bluuebunny/crossref_metadata_2025 huggingface dataset:
Konfirmatorische Prüfung der Skalenstruktur des SF-12 Version 2.0 in einer deutschen bevölkerungs-repräsentativen Stichprobe
Authors: Wirtz Markus Antonius , Morfeld Matthias , Glaesmer Heide , Brähler Elmar
Published: November 2017

Zusammenfassung. Der Short Form Health Survey SF-12 Fragebogen ist die Kurzform des krankheitsübergreifenden Short Form SF-36 Health Survey, der zur generischen Erfassung der gesundheitsbezogenen Lebensqualität eingesetzt wird. Die 12 Items des SF-12 erlauben die Bildung eines körperlichen und eines psychischen Summenwertes. Mittels konkurrierender konfirmatorischer Strukturmodelle wurden auf Basis der Daten einer für Deutschland repräsentativen Normstichprobe von N = 2 524 Personen 3 theoriebasierte bzw. in der Literatur berichtete Modellvarianten geprüft. Nach Modifikation des Messmodells des psychischen Faktors konnte eine gute Datenpassung des zweidimensionalen Modells erreicht werden (CFI = .967, TLI = .992, SRMR = .037). Der beste Modell-Fit ergab sich jedoch für ein dreidimensionales Modell, das die emotionale Rollenfunktion als vom psychischen Faktor separierte Komponente annimmt (CFI = .972, TLI = .991, SRMR = .035). Beide modifizierten Strukturmodelle erlauben eine psychometrisch gut begründete Auswertung der SF-12-Daten. Zusätzlich zu einem körperlichen und psychischen Skalenwert lässt sich ein Skalenwert Emotionale Rollenfunktion zur Beschreibung der gesundheitsbezogenen Lebensqualität bestimmen.
Estrogen induces c-Kit and an aggressive phenotype in a model of invasive lobular breast cancer
Authors: Harrell J. Chuck , Shroka Thomas M. , Jacobsen Britta M.
Published: November 2017

Among the molecular subtypes of breast cancer are luminal (A or B) estrogen receptor positive (ER+), HER2+, and triple negative (basal-like). In addition to the molecular subtypes, there are 18 histologic breast cancer subtypes classified on appearance, including invasive lobular breast carcinoma (ILC), which are 8–15% of all breast cancers and are largely ER+ tumors. We used a new model of ER+ ILC, called BCK4. To determine the estrogen regulated genes in our ILC model, we examined BCK4 xenograft tumors from mice supplemented with or without estrogen using gene expression arrays. Approximately 3000 genes were regulated by estrogen in vivo. Hierarchical cluster analyses of the BCK4 derived tumors compared with ER+ and ER- breast cancer cell lines show the estrogen treated BCK4 tumors group with ER- breast cancers most likely due to a high proliferation score, while tumors from cellulose supplemented mice were more related to ER+ breast tumor cells. To elucidate genes regulated in vitro by estrogen in BCK4 cells, we performed expression profiling using Illumina arrays of the BCK4 cell line, treated with or without estrogen in vitro. A set of ~200 overlapping genes were regulated by estrogen in the BCK4 cell line and xenograft tumors, and pathway analysis revealed that the c-Kit pathway might be a target to reduce estrogen-induced proliferation. Subsequent studies found that inhibition of c-Kit activity using imatinib mesylate (Gleevec®) blocked estrogen mediated stimulation of BCK4 tumors and BCK4 cells in vitro as effectively as the anti-estrogen fulvestrant (Faslodex®). Decreased expression of c-Kit using shRNA also decreased baseline and estrogen induced proliferation in vitro and in vivo. These studies are the first to indicate that c-Kit inhibition is an effective approach to target c-Kit+ ILC.
Mapping microscale wetting variations on biological and synthetic water-repellent surfaces
Authors: Liimatainen Ville , Vuckovac Maja , Jokinen Ville , Sariola Veikko , Hokkanen Matti J. , Zhou Quan , Ras Robin H. A.
Published: November 2017

Droplets slip and bounce on superhydrophobic surfaces, enabling remarkable functions in biology and technology. These surfaces often contain microscopic irregularities in surface texture and chemical composition, which may affect or even govern macroscopic wetting phenomena. However, effective ways to quantify and map microscopic variations of wettability are still missing, because existing contact angle and force-based methods lack sensitivity and spatial resolution. Here, we introduce wetting maps that visualize local variations in wetting through droplet adhesion forces, which correlate with wettability. We develop scanning droplet adhesion microscopy, a technique to obtain wetting maps with spatial resolution down to 10 µm and three orders of magnitude better force sensitivity than current tensiometers. The microscope allows characterization of challenging non-flat surfaces, like the butterfly wing, previously difficult to characterize by contact angle method due to obscured view. Furthermore, the technique reveals wetting heterogeneity of micropillared model surfaces previously assumed to be uniform.
Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs
Authors: Vannini Ivan , Wise Petra M. , Challagundla Kishore B. , Plousiou Meropi , Raffini Mirco , Bandini Erika , Fanini Francesca , Paliaga Giorgia , Crawford Melissa , Ferracin Manuela , Ivan Cristina , Fabris Linda , Davuluri Ramana V. , Guo Zhiyi , Cortez Maria Angelica , Zhang Xinna , Chen Lu , Zhang Shuxing , Fernandez-Cymering Cecilia , Han Leng , Carloni Silvia , Salvi Samanta , Ling Hui , Murtadha Mariam , Neviani Paolo , Gitlitz Barbara J. , Laird-Offringa Ite A. , Nana-Sinkam Patrick , Negrini Massimo , Liang Han , Amadori Dino , Cimmino Amelia , Calin George A. , Fabbri Muller
Published: November 2017

