bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Variability of Dissolved Inorganic Radiocarbon in the Kuroshio Extension of the Northwest North Pacific
Authors: Ding Ling , Ge Tiantian , Gao Huiwang , Luo Chunle , Xue Yuejun , Druffel Ellen R M , Wang Xuchen
Published: January 2018

Radiocarbon (14C) in dissolved inorganic carbon (DIC) was measured for water samples collected from six deep stations in the Kuroshio Extension (KE) region in the northwestern North Pacific in April–May 2015. Vertical profiles of Δ14C-DIC indicate that bomb-produced 14C was present from the surface to ~1500 m water depth. Large variations in Δ14C-DIC values (300‰) were observed at 500 m water depth among the stations and the differences were likely controlled by transport and mixing dynamics of different water masses in the region. The major Pacific western boundary currents, such as Kuroshio and Oyashio and regional mesoscale eddies, could play important roles affecting the observed Δ14C-DIC variability. The depth profiles of both Δ14C-DIC and DIC concentrations can be predicted by the solution mixing model and can be used as conservative tracers of water mass movement and water parcel homogenization in the ocean.
Social network members who engage in activities with older adults: do they bring more social benefits than other members?
Authors: ASHIDA SATO , SEWELL DANIEL K. , SCHAFER ELLEN J. , SCHROER AUDREY , FRIBERG JULIA
Published: January 2018

Active participation in social activities is important for the wellbeing of older adults. This study explored benefits of active social engagement by evaluating whether relationships that comprise active involvement (e.g.co-engagement in activities) bring more social benefits (i.e.social support, companionship, positive social influence) than other relationships that do not involve co-engagement. A total of 133 adults ages 60 years and older living in a rural Midwestern city in the United States of America were interviewed once and provided information on 1,740 social network members. Among 1,506 social relationships in which interactions occurred at least once a month, 52 per cent involved engagement in social activities together and 35 per cent involved eating together regularly. Results of the generalised linear mixed model showed that relationships involving co-engagement were significantly more likely to also convey social support (i.e.emotional, instrumental, informational), companionship and social influence (encouragement for healthy behaviours) than relationships that do not involve co-engagement. Having more network members who provide companionship was associated with higher sense of environmental mastery, positive relations with others and satisfaction with social network. Interventions may focus on maintaining and developing such social relationships and ensuring the presence of social settings in which co-engagement can occur. Future research may explore whether increasing co-engagement leads to an enhanced sense of companionship and psychological wellbeing.
Transcription, Recording, and Authority in ‘Classic’ Minimalism
Authors: NICKLESON PATRICK
Published: January 2018

This article considers several prominent pieces of minimalism in their movement from primary sound recording to secondary transcription. In place of the score-based formalism of much musicological scholarship on minimalism, I draw on my own archival work and interviews to consider the frequency of transcriptions of minimalism, as well as the politico-historical aspects of minimalism's development that are elided when the distinction between score and transcription is not taken into account. I argue that defining minimalism in relation to material practices of composing, writing, performing, and listening – rather than to formal features like gradual process, long duration, and diatonicism – helps in defining minimalism as a cohesive field of musical production.
Transparency in practice: Evidence from ‘verification analyses’ issued by the Polish Agency for Health Technology Assessment in 2012–2015
Authors: Ozierański Piotr , Löblová Olga , Nicholls Natalia , Csanádi Marcell , Kaló Zoltán , McKee Martin , King Lawrence
Published: January 2018

Transparency is recognised to be a key underpinning of the work of health technology assessment (HTA) agencies, yet it has only recently become a subject of systematic inquiry. We contribute to this research field by considering the Polish Agency for Health Technology Assessment (AHTAPol). We situate the AHTAPol in a broader context by comparing it with the National Institute for Health and Care Excellence (NICE) in England. To this end, we analyse all 332 assessment reports, called verification analyses, that the AHTAPol issued from 2012 to 2015, and a stratified sample of 22 Evidence Review Group reports published by NICE in the same period. Overall, by increasingly presenting its key conclusions in assessment reports, the AHTAPol has reached the transparency standards set out by NICE in transparency of HTA outputs. The AHTAPol is more transparent than NICE in certain aspects of the HTA process, such as providing rationales for redacting assessment reports and providing summaries of expert opinions. Nevertheless, it is less transparent in other areas of the HTA process, such as including information on expert conflicts of interest. Our findings have important implications for understanding HTA in Poland and more broadly. We use them to formulate recommendations for policymakers.
The distribution of Schramocaris (Eumalacostraca, Crustacea) along the northwestern coast of the Rheic Ocean during the Lower Carboniferous
Authors: Clark Neil D. L. , Miller Randall F. , Ross Andrew J.
Published: January 2018

