bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential impact of ocean circulation on the declining Japanese eel catches
Authors: Chang Yu-Lin K. , Miyazawa Yasumasa , Miller Michael J. , Tsukamoto Katsumi
Published: March 2018

Recruitment of Japanese eels, Anguilla japonica, has declined in recent decades possibly due to both anthropogenic and ocean-atmosphere factors. The potential impact of ocean circulation on the decreasing Japanese eel catches in the western North Pacific was examined based on a three-dimensional particle-tracking method, in which virtual larvae (v-larvae) were programmed to swim horizontally and vertically, in addition to being transported by ocean currents after being released in their North Equatorial Current (NEC) spawning area. Transport patterns varied among years between 1993 and 2013, and dispersion of v-larvae towards East Asia decreased in the last two decades, especially for the western Taiwan and Japan regions. In recent years, instead of entering the Kuroshio and moving towards East Asia as in the 1990s’, more v-larvae tended to enter the southern areas due to the weakening of the NEC and strengthening of subsurface southward flow near the spawning area. Changes in ocean circulation in the western Pacific appear to be caused by the weakening of subtropical and tropical wind stress curl in the past two decades. This suggests that decadal changes in ocean circulation have occurred that affect the larval migration success of the Japanese eel to their recruitment areas.
Enamel apatite crystallinity significantly contributes to mammalian dental adaptations
Authors: Kallistová Anna , Skála Roman , Šlouf Miroslav , Čejchan Petr , Matulková Irena , Horáček Ivan
Published: March 2018

The monophyodont molar teeth, prismatic enamel and the complexity of enamel microarchitecture are regarded as essential dental apomorphies of mammals. As prominent background factors of feeding efficiency and individual longevity these characters are crucial components of mammalian adaptive dynamics. Little is known, however, to which degree these adaptations are influenced by the crystallographic properties of elementary hydroxyapatite crystallites, the only inorganic component of enamel. In a miniature pig where individual molars differ significantly in duration of their development and in enamel resistance to attrition stress, we found highly significant differences between the molars in the size of crystallites, amount of microstrain, crystallinity and in enamel stiffness and elasticity, all clearly scaled with the duration of tooth calcification. The same pattern was found also in red deer bearing different molar type. The results suggest that the prolongation of tooth development is associated with an increase of crystallinity, i.e. the atomic order of enamel hydroxyapatite, an obvious component of micromechanical property of mature enamel. This relation could contribute to prolongation of dental development, characteristic of mammals in general. The aspects of enamel crystallinity, omitted in previous studies on mammalian and vertebrate dental evolution, are to be taken in account in these topics.
Locus coeruleus complex of the family Delphinidae
Authors: Sacchini Simona , Arbelo Manuel , Bombardi Cristiano , Fernández Antonio , Cozzi Bruno , Bernaldo de Quirós Yara , Herráez Pedro
Published: March 2018

The locus coeruleus (LC) is the largest catecholaminergic nucleus and extensively projects to widespread areas of the brain and spinal cord. The LC is the largest source of noradrenaline in the brain. To date, the only examined Delphinidae species for the LC has been a bottlenose dolphin (Tursiops truncatus). In our experimental series including different Delphinidae species, the LC was composed of five subdivisions: A6d, A6v, A7, A5, and A4. The examined animals had the A4 subdivision, which had not been previously described in the only Delphinidae in which this nucleus was investigated. Moreover, the neurons had a large amount of neuromelanin in the interior of their perikarya, making this nucleus highly similar to that of humans and non-human primates. This report also presents the first description of neuromelanin in the cetaceans’ LC complex, as well as in the cetaceans’ brain.
Attraction and Compaction of Migratory Breast Cancer Cells by Bone Matrix Proteins through Tumor-Osteocyte Interactions
Authors: Chen Andy , Wang Luqi , Liu Shengzhi , Wang Yue , Liu Yunlong , Wang Mu , Nakshatri Harikrishna , Li Bai-Yan , Yokota Hiroki
Published: March 2018