The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call “entrapping”. Our results support a key role for uc.339 in lung cancer.
Sumatran tiger survival threatened by deforestation despite increasing densities in parks
Authors: Luskin Matthew Scott , Albert Wido Rizki , Tobler Mathias W.
Published: November 2017

The continuing development of improved capture–recapture (CR) modeling techniques used to study apex predators has also limited robust temporal and cross-site analyses due to different methods employed. We develop an approach to standardize older non-spatial CR and newer spatial CR density estimates and examine trends for critically endangered Sumatran tigers (Panthera tigris sumatrae) using a meta-regression of 17 existing densities and new estimates from our own fieldwork. We find that tiger densities were 47% higher in primary versus degraded forests and, unexpectedly, increased 4.9% per yr from 1996 to 2014, likely indicating a recovery from earlier poaching. However, while tiger numbers may have temporarily risen, the total potential island-wide population declined by 16.6% from 2000 to 2012 due to forest loss and degradation and subpopulations are significantly more fragmented. Thus, despite increasing densities in smaller parks, we conclude that there are only two robust populations left with >30 breeding females, indicating Sumatran tigers still face a high risk of extinction unless deforestation can be controlled.
Critical role of the HDAC6–cortactin axis in human megakaryocyte maturation leading to a proplatelet-formation defect
Authors: Messaoudi Kahia , Ali Ashfaq , Ishaq Rameez , Palazzo Alberta , Sliwa Dominika , Bluteau Olivier , Souquère Sylvie , Muller Delphine , Diop Khadija M. , Rameau Philippe , Lapierre Valérie , Marolleau Jean-Pierre , Matthias Patrick , Godin Isabelle , Pierron Gérard , Thomas Steven G. , Watson Stephen P. , Droin Nathalie , Vainchenker William , Plo Isabelle , Raslova Hana , Debili Najet
Published: November 2017

Thrombocytopenia is a major side effect of a new class of anticancer agents that target histone deacetylase (HDAC). Their mechanism is poorly understood. Here, we show that HDAC6 inhibition and genetic knockdown lead to a strong decrease in human proplatelet formation (PPF). Unexpectedly, HDAC6 inhibition-induced tubulin hyperacetylation has no effect on PPF. The PPF decrease induced by HDAC6 inhibition is related to cortactin (CTTN) hyperacetylation associated with actin disorganization inducing important changes in the distribution of megakaryocyte (MK) organelles. CTTN silencing in human MKs phenocopies HDAC6 inactivation and knockdown leads to a strong PPF defect. This is rescued by forced expression of a deacetylated CTTN mimetic. Unexpectedly, unlike human-derived MKs, HDAC6 and CTTN are shown to be dispensable for mouse PPF in vitro and platelet production in vivo. Our results highlight an unexpected function of HDAC6–CTTN axis as a positive regulator of human but not mouse MK maturation.
Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients
Authors: Jézéquel Julie , Johansson Emily M. , Dupuis Julien P. , Rogemond Véronique , Gréa Hélène , Kellermayer Blanka , Hamdani Nora , Le Guen Emmanuel , Rabu Corentin , Lepleux Marilyn , Spatola Marianna , Mathias Elodie , Bouchet Delphine , Ramsey Amy J. , Yolken Robert H. , Tamouza Ryad , Dalmau Josep , Honnorat Jérôme , Leboyer Marion , Groc Laurent
Published: November 2017

The identification of circulating autoantibodies against neuronal receptors in neuropsychiatric disorders has fostered new conceptual and clinical frameworks. However, detection reliability, putative presence in different diseases and in health have raised questions about potential pathogenic mechanism mediated by autoantibodies. Using a combination of single molecule-based imaging approaches, we here ascertain the presence of circulating autoantibodies against glutamate NMDA receptor (NMDAR-Ab) in about 20% of psychotic patients diagnosed with schizophrenia and very few healthy subjects. NMDAR-Ab from patients and healthy subjects do not compete for binding on native receptor. Strikingly, NMDAR-Ab from patients, but not from healthy subjects, specifically alter the surface dynamics and nanoscale organization of synaptic NMDAR and its anchoring partner the EphrinB2 receptor in heterologous cells, cultured neurons and in mouse brain. Functionally, only patients’ NMDAR-Ab prevent long-term potentiation at glutamatergic synapses, while leaving NMDAR-mediated calcium influx intact. We unveil that NMDAR-Ab from psychotic patients alter NMDAR synaptic transmission, supporting a pathogenically relevant role.
Reconstitution of the complete pathway of ITS2 processing at the pre-ribosome
Authors: Fromm Lisa , Falk Sebastian , Flemming Dirk , Schuller Jan Michael , Thoms Matthias , Conti Elena , Hurt Ed
Published: November 2017

