bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction to Michael B. Katz 2015 SSHA Memorial Session
Authors: Graff Harvey J.
Published: October 2017

I first met Michael Katz on a clear, cool autumn afternoon in 1970. I was an uncertain first-year graduate student at the University of Toronto intending to complete a doctorate in British history with a project on antisocialism. Feeling confused, anxious, and unsatisfied by my courses, I began to share my concerns with fellow students. One of them, who became a lifelong friend (and editor), suggested that I contact that “young professor up the street” in history of education at the Ontario Institute for Studies in Education who worked in the new social history. Having read Thernstrom, Tilly, E. P. Thompson, Eric Hobsbawm, Barrington Moore, and so forth, in a senior honors seminar, I drew up my courage and went to meet Michael.
Microstream capnography during conscious sedation with midazolam for oral surgery: a randomised controlled trial
Authors: Brady Paul , Iohom Gabriella , O’Halloran Ken D , McCreary Christine , Cronin Michael
Published: October 2017

Objectives/Aims:

There has been no dentistry-specific published data supporting the use of monitoring with capnography for dental sedation. Our aim was to determine if adding capnography to standard monitoring during conscious sedation with midazolam would decrease the incidence of hypoxaemia.

Materials and Methods:

A randomised controlled trial was conducted in which all patients (ASA I and II) received standard monitoring and capnography, but were randomised to whether staff could view the capnography (intervention) or were blinded to it (control). The primary outcome was the incidence of hypoxaemia (SpO2⩽94%).

Results:

We enrolled 190 patients, mean age 31 years (range, 14–62 years). There were 93 patients in the capnography group and 97 in the control group. The mean cumulative dose of midazolam titrated was 6.94 mg (s.d., 2.31; range, 3–20 mg). Six (3%) patients, three in each group, required temporary supplemental oxygen. There was no statistically significant difference between the capnography and control groups for the incidence of hypoxaemia: 34.4 vs 39.2% (P=0.4962, OR=0.81, 95% CI: 0.45–1.47).

Conclusions:

We were unable to confirm an additive role for capnography to prevent hypoxaemia during conscious sedation with midazolam for patients not routinely administered supplemental oxygen.
Use of 21-gene recurrence score assay to individualize adjuvant chemotherapy recommendations in ER+/HER2− node positive breast cancer—A National Cancer Database study
Authors: Peethambaram Prema P. , Hoskin Tanya L. , Day Courtney N. , Goetz Matthew P. , Habermann Elizabeth B. , Boughey Judy C.
Published: October 2017

The 21-gene Recurrence Score (RS) assay is prognostic and predictive of adjuvant chemotherapy benefit in node positive (N+) breast cancer (BC). We sought to evaluate use patterns of RS assay in N+, ER+/HER2− BC and the impact of RS on recommendations for adjuvant chemotherapy. Patients with T1-T4c,N1mi-N3, ER+/HER2− BC diagnosed 2010–2013 in the National Cancer Database were analyzed. Multivariable logistic regression assessed factors influencing RS testing and chemotherapy recommendations based on RS. Among 72,897 patients, RS was obtained in 20.6%, increasing from 15.0% in 2010 to 24.5% in 2013 (p < 0.001). RS testing was most common in N1mi (43.7%) followed by N1 (22.1%) and rare in N2/N3 (3.3%). Of the 12,536 with quantitative RS results, 61.1% were low RS, 32.3% intermediate RS and 6.6% high RS. Chemotherapy was recommended less frequently in patients with RS testing (50.4%) vs. those not tested (81.0%, p < 0.001). In N1mi/N1 patients, chemotherapy recommendation varied by RS; however, in N2/N3 patients, chemotherapy was recommended in the majority (70.9–87.5%) regardless of RS. Most patients (>85%) with RS ≥ 26 were recommended chemotherapy regardless of nodal stage. For patients with RS < 26, chemotherapy recommendations increased with higher N and T stage, grade, and younger age (p < 0.001). Histology was not associated with chemotherapy recommendation in any RS subset. The RS assay is frequently and increasingly being used for decision making in node positive ER+/HER2− breast cancer patients and its use is associated with lower rates of adjuvant chemotherapy.
Evidence for long-term sensitization of the bowel in patients with post-infectious-IBS
Authors: Balemans D. , Mondelaers S. U. , Cibert-Goton V. , Stakenborg N. , Aguilera-Lizarraga J. , Dooley J. , Liston A. , Bulmer D. C. , Vanden Berghe P. , Boeckxstaens G. E. , Wouters M. M.
Published: October 2017

Post-infectious irritable bowel syndrome (PI-IBS) is a common gastrointestinal disorder characterized by persistent abdominal pain despite recovery from acute gastroenteritis. The underlying mechanisms are unclear, although long-term changes in neuronal function, and low grade inflammation of the bowel have been hypothesized. We investigated the presence and mechanism of neuronal sensitization in a unique cohort of individuals who developed PI-IBS following exposure to contaminated drinking water 7 years ago. We provide direct evidence of ongoing sensitization of neuronal signaling in the bowel of patients with PI-IBS. These changes occur in the absence of any detectable tissue inflammation, and instead appear to be driven by pro-nociceptive changes in the gut micro-environment. This is evidenced by the activation of murine colonic afferents, and sensitization responses to capsaicin in dorsal root ganglia (DRGs) following application of supernatants generated from tissue biopsy of patients with PI-IBS. We demonstrate that neuronal signaling within the bowel of PI-IBS patients is sensitized 2 years after the initial infection has resolved. This sensitization appears to be mediated by a persistent pro-nociceptive change in the gut micro-environment, that has the capacity to stimulate visceral afferents and facilitate neuronal TRPV1 signaling.
Odour dialects among wild mammals
Authors: Kean Eleanor Freya , Bruford Michael William , Russo Isa-Rita M. , Müller Carsten Theodor , Chadwick Elizabeth Anna
Published: October 2017