Bone is a frequent site of metastasis from breast cancer. To understand the potential role of osteocytes in bone metastasis, we investigated tumor-osteocyte interactions using two cell lines derived from the MDA-MB-231 breast cancer cells, primary breast cancer cells, and MLO-A5/MLO-Y4 osteocyte cells. When three-dimensional (3D) tumor spheroids were grown with osteocyte spheroids, tumor spheroids fused with osteocyte spheroids and shrank. This size reduction was also observed when tumor spheroids were exposed to conditioned medium isolated from osteocyte cells. Mass spectrometry-based analysis predicted that several bone matrix proteins (e.g., collagen, biglycan) in conditioned medium could be responsible for tumor shrinkage. The osteocyte-driven shrinkage was mimicked by type I collagen, the most abundant organic component in bone, but not by hydroxyapatite, a major inorganic component in bone. RNA and protein expression analysis revealed that tumor-osteocyte interactions downregulated Snail, a transcription factor involved in epithelial-to-mesenchymal transition (EMT). An agarose bead assay showed that bone matrix proteins act as a tumor attractant. Collectively, the study herein demonstrates that osteocytes attract and compact migratory breast cancer cells through bone matrix proteins, suppress tumor migration, by Snail downregulation, and promote subsequent metastatic colonization.
KoVariome: Korean National Standard Reference Variome database of whole genomes with comprehensive SNV, indel, CNV, and SV analyses
Authors: Kim Jungeun , Weber Jessica A. , Jho Sungwoong , Jang Jinho , Jun JeHoon , Cho Yun Sung , Kim Hak-Min , Kim Hyunho , Kim Yumi , Chung OkSung , Kim Chang Geun , Lee HyeJin , Kim Byung Chul , Han Kyudong , Koh InSong , Chae Kyun Shik , Lee Semin , Edwards Jeremy S. , Bhak Jong
Published: March 2018

High-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations, and provides a critical resource that can be used to more accurately identify pathogenic genetic variants. We report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals in order to characterize the benign ethnicity-relevant genetic variation present in the Korean population. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project when prioritizing disease-causing variants. KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.
Ribosome-dependent conformational flexibility changes and RNA dynamics of IRES domains revealed by differential SHAPE
Authors: Lozano Gloria , Francisco-Velilla Rosario , Martinez-Salas Encarnacion
Published: March 2018

Internal ribosome entry site (IRES) elements are RNA regions that recruit the translation machinery internally. Here we investigated the conformational changes and RNA dynamics of a picornavirus IRES upon incubation with distinct ribosomal fractions. Differential SHAPE analysis of the free RNA showed that nucleotides reaching the final conformation on long timescales were placed at domains 4 and 5, while candidates for long-range interactions were located in domain 3. Salt-washed ribosomes induced a fast RNA local flexibility modification of domains 2 and 3, while ribosome-associated factors changed domains 4 and 5. Consistent with this, modeling of the three-dimensional RNA structure indicated that incubation of the IRES with native ribosomes induced a local rearrangement of the apical region of domain 3, and a reorientation of domains 4 and 5. Furthermore, specific motifs within domains 2 and 3 showed a decreased flexibility upon incubation with ribosomal subunits in vitro, and presence of the IRES enhanced mRNA association to the ribosomal subunits in whole cell lysates. The finding that RNA modules can provide direct IRES-ribosome interaction suggests that linking these motifs to additional sequences able to recruit trans-acting factors could be useful to design synthetic IRESs with novel activities.
State-dependent representation of stimulus-evoked activity in high-density recordings of neural cultures
Authors: Nieus Thierry , D’Andrea Valeria , Amin Hayder , Di Marco Stefano , Safaai Houman , Maccione Alessandro , Berdondini Luca , Panzeri Stefano
Published: March 2018

Neuronal responses to external stimuli vary from trial to trial partly because they depend on continuous spontaneous variations of the state of neural circuits, reflected in variations of ongoing activity prior to stimulus presentation. Understanding how post-stimulus responses relate to the pre-stimulus spontaneous activity is thus important to understand how state dependence affects information processing and neural coding, and how state variations can be discounted to better decode single-trial neural responses. Here we exploited high-resolution CMOS electrode arrays to record simultaneously from thousands of electrodes in in-vitro cultures stimulated at specific sites. We used information-theoretic analyses to study how ongoing activity affects the information that neuronal responses carry about the location of the stimuli. We found that responses exhibited state dependence on the time between the last spontaneous burst and the stimulus presentation and that the dependence could be described with a linear model. Importantly, we found that a small number of selected neurons carry most of the stimulus information and contribute to the state-dependent information gain. This suggests that a major value of large-scale recording is that it individuates the small subset of neurons that carry most information and that benefit the most from knowledge of its state dependence.
Systemic and specific effects of antihypertensive and lipid-lowering medication on plasma protein biomarkers for cardiovascular diseases
Authors: Enroth Stefan , Maturi Varun , Berggrund Malin , Enroth Sofia Bosdotter , Moustakas Aristidis , Johansson Åsa , Gyllensten Ulf
Published: March 2018