Removal of internal transcribed spacer 2 (ITS2) from pre-ribosomal RNA is essential to make functional ribosomes. This complicated processing reaction begins with a single endonucleolytic cleavage followed by exonucleolytic trimming at both new cleavage sites to generate mature 5.8S and 25S rRNA. We reconstituted the 7S→5.8S processing branch within ITS2 using purified exosome and its nuclear cofactors. We find that both Rrp44’s ribonuclease activities are required for initial RNA shortening followed by hand over to the exonuclease Rrp6. During the in vitro reaction, ITS2-associated factors dissociate and the underlying ‘foot’ structure of the pre-60S particle is dismantled. 7S pre-rRNA processing is independent of 5S RNP rotation, but 26S→25S trimming is a precondition for subsequent 7S→5.8S processing. To complete the in vitro assay, we reconstituted the entire cycle of ITS2 removal with a total of 18 purified factors, catalysed by the integrated activities of the two participating RNA-processing machines, the Las1 complex and nuclear exosome.
Rods progressively escape saturation to drive visual responses in daylight conditions
Authors: Tikidji-Hamburyan Alexandra , Reinhard Katja , Storchi Riccardo , Dietter Johannes , Seitter Hartwig , Davis Katherine E. , Idrees Saad , Mutter Marion , Walmsley Lauren , Bedford Robert A. , Ueffing Marius , Ala-Laurila Petri , Brown Timothy M. , Lucas Robert J. , Münch Thomas A.
Published: November 2017

Rod and cone photoreceptors support vision across large light intensity ranges. Rods, active under dim illumination, are thought to saturate at higher (photopic) irradiances. The extent of rod saturation is not well defined; some studies report rod activity well into the photopic range. Using electrophysiological recordings from retina and dorsal lateral geniculate nucleus of cone-deficient and visually intact mice, we describe stimulus and physiological factors that influence photopic rod-driven responses. We find that rod contrast sensitivity is initially strongly reduced at high irradiances, but progressively recovers to allow responses to moderate contrast stimuli. Surprisingly, rods recover faster at higher light levels. A model of rod phototransduction suggests that phototransduction gain adjustments and bleaching adaptation underlie rod recovery. Consistently, exogenous chromophore reduces rod responses at bright background. Thus, bleaching adaptation renders mouse rods responsive to modest contrast at any irradiance. Paradoxically, raising irradiance across the photopic range increases the robustness of rod responses.
The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery
Authors: Kumar Ramesh , González-Prieto Román , Xiao Zhenyu , Verlaan-de Vries Matty , Vertegaal Alfred C. O.
Published: November 2017

SUMO-targeted ubiquitin ligases (STUbLs) mediate the ubiquitylation of SUMOylated proteins to modulate their functions. In search of direct targets for the STUbL RNF4, we have developed TULIP (targets for ubiquitin ligases identified by proteomics) to covalently trap targets for ubiquitin E3 ligases. TULIP methodology could be widely employed to delineate E3 substrate wiring. Here we report that the single SUMO E2 Ubc9 and the SUMO E3 ligases PIAS1, PIAS2, PIAS3, ZNF451, and NSMCE2 are direct RNF4 targets. We confirm PIAS1 as a key RNF4 substrate. Furthermore, we establish the ubiquitin E3 ligase BARD1, a tumor suppressor and partner of BRCA1, as an indirect RNF4 target, regulated by PIAS1. Interestingly, accumulation of BARD1 at local sites of DNA damage increases upon knockdown of RNF4. Combined, we provide an insight into the role of the STUbL RNF4 to balance the role of SUMO signaling by directly targeting Ubc9 and SUMO E3 ligases.
Gate-tunable large magnetoresistance in an all-semiconductor spin valve device
Authors: Oltscher M. , Eberle F. , Kuczmik T. , Bayer A. , Schuh D. , Bougeard D. , Ciorga M. , Weiss D.
Published: November 2017

A large spin-dependent and electric field-tunable magnetoresistance of a two-dimensional electron system is a key ingredient for the realization of many novel concepts for spin-based electronic devices. The low magnetoresistance observed during the last few decades in devices with lateral semiconducting transport channels between ferromagnetic source and drain contacts has been the main obstacle for realizing spin field effect transistor proposals. Here, we show both a large two-terminal magnetoresistance in a lateral spin valve device with a two-dimensional channel, with up to 80% resistance change, and tunability of the magnetoresistance by an electric gate. The enhanced magnetoresistance is due to finite electric field effects at the contact interface, which boost spin-to-charge conversion. The gating scheme that we use is based on switching between uni- and bidirectional spin diffusion, without resorting to spin–orbit coupling. Therefore, it can also be employed in materials with low spin–orbit coupling.
A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia
Authors: Knox Hailey J. , Hedhli Jamila , Kim Tae Wook , Khalili Kian , Dobrucki Lawrence W. , Chan Jefferson
Published: November 2017

Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. Thus, detection of hypoxia can guide treatment planning and serve as a predictor of patient prognosis. Unfortunately, current methods suffer from invasiveness, poor resolution and low specificity. To address these limitations, we present Hypoxia Probe 1 (HyP-1), a hypoxia-responsive agent for photoacoustic imaging. This emerging modality converts safe, non-ionizing light to ultrasound waves, enabling acquisition of high-resolution 3D images in deep tissue. HyP-1 features an N-oxide trigger that is reduced in the absence of oxygen by heme proteins such as CYP450 enzymes. Reduction of HyP-1 produces a spectrally distinct product, facilitating identification via photoacoustic imaging. HyP-1 exhibits selectivity for hypoxic activation in vitro, in living cells, and in multiple disease models in vivo. HyP-1 is also compatible with NIR fluorescence imaging, establishing its versatility as a multimodal imaging agent.
Meta-analysis of gut microbiome studies identifies disease-specific and shared responses
Authors: Duvallet Claire , Gibbons Sean M. , Gurry Thomas , Irizarry Rafael A. , Alm Eric J.
Published: November 2017

Hundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge. Results from individual studies can be inconsistent, and comparing published data is further complicated by a lack of standard processing and analysis methods. Here we introduce the MicrobiomeHD database, which includes 28 published case–control gut microbiome studies spanning ten diseases. We perform a cross-disease meta-analysis of these studies using standardized methods. We find consistent patterns characterizing disease-associated microbiome changes. Some diseases are associated with over 50 genera, while most show only 10–15 genus-level changes. Some diseases are marked by the presence of potentially pathogenic microbes, whereas others are characterized by a depletion of health-associated bacteria. Furthermore, we show that about half of genera associated with individual studies are bacteria that respond to more than one disease. Thus, many associations found in case–control studies are likely not disease-specific but rather part of a non-specific, shared response to health and disease.
Break-induced replication promotes formation of lethal joint molecules dissolved by Srs2
Authors: Elango Rajula , Sheng Ziwei , Jackson Jessica , DeCata Jenna , Ibrahim Younis , Pham Nhung T. , Liang Diana H. , Sakofsky Cynthia J. , Vindigni Alessandro , Lobachev Kirill S. , Ira Grzegorz , Malkova Anna
Published: November 2017

Break-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unknown how this ssDNA is prevented from unscheduled pairing with the template, which can lead to genomic instability. Here, we propose that uncontrolled Rad51 binding to this ssDNA promotes formation of toxic joint molecules that are counteracted by Srs2. First, Srs2 dislodges Rad51 from ssDNA preventing promiscuous strand invasions. Second, it dismantles toxic intermediates that have already formed. Rare survivors in the absence of Srs2 rely on structure-specific endonucleases, Mus81 and Yen1, that resolve toxic joint-molecules. Overall, we uncover a new feature of BIR and propose that tight control of ssDNA accumulated during this process is essential to prevent its channeling into toxic structures threatening cell viability.
Longer aftershocks duration in extensional tectonic settings
Authors: Valerio E. , Tizzani P. , Carminati E. , Doglioni C.
Published: November 2017

Aftershocks number decay through time, depending on several parameters peculiar to each seismogenic regions, including mainshock magnitude, crustal rheology, and stress changes along the fault. However, the exact role of these parameters in controlling the duration of the aftershock sequence is still unknown. Here, using two methodologies, we show that the tectonic setting primarily controls the duration of aftershocks. On average and for a given mainshock magnitude (1) aftershock sequences are longer and (2) the number of earthquakes is greater in extensional tectonic settings than in contractional ones. We interpret this difference as related to the different type of energy dissipated during earthquakes. In detail, (1) a joint effect of gravitational forces and pure elastic stress release governs extensional earthquakes, whereas (2) pure elastic stress release controls contractional earthquakes. Accordingly, normal faults operate in favour of gravity, preserving inertia for a longer period and seismicity lasts until gravitational equilibrium is reached. Vice versa, thrusts act against gravity, exhaust their inertia faster and the elastic energy dissipation is buffered by the gravitational force. Hence, for seismic sequences of comparable magnitude and rheological parameters, aftershocks last longer in extensional settings because gravity favours the collapse of the hangingwall volumes.
Genotyping-by-Sequencing Derived High-Density Linkage Map and its Application to QTL Mapping of Flag Leaf Traits in Bread Wheat
Authors: Hussain Waseem , Baenziger P. Stephen. , Belamkar Vikas , Guttieri Mary J. , Venegas Jorge P. , Easterly Amanda , Sallam Ahmed , Poland Jesse
Published: November 2017

Winter wheat parents ‘Harry’ (drought tolerant) and ‘Wesley’ (drought susceptible) were used to develop a recombinant inbred population with future goals of identifying genomic regions associated with drought tolerance. To precisely map genomic regions, high-density linkage maps are a prerequisite. In this study genotyping-by- sequencing (GBS) was used to construct the high-density linkage map. The map contained 3,641 markers distributed on 21 chromosomes and spanned 1,959 cM with an average distance of 1.8 cM between markers. The constructed linkage map revealed strong collinearity in marker order across 21 chromosomes with POPSEQ-v2.0, which was based on a high-density linkage map. The reliability of the linkage map for QTL mapping was demonstrated by co-localizing the genes to previously mapped genomic regions for two highly heritable traits, chaff color, and leaf cuticular wax. Applicability of linkage map for QTL mapping of three quantitative traits, flag leaf length, width, and area, identified 21 QTLs in four environments, and QTL expression varied across the environments. Two major stable QTLs, one each for flag leaf length (Qfll.hww-7A) and flag leaf width (Qflw.hww-5A) were identified. The map constructed will facilitate QTL and fine mapping of quantitative traits, map-based cloning, comparative mapping, and in marker-assisted wheat breeding endeavors.
Prediction of postoperative outcomes using intraoperative hemodynamic monitoring data
Authors: Prasad Varesh , Guerrisi Maria , Dauri Mario , Coniglione Filadelfo , Tisone Giuseppe , De Carolis Elisa , Cillis Annagrazia , Canichella Antonio , Toschi Nicola , Heldt Thomas
Published: November 2017