Across multiple taxa, population structure and dynamics depend on effective signalling between individuals. Among mammals, chemical communication is arguably the most important sense, underpinning mate choice, parental care, territoriality and even disease transmission. There is a growing body of evidence that odours signal genetic information that may confer considerable benefits including inbreeding avoidance and nepotism. To date, however, there has been no clear evidence that odours encode population-level information in wild mammals. Here we demonstrate for the first time the existence of ‘odour dialects’ in genetically distinct mammalian subpopulations across a large geographical scale. We found that otters, Lutra lutra, from across the United Kingdom possess sex and biogeography-specific odours. Subpopulations with the most distinctive odour profiles are also the most genetically diverse but not the most genetically differentiated. Furthermore, geographic distance between individuals does not explain regional odour differences, refuting other potential explanations such as group odour sharing behaviour. Differences in the language of odours between subpopulations have the potential to affect individual interactions, which could impact reproduction and gene-flow.
Correlation between crystallographic anisotropy and dendritic orientation selection of binary magnesium alloys
Authors: Du Jinglian , Guo Zhipeng , Zhang Ang , Yang Manhong , Li Mei , Xiong Shoumei
Published: October 2017

Both synchrotron X-ray tomography and EBSD characterization revealed that the preferred growth directions of magnesium alloy dendrite change as the type and amount of solute elements. Such growth behavior was further investigated by evaluating the orientation-dependent surface energy and the subsequent crystallographic anisotropy via ab-initio calculations based on density functional theory and hcp lattice structure. It was found that for most binary magnesium alloys, the preferred growth direction of the α-Mg dendrite in the basal plane is always $$\langle 11\bar{2}0\rangle $$
〈

11

2
¯

0

〉
, and independent on either the type or concentration of the additional elements. In non-basal planes, however, the preferred growth direction is highly dependent on the solute concentration. In particular, for Mg-Al alloys, this direction changes from $$\langle 11\bar{2}3\rangle $$
〈

11

2
¯

3

〉
to $$\langle 22\bar{4}5\rangle $$
〈

22

4
¯

5

〉
as the Al-concentration increased, and for Mg-Zn alloys, this direction changes from $$\langle 11\bar{2}3\rangle $$
〈

11

2
¯

3

〉
to $$\langle 22\bar{4}5\rangle $$
〈

22

4
¯

5

〉
or $$\langle 11\bar{2}2\rangle $$
〈

11

2
¯

2

〉
as the Zn-content varied. Our results provide a better understanding on the dendritic orientation selection and morphology transition of magnesium alloys at the atomic level.
From Porous to Dense Nanostructured β-Ti alloys through High-Pressure Torsion
Authors: Afonso Conrado R. M. , Amigó Angelica , Stolyarov Vladimir , Gunderov Dmitri , Amigó Vicente
Published: October 2017

β-Ti alloys have low elastic modulus, good specific strength and high corrosion resistance for biomaterial applications. Noble elements, such as Nb, Ta and Mo, are used to obtain β-Ti due to their chemical biocompatibility. However, due to their refractory nature, β-Ti requires specific processing routes. Powder metallurgy (P/M) allows for the development of new β-Ti alloys with decreasing costs, but dealing with high-elemental-content alloys can lead to a lack of diffusion and grain growth. One method to refine the structure and improve mechanical properties is a severe plastic deformation technique through high-pressure torsion (HPT). The aim of this work was to evaluate the conversion of P/M porous β-Ti-35Nb-10Ta-xFe alloys to dense nanostructures through high-pressure torsion in one deformation step and the influence of the structure variation on the properties and microstructure. TEM analysis and ASTAR crystallographic mapping was utilized to characterize the nanostructures, and the properties of P/M β Ti-35Nb-10Ta-xFe alloys processed by HPT were compared. The initial microstructure consisted mainly by the β-Ti phase with some α-Ti phase at the grain boundaries. The HPT process refined the microstructure from 50 µm (P/M) down to nanostructured grains of approximately 50 nm.
Comparative transcriptomics reveal developmental turning points during embryogenesis of a hemimetabolous insect, the damselfly Ischnura elegans
Authors: Simon Sabrina , Sagasser Sven , Saccenti Edoardo , Brugler Mercer R. , Schranz M. Eric , Hadrys Heike , Amato George , DeSalle Rob
Published: October 2017

