Jae Seung , Schmalenberg Paul , Nomura Tsuyoshi , Reynolds Matthew S. , Smith David R. , Urzhumov Yaroslav
Published: August 2015

The control of quasi-static magnetic fields is of considerable interest in applications including the reduction of electromagnetic interference (EMI), wireless power transfer (WPT) and magnetic resonance imaging (MRI). The shielding of static or quasi-static magnetic fields is typically accomplished through the use of inherently magnetic materials with large magnetic permeability, such as ferrites, used sometimes in combination with metallic sheets and/or active field cancellation. Ferrite materials, however, can be expensive, heavy and brittle. Inspired by recent demonstrations of epsilon-, mu- and index-near-zero metamaterials, here we show how a longitudinal mu-near-zero (LMNZ) layer can serve as a strong frequency-selective reflector of magnetic fields when operating in the near-field region of dipole-like sources. Experimental measurements with a fabricated LMNZ sheet constructed from an artificial magnetic conductor – formed from non-magnetic, conducting, metamaterial elements – confirm that the artificial structure provides significantly improved shielding as compared with a commercially available ferrite of the same size. Furthermore, we design a structure to shield simultaneously at the fundamental and first harmonic frequencies. Such frequency-selective behavior can be potentially useful for shielding electromagnetic sources that may also generate higher order harmonics, while leaving the transmission of other frequencies unaffected.
MiR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis
Authors: Zhang Dawei , Cao Xiaorui , Li Jun , Zhao Guangyue
Published: August 2015

Osteoarthritis (OA) is characterized by degradation of articular cartilage and joint inflammation. MicroRNAs have been proved to play an important role in the regulation of chondrogenesis. Previous study showed that microRNA-210 (miR-210) was probably associated with osteoarthritis, while the function of miR-210 in osteoarthritis still remains unknown. The aim of the present study was to investigate the protective effect of miR-210 on osteoarthritis. In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS). Transfection with miR-210 mimic inhibited LPS-induced pro-inflammatory cytokines production, cell viability reduction and cell apoptosis. Results of luciferase activity assay showed that miR-210 targeted 3′-UTR of death receptor 6 (DR6) to inhibit its expression. MiR-210 mimic and DR6 siRNA transfection inhibited the activation of NF-κB pathway and cell apoptosis of chondrocytes. For the in vivo study, OA model was established on rats by anterior cruciate ligament transection (ACLT). MiR-210 expression is reduced in OA rats. MiR-210 over-expressing lentivirus was injected into the OA rats. Cytokines production and NF-κB and DR6 expression in OA rats was inhibited by miR-210 overexpression. The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.
A Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine Production in Macrophages in Response to Toll-like Receptor 4
Authors: Kueanjinda Patipark , Roytrakul Sittiruk , Palaga Tanapat
Published: August 2015

Activation of macrophages triggers the release of pro-inflammatory cytokines leading to inflammation. Numb is a negative regulator of Notch signaling, but the role of Numb in macrophages is not fully understood. In this study, the role of Numb as a regulator of inflammatory responses in macrophages was investigated. Murine bone marrow-derived macrophages, in which expression of Numb was silenced, secreted significantly less TNFα, IL-6 and IL-12 and more IL-10 upon activation by lipopolysaccharide (LPS), a ligand for Toll-like receptor 4 (TLR4), despite increased Notch signaling. The Tnfα mRNA levels both in Numb-deficient and wild-type macrophages were not significantly different, unlike those of Il6 and Il12-p40. In Numb-deficient macrophages, the Tnfα mRNAs were degraded at faster rate, compared to those in control macrophages. Activation of p38 MAPK and NF-κΒ p65 were compromised in activated Numb deficient macrophages. Numb was found to interact with the E3 ubiquitin ligase, Itch, which reportedly regulates p38 MAPK. In addition, blocking the Notch signaling pathway in activated, Numb-deficient macrophages did not further reduce TNFα levels, suggesting a Notch-independent role for Numb. A proteomics approach revealed a novel funciton for Numb in regulating complex signaling cascades downstream of TLRs, partially involving Akt/NF-κB p65/p38 MAPK in macrophages.
ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function
Authors: Cui Dan , Arima Mitsuru , Takubo Keiyo , Kimura Tokuhiro , Horiuchi Keisuke , Minagawa Takuya , Matsuda Satoshi , Ikeda Eiji
Published: August 2015