Major surgeries can result in high rates of adverse postoperative events. Reliable prediction of which patient might be at risk for such events may help guide peri- and postoperative care. We show how archiving and mining of intraoperative hemodynamic data in orthotopic liver transplantation (OLT) can aid in the prediction of postoperative 180-day mortality and acute renal failure (ARF), improving upon predictions that rely on preoperative information only. From 101 patient records, we extracted 15 preoperative features from clinical records and 41 features from intraoperative hemodynamic signals. We used logistic regression with leave-one-out cross-validation to predict outcomes, and incorporated methods to limit potential model instabilities from feature multicollinearity. Using only preoperative features, mortality prediction achieved an area under the receiver operating characteristic curve (AUC) of 0.53 (95% CI: 0.44–0.78). By using intraoperative features, performance improved significantly to 0.82 (95% CI: 0.56–0.91, P = 0.001). Similarly, including intraoperative features (AUC = 0.82; 95% CI: 0.66–0.94) in ARF prediction improved performance over preoperative features (AUC = 0.72; 95% CI: 0.50–0.85), though not significantly (P = 0.32). We conclude that inclusion of intraoperative hemodynamic features significantly improves prediction of postoperative events in OLT. Features strongly associated with occurrence of both outcomes included greater intraoperative central venous pressure and greater transfusion volumes.
Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
Authors: Kubota Tomoya , Dang Bobo , Carvalho-de-Souza Joao L. , Correa Ana M. , Bezanilla Francisco
Published: November 2017

Voltage-gated sodium (Nav) channels play a key role in generating action potentials which leads to physiological signaling in excitable cells. The availability of probes for functional studies of mammalian Nav is limited. Here, by introducing two amino acid substitutions into the beta scorpion toxin Ts1, we have chemically synthesized a novel binder [S14R, W50Pra]Ts1 for Nav with high affinity, low dissociation rate and reduced toxicity while retaining the capability of conjugating Ts1 with molecules of interests for different applications. Using the fluorescent-dye conjugate, [S14R, W50Pra(Bodipy)]Ts1, we confirmed its binding to Nav1.4 through Lanthanide-based Resonance Energy Transfer. Moreover, using the gold nanoparticle conjugate, [S14R, W50Pra(AuNP)]Ts1, we were able to optically stimulate dorsal root ganglia neurons and generate action potentials with visible light via the optocapacitive effect as previously reported. [S14R, W50Pra]Ts1 is a novel probe with great potential for wider applications in Nav-related neuroscience research.
Author Correction: Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients
Authors: Wang Youhong , Guo Zhen , Zhao Yu , Jin Yi , An Liang , Wu Bin , Liu Zhaoqian , Chen Xiaoping , Chen Xiang , Zhou Honghao , Wang Hui , Zhang Wei
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Anions for Near-Infrared Selective Organic Salt Photovoltaics
Authors: Traverse Christopher J. , Young Margaret , Suddard-Bangsund John , Patrick Tyler , Bates Matthew , Chen Pei , Wingate Brian , Lunt Sophia Y. , Anctil Annick , Lunt Richard R.
Published: November 2017

Organic molecular salts are an emerging and highly tunable class of materials for organic and transparent photovoltaics. In this work, we demonstrate novel phenyl borate and carborane-based anions paired with a near-infrared (NIR)-selective heptamethine cation. We further explore the effects of anion structures and functional groups on both device performance and physical properties. Changing the functional groups on the anion significantly alters the open circuit voltage and yields a clear dependence on electron withdrawing groups. Anion exchange is also shown to selectively alter the solubility and film surface energy of the resulting molecular salt, enabling the potential fabrication of solution-deposited cascade or multi-junction devices from orthogonal solvents. This study further expands the catalog and properties of organic salts for inexpensive, and stable NIR-selective molecular salt photovoltaics.
Frequency and reactivity of antigen-specific T cells were concurrently measured through the combination of artificial antigen-presenting cell, MACS and ELISPOT
Authors: Shen Chuanlai , Xu Tao , Wu You , Li Xiaoe , Xia Lingzhi , Wang Wei , Shahzad Khawar Ali , Zhang Lei , Wan Xin , Qiu Jie
Published: November 2017

Conventional peptide-major histocompatibility complex (pMHC) multimer staining, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay cannot concurrently determine the frequency and reactivity of antigen-specific T cells (AST) in a single assay. In this report, pMHC multimer, magnetic-activated cell sorting (MACS), and ELISPOT techniques have been integrated into a micro well by coupling pMHC multimers onto cell-sized magnetic beads to characterize AST cell populations in a 96-well microplate which pre-coated with cytokine-capture antibodies. This method, termed AAPC-microplate, allows the enumeration and local cytokine production of AST cells in a single assay without using flow cytometry or fluorescence intensity scanning, thus will be widely applicable. Here, ovalbumin257–264-specific CD8+T cells from OT-1 T cell receptor (TCR) transgenic mice were measured. The methodological accuracy, specificity, reproducibility, and sensitivity in enumerating AST cells compared well with conventional pMHC multimer staining. Furthermore, the AAPC-microplate was applied to detect the frequency and reactivity of Hepatitis B virus (HBV) core antigen18–27- and surface antigen183–191-specific CD8+T cells for the patients, and was compared with conventional method. This method without the need of high-end instruments may facilitate the routine analysis of patient-specific cellular immune response pattern to a given antigen in translational studies.
Microfluidic-assisted Formation of Highly Monodisperse and Mesoporous Silica Soft Microcapsules
Authors: Bchellaoui Nizar , Hayat Zain , Mami Mohamed , Dorbez-Sridi Rachida , El Abed Abdel Illah
Published: November 2017