Identifying transcriptional changes during embryogenesis is of crucial importance for unravelling evolutionary, molecular and cellular mechanisms that underpin patterning and morphogenesis. However, comparative studies focusing on early/embryonic stages during insect development are limited to a few taxa. Drosophila melanogaster is the paradigm for insect development, whereas comparative transcriptomic studies of embryonic stages of hemimetabolous insects are completely lacking. We reconstructed the first comparative transcriptome covering the daily embryonic developmental progression of the blue-tailed damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative. We identified a “core” set of 6,794 transcripts – shared by all embryonic stages – which are mainly involved in anatomical structure development and cellular nitrogen compound metabolic processes. We further used weighted gene co-expression network analysis to identify transcriptional changes during Odonata embryogenesis. Based on these analyses distinct clusters of transcriptional active sequences could be revealed, indicating that embryos at different development stages have their own transcriptomic profile according to the developmental events and leading to sequential reprogramming of metabolic and developmental genes. Interestingly, a major change in transcriptionally active sequences is correlated with katatrepsis (revolution) during mid-embryogenesis, a 180° rotation of the embryo within the egg and specific to hemimetabolous insects.
A new cellular type in invertebrates: first evidence of telocytes in leech Hirudo medicinalis
Authors: Pulze Laura , Baranzini Nicolò , Girardello Rossana , Grimaldi Annalisa , Ibba-Manneschi Lidia , Ottaviani Enzo , Reguzzoni Marcella , Tettamanti Gianluca , de Eguileor Magda
Published: October 2017

Telocytes, a peculiar cell type, were recently found in vertebrates. Hence this cell system has been reported as ubiquitous in the bodies of mammals and interpreted as an important player in innate immunity and tissue regeneration, it is reasonable to look for it also in invertebrates, that rely their integrity solely by innate immunity. Here we describe, at morphological and functional level, invertebrate telocytes from the body of leechHirudo medicinalis(Annelida), suggesting how these cells, forming a resident stromal 3D network, can influence or participate in different events. These findings support the concepts that leech telocytes: i) are organized in a cellular dynamic and versatile 3D network likewise the vertebrate counterpart; ii) are an evolutionarily conserved immune-neuroendocrine system; iii) form an immuno-surveillance system of resident cells responding faster than migrating immunocytes recruited in stimulated area; iv) communicate with neighbouring cells directly and indirectly, via cell-cell contacts and soluble molecules secreted by multivesicular bodies; v) present within neo-vessels, share with immunocytes the mesodermal lineage; vi) are involved in regenerative processes. In conclusion, we propose that HmTCs, integrating so different functions, might explain the innate immune memory and can be associated with several aged related diseases.
The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats
Authors: Thongnak Laongdao , Pongchaidecha Anchalee , Jaikumkao Krit , Chatsudthipong Varanuj , Chattipakorn Nipon , Lungkaphin Anusorn
Published: October 2017

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several “pleiotropic” effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.
Genome-Guided Phylo-Transcriptomic Methods and the Nuclear Phylogenetic Tree of the Paniceae Grasses
Authors: Washburn Jacob D. , Schnable James C. , Conant Gavin C. , Brutnell Thomas P. , Shao Ying , Zhang Yang , Ludwig Martha , Davidse Gerrit , Pires J. Chris
Published: October 2017

The past few years have witnessed a paradigm shift in molecular systematics from phylogenetic methods (using one or a few genes) to those that can be described as phylogenomics (phylogenetic inference with entire genomes). One approach that has recently emerged is phylo-transcriptomics (transcriptome-based phylogenetic inference). As in any phylogenetics experiment, accurate orthology inference is critical to phylo-transcriptomics. To date, most analyses have inferred orthology based either on pure sequence similarity or using gene-tree approaches. The use of conserved genome synteny in orthology detection has been relatively under-employed in phylogenetics, mainly due to the cost of sequencing genomes. While current trends focus on the quantity of genes included in an analysis, the use of synteny is likely to improve the quality of ortholog inference. In this study, we combine de novo transcriptome data and sequenced genomes from an economically important group of grass species, the tribe Paniceae, to make phylogenomic inferences. This method, which we call “genome-guided phylo-transcriptomics”, is compared to other recently published orthology inference pipelines, and benchmarked using a set of sequenced genomes from across the grasses. These comparisons provide a framework for future researchers to evaluate the costs and benefits of adding sequenced genomes to transcriptome data sets.
Dopamine-mediated photothermal theranostics combined with up-conversion platform under near infrared light
Authors: Lv Ruichan , Yang Piaoping , Chen Guanying , Gai Shili , Xu Jiating , Prasad Paras N.
Published: October 2017

An organic-inorganic hybrid core-shell nanostructure, based on mesoporous silica coated upconversion core-shell nanoparticles (NaGdF4:Yb,Er@NaGdF4:Yb@mSiO2-Dopa abbreviated here as UCNP@mSiO2-Dopa) that stably incorporates dopamine (Dopa) in the silica layer was introduced as a theranostic nanoplatform for optical imaging guided photothermal therapy (PTT) using NIR excitation. Silica-attaching polyethylenimine make the Dopa transforms into an active form (transferred Dopa) that strongly absorbs light under single 980 nm irradiation. We show that the activated UCNP@mSiO2-Dopa nanoplatform is able to produce a pronounced photothermal effect, that elevates water temperature from room temperature to 41.8 °C within 2 minutes, while concurrently emitting strong upconverted luminescence (UCL) for visualized guidance under 980 nm laser. In addition, we demonstrate the application of the same UCNP@mSiO2-Dopa nanoplatform for magnetic resonance imaging (MRI) and x-ray computed tomography (CT) enabled by the gadolinium (Gd) element contained in the UCNP. Importantly, thein vitroandin vivoanti-cancer therapeutic effects have been shown efficacious, implying the use of the described nanoplatform as an effective multi-modal imaging enabled PTT agent. Results from thein vivobiodistribution of UCNPs@mSiO2, cellular live/dead assay, and histologic analysis of main organs of treated mice, reveal that the UCNP@mSiO2-Dopa agents are bio-compatible with low toxicity.
Microtome-integrated microscope system for high sensitivity tracking of in-resin fluorescence in blocks and ultrathin sections for correlative microscopy
Authors: Lemercier Nicolas , Middel Volker , Hentsch Didier , Taubert Serge , Takamiya Masanari , Beil Tanja , Vonesch Jean-Luc , Baumbach Tilo , Schultz Patrick , Antony Claude , Strähle Uwe
Published: October 2017

