bluuebunny/crossref_metadata_2025 huggingface dataset:
Paraneoplastic cerebellar degeneration and lambert‐eaton myasthenia in a patient with merkel cell carcinoma and voltage‐gated calcium channel antibodies
Authors: Pavolucci Lucia , Giannini Giulia , Giannoccaro Maria Pia , Foschini Maria Pia , Lang Bethan , Avoni Patrizia , Tinuper Paolo , Vincent Angela , Liguori Rocco
Published: December 2016

Introduction

Merkel cell carcinoma is a rare cutaneous, aggressive tumor. Although it shares many neuroendocrine features with small cell lung carcinoma, it has only occasionally been reported with paraneoplastic neurological syndromes.

Methods

A healthy 67‐year‐old man developed acute ataxia, vertigo, and nausea. Subsequently he also developed dysarthria, diplopia, xerostomia, fatigability and progressive anorexia. He underwent a full diagnostic workup and was found to have a high titer of voltage‐gated calcium channel antibodies in serum and cerebrospinal fluid, neurophysiological findings compatible with Lambert‐Eaton myasthenia and neurological signs compatible with cerebellar degeneration.

Results

A positron emission tomography study revealed a hypermetabolic lesion in the axilla, subsequently biopsied and consistent with Merkel cell carcinoma.

Conclusions

In most previous reports, neurological symptoms preceded the Merkel cell carcinoma diagnosis, and the primary localization was in lymph nodes. This tumor should be considered in patients with paraneoplastic syndrome, and particularly Lambert‐Eaton myasthenia after exclusion of small cell lung carcinoma. Muscle Nerve 56: 998–1000, 2017
Neuromuscular ultrasound for evaluation of scapular winging
Authors: Krzesniak‐Swinarska Monika , Caress James B. , Cartwright Michael S.
Published: December 2016

Introduction

Clinicians who treat nerve and muscle disorders may be asked to evaluate patients who have unilateral or bilateral scapular winging. Traditionally, this evaluation has relied upon a thorough history, physical examination, and electrodiagnostic testing to localize the cause of winging and detect the underlying neuromuscular pathology. Neuromuscular ultrasound has emerged as a non‐invasive technique that can be used for structural evaluation of nerve and muscle abnormalities.

Methods

Previous studies of imaging in scapular winging and experiences from our diagnostic laboratory are reviewed. Results: Four standard and 4 ancillary ultrasound views are described for evaluation of scapular winging.

Conclusion

Ultrasound is a non‐invasive, painless, and radiation‐free technology that can be used to evaluate scapular winging. Muscle Nerve 56: 7–14, 2017.
Heavier and lighter load resistance training to momentary failure produce similar increases in strength with differing degrees of discomfort
Authors: Fisher James Peter , Steele James
Published: December 2016

Introduction

It has been suggested that disparities in effort and discomfort between high‐ and low‐load resistance training might exist, which in turn have produced unequivocal adaptations between studies.

Methods

Strength responses to heavier load (HL; 80% maximum voluntary isometric torque; MVIT) and lighter load (LL; 50% MVIT) resistance training were examined in addition to acute perceptions of effort and discomfort. Seven men (20.6 ± 0.5 years, 178.9 ± 3.2 cm, 77.1 ± 2.7 kg) performed unilateral resistance training of the knee extensors to momentary failure using HL and LL.

Results

Analyses revealed significant pre‐ to post‐intervention increases in strength for both HL and LL, with no significant between‐group differences (P > 0.05). Mean repetitions per set, total training time, and discomfort were all significantly higher for LL compared with HL (P < 0.05).

Conclusion

This study indicates that resistance training with HL and LL produces similar strength adaptations, but discomfort should be considered before selecting a training load.Muscle Nerve56: 797–803, 2017
Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE 1H MRS at 7 T
Authors: Mekle Ralf , Kühn Simone , Pfeiffer Harald , Aydin Semiha , Schubert Florian , Ittermann Bernd
Published: December 2016

The two‐fold benefit of 1H magnetic resonance spectroscopy (MRS) at high B0 fields – enhanced sensitivity and increased spectral dispersion – has been used previously to study dynamic changes in metabolite concentrations in the human brain in response to visual stimulation. In these studies, a strong visual on/off stimulus was combined with MRS data acquisition in a voxel location in the occipital cortex determined by an initial functional magnetic resonance imaging experiment. However, 1) to exclude the possibility of systemic effects (heartbeat, blood flow, etc.), which tend to be different for on/off conditions, a modified stimulation condition not affecting the target voxel needs to be employed, and 2) to assess important neurotransmitters of low concentration, in particular γ‐aminobutyric acid (GABA), it may be advantageous to analyze steady‐state, rather than dynamic, conditions. Thus, the aim of this study was to use short‐TE 1H MRS methodology at 7 T to detect differences in steady‐state metabolite levels in response to a varying stimulation paradigm in the human visual cortex. The two different stimulation conditions were termed voxel and control activation. Localized MR spectra were acquired using the SPECIAL (spin‐echo full‐intensity acquired localized) sequence. Data were analyzed using LCModel. Fifteen individual metabolites were reliably quantified. On comparison of steady‐state concentrations for voxel versus control activation, a decrease in GABA of 0.05 mmol/L (5%) and an increase in lactate of 0.04 mmol/L (7%) were found to be the only significant effects. The observed reduction in GABA can be interpreted as reduced neuronal inhibition during voxel activation, whereas the increase in lactate hints at an intensification of anaerobic glycolysis. Differences from previous studies, notably the absence of any changes in glutamate, are attributed to the modified experimental conditions. This study demonstrates that the use of advanced 1H MRS methodology at 7 T allows the detection of subtle changes in metabolite concentrations involved in neuronal activation and inhibition.
High‐performance polyimide film based hybrid nanostructures: Synthesis, characterization, and properties investigation
Authors: Shimpi Navinchandra , Hansora D.P. , Mishra Satyendra
Published: December 2016