A large fraction of the adult population is on lifelong medication for cardiovascular disorders, but the metabolic consequences are largely unknown. This study determines the effects of common anti-hypertensive and lipid lowering drugs on circulating plasma protein biomarkers. We studied 425 proteins in plasma together with anthropometric and lifestyle variables, and the genetic profile in a cross-sectional cohort. We found 8406 covariate-protein associations, and a two-stage GWAS identified 17253 SNPs to be associated with 109 proteins. By computationally removing variation due to lifestyle and genetic factors, we could determine that medication, per se, affected the abundance levels of 35.7% of the plasma proteins. Medication either affected a single, a few, or a large number of protein, and were found to have a negative or positive influence on known disease pathways and biomarkers. Anti-hypertensive or lipid lowering drugs affected 33.1% of the proteins. Angiotensin-converting enzyme inhibitors showed the strongest lowering effect by decreasing plasma levels of myostatin. Cell-culture experiments showed that angiotensin-converting enzyme inhibitors reducted myostatin RNA levels. Thus, understanding the effects of lifelong medication on the plasma proteome is important both for sharpening the diagnostic precision of protein biomarkers and in disease management.
A porcine ex vivo model of pigmentary glaucoma
Authors: Dang Yalong , Waxman Susannah , Wang Chao , Loewen Ralitsa T. , Sun Ming , Loewen Nils A.
Published: March 2018

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.
Effect of magnetic fullerene on magnetization reversal created at the Fe/C60 interface
Authors: Mallik Srijani , Mattauch Stefan , Dalai Manas Kumar , Brückel Thomas , Bedanta Subhankar
Published: March 2018

Probing the hybridized magnetic interface between organic semiconductor (OSC) and ferromagnetic (FM) layers has drawn significant attention in recent years because of their potential in spintronic applications. Recent studies demonstrate various aspects of organic spintronics such as magnetoresistance, induced interface moment etc. However, not much work has been performed to investigate the implications of such OSC/FM interfaces on the magnetization reversal and domain structure which are the utmost requirements for any applications. Here, we show that non-magnetic Fullerene can obtain non-negligible magnetic moment at the interface of Fe(15 nm)/C60(40 nm) bilayer. This leads to substantial effect on both the magnetic domain structure as well as the magnetization reversal when compared to a single layer of Fe(15 nm). This is corroborated by the polarized neutron reflectivity (PNR) data which indicates presence of hybridization at the interface by the reduction of magnetic moment in Fe. Afterwards, upto 1.9 nm of C60 near the interface exhibits magnetic moment. From the PNR measurements it was found that the magnetic C60 layer prefers to be aligned anti-parallel with the Fe layer at the remanant state. The later observation has been confirmed by domain imaging via magneto-optic Kerr microscopy.
NMR Structure, Dynamics and Interactions of the Integrin β2 Cytoplasmic Tail with Filamin Domain IgFLNa21
Authors: Chatterjee Deepak , Zhiping Lewis Lu , Tan Suet-Mien , Bhattacharjya Surajit
Published: March 2018

Integrins are transmembrane proteins that mediate cell adhesion and migration. Each integrin is a heterodimer formed by an α and a β subunit. A large number of cytoplasmic proteins interact with the cytoplasmic tails (CTs) of integrins. The actin-binding cytoskeletal protein filamin A is a negative regulator of integrin activation. The IgFLNa21 domain of filamin A binds to the C-terminus of β2 CT that contains a TTT-motif. Based on x-ray crystallography, it has been reported that the integrin β2 CT forms a β strand that docks into the β strands C and D of IgFLNa21. In this study, we performed solution NMR analyses of IgFLNa21 in the presence of integrin β2 CT peptides, and hybrid IgFLNa21, a construct of covalently linked IgFLNa21 and β2 CT. The atomic resolution structure of the hybrid IgFLNa21 demonstrated conserved binding mode with β2 CT. Although,15N relaxation, model free analyses and H-D exchange studies have uncovered important insights into the conformational dynamics and stability of β2 CT in complex with IgFLNa21. Such dynamical characteristics are likely to be necessary for the TTT-motif to serve as a phosphorylation switch that regulates filamin A binding to integrin β2 CT.
Dysbiosis of the salivary microbiota in pediatric-onset primary sclerosing cholangitis and its potential as a biomarker
Authors: Iwasawa Kentaro , Suda Wataru , Tsunoda Tomoyuki , Oikawa-Kawamoto Manari , Umetsu Shuichiro , Takayasu Lena , Inui Ayano , Fujisawa Tomoo , Morita Hidetoshi , Sogo Tsuyoshi , Hattori Masahira
Published: March 2018