Neural vascular barrier is essential for the life of multicellular organisms and its impairment by tissue hypoxia is known to be a central of pathophysiology accelerating the progression of various intractable neural diseases. Therefore, the molecules involved in hypoxia-induced impairment of vascular barrier can be the targets to establish new therapies for intractable diseases. Here, we demonstrate that a disintegrin and metalloproteinases (ADAMs) 12 and 17 expressed in endothelial cells are the molecules responsible for the impairment of neural vascular barrier by hypoxia. Brain microvascular endothelial cells in vitro lost their barrier properties immediately after hypoxic stimulation through diminished localization of claudin-5, a tight junction molecule, on cell membranes. Hypoxic disappearance of claudin-5 from cell membranes and the consequent loss of barrier properties were completely suppressed by inhibition of the metalloproteinase activity which was found to be attributed to ADAM12 and ADAM17. Inhibition of either ADAM12 or ADAM17 was sufficient to rescue the in vivo neural vasculature under hypoxia from the loss of barrier function. This is the first report to specify the molecules which are responsible for hypoxia-induced impairment of neural vascular barrier and furthermore can be the targets of new therapeutic strategies for intractable neural diseases.
The de novo synthesis of ubiquitin: identification of deubiquitinases acting on ubiquitin precursors
Authors: Grou Cláudia P. , Pinto Manuel P. , Mendes Andreia V. , Domingues Pedro , Azevedo Jorge E.
Published: August 2015

Protein ubiquitination, a major post-translational modification in eukaryotes, requires an adequate pool of free ubiquitin. Cells maintain this pool by two pathways, both involving deubiquitinases (DUBs): recycling of ubiquitin from ubiquitin conjugates and processing of ubiquitin precursors synthesized de novo. Although many advances have been made in recent years regarding ubiquitin recycling, our knowledge on ubiquitin precursor processing is still limited and questions such as when are these precursors processed and which DUBs are involved remain largely unanswered. Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. The identification of these DUBs together with their properties suggests that each ubiquitin precursor can be processed in at least two different manners, explaining the robustness of the ubiquitin de novo synthesis pathway.
Atlantic hurricane activity during the last millennium
Authors: Burn Michael J. , Palmer Suzanne E.
Published: August 2015

Hurricanes are a persistent socio-economic hazard for countries situated in and around the Main Development Region (MDR) of Atlantic tropical cyclones. Climate-model simulations have attributed their interdecadal variability to changes in solar and volcanic activity, Saharan dust flux, anthropogenic greenhouse gas and aerosol emissions and heat transport within the global ocean conveyor belt. However, the attribution of hurricane activity to specific forcing factors is hampered by the short observational record of Atlantic storms. Here, we present the Extended Hurricane Activity (EHA) index, the first empirical reconstruction of Atlantic tropical cyclone activity for the last millennium, derived from a high-resolution lake sediment geochemical record from Jamaica. The EHA correlates significantly with decadal changes in tropical Atlantic sea surface temperatures (SSTs; r = 0.68; 1854–2008), the Accumulated Cyclone Energy index (ACE; r = 0.90; 1851–2010) and two annually-resolved coral-based SST reconstructions (1773–2008) from within the MDR. Our results corroborate evidence for the increasing trend of hurricane activity during the Industrial Era; however, we show that contemporary activity has not exceeded the range of natural climate variability exhibited during the last millennium.
Associations of prepregnancy body mass index and gestational weight gain with pregnancy outcomes in nulliparous women delivering single live babies
Authors: Liu Lu , Hong Zhongxin , Zhang Lihong
Published: August 2015