In this research work, multihybrid nanostructures (carbon nanotube‐graphene oxide‐zinc oxide) based high‐performance polyimide (PI) nanocomposites were prepared viain situpolymerization and their properties (morphological, electrical, and viscous behaviors) were investigated. PI of industrial and laboratory grades was used to study their thermal imidization step after addition of various loadings of multihybrid nanostructures. The use of optimum amount of multihybrid nanostructures seems to be useful to overcome the use of higher amount of different conductive fillers to prepare PI‐based high‐performance nanocomposites for various applications. This study also provides a facile and promising strategy to fabricate multihybrid nanostructured high‐performance PI nanocomposites, which can be used as coating materials in various harsh conditions. POLYM. COMPOS., 39:2650–2661, 2018. © 2016 Society of Plastics Engineers
Crown‐rump length audit plots with the use of operator‐specific PAPP‐A and β‐hCG median MoM
Authors: Sabria Joan , Guirado Laura , Miró Isabel , Gómez‐Roig Maria Dolors , Borrell Antoni
Published: December 2016

Objective

Audit the crown‐rump length (CRL) measurements taken at 11 to 13 weeks scan, using operator‐specific median multiples of the median (MoM) for pregnancy‐associated plasma protein‐A (PAPP‐A) and free β‐human chorionic gonadotropin (β‐hCG) plots, to identify deviations potentially related to a systematic CRL bias.

Methods

Study population included consecutive singleton pregnancies undergoing first trimester combined screening, scanned by sonologists with at least 100 scans, during the 2011 to 2012 period. Previously described plots for PAPP‐A and β‐hCG median MoM points, with their 95% confidence intervals circles, in relation with the expected deviation line were used. These plots have been modified to adjust the deviation line to the sonologist‐specific expected MoM variation for each CRL millimetre bias according to each sonologist‐specific median gestational ages at both blood sampling and ultrasound.

Results

Twenty‐eight sonologists performing 9472 scans were included, accounting for 36% of the 77 sonologists and 70% of the 13 643 scans initially considered. Mean gestational age was 10 + 2 weeks at blood sampling and 12 + 4 weeks at ultrasound. Fifteen sonologists (53%) did not demonstrate any CRL bias, 10 (36%) present with a significant CRL underestimation, being above 2 mm in 6 (21%), and in 3 (11%) the observed deviation could not be explained by a systematic CRL bias.

Conclusions

In sonologists with more than 100 NT measurements, operator‐specific PAPP‐A and β‐hCG median MoM plots are able to identify deviations potentially related to a systematic CRL bias. Systematic underestimation above 2 mm was observed in 1/5 of them. © 2016 John Wiley & Sons, Ltd.
Staring at the masses
Authors: Lawrence Graeme
Published: December 2016

The science of people‐watching
Research Heroes
Authors: Bowman Jo
Published: December 2016

Influencing the influential
Keeping up with political polls
Authors: Macer Tim
Published: December 2016

We talk to five polling experts about one of the most visible and exacting activities undertaken by research organisations, where it is only ever a matter of time before the poll is judged as right or wrong.
Natural born allies
Authors: Birch Dave
Published: December 2016

Technology and market research
Growing Our Industry!
Authors: Raben Finn , Joe Kathy
Published: December 2016

How is our sector expanding and what does this mean for research?
5 nm Silver Nanoparticles Amplify Clinical Features of Atopic Dermatitis in Mice by Activating Mast Cells
Authors: Kang HanGoo , Kim Seungjae , Lee Kwang Hoon , Jin Shan , Kim Seo Hyeong , Lee Kangtaek , Jeon Hyungjoon , Song Young‐Geon , Lee Sang‐Won , Seo Jinwon , Park Soomin , Choi In‐Hong
Published: December 2016

The triggering effect of silver nanoparticles (NPs) on the induction of allergic reactions is evaluated, by studying the activation of mast cells and the clinical features of atopic dermatitis in a mouse model. Granule release is induced in RBL‐2H3 mast cells by 5 nm, but not 100 nm silver NPs. Increases in the levels of reactive oxygen species (hydrogen peroxide and mitochondrial superoxide) and intracellular Ca++ in mast cells are induced by 5 nm silver NPs. In a mouse model of atopic dermatitis induced by a mite allergen, the skin lesions are more severe and appear earlier in mice treated simultaneously with 5 nm silver NPs and allergen compared with mice treated with allergen alone or 100 nm silver NPs and allergen. The histological findings reveal that number of tryptase‐positive mast cells and total IgE levels in the serum increase in mice treated with 5 nm silver NPs and allergen. The results in this study indicate that cotreatment with 5 nm silver NPs stimulates mast cell degranulation and induces earlier and more severe clinical alterations in allergy‐prone individuals.
Stimuli‐Responsive Self‐Assembled DNA Nanomaterials for Biomedical Applications
Authors: Dai Ziwen , Leung Hoi Man , Lo Pik Kwan
Published: December 2016