Primary sclerosing cholangitis (PSC) is a liver disease known for its frequent concurrence with inflammatory bowel disease. Dysbiosis of the gut microbiota in PSC was reported in several studies, but the microbiological features of the salivary microbiota in PSC have not been established. Here we compared the salivary microbial communities of 24 pediatric-onset PSC patients, 16 age-matched ulcerative colitis (UC) patients, and 24 healthy controls (HCs) by analyzing the bacterial 16S rRNA gene sequence data. The species-richness (α-diversity) showed no significant between-group differences, whereas the overall salivary microbiota structure (β-diversity) showed significant differences among the three groups. Taxonomic assignment revealed that the PSC salivary microbiota were characterized by significant decreases in the abundance of Rothia and Haemophilus compared to the HC group, and significantly decreased Haemophilus and increased Oribacterium compared to the UC group. By combining the genera selected by the random forest algorithm in machine learning, followed by confirmation with 10-fold cross-validation, we were able to distinguish the PSC group from the HC group with the area under the curve (AUC) of 0.7423, and from the UC group with the AUC of 0.8756. Our results indicate the potential of salivary microbiota as biomarkers for a noninvasive diagnosis of PSC.
Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis
Authors: Wall Richard J. , Ferguson David J. P. , Freville Aline , Franke-Fayard Blandine , Brady Declan , Zeeshan Mohammad , Bottrill Andrew R. , Wheatley Sally , Fry Andrew M. , Janse Chris J. , Yamano Hiroyuki , Holder Anthony A. , Guttery David S. , Tewari Rita
Published: March 2018

The anaphase promoting complex/cyclosome (APC/C) is a highly conserved multi-subunit E3 ubiquitin ligase that controls mitotic division in eukaryotic cells by tagging cell cycle regulators for proteolysis. APC3 is a key component that contributes to APC/C function. Plasmodium, the causative agent of malaria, undergoes atypical mitotic division during its life cycle. Only a small subset of APC/C components has been identified in Plasmodium and their involvement in atypical cell division is not well understood. Here, using reverse genetics we examined the localisation and function of APC3 in Plasmodium berghei. APC3 was observed as a single focus that co-localised with the centriolar plaque during asexual cell division in schizonts, whereas it appeared as multiple foci in male gametocytes. Functional studies using gene disruption and conditional knockdown revealed essential roles of APC3 during these mitotic stages with loss resulting in a lack of chromosome condensation, abnormal cytokinesis and absence of microgamete formation. Overall, our data suggest that Plasmodium utilises unique cell cycle machinery to coordinate various processes during endomitosis, and this warrants further investigation in future studies.
Disturbed retrieval network and prospective memory decline in postpartum women
Authors: Shin Na-Young , Bak Yunjin , Nah Yoonjin , Han Sanghoon , Kim Dong Joon , Kim Se Joo , Lee Jong Eun , Lee Sang-Guk , Lee Seung-Koo
Published: March 2018

Prospective memory (PM) refers to the ability to remember to execute an intended action in the future. For successful PM performance, both top-down strategic monitoring and bottom-up spontaneous retrieval processes need to be appropriately recruited. We assessed PM performance and used fMRI to discover relevant neural correlates and possible predictors for PM performance in 25 postpartum and 26 nulliparous age- and education-matched women. Postpartum women showed decreased PM performance, a higher number of nocturnal awakenings, and lower estradiol level. The postpartum women had decreased functional connectivity (FC) in the right hippocampus and ventral frontoparietal networks (FPN) during retrieval-dominant PM trials relative to maintenance-dominant ongoing trials in the PM block. On multivariate analyses, decreased FC between the right hippocampus and ventral FPN and a higher number of nocturnal awakenings were independent predictors for poor PM performance after adjusting for age, education, estradiol level, and depressive symptoms. On mediation analyses, the estradiol level was found to have an indirect effect on PM accuracy via altered FC as a mediator. This suggests that decreased FC within the spontaneous retrieval-related regions including the right hippocampus and ventral FPN, disrupted sleep rhythms, and decreased estradiol level may contribute to poor PM performance in postpartum women.
Mixture toxicity assisting the design of eco-friendlier plant protection products: a case-study using a commercial herbicide combining nicosulfuron and terbuthylazine
Authors: Queirós Libânia , Vidal Tânia , Nogueira António J. A. , Gonçalves Fernando J. M. , Pereira Joana Luísa
Published: March 2018