Many areas of biological research demand the combined use of different imaging modalities to cover a wide range of magnifications and measurements or to place fluorescent patterns into an ultrastructural context. A technically difficult problem is the efficient specimen transfer between different imaging modalities without losing the coordinates of the regions-of-interest (ROI). Here, we report a new and highly sensitive integrated system that combines a custom designed microscope with an ultramicrotome for in-resin-fluorescence detection in blocks, ribbons and sections on EM-grids. Although operating with long-distance lenses, this system achieves a very high light sensitivity. Our instrumental set-up and operating workflow are designed to investigate rare events in large tissue volumes. Applications range from studies of individual immune, stem and cancer cells to the investigation of non-uniform subcellular processes. As a use case, we present the ultrastructure of a single membrane repair patch on a muscle fiber in intact muscle in a whole animal context.
One-dimensional Confinement Effect on the Self-assembly of Symmetric H-shaped Copolymers in a Thin Film
Authors: Mu Dan , Li Jian-quan , Feng Sheng-yu
Published: October 2017

The self-assembly of a reformed symmetric H-shaped copolymer with four hydrophilic branches and one hydrophobic stem was systematically investigated. The existence of vacancies is vital to regulate the sizes of self-assembled cylinders to be able to form a hexagonal arrangement. With the introduction of horizontal-orientated confinement, a micellar structure is formed through a coalescence mechanism. The short acting distance and large influencing area of the confinement produces numerous small-sized micelles. Additionally, the cycled “contraction-expansion” change helps achieve hexagonal arrangement. In contrast, the introduction of lateral-oriented confinement with long acting distance and small influencing area cannot change the cylindrical structure. Under the fission mechanism, in which the larger cylinder splits into smaller ones, it is quite efficient to generate hierarchical-sized cylinders from larger-sized cylinders in the middle region and smaller-sized cylinders near both walls. The results indicate the possibility of regulating the characteristics of a nanomaterial by tuning the molecular structure of the copolymer and the parameters of the introduced confinement, which are closely related to the self-assembly structure.
Identification and characterization of a putative protein disulfide isomerase (HsPDI) as an alleged effector of Heterodera schachtii
Authors: Habash Samer S. , Sobczak Miroslaw , Siddique Shahid , Voigt Boris , Elashry Abdelnaser , Grundler Florian M. W.
Published: October 2017

The plant-parasitic nematode Heterodera schachtii is an obligate biotroph that induces syncytial feeding sites in roots of its hosts. Nematodes produce effectors that are secreted into the host and facilitate infection process. Here we identified H. schachtii protein disulphide isomerase (HsPDI) as a putative effector that interferes with the host’s redox status. In situ hybridization showed that HsPdi is specifically localized within esophageal glands of pre-parasitic second stage juveniles (J2). HsPdi is up-regulated in the early parasitic J2s. Silencing of HsPdi by RNA interference in the J2s hampers their development and leads to structural malfunctions in associated feeding sites induced in Arabidopsis roots. Expression of HsPDI in Arabidopsis increases plant’s susceptibility towards H. schachtii. HsPdi expression is up-regulated in the presence of exogenous H2O2, whereas HsPdi silencing results in increased mortality under H2O2 stress. Stable expression of HsPDI in Arabidopsis plants decreases ROS burst induced by flg22. Transiently expressed HsPDI in N. benthamiana leaves is localized in the apoplast. HsPDI plays an important role in the interaction between nematode and plant, probably through inducing local changes in the redox status of infected host tissue. It also contributes to protect the nematode from exogenous H2O2 stress.
The Orbiting Carbon Observatory (OCO-2) tracks 2–3 peta-gram increase in carbon release to the atmosphere during the 2014–2016 El Niño
Authors: Patra Prabir K. , Crisp David , Kaiser Johannes W. , Wunch Debra , Saeki Tazu , Ichii Kazuhito , Sekiya Takashi , Wennberg Paul O. , Feist Dietrich G. , Pollard David F. , Griffith David W. T. , Velazco Voltaire A. , De Maziere M. , Sha Mahesh K. , Roehl Coleen , Chatterjee Abhishek , Ishijima Kentaro
Published: October 2017

The powerful El Niño event of 2015–2016 – the third most intense since the 1950s – has exerted a large impact on the Earth’s natural climate system. The column-averaged CO2 dry-air mole fraction (XCO2) observations from satellites and ground-based networks are analyzed together with in situ observations for the period of September 2014 to October 2016. From the differences between satellite (OCO-2) observations and simulations using an atmospheric chemistry-transport model, we estimate that, relative to the mean annual fluxes for 2014, the most recent El Niño has contributed to an excess CO2 emission from the Earth’s surface (land + ocean) to the atmosphere in the range of 2.4 ± 0.2 PgC (1 Pg = 1015 g) over the period of July 2015 to June 2016. The excess CO2 flux is resulted primarily from reduction in vegetation uptake due to drought, and to a lesser degree from increased biomass burning. It is about the half of the CO2 flux anomaly (range: 4.4–6.7 PgC) estimated for the 1997/1998 El Niño. The annual total sink is estimated to be 3.9 ± 0.2 PgC for the assumed fossil fuel emission of 10.1 PgC. The major uncertainty in attribution arise from error in anthropogenic emission trends, satellite data and atmospheric transport.
Surface marker profiling of SH-SY5Y cells enables small molecule screens identifying BMP4 as a modulator of neuroblastoma differentiation
Authors: Ferlemann Fraua Christina , Menon Vishal , Condurat Alexandra Larisa , Rößler Jochen , Pruszak Jan
Published: October 2017