Stimuli‐responsive DNA‐based materials represent a major class of remarkable functional nanomaterials for nano‐biotechnological applications. In this review, recent progress in the development of stimuli‐responsive systems based on self‐assembled DNA nanostructures is introduced and classified. Representative examples are presented in terms of their design, working principles and mechanisms to trigger the response of the stimuli‐responsive DNA system upon expose to a large variety of stimuli including pH, metal ions, oligonucleotides, small molecules, enzymes, heat, and light. Substantial in vitro studies have clearly revealed the advantages of the use of stimuli‐responsive DNA nanomaterials in different biomedical applications, particularly for biosensing, drug delivery, therapy and diagnostic purposes in addition to bio‐computing. Some of the challenges faced and suggestions for further development are also highlighted.
The Effect of γ‐APS Coupling Agent on High Density Polyethylene/Acrylonitrile‐Butadiene Rubber/Palm Pressed Fibre Composites
Authors: Santiagoo Ragunathan , Norizan Nabila N. , Saad Farah N. , Ismail Hanafi
Published: December 2016

The effect of γ‐aminopropyltriethoxysilane (γ‐APS) as coupling agent on the properties of High‐Density Polyethylene (HDPE)/Acrylonitrile‐butadiene rubber (NBR)/Palm Pressed Fiber (PPF) composite were studied. The composites were melt mixed using heated two roll mill at 180°C and speed of 15 rpm with six different loading (100/0/10, 80/20/10, 70/30/10, 60/40/10, 50/50/10, and 40/60/10). The effects of γ‐APS on mechanical, morphological, and chemical properties were investigated. The results showed that the treatment of γ‐APS has improved the tensile properties, morphological, and chemical properties. This may due to the good adhesion of PPF filler with HDPE/NBR matrices in the presence of γ‐APS coupling agent. Fourier Transform Infra‐red chemical analysis proves formation of Si–O–Si bond between PPF filler and HDPE/NBR matrices were responsible for this improvement. J. VINYL ADDIT. TECHNOL., 24:E71–E76, 2018. © 2016 Society of Plastics Engineers
The exon junction complex: a lifelong guardian of mRNA fate
Authors: Woodward Lauren A. , Mabin Justin W. , Gangras Pooja , Singh Guramrit
Published: December 2016

During messenger RNA (mRNA) biogenesis and processing in the nucleus, many proteins are imprinted on mRNAs assembling them into messenger ribonucleoproteins (mRNPs). Some of these proteins remain stably bound within mRNPs and have a long‐lasting impact on their fate. One of the best‐studied examples is the exon junction complex (EJC), a multiprotein complex deposited primarily 24 nucleotides upstream of exon–exon junctions as a consequence of pre‐mRNA splicing. The EJC maintains a stable, sequence‐independent, hold on the mRNA until its removal during translation in the cytoplasm. Acting as a molecular shepherd, the EJC travels with mRNA across the cellular landscape coupling pre‐mRNA splicing to downstream, posttranscriptional processes such as mRNA export, mRNA localization, translation, and nonsense‐mediated mRNA decay (NMD). In this review, we discuss our current understanding of the EJC’s functions during these processes, and expound its newly discovered functions (e.g., pre‐mRNA splicing). Another focal point is the recently unveiled in vivo EJC interactome, which has shed new light on the EJC's location on the spliced RNAs and its intimate relationship with other mRNP components. We summarize new strides being made in connecting the EJC’s molecular function with phenotypes, informed by studies of human disorders and model organisms. The progress toward understanding EJC functions has revealed, in its wake, even more questions, which are discussed throughout. WIREs RNA 2017, 8:e1411. doi: 10.1002/wrna.1411

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

RNA Processing > Splicing Regulation/Alternative Splicing

RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms
Hydrolase BioH knockout inE. colienables efficient fatty acid methyl ester bioprocessing
Authors: Kadisch Marvin , Schmid Andreas , Bühler Bruno
Published: December 2016

Fatty acid methyl esters (FAMEs) originating from plant oils are most interesting renewable feedstocks for biofuels and bio-based materials. FAMEs can also be produced and/or functionalized by engineered microbes to give access to, e.g., polymer building blocks. Yet, they are often subject to hydrolysis yielding free fatty acids, which typically are degraded by microbes. We identified BioH as the key enzyme responsible for the hydrolysis of medium-chain length FAME derivatives in different E. coli K-12 strains. E. coli ΔbioH strains showed up to 22-fold reduced FAME hydrolysis rates in comparison with respective wild-type strains. Knockout strains showed, beside the expected biotin auxotrophy, unchanged growth behavior and biocatalytic activity. Thus, high specific rates (~80 U gCDW  −1) for terminal FAME oxyfunctionalization catalyzed by a recombinant alkane monooxygenase could be combined with reduced hydrolysis. Biotransformations in process-relevant two-liquid phase systems profited from reduced fatty acid accumulation and/or reduced substrate loss via free fatty acid metabolization. The BioH knockout strategy was beneficial in all tested strains, although its effect was found to differ according to specific strain properties, such as FAME hydrolysis and FFA degradation activities. BioH or functional analogs can be found in virtually all microorganisms, making bioH deletion a broadly applicable strategy for efficient microbial bioprocessing involving FAMEs.
Sustainable Synthetic Approaches for the Preparation of Plant Oil‐Based Thermosets
Authors: Llevot Audrey
Published: December 2016