Two new species of Schramocaris from the Viséan, Lower Carboniferous of Scotland and eastern Canada extend the range and distribution of this crustacean along the northwestern coast of the Rheic Ocean. New species from Glencartholm, southern Scotland and Upperton, New Brunswick, Canada represents the first recognised occurrence of this genus in Scotland and Canada. The Scottish species is here named S. clarksoni; it lacks the rugosity of the carinae of Schramocaris gilljonesorum, but has the same relative position of the carinae, as well as similar characteristics of the pleon, such as the relative lengths of the somites and the shape of the telson. The Canadian species is named Schramocaris matthewi on the basis of the papillations on the cuticle and robust second carinae of the carapace. The deposits at both these localities are that of a shallow marine argillaceous environment, although the Glencartholm deposit contains more lime. Schramocaris has previously only been known from the Avon Group (Hastarian) of the Forest of Dean, England.
Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
Authors: Stamouli Sofia , Anderlid Britt-Marie , Willfors Charlotte , Thiruvahindrapuram Bhooma , Wei John , Berggren Steve , Nordgren Ann , Scherer Stephen W. , Lichtenstein Paul , Tammimies Kristiina , Bölte Sven
Published: January 2018

Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood, and suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.
Environmental Factors Moderate Glyphosate-induced Antagonism of POST Herbicides on the Rapid Response Biotype of Glyphosate-Resistant Giant Ragweed (Ambrosia trifida)
Authors: Harre Nick T. , Young Julie M. , Young Bryan G.
Published: January 2018

In the rapid response (RR) biotype of glyphosate-resistant (GR) giant ragweed (Ambrosia trifidaL.), exposure to glyphosate elicits H2O2production in mature leaves, resulting in foliage loss and reduced glyphosate translocation. When glyphosate is applied with POST herbicides intended to improve control ofA. trifida, the RR to glyphosate has the propensity to antagonize these herbicide combinations. This research documents how transient changes in air temperature, soil moisture, and light intensity during a 6-d period surrounding herbicide application regulate induction of the RR and the effect on POST herbicide interactions with glyphosate. Air temperature had the greatest influence on H2O2accumulation in leaf disks following treatment with glyphosate, as plants at 30 C produced more than twice the amount of H2O2at 2.5 h after treatment compared with 10 C. Plants under field capacity conditions accumulated nearly 50% more H2O2than those at one-third field capacity, while those under no shade had only 18% more H2O2compared with those in a shaded environment. Despite these initial results, dry weight reduction at 21 d after treatment never differed by more than 8% between levels of environmental factors, thus indicating a negligible influence on glyphosate efficacy. The magnitude of glyphosate-induced antagonism was generally greater at 30 C (12% to 21% less than expected control) versus 10 C (11% to 16%) on atrazine, cloransulam, dicamba, and topramezone and was greater at field capacity (20% to 24%) versus one-third field capacity (11% to 15%) on cloransulam and topramezone. These results indicate air temperatures and soil moisture levels conducive to optimal plant growth accelerate the RR to glyphosate, thereby increasing the likelihood of glyphosate-induced antagonism on several translocated herbicides.
The stoichiometry of coral-dinoflagellate symbiosis: carbon and nitrogen cycles are balanced in the recycling and double translocation system
Authors: Tanaka Yasuaki , Suzuki Atsushi , Sakai Kazuhiko
Published: January 2018

Symbioses between microalgae and animal hosts have the advantage of acquiring and sharing autotrophically produced organic carbon (C) as their energy source. However, the stoichiometry and turnover rates of biological elements in symbioses are not fully understood because of complicated metabolic interactions. We report the first comprehensive and simultaneous measurement of C and nitrogen (N) flows through coral–dinoflagellate symbiosis by using the unique approach of dual-isotope labeling with 13C and 15N, in situ chasing, and isotope-mixing models. The coral autotrophy occurred with much lower C:N ratios than previously thought, and the autotrophically produced N-rich organic matter was efficiently transferred to the animal host through two different pathways. In contrast to the dynamic N cycles within the symbiosis, the N uptake from the ambient seawater was extremely limited, which enabled the coral symbiosis to sustain N with a long turnover time (1 year). These findings suggest that coral endosymbionts are not under N limitation but are actively producing organic N and driving microscale N cycles in the reef ecosystem. The present techniques could be applied to further quantify the C and N cycles in other symbiotic interactions and reveal their ecological advantages.
Carbon limitation drives GC content evolution of a marine bacterium in an individual-based genome-scale model
Authors: Hellweger Ferdi L , Huang Yongjie , Luo Haiwei
Published: January 2018