Neuroblastoma is the most common extra-cranial solid tumor in children. Its broad spectrum of clinical outcomes reflects the underlying inherent cellular heterogeneity. As current treatments often do not lead to tumor eradication, there is a need to better define therapy-resistant neuroblastoma and to identify new modulatory molecules. To this end, we performed the first comprehensive flow cytometric characterization of surface molecule expression in neuroblastoma cell lines. Exploiting an established clustering algorithm (SPADE) for unbiased visualization of cellular subsets, we conducted a multiwell screen for small molecule modulators of neuroblastoma phenotype. In addition to SH-SY5Y cells, the SH-EP, BE(2)-M17 and Kelly lines were included in follow-up analysis as in vitro models of neuroblastoma. A combinatorial detection of glycoprotein epitopes (CD15, CD24, CD44, CD57, TrkA) and the chemokine receptor CXCR4 (CD184) enabled the quantitative identification of SPADE-defined clusters differentially responding to small molecules. Exposure to bone morphogenetic protein (BMP)-4 was found to enhance a TrkAhigh/CD15−/CD184− neuroblastoma cellular subset, accompanied by a reduction in doublecortin-positive neuroblasts and of NMYC protein expression in SH-SY5Y cells. Beyond yielding novel marker candidates for studying neuroblastoma pathology, our approach may provide tools for improved pharmacological screens towards developing novel avenues of neuroblastoma diagnosis and treatment.
The efficacy and further functional advantages of random-base molecular barcodes for absolute and digital quantification of nucleic acid molecules
Authors: Ogawa Taisaku , Kryukov Kirill , Imanishi Tadashi , Shiroguchi Katsuyuki
Published: October 2017

Accurate quantification of biomolecules in system-wide measurements is in high demand, especially for systems with limited sample amounts such as single cells. Because of this, digital quantification of nucleic acid molecules using molecular barcodes has been developed, making, e.g., transcriptome analysis highly reproducible and quantitative. This counting scheme was shown to work using sequence-restricted barcodes, and non-sequence-restricted (random-base) barcodes that may provide a much higher dynamic range at significantly lower cost have been widely used. However, the efficacy of random-base barcodes is significantly affected by base changes due to amplification and/or sequencing errors and has not been investigated experimentally or quantitatively. Here, we show experimentally that random-base barcodes enable absolute and digital quantification of DNA molecules with high dynamic range (from one to more than 104, potentially up to 1015 molecules) conditional on our barcode design and variety, a certain range of sequencing depths, and computational analyses. Moreover, we quantitatively show further functional advantages of the molecular barcodes: the molecular barcodes enable one to find contaminants and misidentifications of target sequences. Our scheme here may be generally used to confirm that the digital quantification works in each platform.
A role for the purinergic receptor P2X3 in astrocytes in the mechanism of craniofacial neuropathic pain
Authors: Mah Won , Lee Sang Man , Lee Jaekwang , Bae Jin Young , Ju Jin Sook , Lee C. Justin , Ahn Dong Kuk , Bae Yong Chul
Published: October 2017

The purinergic receptor P2X3, expressed in the central terminals of primary nociceptive neurons in the brainstem, plays an important role in pathological pain. However, little is known about expression of P2X3 in the brainstem astrocytes and its involvement in craniofacial pathologic pain. To address this issue, we investigated the expression of P2X3 in astrocytes in the trigeminal caudal nucleus (Vc) in a rat model of craniofacial neuropathic pain, chronic constriction injury of infraorbital nerve (CCI-ION). We found that 1) P2X3-immunoreactivity is observed in the brainstem astrocytes, preferentially in their fine processes, 2) the number of P2X3-positive fine astrocytic processes and the density of P2X3 in these processes were increased significantly in CCI-ION rats, compared to control rats, and 3) administration of MPEP, a specific mGluR5 antagonist, alleviated the mechanical allodynia and abolished the increase in density of P2X3 in fine astrocytic processes caused by CCI-ION. These findings reveal preferential expression of P2X3 in the fine astrocytic processes in the brainstem, propose a novel role of P2X3 in the fine astrocytic process in the mechanism of craniofacial neuropathic pain, and suggest that the expression of astrocytic P2X3 may be regulated by astrocytic mGluR5.
Chronic antidepressant potentiates spontaneous activity of dorsal raphe serotonergic neurons by decreasing GABAB receptor-mediated inhibition of L-type calcium channels
Authors: Asaoka Nozomi , Nishitani Naoya , Kinoshita Haruko , Kawai Hiroyuki , Shibui Norihiro , Nagayasu Kazuki , Shirakawa Hisashi , Nakagawa Takayuki , Kaneko Shuji
Published: October 2017