The good availability and high degree of functionalization possibilities of plant oils entitles them to be one of the most intensively studied renewable resources, especially in polymer science. However, in line with the principles of green chemistry, the use of renewable resources should be accompanied with catalytic procedures, comparably less or non‐toxic chemicals, as well as reduction of waste and energy consumption to achieve an overall sustainable process. In this review, these aspects are addressed using the example of plant oil‐based thermoset materials, which bear the advantage, in terms of sustainability, of not requiring a separation or purification step prior to polymerization. The direct homopolymerization of plant oils, as well as copolymerization, exclusively with other renewable resources, are highlighted. The sustainability of the synthesis of a broad range of thermosets including epoxy resins, polyurethane networks, polybenzoxazines and unsaturated polyesters is discussed.
Determination of Mineral Oil‐Saturated Hydrocarbons (MOSH) in Vegetable Oils by Large Scale Off‐Line SPE Combined with GC‐FID
Authors: Li Bingning , Wu Yanwen , Liu Lingling , Ouyang Jie , Ren Jiajia , Wang Yu , Wang Xinxin
Published: December 2016

A method based on an off‐line large‐scale solid phase extraction (SPE) approach combined with conventional gas chromatographic‐flame ionization detection (GC‐FID) was developed to determine the mineral oil‐saturated hydrocarbons (MOSH) in vegetable oils. A large‐scale SPE column loaded with 10 g of activated silica gel impregnated with 1% silver nitrate which was used to retain lipids and olefins in vegetable oils and the MOSH in the oil samples was eluted with hexane. Then 2 μL concentrated solution was splitlessly injected into a common GC‐FID instrument. The quantification limit reached 2.5 mg/kg when the MOSH fraction was concentrated to 0.1 mL. The accuracy of this procedure, as assessed by measuring the recoveries from spiked oil samples, was higher than 80%. This procedure was applied to analyze the MOSH in 38 commercial vegetable oils from Chinese market, which was the first survey of mineral oil contaminant in Chinese edible oils. The oil samples contaminated with different levels of MOSH, among which, 15 samples contained no mineral oils and 3 samples were contaminated with more than 50 mg/kg of MOSH. The highest contamination level was found in one of rice oils, in which the concentration of MOSH was up to 713.36 mg/kg. Of the 9 types of oils analyzed, camellia oil contained MOSH ranging between 6.76 and 78.49 mg/kg, averaging 46.72 mg/kg, indicating a higher contamination level than other types of oils. The results suggested that it is necessary to routinely detect mineral oil contamination in vegetable oils for food safety.
Prenatal Diagnosis of Rhombencephalosynapsis
Authors: Gupta Ashutosh , Fazal Tauqeer Syed , Kumar Anjali , Mehta Sanjay , Saini Pankaj
Published: December 2016

Rhombencephalosynapsis (RS) is a rare and sporadic cerebellar malformation characterized by agenesis of cerebellar vermis, fusion of the cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles. In majority of cases, RS is associated with wide range of cerebral malformations (dysgenesis or agensis of corpus callosum (ACC) and anterior commissurae, fusion of the inferior colliculi, cerebral peduncles, or thalami and hydrocephalus). A third gravida with 32 weeks of pregnancy was evaluated for hydrocephalus. The fetus had teardrop lateral ventricles, colpocephaly, upward displacement of third ventricle with abnormal posterior fossa, and an abnormal cerebellum formed by partly fused cerebellum in a single block with no individualization of the vermian structure suggestive of complete ACC with RS. Fetal MRI showed teardrop lateral ventricles, upward displacement of the third ventricle and colpocephaly partially fused cerebellar hemispheres, and no visualization of separate and distinct vermis with suspected fused superior cerebellar peduncles corroborating the ultrasound findings of complete ACC and partial RS. The baby had a very difficult postnatal course and succumbed on postnatal day 4. Prenatal diagnosis of RS and ACC is of utmost importance for prenatal counseling, as these abnormalities are uncorrectable and in most of the cases carries poor prognosis.
Summary and consensus in 7th International Conference on acoustic neuroma: An update for the management of sporadic acoustic neuromas
Authors: Wu Hao , Zhang Liwei , Han Dongyi , Mao Ying , Yang Jun , Wang Zhaoyan , Jia Wang , Zhong Ping , Jia Huan
Published: December 2016