The fabrication of mesoporous silica microcapsules with a highly controlled particle size ranging in the micrometer size presents a major challenge in many academic and industrial research areas, such as for the developement of smart drug delivery systems with a well controlled loading and release of (bio)active molecules. Many studies based on the solvent evaporation or solvent diffusion methods have been developed during the last two decades in order to control the particle size, which is often found to range at a sub-micrometer scale. Droplet-based microfluidics proved during the last decade a powerful tool to produce highly monodisperse and mesoporous silica solid microspheres with a controllable size in the micrometer range. We show in the present study, in contrast with previous microfluidic-assisted approaches, that a better control of the diffusion of the silica precursor sol in a surrounding perfluorinated oil phase during the silica formation process allows for the formation of highly monodisperse mesoporous silica microcapsules with a diameter ranging in the 10 micrometer range. We show also, using optical, scanning and transmission electron microscopies, small angle x-ray diffraction and BET measurements, that the synthesized mesoporous silica microcapsules exhibit a soft-like thin shell with a thickness of about 1 μm, across which 5.9 nm sized mesopores form a well-ordered hexagonal 2D network. We suggest and validate experimentally a model where the formation of such microcapsules is controlled by the solvent evaporation process at the droplet-air interface.
Characteristics of martensitic and strain-glass transitions of the Fe-substituted TiNi shape memory alloys probed by transport and thermal measurements
Authors: Ramachandran Balakrishnan , Chang Pei-Chi , Kuo Yung-Kang , Chien Chen , Wu Shyi-Kaan
Published: November 2017

The electrical resistivity, Seebeck coefficient, thermal conductivity, and specific heat of Ti50Ni50-x
Fe
x
(x = 2.0–10.0 at.%) shape memory alloys (SMAs) were measured to investigate the influence of point defects (Fe) on the martensitic transformation characteristics. Our results show that the Ti50Ni48Fe2 and Ti50Ni47Fe3 SMAs have a two-step martensitic transformation (B2 → R and R → B19′), while the Ti50Ni46Fe4, Ti50Ni44.5Fe5.5, and Ti50Ni44Fe6 SMAs display a one-step martensitic transition (B2 → R). However, the compounds Ti50Ni42Fe8 and Ti50Ni40Fe10 show strain glass features (frozen strain-ordered state). Importantly, the induced point defects significantly alter the martensitic transformation characteristics, namely transition temperature and width of thermal hysteresis during the transition. This can be explained by the stabilization of austenite B2 phase upon Fe substitution, which ultimately leads to the decrease in enthalpy that associated to the martensitic transition. To determine the boundary composition that separates the R-phase and strain glass systems in this series of SMAs, a Ni-rich specimen Ti49Ni45Fe6 was fabricated. Remarkably, a slight change in Ti/Ni ratio converts Ti49Ni45Fe6 SMA into a strain glass system. Overall, the evolution of phase transformation in the Fe-substituted TiNi SMAs is presumably caused by the changes in local lattice structure via the induced local strain fields by Fe point defects.
OCT4 supports extended LIF-independent self-renewal and maintenance of transcriptional and epigenetic networks in embryonic stem cells
Authors: He Runsheng , Xhabija Besa , Al-Qanber Batool , Kidder Benjamin L.
Published: November 2017

Embryonic stem (ES) cell pluripotency is governed by OCT4-centric transcriptional networks. Conventional ES cells can be derived and maintained in vitro with media containing the cytokine leukemia inhibitory factor (LIF), which propagates the pluripotent state by activating STAT3 signaling, and simultaneous inhibition of glycogen synthase kinase-3 (GSK3) and MAP kinase/ERK kinase signaling. However, it is unclear whether overexpression of OCT4 is sufficient to overcome LIF-dependence. Here, we show that inducible expression of OCT4 (iOCT4) supports long-term LIF-independent self-renewal of ES cells cultured in media containing fetal bovine serum (FBS) and a glycogen synthase kinase-3 (GSK3) inhibitor, and in serum-free media. Global expression analysis revealed that LIF-independent iOCT4 ES cells and control ES cells exhibit similar transcriptional programs relative to epiblast stem cells (EpiSCs) and differentiated cells. Epigenomic profiling also demonstrated similar patterns of histone modifications between LIF-independent iOCT4 and control ES cells. Moreover, LIF-independent iOCT4 ES cells retain the capacity to differentiate in vitro and in vivo upon downregulation of OCT4 expression. These findings indicate that OCT4 expression is sufficient to sustain intrinsic signaling in a LIF-independent manner to promote ES cell pluripotency and self-renewal.
MiR-16-5p mediates a positive feedback loop in EV71-induced apoptosis and suppresses virus replication
Authors: Zheng Caishang , Zheng Zhenhua , Sun Jianhong , Zhang Yuan , Wei Chunyu , Ke Xianliang , Liu Yan , Deng Li , Wang Hanzhong
Published: November 2017

Enterovirus 71 (EV71) is the predominant causative pathogen of hand-foot-and-mouth disease (HFMD). Contrary to other HFMD-causing enterovirus, EV71 can lead to severe neurological complications, even death. MicroRNAs (miRNAs) are small non-coding RNAs that constitute the largest family of gene regulators participating in numerous biological or pathological processes. We previously reported that miR-16-5p increases with severity of HFMD by investigating the expression patterns of host miRNAs in patients with HFMD. However, the mechanisms by which EV71 induces miR-16-5p expression are not clear, and the interaction between EV71 and miR-16-5p is not yet fully understood. Here, we confirmed EV71-induced expression of miR-16-5p both in vitro and in vivo and show that upregulation of miR-16-5p by EV71 infection may occur at the posttranscriptional level. Moreover, EV71-induced caspase activation facilitates the processing of pri-miR-16-1. We also revealed that miR-16-5p can promote EV71-induced nerve cells apoptosis through activating caspase-3. In addition, we found that miR-16-5p can inhibit EV71 replication. CCNE1 and CCND1, two important cell cycle regulators, play an important role in the suppression of EV71 replication by miR-16-5p. Therefore, miR-16-5p is a positive feedback regulator in EV71-induced apoptosis and a suppressor of virus replication. These results help in understanding the interaction network between miRNA and EV71 infection and provide a potential target for the development of antiviral therapy.
Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease
Authors: Jokela Heli , Hakkarainen Janne , Kätkänaho Laura , Pakarinen Pirjo , Ruohonen Suvi T. , Tena-Sempere Manuel , Zhang Fu-Ping , Poutanen Matti
Published: November 2017