The development of environmentally friendly plant protection products (PPPs), including pesticides, is a challenge nowadays. A commercial herbicide combining terbuthylazine and nicosulfuron as active substances (a.s.) was selected as a model PPP. The suitability of manipulating the ratio between a.s. towards alternative formulations with reduced impacts in a non-target indicator (Lemna minor) was assessed. The efficacy of such eco-friendlier a.s. ratios was then assessed using a target weed,Portulaca oleracea. Single and mixture toxicity testing withL. minorrevealed an antagonistic joint action of the a.s., suggesting an environmentally protective effect of the combination compared to single dosing of a.s. The efficacy testing against the target weed of single and combined treatments of the a.s. showed that (i) the a.s. behave antagonistically throughout the wholeP. oleracearesponse surface; (ii) there were no environmentally safe a.s. combinations ensuring target-efficacy; (iii) terbuthylazine alone was effective in controllingP. oleraceawith no environmental hazardous potential, dosed at concentrations 10-fold lower than those involved in commercially recommended application doses. Overall, this case-study suggests that modelling tools widely used in the field of environmental risk assessment of PPPs may also have application in PPP design stages for a more efficient meeting of efficacy and environmental friendliness requirements.
Structure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapy
Authors: Nosanchuk J. D. , Jeyakumar A. , Ray A. , Revskaya E. , Jiang Z. , Bryan R. A. , Allen K. J. H. , Jiao R. , Malo M. E. , Gómez B. L. , Morgenstern A. , Bruchertseifer F. , Rickles D. , Thornton G. B. , Bowen A. , Casadevall A. , Dadachova E.
Published: March 2018

Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3. The therapeutic efficacy of213Bi- and188Re-labeled 8C3 and its comparison with anti-CTLA4 immunotherapy was performed in B16-F10 murine melanoma model. The primary structures of these antibodies revealed significant homology, with the CDRs containing a high percentage of positively charged amino acids. The 8C3 model has a negatively charged binding surface and significant number of aromatic residues in its H3 domain, suggesting that hydrophobic interactions contribute to the antibody-melanin interaction. Radiolabeled IgG 8C3 showed significant therapeutic efficacy in murine melanoma, safety towards healthy melanin-containing tissues and favorable comparison with the anti-CTLA4 antibody. We have demonstrated that antibody binding to melanin relies on both charge and hydrophobic interactions while thein vivodata supports further development of 8C3 IgG as radioimmunotherapy reagent for metastatic melanoma.
Human Sertoli cells support high levels of Zika virus replication and persistence
Authors: Kumar Anil , Jovel Juan , Lopez-Orozco Joaquin , Limonta Daniel , Airo Adriana M. , Hou Shangmei , Stryapunina Iryna , Fibke Chad , Moore Ronald B. , Hobman Tom C.
Published: March 2018

Zika virus is a teratogenic mosquito-transmitted flavivirus that is associated with birth defects in newborns and Guillain–Barré syndrome in adults. The virus can also be sexually transmitted, but currently, very little is known about the cell types supporting virus replication and persistence in human testes. Using primary cell cultures, we observed that Sertoli but not Leydig cells are highly susceptible to Zika virus infection, a process that is dependent on the TAM family receptor Axl. In cell culture, Sertoli cells could be productively infected with Zika virus for at least 6-weeks. Infection of Sertoli cells resulted in dramatic changes to the transcriptional profile of these cells. The most upregulated mRNA in infected cells was basic fibroblast growth factor (FGF2), a cytokine that was found to enhance Zika virus replication and support viral persistence. Together these findings provide key insights into understanding how Zika virus persists in the male reproductive tract and in turn may aid in developing antiviral therapies or strategies to minimize sexual transmission of this pathogen.
A comparative analysis of rod bipolar cell transcriptomes identifies novel genes implicated in night vision
Authors: Woods Sasha M. , Mountjoy Edward , Muir Duncan , Ross Sarah E. , Atan Denize
Published: March 2018