Spontaneous activity of serotonergic neurons of the dorsal raphe nucleus (DRN) regulates mood and motivational state. Potentiation of serotonergic function is one of the therapeutic strategies for treatment of various psychiatric disorders, such as major depression, panic disorder and obsessive-compulsive disorder. However, the control mechanisms of the serotonergic firing activity are still unknown. In this study, we examined the control mechanisms for serotonergic spontaneous activity and effects of chronic antidepressant administration on these mechanisms by using modified ex vivo electrophysiological recording methods. Serotonergic neurons remained firing even in the absence of glutamatergic and GABAergic ionotropic inputs, while blockade of L-type voltage dependent Ca2+ channels (VDCCs) in serotonergic neurons decreased spontaneous firing activity. L-type VDCCs in serotonergic neurons received gamma-aminobutyric acid B (GABAB) receptor-mediated inhibition, which maintained serotonergic slow spontaneous firing activity. Chronic administration of an antidepressant, citalopram, disinhibited the serotonergic spontaneous firing activity by weakening the GABAB receptor-mediated inhibition of L-type VDCCs in serotonergic neurons. Our results provide a new mechanism underlying the spontaneous serotonergic activity and new insights into the mechanism of action of antidepressants.
Emotion Regulating Attentional Control Abnormalities In Major Depressive Disorder: An Event-Related Potential Study
Authors: Hu Bin , Rao Juan , Li Xiaowei , Cao Tong , Li Jianxiu , Majoe Dennis , Gutknecht Jürg
Published: October 2017

Major depressive disorders (MDD) exhibit cognitive dysfunction with respect to attention. The deficiencies in cognitive control of emotional information are associated with MDD as compared to healthy controls (HC). However, the brain mechanism underlying emotion that influences the attentional control in MDD necessitates further research. The present study explores the emotion-regulated cognitive competence in MDD at a dynamic attentional stage. Event-Related Potentials (ERPs) were recorded from 35 clinical MDD outpatients and matched HCs by applying a modified affective priming dot-probe paradigm, which consisted of various emotional facial expression pairs. From a dynamic perspective, ERPs combined with sLORETA results showed significant differences among the groups. In compared to HC, 100 ms MDD group exhibited a greater interior-prefrontal N100, sensitive to negative-neutral faces. 200 ms MDD showed an activated parietal-occipital P200 linked to sad face, suggesting that the attentional control ability concentrated on sad mood-congruent cognition. 300 ms, a distinct P300 was observed at dorsolateral parietal cortex, representing a sustained attentional control. Our findings suggested that a negatively sad emotion influenced cognitive attentional control in MDD in the early and late attentional stages of cognition. P200 and P300 might be predictors of potential neurocognitive mechanism underlying the dysregulated attentional control of MDD.
Energy-efficient waveform for electrical stimulation of the cochlear nerve
Authors: Yip Marcus , Bowers Peter , Noel Victor , Chandrakasan Anantha , Stankovic Konstantina M.
Published: October 2017

The cochlear implant (CI) is the most successful neural prosthesis, restoring the sensation of sound in people with severe-to-profound hearing loss by electrically stimulating the cochlear nerve. Existing CIs have an external, visible unit, and an internal, surgically-placed unit. There are significant challenges associated with the external unit, as it has limited utility and CI users often report a social stigma associated with prosthesis visibility. A fully-implantable CI (FICI) would address these issues. However, the volume constraint imposed on the FICI requires less power consumption compared to today’s CI. Because neural stimulation by CI electrodes accounts for up to 90% of power consumption, reduction in stimulation power will result directly in CI power savings. To determine an energy-efficient waveform for cochlear nerve stimulation, we used a genetic algorithm approach, incorporating a computational model of a single mammalian myelinated cochlear nerve fiber coupled to a stimulator-electrode-tissue interface. The algorithm’s prediction was tested in vivo in human CI subjects. We find that implementation of a non-rectangular biphasic neural stimulation waveform may result in up to 25% charge savings and energy savings within the comfortable range of hearing for CI users. The alternative waveform may enable future development of a FICI.
Gastrointestinal Hemorrhage after Spontaneous Subarachnoid Hemorrhage: A Single-Center Cohort Study
Authors: Wang Shang-Po , Huang Yu-Hua
Published: October 2017

Spontaneous subarachnoid hemorrhage (SAH) is a devastating disease, and gastrointestinal hemorrhage is one of several potential complications of acute strokes. We aim to analyze its prevalence, risk factors, and association with in-hospital prognosis following SAH. A total of 1047 adult patients with a primary diagnosis of spontaneous SAH were retrospectively enrolled. We retrieved medical information from the administrative database utilizing diagnostic and procedure codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Patients with SAH included 418 men and 629 women, and their mean age was 57.2 (standard deviation 14.6) years (range, 18–93 years). Gastrointestinal hemorrhage occurred in 30 of the 1047 patients, accounting for 2.9%. In a multivariate logistic regression model, the independent risk factors for gastrointestinal hemorrhage were liver disease and hydrocephalus. The in-hospital mortality rates were 43.3% and 29.3% in patients with and without gastrointestinal hemorrhage, respectively, but the difference was not statistically significant. In conclusion, the prevalence of gastrointestinal hemorrhage was 2.9% in patients hospitalized for spontaneous SAH. Underlying liver disease and the presence of hydrocephalus were both independent risk factors for this complication, which is a reminder to clinicians to pay increased attention in such cases.
Fabrication of a conjugated microporous polymer membrane and its application for membrane catalysis
Authors: Lee Jieun , Kim Jong Gil , Chang Ji Young
Published: October 2017