Sporadic vestibular schwannoma (acoustic neuroma) is a benign tumor arising from cochleovestibular nerve. Nowadays, various specialties and medical centers are treating this disease, and the multidisciplinary collaboration is the trend. In an effort to promote a uniform standard for reporting clinical results, even for treatment indications, the mainly controversies were posed and discussed during the 7th International Conference on acoustic neuroma, and the agreement was summarized by the Committee of this conference. The main symptoms grading and tumor stage should note its name of classification for making them comparable. The goal of the modern managements for vestibular schwannoma is to improve the quality of life with lower mortality, lower morbidity and better neurological function preservation. The experience of surgical team and their preference might be a major factor for the outcome. Because of lacking of long‐term follow‐up large data after radiotherapy, and with the development of microsurgery, radiotherapy is now less recommended except for recurrent cases or elderly patients.
The Curious Case of Titan's Missing Clouds
Authors: Wendel JoAnna
Published: December 2016

Two instruments, one region on Titan: One instrument saw clouds, the other didn't—what's going on?
Assessing dental professionals’ understanding of tobacco prevention and control: a qualitative study in Västerbotten County, Sweden
Authors: Preet Raman , Khan Nausheen , Blomstedt Yulia , Nilsson Maria , Stewart Williams Jennifer
Published: December 2016

Aim:

To assess dental professionals’ understanding of tobacco prevention and control.

Materials and methods:

In Sweden dental hygienists receive training in tobacco prevention and control. The study setting is Västerbotton County in the north of Sweden where a number of successful tobacco control initiatives have been established. A purposeful sample comprising five male and four female dental professionals and trainees was selected. Data were collected through in-depth semi-structured individual interviews and analysed using content analysis.

Results:

Informants acknowledged limited adherence to tobacco prevention. They were not confident of their knowledge of tobacco and non-communicable disease prevention and had limited awareness of global oral health policies. Reasons for poor adherence included professional fragmentation, lack of training, and the absence of reimbursement for time spent on prevention activities.

Discussion:

The success of efforts to reduce smoking in Västerbotton County is attributed to the network of local public health initiatives with very limited involvement by local dental professionals.

Conclusions:

The findings highlight the need to more actively engage the dental workforce in tobacco control and prevention. Moreover, it is important to recognise that dental professionals can be public health advocates for tobacco control and prevention at global, national and local levels.
Vaccination to gain humoral immune memory
Authors: Sarkander Jana , Hojyo Shintaro , Tokoyoda Koji
Published: December 2016

The concept of immune memory forms the biological basis for vaccination programs. Despite advancements in the field of immune memory and vaccination, most current vaccines are evaluated by magnitude of antigen‐specific antibody titers in serum or mucosa after vaccination. It has been shown, however, that antibody‐mediated humoral immune memory is established regardless of the magnitude and duration of immune reactions, suggesting that assessment of vaccine efficacy should be performed for several years after vaccination. This long‐term investigation is disadvantageous for prevalent and pandemic infections. Long‐lived memory plasma cells and memory helper T cells which contribute to humoral immune memory are generated in the bone marrow after migration of memory cell precursors through bloodstream. Thus, it may be a novel evaluation strategy to assess the precursors of memory cells in the blood in the early phase of the immune reaction(s). We here review recent advances on the generation and maintenance of immune memory cells involved in humoral immunity and introduce a current concept of direct and short‐term assessment of humoral immune memory formation upon vaccination as a correlate of protection.
The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity
Authors: Laoui Damya , Keirsse Jiri , Morias Yannick , Van Overmeire Eva , Geeraerts Xenia , Elkrim Yvon , Kiss Mate , Bolli Evangelia , Lahmar Qods , Sichien Dorine , Serneels Jens , Scott Charlotte L. , Boon Louis , De Baetselier Patrick , Mazzone Massimiliano , Guilliams Martin , Van Ginderachter Jo A.
Published: December 2016

Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets. Monocyte-derived TADCs are prominent in tumour antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADCs have lymph node migratory potential, whereby cDC1s efficiently activate CD8+ T cells and cDC2s induce Th17 cells. Mice vaccinated with cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural TAMs and a reduction of MDSCs, while cDC1 vaccination strongly induces anti-tumour CTLs. Our data might prove important for therapeutic interventions targeted at specific TADC subsets or their precursors.
Single-cycle surface plasmon polaritons on a bare metal wire excited by relativistic electrons
Authors: op ‘t Root W.P.E.M. , Brussaard G.J.H. , Smorenburg P.W. , Luiten O.J.
Published: December 2016

Terahertz (THz) pulses are applied in areas as diverse as materials science, communication and biosensing. Techniques for subwavelength concentration of THz pulses give access to a rapidly growing range of spatial scales and field intensities. Here we experimentally demonstrate a method to generate intense THz pulses on a metal wire, thereby introducing the possibility of wave-guiding and focussing of the full THz pulse energy to subwavelength spotsizes. This enables endoscopic sensing, single-shot subwavelength THz imaging and study of strongly nonlinear THz phenomena. We generate THz surface plasmon polaritons (SPPs) by launching electron bunches onto the tip of a bare metal wire. Bunches with 160 pC charge and ≈6 ps duration yield SPPs with 6–10 ps duration and 0.4±0.1 MV m−1 electric field strength on a 1.5 mm diameter aluminium wire. These are the most intense SPPs reported on a wire. The SPPs are shown to propagate around a 90° bend.
Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines
Authors: Rong Jiawei , Collados Juan F. , Ortiz Pablo , Jumde Ravindra P. , Otten Edwin , Harutyunyan Syuzanna R.
Published: December 2016