An important unanswered question in evolutionary genomics is the source of considerable variation of genomic base composition (GC content) even among organisms that share one habitat. Evolution toward GC-poor genomes has been considered a major adaptive pathway in the oligotrophic ocean, but GC-rich bacteria are also prevalent and highly successful in this environment. We quantify the contribution of multiple factors to the change of genomic GC content of Ruegeria pomeroyi DSS-3, a representative and GC-rich member in the globally abundant Roseobacter clade, using an agent-based model. The model simulates 2 × 108 cells, which allows random genetic drift to act in a realistic manner. Each cell has a whole genome subject to base-substitution mutation and recombination, which affect the carbon and nitrogen requirements of DNA and protein pools. Nonsynonymous changes can be functionally deleterious. Together, these factors affect the growth and fitness. Simulations show that experimentally determined mutation bias toward GC is not sufficient to build the GC-rich genome of DSS-3. While nitrogen availability has been repeatedly hypothesized to drive the evolution of GC content in marine bacterioplankton, our model instead predicts that DSS-3 and its ancestors have been evolving in environments primarily limited by carbon.
Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior
Authors: Sun Dong , Sun Xiang-Dong , Zhao Lu , Lee Dae-Hoon , Hu Jin-Xia , Tang Fu-Lei , Pan Jin-Xiu , Mei Lin , Zhu Xiao-Juan , Xiong Wen-Cheng
Published: January 2018

Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation. Mechanistic studies revealed a role for neogenin to positively regulate Gli1, a crucial downstream transcriptional factor of sonic hedgehog, and expression of Gli1 into neogenin depleted NSCs/NPCs restores their proliferation. Further morphological and functional studies showed additional abnormities, including reduced dendritic branches and spines, and impaired glutamatergic neuro-transmission, in neogenin-depleted new-born DG neurons; and mice with depletion of neogenin in NSCs/NPCs exhibited depressive-like behavior. These results thus demonstrate unrecognized functions of neogenin in adult hippocampal NSCs/NPCs-promoting NSCs/NPCs proliferation and neurogenesis and preventing astrogliogenesis and depressive-like behavior, and suggest neogenin regulation of Gli1 signaling as a possible underlying mechanism.
Fibre-optic metadevice for all-optical signal modulation based on coherent absorption
Authors: Xomalis Angelos , Demirtzioglou Iosif , Plum Eric , Jung Yongmin , Nalla Venkatram , Lacava Cosimo , MacDonald Kevin F. , Petropoulos Periklis , Richardson David J. , Zheludev Nikolay I.
Published: January 2018

Recently, coherent control of the optical response of thin films in standing waves has attracted considerable attention, ranging from applications in excitation-selective spectroscopy and nonlinear optics to all-optical image processing. Here, we show that integration of metamaterial and optical fibre technologies allows the use of coherently controlled absorption in a fully fiberized and packaged switching metadevice. With this metadevice, which controls light with light in a nanoscale plasmonic metamaterial film on an optical fibre tip, we provide proof-of-principle demonstrations of logical functions XOR, NOT and AND that are performed within a coherent fibre network at wavelengths between 1530 and 1565 nm. The metadevice has been tested at up to 40 gigabits per second and sub-milliwatt power levels. Since coherent absorption can operate at the single-photon level and with 100 THz bandwidth, we argue that the demonstrated all-optical switch concept has potential applications in coherent and quantum information networks.
20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1
Authors: Tunaru Sorin , Bonnavion Remy , Brandenburger Isabell , Preussner Jens , Thomas Dominique , Scholich Klaus , Offermanns Stefan
Published: January 2018

The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose. Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated 20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced. We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20-HETE formation contributes to inefficient GSIS in type-2 diabetes.
Architecture of a mammalian glomerular domain revealed by novel volume electroporation using nanoengineered microelectrodes
Authors: Schwarz D. , Kollo M. , Bosch C. , Feinauer C. , Whiteley I. , Margrie T. W. , Cutforth T. , Schaefer A. T.
Published: January 2018

Dense microcircuit reconstruction techniques have begun to provide ultrafine insight into the architecture of small-scale networks. However, identifying the totality of cells belonging to such neuronal modules, the “inputs” and “outputs,” remains a major challenge. Here, we present the development of nanoengineered electroporation microelectrodes (NEMs) for comprehensive manipulation of a substantial volume of neuronal tissue. Combining finite element modeling and focused ion beam milling, NEMs permit substantially higher stimulation intensities compared to conventional glass capillaries, allowing for larger volumes configurable to the geometry of the target circuit. We apply NEMs to achieve near-complete labeling of the neuronal network associated with a genetically identified olfactory glomerulus. This allows us to detect sparse higher-order features of the wiring architecture that are inaccessible to statistical labeling approaches. Thus, NEM labeling provides crucial complementary information to dense circuit reconstruction techniques. Relying solely on targeting an electrode to the region of interest and passive biophysical properties largely common across cell types, this can easily be employed anywhere in the CNS.
Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability
Authors: Williams Jamie J. L. , Alotaiq Nasser , Mullen William , Burchmore Richard , Liu Libin , Baillie George S. , Schaper Fred , Pilch Paul F. , Palmer Timothy M.
Published: January 2018