The study was to assess the associations of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes. This was a retrospective analysis of 2973 nulliparous women who delivered single live babies. Prepregnancy BMI was categorized as underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2) or overweight/obese (≥25.0 kg/m2). GWG was categorized as inadequate, adequate or excessive. 567 (19.1%) women were overweight/obese and 1600 (53.8%) exhibited excessive GWG. Compared with women of normal weight, overweight/obese women had a higher incidence of cesarean section (odds ratio, 95% confidence interval: 2.02, 1.59–2.56), postpartum hemorrhage (1.50, 1.05–2.14), preterm delivery (2.51, 1.83–3.45), preterm premature rupture of membranes (2.11, 1.32–3.38), gestational diabetes mellitus (2.04, 1.65–2.53), gestational hypertension (7.68, 4.21–14.00), preeclampsia (1.98, 1.18–3.33) and small for gestational age (2.81, 1.21–6.54). Compared with adequate GWG, excessive GWG increased the incidence of cesarean section (2.02, 1.59–2.56), preterm delivery (1.48, 1.05–2.71), preeclampsia (1.78, 1.34–4.27) and macrosomia (2.61, 1.61–4.25) and reduced the incidence of gestational diabetes mellitus (0.75, 0.62–0.92). High prepregnancy BMI and excessive GWG in nulliparous Chinese women are associated with adverse pregnancy outcomes. Weight control before and during pregnancy could reduce the complications of pregnancy.
Inspired and stabilized by nature: ribosomal synthesis of the human voltage gated ion channel (VDAC) into 2D-protein-tethered lipid interfaces
Authors: Damiati Samar , Zayni Sonja , Schrems Angelika , Kiene Elisabeth , Sleytr Uwe B. , Chopineau Joël , Schuster Bernhard , Sinner Eva-Kathrin
Published: August 2015

The scheme of the cell-free, ribosomal synthesis of a VDAC protein in the presence of an S-layer supported lipid membrane. The VDAC protein is adapted from S. Hiller et al., Science, 2008, 321, 1206–1210.
Reversible DNA i-motif to hairpin switching induced by copper(ii) cations
Authors: Day Henry Albert , Wright Elisé Patricia , MacDonald Colin John , Gates Andrew James , Waller Zoë Ann Ella
Published: August 2015

i-Motif forming DNA sequences have previously been used for many different nanotechnological applications, but all have used changes in pH to fold the DNA. Here it is shown that Cu(ii) cations can be used to re-fold i-motifs into hairpin structures, without changing the pH.
Application of Good's buffers to pH imaging using hyperpolarized13C MRI
Authors: Flavell Robert R. , von Morze Cornelius , Blecha Joseph E. , Korenchan David E. , Van Criekinge Mark , Sriram Renuka , Gordon Jeremy W. , Chen Hsin-Yu , Subramaniam Sukumar , Bok Robert A. , Wang Zhen J. , Vigneron Daniel B. , Larson Peder E. , Kurhanewicz John , Wilson David M.
Published: August 2015

ACES, one of Good's buffers, was applied to pH imaging with hyperpolarized13C spectroscopy.
Glycan reducing end dual isotopic labeling (GREDIL) for mass spectrometry-based quantitative N-glycomics
Authors: Cao Weiqian , Zhang Wei , Huang Jiangming , Jiang Biyun , Zhang Lijuan , Yang Pengyuan
Published: August 2015

GREDIL for quantitative N-glycomics largely improves the stability of N-glycan 18O-labeling and greatly decreases the interference of isotopic cluster overlap.
Homo- and heteroepitaxial growth of Sn-doped β-Ga2O3 layers by MOVPE
Authors: Gogova D. , Schmidbauer M. , Kwasniewski A.
Published: August 2015

For the first time, n-type homoepitaxial semiconducting β-Ga2O3 layers were attained by MOVPE.
Cobalt(ii/iii), nickel(ii) and copper(ii) coordination clusters employing a monoanionic Schiff base ligand: synthetic, topological and computational mechanistic aspects
Authors: Loukopoulos Edward , Berkoff Benjamin , Griffiths Kieran , Keeble Victoria , Dokorou Vassiliki N. , Tsipis Athanassios C. , Escuer Albert , Kostakis George E.
Published: August 2015