HSD17B1 is a steroid metabolising enzyme. We have previously generated knockout mice that had the entire coding region of Hsd17b1 replaced with lacZ-neo cassette (Hsd17b1-LacZ/Neo mice). This resulted in a 90% reduction of HSD17B1 activity, associated with severe subfertility in the knockout females. The present study indicates that Hsd17b1-LacZ/Neo male mice have a metabolic phenotype, including reduced adipose mass, increased lean mass and lipid accumulation in the liver. During the characterisation of this metabolic phenotype, it became evident that the expression of the Naglu gene, located closely upstream of Hsd17b1, was severely reduced in all tissues analysed. Similar results were obtained from Hsd17b1-LacZ mice after removing the neo cassette from the locus or by crossing the Hsd17b1-LacZ/Neo mice with transgenic mice constitutively expressing human HSD17B1. The deficiency of Naglu caused the accumulation of glycosaminoglycans in all studied mouse models lacking the Hsd17b1 gene. The metabolic phenotypes of the Hsd17b1 knockout mouse models were recapitulated in Naglu knockout mice. Based on the data we propose that the Hsd17b1 gene includes a regulatory element controlling Naglu expression and the metabolic phenotype in mice lacking the Hsd17b1 genomic region is caused by the reduced expression of Naglu rather than the lack of Hsd17b1.
Paleoclimatic information recorded in fluid inclusions in halites from Lop Nur, Western China
Authors: Sun Xiao-hong , Zhao Yan-jun , Liu Cheng-lin , Jiao Peng-cheng , Zhang Hua , Wu Chi-hua
Published: November 2017

The homogenization temperature (Th) of primary fluid inclusions in halite can be used for paleoclimate interpretations. Lop Nur, in Central Asia, is an extremely arid zone where large amounts of glauberite were deposited from the late Middle to Late Pleistocene. This deposition was accompanied by formation of large-scale potash-bearing brines. However, quantitative paleotemperature data are still lacking, hindering reconstruction of Quaternary climate conditions and their control over potash formation. We measured the Thof inclusions in halite from the salt field and the top of Upper Pleistocene strata in Lop Nur. The maximum homogenization temperature (ThMAX) of inclusions in halite from the salt field was 41.1 °C, consistent with the maximum ambient temperature (43.4 °C) in the same period. The ThMAXof inclusions in halite from the Upper Pleistocene strata ranged from 35.6 °C to 43 °C, where maximum air temperatures may have reached 37.9 °C to 45.3 °C. The results show that a hot and arid climate prevailed in Lop Nur at the end of the Late Pleistocene. Furthermore, changes of the brine chemical composition due to supply variations instead of climate change, may have caused glauberite deposition to cease at the end of the Late Pleistocene.
Present and past selves: a steady-state visual evoked potentials approach to self-face processing
Authors: Kotlewska I. , Wójcik M. J. , Nowicka M. M. , Marczak K. , Nowicka A.
Published: November 2017

The self-face has a prioritized status in the processing of incoming visual inputs. As the self-face changes over the lifespan, this stimulus seems to be well-suited for investigation of the self across time. Here, steady-state visual evoked potentials (SSVEP, oscillatory responses to periodic stimulation with a frequency that mirrors the frequency of stimulation) were used to investigate this topic. Different types of faces (present self, past self, close-other’s, unknown, scrambled) flickered four times per second in two types of stimulation (‘identical’, with the same image of a given type of face; ‘different’, with different images of the same type of face). Each of the 10 stimulation sessions lasted 90 seconds and was repeated three times. EEG data were recorded and analyzed in 20 participants. In general, faces evoked higher SSVEP than scrambled faces. The impact of identical and different stimulation was similar for faces and scrambled faces: SSVEP to different stimuli (faces, scrambled faces) was enhanced in comparison to identical ones. Present self-faces evoked higher SSVEP responses than past self-faces in the different stimulation condition only. Thus, our results showed that the physical aspects of the present and past selves are differentiated on the neural level in the absence of an overt behavior.
The inhibitory effect of minocycline on radiation-induced neuronal apoptosis via AMPKα1 signaling-mediated autophagy
Authors: Zhang Liyuan , Huang Ping , Chen Hui , Tan Wen , Lu Jiawei , Liu Wei , Wang Jingdong , Zhang Shuyu , Zhu Wei , Cao Jianping , Tian Ye , Yang Hongying
Published: November 2017