Effective suppression of JAK–STAT signalling by the inducible inhibitor “suppressor of cytokine signalling 3” (SOCS3) is essential for limiting signalling from cytokine receptors. Here we show that cavin-1, a component of caveolae, is a functionally significant SOCS3-interacting protein. Biochemical and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins, thereby reducing caveola abundance in endothelial cells. Moreover, the interaction of cavin-1 and SOCS3 is essential for SOCS3 function, as loss of cavin-1 enhances cytokine-stimulated STAT3 phosphorylation and abolishes SOCS3-dependent inhibition of IL-6 signalling by cyclic AMP. Together, these findings reveal a new functionally important mechanism linking SOCS3-mediated inhibition of cytokine signalling to localisation at the plasma membrane via interaction with and stabilisation of cavin-1.
Author Correction: REST regulates the cell cycle for cardiac development and regeneration
Authors: Zhang Donghong , Wang Yidong , Lu Pengfei , Wang Ping , Yuan Xinchun , Yan Jianyun , Cai Chenleng , Chang Ching-Pin , Zheng Deyou , Wu Bingruo , Zhou Bin
Published: January 2018

The original version of this Article contained an error in the spelling of the author Jianyun Yan, which was incorrectly given as Jiangyun Yan. This has now been corrected in both the PDF and HTML versions of the Article.
Determination of triacylglycerol oxidation mechanisms in canola oil using liquid chromatography–tandem mass spectrometry
Authors: Kato Shunji , Shimizu Naoki , Hanzawa Yasuhiko , Otoki Yurika , Ito Junya , Kimura Fumiko , Takekoshi Susumu , Sakaino Masayoshi , Sano Takashi , Eitsuka Takahiro , Miyazawa Teruo , Nakagawa Kiyotaka
Published: January 2018

Triacylglycerol (TG), the main component of edible oil, is oxidized by thermal- or photo- oxidation to form TG hydroperoxide (TGOOH) as the primary oxidation product. Since TGOOH and its subsequent oxidation products cause not only the deterioration of oil quality but also various toxicities, preventing the oxidation of edible oils is essential. Therefore understanding oxidation mechanisms that cause the formation of TGOOH is necessary. Since isomeric information of lipid hydroperoxide provides insights about oil oxidation mechanisms, we focused on dioleoyl-(hydroperoxy octadecadienoyl)-TG (OO-HpODE-TG) isomers, which are the primary oxidation products of the most abundant TG molecular species (dioleoyl-linoleoyl-TG) in canola oil. To secure highly selective and sensitive analysis, authentic OO-HpODE-TG isomer references (i.e., hydroperoxide positional/geometrical isomers) were synthesized and analyzed with HPLC-MS/MS. With the use of the method, photo- or thermal- oxidized edible oils were analyzed. While dioleoyl-(10-hydroperoxy-8E,12Z-octadecadienoyl)-TG (OO-(10-HpODE)-TG) and dioleoyl-(12-hydroperoxy-9Z,13E-octadecadienoyl)-TG (OO-(12-HpODE)-TG) were characteristically detected in photo-oxidized oils, dioleoyl-(9-hydroperoxy-10E,12E-octadecadienoyl)-TG and dioleoyl-(13-hydroperoxy-9E,11E-octadecadienoyl)-TG were found to increase depending on temperature in thermal-oxidized oils. These results prove that our methods not only evaluate oil oxidation in levels that are unquantifiable with peroxide value, but also allows for the determination of oil oxidation mechanisms. From the analysis of marketed canola oils, photo-oxidized products (i.e., OO-(10-HpODE)-TG and OO-(12-HpODE)-TG) were characteristically accumulated compared to the oil analyzed immediately after production. The method described in this paper is valuable in the understanding of oil and food oxidation mechanisms, and may be applied to the development of preventive methods against food deterioration.
Dynamic malaria hotspots in an open cohort in western Kenya
Authors: Platt Alyssa , Obala Andrew A. , MacIntyre Charlie , Otsyula Barasa , Meara Wendy Prudhomme O’
Published: January 2018

Malaria hotspots, defined as areas where transmission intensity exceeds the average level, become more pronounced as transmission declines. Targeting hotspots may accelerate reductions in transmission and could be pivotal for malaria elimination. Determinants of hotspot location, particularly of their movement, are poorly understood. We used spatial statistical methods to identify foci of incidence of self-reported malaria in a large census population of 64,000 people, in 8,290 compounds over a 2.5-year study period. Regression models examine stability of hotspots and identify static and dynamic correlates with their location. Hotspot location changed over short time-periods, rarely recurring in the same area. Hotspots identified in spring versus fall season differed in their stability. Households located in a hotspot in the fall were more likely to be located in a hotspot the following fall (RR = 1.77, 95% CI: 1.66–1.89), but the opposite was true for compounds in spring hotspots (RR = 0.15, 95% CI: 0.08–0.28). Location within a hotspot was related to environmental and static household characteristics such as distance to roads or rivers. Human migration into a household was correlated with risk of hotspot membership, but the direction of the association differed based on the origin of the migration event.
Identification of shared genetic variants between schizophrenia and lung cancer
Authors: Zuber Verena , Jönsson Erik G. , Frei Oleksandr , Witoelar Aree , Thompson Wesley K. , Schork Andrew J. , Bettella Francesco , Wang Yunpeng , Djurovic Srdjan , Smeland Olav B. , Dieset Ingrid , Fanous Ayman H. , Desikan Rahul S. , Küry Sébastien , Bézieau Stéphane , Dale Anders M. , Mills Ian G. , Andreassen Ole A.
Published: January 2018

Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate. We analyzed the largest genome-wide association studies of schizophrenia and lung, breast, prostate, ovary, and colon-rectum cancer including more than 220,000 subjects, and included genetic association with smoking behavior. Polygenic enrichment of associations with lung cancer was observed in schizophrenia, and weak enrichment for the remaining cancer sites. After excluding the major histocompatibility complex region, we identified three independent loci jointly associated with schizophrenia and lung cancer. The strongest association included nicotinic acetylcholine receptors and is an established pleiotropic locus shared between lung cancer and smoking. The two other loci were independent of genetic association with smoking. Functional analysis identified downstream pleiotropic effects on epigenetics and gene-expression in lung and brain tissue. These findings suggest that genetic factors may explain partly the observed epidemiological association of lung cancer and schizophrenia.
Parkinson disease with constipation: clinical features and relevant factors
Authors: Yu Qiu-Jin , Yu Shu-Yang , Zuo Li-Jun , Lian Teng-Hong , Hu Yang , Wang Rui-Dan , Piao Ying-Shan , Guo Peng , Liu Li , Jin Zhao , Li Li-Xia , Chan Piu , Chen Sheng-Di , Wang Xiao-Min , Zhang Wei
Published: January 2018

Constipation is one of the most frequent non-motor symptoms of Parkinson disease (PD) and it may be ignored by PD patients, leading to this problem not to be reported in time. The relationships between constipation and demographic variables, motor symptoms and other non-motor symptoms of PD are still unknown. PD patients were evaluated by diagnostic criteria of functional constipation in Rome III and divided into PD with constipation (PD-C) and PD with no constipation (PD-NC) groups. PD patients were assessed by rating scales of motor symptoms and other non-motor symptoms, activity of daily living and quality of life. The frequency of constipation in PD patients was 61.4%, and 24.5% of PD patients had constipation before the onset of motor symptoms. PD-C group had older age and age of onset, longer disease duration, more advanced disease stage, and more severe motor symptoms and non-motor symptoms, including worse cognition and emotion, poorer sleep quality, severer autonomic symptoms, fatigue and apathy. Binary Logistic regression analysis showed that the age, H-Y stage, depression, anxiety and autonomic dysfunction increased the risk of constipation in PD patients. Constipation exerted serious impact on the activity of daily living and quality of life in PD patients.
Characterizing the bacterial microbiota in different gastrointestinal tract segments of the Bactrian camel
Authors: He Jing , Yi Li , Hai Le , Ming Liang , Gao Wanting , Ji Rimutu
Published: January 2018

The bacterial community plays important roles in the gastrointestinal tracts (GITs) of animals. However, our understanding of the microbial communities in the GIT of Bactrian camels remains limited. Here, we describe the bacterial communities from eight different GIT segments (rumen, reticulum, abomasum, duodenum, ileum, jejunum, caecum, colon) and faeces determined from 11 Bactrian camels using 16S rRNA gene amplicon sequencing. Twenty-seven bacterial phyla were found in the GIT, with Firmicutes, Verrucomicrobia and Bacteroidetes predominating. However, there were significant differences in microbial community composition between segments of the GIT. In particular, a greater proportion of Akkermansia and Unclassified Ruminococcaceae were found in the large intestine and faecal samples, while more Unclassified Clostridiales and Unclassified Bacteroidales were present in the in forestomach and small intestine. Comparative analysis of the microbiota from different GIT segments revealed that the microbial profile in the large intestine was like that in faeces. We also predicted the metagenomic profiles for the different GIT regions. In forestomach, there was enrichment associated with replication and repair and amino acid metabolism, while carbohydrate metabolism was enriched in the large intestine and faeces. These results provide profound insights into the GIT microbiota of Bactrian camels.
Blood transcriptomics of captive forest musk deer (Moschus berezovskii) and possible associations with the immune response to abscesses
Authors: Sun Xiaoning , Cai Ruibo , Jin Xuelin , Shafer Aaron B. A. , Hu Xiaolong , Yang Shuang , Li Yimeng , Qi Lei , Liu Shuqiang , Hu Defu
Published: January 2018