A flexible and free standing conjugated microporous polymer (CMP) membrane was prepared using a polyvinylpyrrolidone (PVP) electrospun membrane as a template. The PVP nanofibers of the template membrane were coated with a thin layer of the CMP through the in situ Sonogashira-Hagihara coupling reaction of 1,3,5-triethynylbenzene and 1,4-diiodobenzene. The PVP nanofibers were removed by the solvent extraction to produce the CMP membrane, which retained the entangled fibrous structure of the template membrane. Each fiber showed a hollow tubular structure having a CMP wall with a thickness of tens of nanometers. The microporous polymer membrane exhibited a high BET surface area with hierarchical porosity and good permeability. As a catalytic CMP membrane, the Ag nanoparticle-immobilized microporous polymer membrane was fabricated using an electrospun PVP@Ag membrane as a template. After being coated with the CMP, the PVP nanofibers were removed by the solvent extraction, but the Ag nanoparticles were trapped in the microporous polymer shell. The catalytic CMP membrane was successfully used for the catalytic reduction reaction of 4-nitrophenol. The hollow tubular structure and hierarchical porosity of the membrane allowed for the reactants to easily penetrate into the CMP wall and to contact the Ag nanoparticles, resulting in the high catalytic activity.
Florfenicol-induced Mitochondrial Dysfunction Suppresses Cell Proliferation and Autophagy in Fibroblasts
Authors: Hu Dongfang , Cao Shengliang , Zhang Guihua , Xiao Yihong , Liu Sidang , Shang Yingli
Published: October 2017

Florfenicol (FLO) is one of the most popular antibiotics used in veterinary clinic and aquaculture. FLO can inhibit both bacterial and mitochondrial protein synthesis. However, the effects of FLO on mitochondrial function and cellular homeostasis remain unclear. Here we show that FLO inhibits expression of mitochondrial DNA-encoded proteins, decreases mitochondrial membrane potential, and promotes generation of reactive oxygen species (ROS) in vitro. As a result, activities of mitochondrial respiratory chain complex I and IV and the cellular ATP level are decreased and mitochondrial morphology is damaged. FLO represses cell growth and proliferation by suppression of phosphorylation of p70S6K through AMPK/mTOR/p70S6K pathway. Furthermore, FLO also induces G0/G1 cell cycle arrest via increase of p21 levels through activating ROS/p53/p21 pathway. Moreover, the clearance of damaged mitochondria by autophagy is impaired, leading to cell proliferation inhibition and promotes cell senescence. In addition, FLO-induced upregulation of cytosolic p53 may contribute to mitophagy deficiency via regulation of Parkin recruitment. In summary, our data suggest that florfenicol is an inhibitor of mitochondrial protein synthesis that can induce noticeable cytotoxicity. Thus, these findings can be useful for guiding the proper use of FLO and the development of safe drugs.
Reference genes validation in Phenacoccus solenopsis under various biotic and abiotic stress conditions
Authors: Arya Surjeet Kumar , Jain Gourav , Upadhyay Santosh Kumar , Sarita  , Singh Harpal , Dixit Sameer , Verma Praveen Chandra
Published: October 2017

Real-time PCR (RT-qPCR) expression analysis is a powerful analytical technique, but for normalization of data requires the use of stable reference genes. However, suitable reference genes are still not known in the case ofPhenacoccus solenopsisunder variable experimental treatments. The present study focused on the identification of stable housekeeping genes as a reference for analysis under different abiotic and biotic factors inP.solenopsis. We analyzed the relative expression of six commonly used candidate reference genes in different developmental stages, host-feeding assay, temperature treatments and field distribution conditions. Expression stabilities were analyzed by geNorm, NormFinder, and RefFinder. Under developmental and field distribution conditions,β-Tubulinwas found to be most stable reference genes followed byrpl32 and α-Tubulin. In the case host feeding treatment conditions,β-Tubulinandα-tubulinidentified to be the most stable reference genes, while in temperature stress, a combination ofα-Tubulinandrpl32found to be suitable for normalizing the RT-qPCR data. Further, the above-identified genes were validated using RT-qPCR based gene expression analysis of four objective genes namely,Myoinhibitory peptides(MIPs),Zinc_metalloprotease(Zn_Mp),fatty acid synthase(fas)and alpha-glucosidase. Identified reference genes will facilitate gene expression studies in future under different stress treatments inP.solenopsis.
Decreasing Bacillus thuringiensis israelensis sensitivity of Chironomus riparius larvae with age indicates potential environmental risk for mosquito control
Authors: Kästel Anna , Allgeier Stefanie , Brühl Carsten A.
Published: October 2017

Mosquito control based on the use ofBacillus thuringiensis israelensis(Bti) is regarded as an environmental friendly method. However, Bti also affects non-target chironomid midges that are recognized as a central resource in wetland food webs. To evaluate the risk for different larval stages ofChironomus ripariuswe performed a test series of daily acute toxicity laboratory tests following OECD guideline 235 over the entire aquatic life cycle of 28 days. Our study is the first approach that performs an OECD approved test design with Bti andC. ripariusas a standard organism in ecotoxicological testing. First-instar larvae ofChironomus ripariusshow an increased sensitivity towards Bti which is two orders of magnitude higher than for fourth instar larvae. Most EC50 values described in the literature are based on acute toxicity tests using third and fourth instar larvae. The risk for chironomids is underestimated when applying the criteria of the biocide regulation EU 528/2012 to our data and therefore the existing assessment approval is not protective. Possible impacts of Bti induced changes in chironomid abundances and community composition may additionally affect organisms at higher trophic levels, especially in spring when chironomid midges represent a key food source for reproducing vertebrates.
Nuclear fragments of the neural cell adhesion molecule NCAM with or without polysialic acid differentially regulate gene expression
Authors: Westphal Nina , Theis Thomas , Loers Gabriele , Schachner Melitta , Kleene Ralf
Published: October 2017