α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N-sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure.
Observation of the topological soliton state in the Su–Schrieffer–Heeger model
Authors: Meier Eric J. , An Fangzhao Alex , Gadway Bryce
Published: December 2016

The Su–Schrieffer–Heeger (SSH) model, which captures the most striking transport properties of the conductive organic polymer trans-polyacetylene, provides perhaps the most basic model system supporting topological excitations. The alternating bond pattern of polyacetylene chains is captured by the bipartite sublattice structure of the SSH model, emblematic of one-dimensional chiral symmetric topological insulators. This structure supports two distinct nontrivial topological phases, which, when interfaced with one another or with a topologically trivial phase, give rise to topologically protected, dispersionless boundary states. Here, using 87Rb atoms in a momentum-space lattice, we realize fully tunable condensed matter Hamiltonians, allowing us to probe the dynamics and equilibrium properties of the SSH model. We report on the experimental quantum simulation of this model and observation of the localized topological soliton state through quench dynamics, phase-sensitive injection, and adiabatic preparation.
ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons
Authors: Serdar Lucas D. , Whiteside DaJuan L. , Baker Kristian E.
Published: December 2016

Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon. UPF1 ATPase mutants accumulate 3′ RNA decay fragments harbouring a ribosome stalled during premature termination that impedes complete degradation of the mRNA. The ability of UPF1 to impinge on premature termination, moreover, requires ATP-binding, RNA-binding and NMD cofactors UPF2 and UPF3. Our results reveal that ATP hydrolysis by UPF1 modulates a functional interaction between the NMD machinery and terminating ribosomes necessary for targeting substrates to accelerated degradation.
Erratum: Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation
Authors: Zydziak Nicolas , Konrad Waldemar , Feist Florian , Afonin Sergii , Weidner Steffen , Barner-Kowollik Christopher
Published: December 2016

Nature Communications 7: Article number: 13672 (2016); Published 30 November 2016; Updated 23 December 2016 Figures 1 and 6 of this Article contain errors that were introduced during the production process. In Fig. 1, the reaction conditions required to convert 1 to 7d, 2e to 9c and 1d to 10d shouldbe described by (i) and not (iv).
Validation of a genome-wide association study implied that SHTIN1 may involve in the pathogenesis of NSCL/P in Chinese population
Authors: Wang Yirui , Sun Yimin , Huang Yongqing , Pan Yongchu , Yin Aihua , Shi Bing , Du Xuefei , Ma Lan , Lan Feifei , Jiang Min , Shi Jiayu , Zhang Lei , Xiao Xue , Zhou Zhongwei , Jiang Hongbing , Wang Lin , Yang Yinxue , Cheng Jing
Published: December 2016

Orofacial clefts are among the most common birth defects in humans worldwide. A large-scale, genome-wide association study (GWAS) in the Chinese population recently identified several genetic risk variants for nonsyndromic cleft lip with or without cleft palate (NSCL/P). We selected 16 significant SNPs from the GWAS I stage (P < 1.00E-5) that had not been replicated to validate their association with NSCL/P in 1931 NSCL/P cases and 2258 controls. Ultimately, we identified a NSCL/P susceptibility loci (rs17095681 at 10q25.3, intron of SHTN1 and 27.2 kb downstream of VAX1, Pmeta = 3.80E-9, OR = 0.64) in Chinese Han and Hui populations. This locus was not high LD with the reported loci in 10q25.3. It was a newly identified independent locus in 10q25.3 associated with NSCL/P. These results imply that SHTIN1 may involve in the pathogenesis of NSCL/P advance our understanding of the genetic susceptibility to NSCL/P.
Auditory biological marker of concussion in children
Authors: Kraus Nina , Thompson Elaine C. , Krizman Jennifer , Cook Katherine , White-Schwoch Travis , LaBella Cynthia R.
Published: December 2016

Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries.
Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation
Authors: Nardini Christine , Devescovi Valentina , Liu Yuanhua , Zhou Xiaoyuan , Lu Youtao , Dent Jennifer E.
Published: December 2016

Degeneration is a hallmark of autoimmune diseases, whose incidence grows worldwide. Current therapies attempt to control the immune response to limit degeneration, commonly promoting immunodepression. Differently, mechanical stimulation is known to trigger healing (regeneration) and it has recently been proposed locally for its therapeutic potential on severely injured areas. As the early stages of healing consist of altered intra- and inter-cellular fluxes of soluble molecules, we explored the potential of this early signal to spread, over time, beyond the stimulation district and become systemic, to impact on distributed or otherwise unreachable injured areas. We report in a model of arthritis in rats how stimulations delivered in the subcutaneous dorsal tissue result, over time, in the control and healing of the degeneration of the paws’ joints, concomitantly with the systemic activation of wound healing phenomena in blood and in correlation with a more eubiotic microbiome in the gut intestinal district.
An Exceptionally Facile Two-Step Structural Isomerization and Detoxication via a Water-Assisted Double Lossen Rearrangement
Authors: Li Feng , Huang Chun-Hua , Xie Lin-Na , Qu Na , Shao Jie , Shao Bo , Zhu Ben-Zhan
Published: December 2016