Forest musk deer (Moschus berezovskii; FMD) are both economically valuable and highly endangered. A problem for FMD captive breeding programs has been the susceptibility of FMD to abscesses. To investigate the mechanisms of abscess development in FMD, the blood transcriptomes of three purulent and three healthy individuals were generated. A total of ~39.68 Gb bases were generated using Illumina HiSeq 4000 sequencing technology and 77,752 unigenes were identified after assembling. All the unigenes were annotated, with 63,531 (81.71%) mapping to at least one database. Based on these functional annotations, 45,798 coding sequences (CDS) were detected, along with 12,697 simple sequence repeats (SSRs) and 65,536 single nucleotide polymorphisms (SNPs). A total of 113 unigenes were found to be differentially expressed between healthy and purulent individuals. Functional annotation indicated that most of these differentially expressed genes were involved in the regulation of immune system processes, particularly those associated with parasitic and bacterial infection pathways.
Docking, thermodynamics and molecular dynamics (MD) studies of a non-canonical protease inhibitor, MP-4, from Mucuna pruriens
Authors: Kumar Ashish , Kaur Harmeet , Jain Abha , Nair Deepak T. , Salunke Dinakar M.
Published: January 2018

Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens belongs to Kunitz-type protease inhibitor family. However, biochemical assays showed that this protein is a poor inhibitor of trypsin. To understand the basis of observed poor inhibition, thermodynamics and molecular dynamics (MD) simulation studies on binding of MP-4 to trypsin were carried out. Molecular dynamics simulations revealed that temperature influences the spectrum of conformations adopted by the loop regions in the MP-4 structure. At an optimal temperature, MP-4 achieves maximal binding while above and below the optimum temperature, its functional activity is hampered due to unfavourable flexibility and relative rigidity, respectively. The low activity at normal temperature is due to the widening of the conformational spectrum of the Reactive Site Loop (RSL) that reduces the probability of formation of stabilizing contacts with trypsin. The unique sequence of the RSL enhances flexibility at ambient temperature and thus reduces its ability to inhibit trypsin. This study shows that temperature influences the function of a protein through modulation in the structure of functional domain of the protein. Modulation of function through appearance of new sequences that are more sensitive to temperature may be a general strategy for evolution of new proteins.
Alteration in yield and oil quality traits of winter rapeseed by lodging at different planting density and nitrogen rates
Authors: Khan Shahbaz , Anwar Sumera , Kuai Jie , Noman Ali , Shahid Muhammad , Din Mairaj , Ali Ahmed , Zhou Guangsheng
Published: January 2018

Lodging is a factor that negatively affects yield, seed quality, and harvest ability in winter rapeseed (Brassica napus L.). In this study, we quantified the lodging-induced yield losses, changes in fatty acid composition, and oil quality in rapeseed under different nitrogen application rates and planting densities. Field experiments were conducted in 2014–2017 for studying the effect of manually-induced lodging angles (0°, 30°, 60°, and 90°), 10, 20 and 30 d post-flowering at different densities and nitrogen application rates. The fertilization/planting density combination N270D45 produced the maximum observed yield and seed quality. Timing and angle of lodging had significant effects on yield. Lodging at 90° induced at 10 d post-flowering caused the maximum reduction in yield, biomass, and silique photosynthesis. Seed yield losses were higher at high N application rates, the maximum being at N360D45. Lodging decreased seed oil content and altered its fatty acid composition by increasing stearic and palmitic acid content, while decreasing linoleic and linolenic acid content, and deteriorating oil quality by increasing erucic acid and glucosinolate content. Therefore, lodging-induced yield loss and reduction in oil content might be reduced by selecting optimum N level and planting density.
Development of a PET radioligand for potassium channels to image CNS demyelination
Authors: Brugarolas Pedro , Sánchez-Rodríguez Jorge E. , Tsai Hsiu-Ming , Basuli Falguni , Cheng Shih-Hsun , Zhang Xiang , Caprariello Andrew V. , Lacroix Jerome J. , Freifelder Richard , Murali Dhanabalan , DeJesus Onofre , Miller Robert H. , Swenson Rolf E. , Chen Chin-Tu , Herscovitch Peter , Reich Daniel S. , Bezanilla Francisco , Popko Brian
Published: January 2018

Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties and can be labeled with 18F for PET imaging. Additionally, we demonstrate that [18F]3-F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas and excellent properties for brain imaging. Together, these data indicate that [18F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination noninvasively.
RGS7 is recurrently mutated in melanoma and promotes migration and invasion of human cancer cells
Authors: Qutob Nouar , Masuho Ikuo , Alon Michal , Emmanuel Rafi , Cohen Isadora , Di Pizio Antonella , Madore Jason , Elkahloun Abdel , Ziv Tamar , Levy Ronen , Gartner Jared J. , Hill Victoria K. , Lin Jimmy C. , Hevroni Yael , Greenberg Polina , Brodezki Alexandra , Rosenberg Steven A. , Kosloff Mickey , Hayward Nicholas K. , Admon Arie , Niv Masha Y. , Scolyer Richard A. , Martemyanov Kirill A. , Samuels Yardena
Published: January 2018