The neural cell adhesion molecule (NCAM) is the major carrier of polysialic acid (PSA) which modulates NCAM functions of neural cells at the cell surface. In previous studies, we have shown that stimulation of cultured neurons with surrogate NCAM ligands leads to the generation and nuclear import of PSA-lacking and -carrying NCAM fragments. Here, we show that the nuclear import of the PSA-carrying NCAM fragment is mediated by positive cofactor 4 and cofilin, which we identified as novel PSA-binding proteins. In the nucleus, the PSA-carrying NCAM fragment interacts via PSA with PC4 and cofilin, which are involved in RNA polymerase II-dependent transcription. Microarray analysis revealed that the nuclear PSA-carrying and -lacking NCAM fragments affect expression of different genes. By qPCR and immunoblot analysis we verified that the nuclear PSA-carrying NCAM fragment increases mRNA and protein expression of nuclear receptor subfamily 2 group F member 6, whereas the PSA-lacking NCAM fragment increases mRNA and protein expression of low density lipoprotein receptor-related protein 2 and α-synuclein. Differential gene expression evoked by nuclear NCAM fragments without and with PSA indicates that PSA-carrying and -lacking NCAM play different functional roles in the nervous system.
A virus carries a gene encoding juvenile hormone acid methyltransferase, a key regulatory enzyme in insect metamorphosis
Authors: Takatsuka Jun , Nakai Madoka , Shinoda Tetsuro
Published: October 2017

Microbial parasitism, infection, and symbiosis in animals often modulate host endocrine systems, resulting in alterations of phenotypic traits of the host that can have profound effects on the ecology and evolution of both the microorganisms and their hosts. Information about the mechanisms and genetic bases of such modulations by animal parasites is available from studies of steroid hormones. However, reports involving other hormones are scarce. We found that an insect virus, a betaentomopoxvirus, encodes a juvenile hormone acid methyltransferase that can synthesize an important insect hormone, the sesquiterpenoid juvenile hormone. Phylogenetic analysis suggested that this gene is of bacterial origin. Our study challenges the conventional view that functional enzymes in the late phase of the juvenile hormone biosynthesis pathway are almost exclusive to insects or arthropods, and shed light on juvenoid hormone synthesis beyond Eukaryota. This striking example demonstrates that even animal parasites having no metabolic pathways for molecules resembling host hormones can nevertheless influence the synthesis of such hormones, and provides a new context for studying animal parasite strategies in diverse systems such as host-parasite, host-symbiont or host-vector-parasite.
Novel cycloneolignans from Vernicia fordii with inhibitory effects on over-activation of BV2 cells in vitro
Authors: Zhao Wei-Hong , Li Ning , Chu Yang , Sun Tao , Wang Jian , Wang Wen-Li , Li Jia-Yuan , Lin Bin , Chen Ru , Hou Yue
Published: October 2017

Novel natural products 7R, 8R, 7′R, 9′S-verniciasin A (1a), 7S, 8S, 7′S, 9′R- verniciasin A (1b), 7R, 8R, 7′R, 9′S−7′-methoxylverniciasin A (2a) and 7S, 8S, 7′S, 9′R−7′-methoxylverniciasin A (2b) were characterized from the seed capsule of Vernicia fordii. And the unique 9-O-9′−7, 9′-cyclo-8, 1′-neolignan skeleton with a seven-membered ring, was identified by extensive spectroscopic analysis. Further the possible biosynthetic pathway was briefly discussed. Interestingly, 1a, 2a, 1b and 2b all exhibited significant stereoselective inhibitory effects on NO production in LPS-induced BV2 microglia cell. Then the primary mechanism of the bioactivities and stereoselectivity was explored by means of bioassay and molecular docking.
Autophagy induces apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV
Authors: Gou Hongchao , Zhao Mingqiu , Fan Shuangqi , Yuan Jin , Liao Jiedan , He Wencheng , Xu Hailuan , Chen Jinding
Published: October 2017

Lymphocyte depletion and immunosuppression are typical clinical characteristics of pigs infected with classical swine fever virus (CSFV). The apoptosis of virus-infected and bystander cells plays a role in the immunopathology of classical swine fever (CSF). Here, we offer the first evidence that autophagy is involved in apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV. Using immunohistochemical assays, we observed that more LC3II-positive cells appear in the T-cell zone of spleens. Spleen cell apoptosis was demonstrated using flow cytometry and TUNEL staining. Confocal immunofluorescence revealed that partial LC3II-positive cells were simultaneously TUNEL-positive. By cultivating spleen cells ex vivo, we demonstrated that the inhibition of autophagy by 3-MA treatment inhibited apoptosis and death of T lymphocytes caused by CSFV infection but did not have this effect  on B lymphocytes. Further observations demonstrated that uninfected cells in the spleen were also undergoing autophagy in vivo. In summary, these results linked autophagy with the apoptosis and cell death of splenic T cells, providing a new outlook to understand the mechanism of T lymphocyte depletion and immunosuppression during CSF.