N-hydroxyphthalimide (NHPI), which is best known as an organocatalyst for efficient C-H activation, has been found to be oxidized by quinoid compounds to its corresponding catalytically active nitroxide-radical. Here, we found that NHPI can be isomerized into isatoic anhydride by an unusually facile two-step method using tetrachloro-1,4-benzoquinone (TCBQ, p-chloranil), accompanied by a two-step hydrolytic dechlorination of highly toxic TCBQ into the much less toxic dihydroxylation product, 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone (chloranilic acid). Interestingly, through the complementary application of oxygen-18 isotope-labeling, HPLC combined with electrospray ionization quadrupole time-of-flight and high resolution Fourier transform ion cyclotron resonance mass spectrometric studies, we determined that water was the source and origin of oxygen for isatoic anhydride. Based on these data, we proposed that nucleophilic attack with a subsequent water-assisted Lossen rearrangement coupled with rapid intramolecular addition and cyclization in two consecutive steps was responsible for this unusual structural isomerization of NHPI and concurrent hydroxylation/detoxication of TCBQ. This is the first report of an exceptionally facile double-isomerization of NHPI via an unprecedented water-assisted double-Lossen rearrangement under normal physiological conditions. Our findings may have broad implications for future research on hydroxamic acids and polyhalogenated quinoid carcinogens, two important classes of compounds of major chemical and biological interest.
Timing and quality of sleep in a rural Brazilian family-based cohort, the Baependi Heart Study
Authors: Beijamini F. , Knutson K. L. , Lorenzi-Filho G. , Egan K. J. , Taporoski T. P. , De Paula L. K. G. , Negrão A. B. , Horimoto A. R. V. R. , Duarte N. E. , Vallada H. , Krieger J. E. , Pedrazzoli M. , Pereira A. C. , von Schantz M.
Published: December 2016

Sleep is modulated by several factors, including sex, age, and chronotype. It has been hypothesised that contemporary urban populations are under pressure towards shorter sleep duration and poorer sleep quality. Baependi is a small town in Brazil that provides a window of opportunity to study the influence of sleep patterns in a highly admixed rural population with a conservative lifestyle. We evaluated sleep characteristics, excessive daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire questionnaires, respectively. The sample consisted of 1,334 subjects from the Baependi Heart study (41.5% male; age: 46.5 ± 16.2 y, range: 18–89 years). Average self-reported sleep duration was 07:07 ± 01:31 (bedtime 22:32 ± 01:27, wake up time: 06:17 ± 01:25 hh:min), sleep quality score was 4.9 + 3.2, chronotype was 63.6 ± 10.8 and daytime sleepiness was 7.4 ± 4.8. Despite a shift towards morningness in the population, chronotype remained associated with reported actual sleep timing. Age and sex modulated the ontogeny of sleep and chronotype, increasing age was associated with earlier sleep time and shorter sleep duration. Women slept longer and later, and reported poorer sleep quality than men (p < 0.0001). This study provides indirect evidence in support of the hypothesis that sleep timing was earlier prior to full urbanisation.
Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway
Authors: Li Shao , Wang Xi , Ma Quan-Hong , Yang Wu-lin , Zhang Xiao-Gang , Dawe Gavin S. , Xiao Zhi-Cheng
Published: December 2016

Amyloid precursor protein (APP), commonly associated with Alzheimer’s disease, also marks axonal degeneration. In the recent studies, we demonstrated that APP aggregated at nodes of Ranvier (NORs) in myelinated central nervous system (CNS) axons and interacted with Nav1.6. However, the physiological function of APP remains unknown. In this study, we described reduced sodium current densities in APP knockout hippocampal neurons. Coexpression of APP or its intracellular domains containing a VTPEER motif with Nav1.6 sodium channels in Xenopus oocytes resulted in an increase in peak sodium currents, which was enhanced by constitutively active Go mutant and blocked by a dominant negative mutant. JNK and CDK5 inhibitor attenuated increases in Nav1.6 sodium currents induced by overexpression of APP. Nav1.6 sodium currents were increased by APPT668E (mutant Thr to Glu) and decreased by T668A (mutant Thr to ALa) mutant, respectively. The cell surface expression of Nav1.6 sodium channels in the white matter of spinal cord and the spinal conduction velocity is decreased in APP, p35 and JNK3 knockout mice. Therefore, APP modulates Nav1.6 sodium channels through a Go-coupled JNK pathway, which is dependent on phosphorylation of APP at Thr668.
The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis
Authors: Hwang Jae Ryoung , Cho Young-Jae , Lee Yoonna , Park Youngmee , Han Hee Dong , Ahn Hyung Jun , Lee Je-Ho , Lee Jeong-Won
Published: December 2016