Analysis of 501 melanoma exomes revealed RGS7, which encodes a GTPase-accelerating protein (GAP), to be a tumor-suppressor gene. RGS7 was mutated in 11% of melanomas and was found to harbor three recurrent mutations (p.R44C, p.E383K and p.R416Q). Structural modeling of the most common recurrent mutation of the three (p.R44C) predicted that it destabilizes the protein due to the loss of an H-bond and salt bridge network between the mutated position and the serine and aspartic acid residues at positions 58 as 61, respectively. We experimentally confirmed this prediction showing that the p.R44C mutant protein is indeed destabilized. We further show RGS7 p.R44C has weaker catalytic activity for its substrate Gαo, thus providing a dual mechanism for its loss of function. Both of these effects are expected to contribute to loss of function of RGS7 resulting in increased anchorage-independent growth, migration and invasion of melanoma cells. By mutating position 56 in the R44C mutant from valine to cysteine, thereby enabling the formation of a disulfide bridge between the two mutated positions, we slightly increased the catalytic activity and reinstated protein stability, leading to the rescue of RGS7′s function as a tumor suppressor. Our findings identify RGS7 as a novel melanoma driver and point to the clinical relevance of using strategies to stabilize the protein and, thereby, restore its function.
Development of versatile non-homologous end joining-based knock-in module for genome editing
Authors: Sawatsubashi Shun , Joko Yudai , Fukumoto Seiji , Matsumoto Toshio , Sugano Shigeo S.
Published: January 2018

CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering. An important aspect of genome engineering is efficient knock-in technology. For improved knock-in efficiency, the non-homologous end joining (NHEJ) repair pathway has been used over the homology-dependent repair pathway, but there remains a need to reduce the complexity of the preparation of donor vectors. We developed the versatile NHEJ-based knock-in module for genome editing (VIKING). Using the consensus sequence of the time-honored pUC vector to cut donor vectors, any vector with a pUC backbone could be used as the donor vector without customization. Conditions required to minimize random integration rates of the donor vector were also investigated. We attempted to isolate null lines of the VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection marker cassette, and found 75% of clones isolated were successfully knocked-in. Although HaCaT cells have hypotetraploid genome composition, the results suggest multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient knock-in of any vectors harboring pUC vectors. Users now can insert various existing vectors into an arbitrary locus in the genome. VIKING will contribute to low-cost genome engineering.
Novel endogenous simian retroviral integrations in Vero cells: implications for quality control of a human vaccine cell substrate
Authors: Sakuma Chisato , Sekizuka Tsuyoshi , Kuroda Makoto , Kasai Fumio , Saito Kyoko , Ikeda Masaki , Yamaji Toshiyuki , Osada Naoki , Hanada Kentaro
Published: January 2018

African green monkey (AGM)-derived Vero cells have been utilized to produce various human vaccines. The Vero cell genome harbors a variety of simian endogenous type D retrovirus (SERV) sequences. In this study, a transcriptome analysis showed that DNA hypomethylation released the epigenetic repression of SERVs in Vero cells. Moreover, comparative genomic analysis of three Vero cell sublines and an AGM reference revealed that the genomes of the sublines have ~80 SERV integrations. Among them, ~60 integrations are present within all three cell sublines and absent from the reference sequence. At least several of these integrations consist of complete SERV proviruses. These results strongly suggest that SERVs integrated in the genome of Vero cells did not retrotranspose after the establishment of the cell lineage as far as cells were maintained under standard culture and passage conditions, providing a scientific basis for controlling the quality of pharmaceutical cell substrates and their derived biologics.
Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells
Authors: Wu Chuanhong , Zhao Wenwen , Yu Jie , Li Shaojing , Lin Ligen , Chen Xiuping
Published: January 2018

Neurodegenerative diseases (NDD) are typically associated with neuron loss in nervous system areas. Interventions with related death mechanisms may ameliorate NDD progression. Oxidative stress plays an important role in NDD cell death routines. However, tert-butylhydroperoxide (t-BHP), a widely used oxidative stress stimulus, induces neural cell death through a mechanism that remains elusive. In our study, the ferroptosis marker events occurred after co-treatment with 100 μM t-BHP for 1 h, all of which were reversed in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine, implying the occurrence of ferroptosis. Moreover, mitochondrial dysfunction accompanied by a decreased in membrane potential and ATP production, increased mitochondrial ROS generation. Furthermore, this mitochondrial dysfunction could be reversed by Fer-1. In addition, JNK1/2 and ERK1/2 were activated upstream of the ferroptosis and mitochondrial dysfunction. In summary, these data suggest that ferroptosis, coupled with mitochondrial dysfunction, was involved in t-BHP-induced PC12 death. JNK1/2 and ERK1/2 played important roles in t-BHP-induced cell death. Overall, this study might provide clues to the oxidative stress-based strategies for cell protection in NDD.
Titania (TiO2) nanoparticles enhance the performance of growth-promoting rhizobacteria
Authors: Timmusk Salme , Seisenbaeva Gulaim , Behers Lawrence
Published: January 2018