Nine coordination clusters (M = CoII/III, NiII, CuII) using a monoanionic Schiff base ligand were synthesized and characterized. A series of transformations occur in the ligand in certain compounds.
Predictive modeling of synergistic effects in nanoscale ion track formation
Authors: Zarkadoula Eva , Pakarinen Olli H. , Xue Haizhou , Zhang Yanwen , Weber William J.
Published: August 2015

Cross sections of five pre-damaged systems with different initial defect concentration along the [001] direction, after irradiation with 21 MeV Ni ions. Sr is shown in blue, Ti in green, and O in purple.
Metallonaphthalocyanines as triplet sensitizers for near-infrared photon upconversion beyond 850 nm
Authors: Amemori Shogo , Yanai Nobuhiro , Kimizuka Nobuo
Published: August 2015

The photon upconversion of near-infrared light over 850 nm to the visible region is accomplished by utilizing metallonaphthalocyanines as superior NIR triplet sensitizers.
Progress towards high-power Li/CFxbatteries: electrode architectures using carbon nanotubes with CFx
Authors: Zhang Qing , Takeuchi Kenneth J. , Takeuchi Esther S. , Marschilok Amy C.
Published: August 2015

This perspective describes the current status of lithium–carbon monofluoride batteries and highlights the opportunities for the development of high-power Li/CFxbatteriesviautilization of carbon nanotubes.
Tip-enhanced Raman spectroscopy of bradykinin and its B2receptor antagonists adsorbed onto colloidal suspended Ag nanowires
Authors: Święch D. , Tanabe I. , Vantasin S. , Sobolewski D. , Ozaki Y. , Prahl A. , Maćkowski S. , Proniewicz E.
Published: August 2015

TERS spectra of bradykinin (BK) and its potent B2receptor antagonists, [d-Arg0,Hyp3,Thi5,8,l-Pip7]BK and [d-Arg0,Hyp3,Thi5,d-Phe7,l-Pip8]BK, approximately with a size of 40 nm, adsorbed onto colloidal suspended Ag nanowires with diameter of 350–500 nm and length of 2–50 μm were recorded.
Finite lattice model for molecular aggregation equilibria. Boolean statistics, analytical approximations, and the macroscopic limit
Authors: Rankin Blake M. , Ben-Amotz Dor , Widom B.
Published: August 2015

Exact finite lattice statistics and analytical approximations are used to model molecular aggregation processes.
Deciphering the reaction between a hydrated electron and a hydronium ion at elevated temperatures
Authors: Ma Jun , Yamashita Shinichi , Muroya Yusa , Katsumura Yosuke , Mostafavi Mehran
Published: August 2015

The formation of a H˙ atom in liquid water from the reaction of a hydrated electron with a hydronium cation is a very challenging subject in chemical processes.
Quantum and classical dynamics of reactive scattering of H2 from metal surfaces
Authors: Kroes Geert-Jan , Díaz Cristina
Published: August 2015

State-of-the-art theoretical models allow nowadays an accurate description of H2/metal surface systems and phenomena relative to heterogeneous catalysis. Here we review the most relevant ones investigated during the last 10 years.
In vitro photodynamic therapy based on magnetic-luminescent Gd2O3:Yb,Er nanoparticles with bright three-photon up-conversion fluorescence under near-infrared light
Authors: Li Hao , Song Shaoxin , Wang Wei , Chen Kezheng
Published: August 2015

Gd2O3:Yb,Er nanoparticles that can be used as promising dual-modal samples for simultaneous magnetic/optical bimodal imaging and near-infrared laser-triggered photodynamic therapy were fabricated via a homogeneous precipitation method.
Metalloisoporphyrins: from synthesis to applications
Authors: Bhuyan Jagannath
Published: August 2015

An overview of the chemistry of isoporphyrin, the tautomer of porphyrin, whose existence was predicated by the Noble laureate Woodward, is presented with emphasis on hydroxy-isoporphyrins of tetra-aryl derivatives.