Due to an increasing concern about radiation-induced cognitive deficits for brain tumor patients receiving radiation therapy, developing and evaluating countermeasures has become inevitable. Our previous study has found that minocycline, a clinical available antibiotics that can easily cross the blood brain barrier, mitigates radiation-induced long-term memory loss in rats, accompanied by decreased hippocampal neuron apoptosis. Thus, in the present study, we report an unknown mechanism underlying the neuroprotective effect of minocycline. We demonstrated that minocycline prevented primary neurons from radiation-induced apoptosis and promoted radiation-induced autophagy in vitro. Moreover, using an immortalized mouse hippocampal neuronal cell line, HT22 cells, we found that the protective effect of minocycline on irradiated HT22 cells was not related to DNA damage repair since minocycline did not facilitate DNA DSB repair in irradiated HT22 cells. Further investigation showed that minocycline significantly enhanced X-irradiation-induced AMPKα1 activation and autophagy, thus resulting in decreased apoptosis. Additionally, although the antioxidant potential of minocycline might contribute to its apoptosis-inhibitory effect, it was not involved in its enhancive effect on radiation-induced AMPKα1-mediated autophagy. Taken together, we have revealed a novel mechanism for the protective effect of minocycline on irradiated neurons, e.g. minocycline protects neurons from radiation-induced apoptosis via enhancing radiation-induced AMPKα1-mediated autophagy.
Assessment of Unusual Gigantic Jets observed during the Monsoon season: First observations from Indian Subcontinent
Authors: Singh Rajesh , Maurya Ajeet K. , Chanrion Olivier , Neubert Torsten , Cummer Steven A. , Mlynarczyk Janusz , Cohen Morris B. , Siingh Devendraa , Kumar Sushil
Published: November 2017

Gigantic Jets are electric discharges from thunderstorm cloud tops to the bottom of ionosphere at ~90 km altitude and electrically connect the troposphere and lower ionosphere. Since their first report in 2002, sporadic observations have been reported from ground and space based observations. Here we report first observations of Gigantic Jets in Indian subcontinent over the Indo-Gangetic plains during the monsoon season. Two storms each produced two jets with characteristics not documented so far. Jets propagated ~37 km up remarkably in ~5 ms with velocity of ~7.4 × 106ms−1 and disappeared within ~40–80 ms, which is faster compared to jets reported earlier. The electromagnetic signatures show that they are of negative polarity, transporting net negative charge of ~17–23 C to the lower ionosphere. One jet had an unusual form observed for the first time, which emerged from the leading edge of a slowly drifting complex convective cloud close to the highest regions at ~17 km altitude. A horizontal displacement of ~10 km developed at ~50 km altitude before connecting to the lower ionosphere. Modeling of these Gigantic jets suggests that Gigantic Jets may bend when initiated at the edge of clouds with misaligned vertical charge distribution.
The interactive effects of arbuscular mycorrhiza and plant growth-promoting rhizobacteria synergistically enhance host plant defences against pathogens
Authors: Pérez-de-Luque Alejandro , Tille Stefanie , Johnson Irene , Pascual-Pardo David , Ton Jurriaan , Cameron Duncan D.
Published: November 2017

Belowground interactions between plant roots, mycorrhizal fungi and plant growth-promoting rhizobacteria (PGPR) can improve plant health via enhanced nutrient acquisition and priming of the plant immune system. Two wheat cultivars differing in their ability to form mycorrhiza were (co)inoculated with the mycorrhizal fungusRhizophagus irregularisand the rhizobacterial strainPseudomonas putidaKT2440. The cultivar with high mycorrhizal compatibility supported higher levels of rhizobacterial colonization than the low compatibility cultivar. Those levels were augmented by mycorrhizal infection. Conversely, rhizobacterial colonization of the low compatibility cultivar was reduced by mycorrhizal arbuscule formation. Single inoculations withR. irregularisorP. putidahad differential growth effects on both cultivars. Furthermore, while both cultivars developed systemic priming of chitosan-induced callose after single inoculations withR. irregularisorP. putida, only the cultivar with high mycorrhizal compatibility showed a synergistic increase in callose responsiveness following co-inoculation with both microbes. Our results show that multilateral interactions between roots, mycorrhizal fungi and PGPR can have synergistic effects on growth and systemic priming of wheat.
Impact of Oxidant Gases on the Relationship between Outdoor Fine Particulate Air Pollution and Nonaccidental, Cardiovascular, and Respiratory Mortality
Authors: Weichenthal Scott , Pinault Lauren L. , Burnett Richard T.
Published: November 2017

Outdoor fine particulate air pollution (PM2.5) is known to increase mortality risk and is recognized as an important contributor to global disease burden. However, less is known about how oxidant gases may modify the chronic health effects of PM2.5. In this study, we examined how the oxidant capacity of O3 and NO2 (using a redox-weighted average, Ox) may modify the relationship between PM2.5 and mortality in the 2001 Canadian Census Health and Environment Cohort. In total, 2,448,500 people were followed over a 10.6-year period. Each 3.86 µg/m3 increase in PM2.5 was associated with nonaccidental (Hazard Ratio (HR) = 1.095, 95% CI: 1.077, 1.112), cardiovascular (HR = 1.088, 95% CI: 1.059, 1.118), and respiratory mortality (HR = 1.110, 95% CI: 1.051, 1.171) in the highest tertile of Ox whereas weaker/null associations were observed in the middle and lower tertiles. Analysis of joint non-linear concentration-response relationships for PM2.5 and Ox suggested threshold concentrations between approximately 23 and 25 ppb with Ox concentrations above these values strengthening PM2.5-mortality associations. Overall, our findings suggest that oxidant gases enhance the chronic health risks of PM2.5. In some areas, reductions in Ox concentrations may have the added benefit of reducing the public health impacts of PM2.5 even if mass concentrations remain unchanged.