Insulin-like growth factor-binding protein 5 (IGFBP-5) plays a role in cell growth, differentiation, and apoptosis. In this study, we found that IGFBP5 was markedly downregulated in ovarian cancer tissue. We investigated the functional significance of IGFBP-5 as a tumor suppressor. To determine functional regions of IGFBP-5, truncation mutants were prepared and were studied the effect on tumor growth. Expression of C-terminal region of IGFBP-5 significantly decreased tumor growth in an ovarian cancer xenograft. A peptide derived from the C-terminus of IGFBP-5 (BP5-C) was synthesized to evaluate the minimal amino acid motif that retained anti-tumorigenic activity and its effect on angiogenesis was studied. BP5-C peptide decreased the expression of VEGF-A and MMP-9, phosphorylation of Akt and ERK, and NF-kB activity, and inhibited angiogenesis in in vitro and ex vivo systems. Furthermore, BP5-C peptide significantly decreased tumor weight and angiogenesis in both ovarian cancer orthotopic xenograft and patient-derived xenograft mice. These results suggest that the C-terminus of IGFBP-5 exerts anti-cancer activity by inhibiting angiogenesis via regulation of the Akt/ERK and NF-kB–VEGF/MMP-9 signaling pathway, and might be considered as a novel angiogenesis inhibitor for the treatment of ovarian cancer.
Correction: Corrigendum: UPLC-PDA-QTOFMS-guided isolation of prenylated xanthones and benzoylphloroglucinols from the leaves of Garcinia oblongifolia and their migration-inhibitory activity
Authors: Zhang Hong , Zheng Dan , Ding Zhi-Jie , Lao Yuan-Zhi , Tan Hong-Sheng , Xu Hong-Xi
Published: December 2016

Scientific Reports 6: Article number: 35789; published online: 21 October 2016; updated: 23 December 2016
Glycosuria and Renal Outcomes in Patients with Nondiabetic Advanced Chronic Kidney Disease
Authors: Hung Chi-Chih , Lin Hugo You-Hsien , Lee Jia-Jung , Lim Lee Moay , Chiu Yi-Wen , Chiang Heng-Pin , Hwang Shang-Jyh , Chen Hung-Chun
Published: December 2016

Sodium glucose cotransporter 2 inhibitors have shown a potential for renoprotection beyond blood glucose lowering. Glycosuria in nondiabetic patients with chronic kidney disease (CKD) is sometimes noted. Whether glycosuria in CKD implies a channelopathy or proximal tubulopathy is not known. The consequence of glycosuria in CKD is also not studied. We performed a cross-sectional study for the association between glycosuria and urine electrolyte excretion in 208 nondiabetic patients. Fractional excretion (FE) of glucose >4% was 3.4%, 6.3% and 62.5% in CKD stage 3, 4 and 5, respectively. These patients with glycosuria had higher FE sodium, FE potassium, FE uric acid, UPCR, and urine NGAL-creatinine ratio. We conducted a longitudinal study for the consequence of glycosuria, defined by dipstick, in 769 nondiabetic patients with stage 4–5 CKD. Glycosuria was associated with a decreased risk for end-stage renal disease (adjusted hazard ratio: 0.77; CI = 0.62–0.97; p = 0.024) and for rapid renal function decline (adjusted odds ratio: 0.63; CI = 0.43–0.95; p = 0.032); but glycosuria was not associated with all-cause mortality or cardiovascular events. The results were consistent in the propensity-score matched cohort. Glycosuria is associated with increased fractional excretion of electrolytes and is related to favorable renal outcomes in nondiabetic patients with stage 5 CKD.
Down-regulation of common NFκB-iNOS pathway by chronic Thalidomide treatment improves Hepatopulmonary Syndrome and Muscle Wasting in rats with Biliary Cirrhosis
Authors: Li Tzu-Hao , Lee Pei-Chang , Lee Kuei-Chuan , Hsieh Yun-Cheng , Tsai Chang-Youh , Yang Ying-Ying , Huang Shiang-Fen , Tsai Tung-Hu , Hsieh Shie-Liang , Hou Ming-Chih , Lin Han-Chieh , Lee Shou-Dong
Published: December 2016

Thalidomide can modulate the TNFα-NFκB and iNOS pathway, which involve in the pathogenesis of hepatopulmonary syndrome (HPS) and muscle wasting in cirrhosis. In bile duct ligated-cirrhotic rats, the increased circulating CD16+(inflammatory) monocytes and its intracellular TNFα, NFκB, monocyte chemotactic protein (MCP-1) and iNOS levels were associated with increased circulating MCP-1/soluable intercellular cell adehesion molecule-1 (sICAM-1), pulmonary TNFα/NOx, up-regulated M1 polarization, exacerbated angiogenesis and hypoxemia (increased AaPO2) in bronchoalveolar lavage (BAL) fluid and pulmonary homogenates. Meanwhile, a significant correlation was noted between circulating CD16+monocyte/M1 (%) macrophages in BAL; M1 (%) macrophages in BAL/pulmonary iNOS mRNA expression; pulmonary iNOS mRNA expression/relative pulmonary MVD; pulmonary NOx level/AaPO2; circulating CD16+monocyte/M1 (%) macrophages in muscle homogenates; 3-nitrotyrosine (representative of peroxynitrite) concentration/M1 (%) macrophages in muscle homogenates. Thein vitrodata demonstrated an iNOS-dependent inhibition of thalidomide on the TNFα-stimulated angiogenesis and myogenesis in human pulmonary artery endothelial cells (HPAECs) and C2C12 myoblasts. Significantly, the co-culture of CD16+monocyte from different rats with HPAECs, or co-culture of supernatant of above mixed cultures with HPAECs or C2C12 myoblasts stimulated angiogenesis, migration and myogenesis. Our findings demonstrate that TNFα inhibitor thalidomide markedly diminishes the severity of experimental HPS and muscle wasting by down-regulation of common peripheral and local NFκB-iNOS pathway.