A novel use of nanotitania (TNs) as agents in the nanointerface interaction between plants and colonization of growth promoting rhizobacteria (PGPR) is presented. The effectiveness of PGPRs is related to the effectiveness of the technology used for their formulation. TNs produced by the Captigel patented SolGel approach, characterized by the transmission and scanning electron microscopy were used for formulation of the harsh environment PGPR strains. Changes in the biomass of wheat seedlings and in the density of single and double inoculants with and without TNs were monitored during two weeks of stress induced by drought salt and by the pathogen Fusarium culmorum. We show that double inoculants with TNs can attach stably to plant roots. Regression analysis indicates that there is a positive interaction between seedling biomass and TN-treated second inoculant colonization. We conclude that TN treatment provides an effectual platform for PGPR rational application via design of root microbial community. Our studies illustrate the importance of considering natural soil nanoparticles for PGPR application and thereby may explain the generally observed inconsistent behavior of PGPRs in the field. These new advancements importantly contribute towards solving food security issues in changing climates. The model systems established here provide a basis for new PGPR nanomaterials research.
Multiscale and luminescent, hollow microspheres for gas phase thermometry
Authors: Bischoff Lothar , Stephan Michael , Birkel Christina S. , Litterscheid Christian F. , Dreizler Andreas , Albert Barbara
Published: January 2018

Recently developed laser-based measurement techniques are used to image the temperatures and velocities in gas flows. They require new phosphor materials with an unprecedented combination of properties. A novel synthesis procedure is described here; it results in hierarchically structured, hollow microspheres of Eu3+-doped Y2O3, with unusual particle sizes and very good characteristics compared to full particles. Solution-based precipitation on polymer microballoons produces very stable and luminescent, ceramic materials of extremely low density. As a result of the – compared to established template-directed syntheses – reduced mass of polymer that is lost upon calcination, micron-sized particles are obtained with mesoporous walls, low defect concentrations, and nanoscale wall thicknesses. They can be produced with larger diameters (~25 µm) compared to known hollow spheres and exhibit an optimized flow behavior. Their temperature sensing properties and excellent fluidic follow-up behavior are shown by determining emission intensity ratios in a specially designed heating chamber. Emission spectroscopy and imaging, electron microscopy and X-ray diffraction results are presented for aerosolizable Y2O3 with an optimized dopant concentration (8%). Challenges in the field of thermofluids can be addressed by combined application of thermometry and particle image velocimetry with such hollow microparticles.
Three-Dimensional Speckle Light Self-Healing-Based Imaging System
Authors: Pires Danilo G. , Sonsin Artur F. , Jesus-Silva Alcenísio J. , Fonseca Eduardo J. S.
Published: January 2018

Recently new methodologies for imaging have been achieved making use of multiple light scattering. Here we present the self-healing effect using a speckled light field. We present an experiment that constitutes a useful application for a three-dimensional light sheet-based imaging system through an inhomogeneous medium. Each layer can be imaged independently of the others. The axial resolution basically depends on the coherence length, which can be sub-wavelength and controllable. This allows for a simple and direct technique for imaging through scattering layers with axial resolution improvement. Our results may find applications not only in bio-microscopy systems but also in data transmission.
Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases
Authors: Sebastián-Martín Alba , Barrioluengo Verónica , Menéndez-Arias Luis
Published: January 2018

In M13mp2 lacZα forward mutation assays measuring intrinsic fidelity of DNA-dependent DNA synthesis, wild-type human immunodeficiency virus type 1 (HIV-1) RTs of group M/subtype B previously showed >10-fold higher error rates than murine leukaemia virus (MLV) and avian myeloblastosis virus (AMV) RTs. An adapted version of the assay was used to obtain error rates of RNA-dependent DNA synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I. Our results showed that there were less than two-fold differences in fidelity between the studied RTs with error rates ranging within 2.5 × 10−5 and 3.5 × 10−5. These results were consistent with the existence of a transcriptional inaccuracy threshold, generated by the RNA polymerase while synthesizing the RNA template used in the assay. A modest but consistent reduction of the inaccuracy threshold was achieved by lowering the pH and Mg2+ concentration of the transcription reaction. Despite assay limitations, we conclude that HIV-1BH10 and HIV-1ESP49 RTs are less accurate when copying DNA templates than RNA templates. Analysis of the RNA-dependent mutational spectra revealed a higher tendency to introduce large deletions at the initiation of reverse transcription by all HIV-1 RTs except the double-mutant K65R/V75I.