In the mammalian retina, rods and a specialised rod-driven signalling pathway mediate visual responses under scotopic (dim light) conditions. As rods primarily signal to rod bipolar cells (RBCs) under scoptic conditions, disorders that affect rod or RBC function are often associated with impaired night vision. To identify novel genes expressed by RBCs and, therefore, likely to be involved in night vision, we took advantage of the adultBhlhe23−/−mouse retina (that lacks RBCs) to derive the RBC transcriptome. We found that genes expressed by adult RBCs are mainly involved in synaptic structure and signalling, whereas genes that influence RBC development are also involved in the cell cycle and transcription/translation. By comparing our data with other published retinal and bipolar cell transcriptomes (where we identify RBCs by the presence ofPrkcaand/orPcp2transcripts), we have derived a consensus for the adult RBC transcriptome. These findings ought to facilitate further research into physiological mechanisms underlying mammalian night vision as well as proposing candidate genes for patients with inherited causes of night blindness.
Simple Method for De Novo Structural Determination of Underivatised Glucose Oligosaccharides
Authors: Hsu Hsu Chen , Liew Chia Yen , Huang Shih-Pei , Tsai Shang-Ting , Ni Chi-Kung
Published: March 2018

Carbohydrates have various functions in biological systems. However, the structural analysis of carbohydrates remains challenging. Most of the commonly used methods involve derivatization of carbohydrates or can only identify part of the structure. Here, we report a de novo method for completely structural identification of underivatised oligosaccharides. This method, which can provide assignments of linkages, anomeric configurations, and branch locations, entails low-energy collision-induced dissociation (CID) of sodium ion adducts that enable the cleavage of selective chemical bonds, a logical procedure to identify structurally decisive fragment ions for subsequent CID, and the specially prepared disaccharide CID spectrum databases. This method was first applied to determine the structures of four underivatised glucose oligosaccharides. Then, high-performance liquid chromatography and a mass spectrometer with a built-in logical procedure were established to demonstrate the capability of the in situ CID spectrum measurement and structural determination of the oligosaccharides in chromatogram. This consolidation provides a simple, rapid, sensitive method for the structural determination of glucose oligosaccharides, and applications to oligosaccharides containing hexoses other than glucose can be made provided the corresponding disaccharide databases are available.
Health status in subjects with suspected obstructive sleep apnea and comparison with a general population
Authors: Beiske Kornelia K. , Stavem Knut
Published: March 2018

The purpose of this study was to assess health status (HS) in patients with clinical suspicion of obstructive sleep apnea (OSA) in order to estimate the dose response relationship between HS and OSA severity, and to compare HS in this clinical cohort with a general population sample (N = 5000). Patients referred to an overnight sleep study due to suspected OSA, whom also responded to the SF-36 questionnaire, were included (N = 418). Of these, 194 showed normal findings, while 111, 60 and 53 demonstrated mild, moderate and severe OSA, respectively. Mean age was 47.5 (SD 11.9) and 69% were males. Only the mental health scale (p = 0.015) and mental component summary score (p = 0.023) were associated with OSA severity. This association, however, disappeared in multivariable analysis. All SF-36 scores in the sleep study group were lower than that of the general population sample, in both unadjusted and multivariable linear regression analysis. In this study, there was a lack of association between OSA severity and general HS. However, as a whole, patients in this clinical population referred to an overnight sleep study due to suspected OSA had impaired HS on all scales compared to a general population, with greatest differences in the vitality domain.
High hemoglobin levels are associated with decreased risk of diabetic retinopathy in Korean type 2 diabetes
Authors: Lee Min-Kyung , Han Kyung-Do , Lee Jae-Hyuk , Sohn Seo-Young , Jeong Jee-Sun , Kim Mee-Kyoung , Baek Ki-Hyun , Song Ki-Ho , Kwon Hyuk-Sang
Published: March 2018

Anemia is an independent risk factor for the development of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). Hemoglobin levels may also be associated with DR. We investigated the association between hemoglobin levels and DR risk. This cross-sectional, population-based study utilized data from 2,123 type 2 DM patients aged ≥30 years who participated in the Korea National Health and Nutrition Examination Survey from 2008 to 2012. Participants underwent an ophthalmic examination, including fundus photographs. A multiple logistic regression analysis was performed to evaluate the relationship between hemoglobin levels and DR risk. The mean hemoglobin levels in patients with and without DR were 13.76 ± 0.12 and 14.33 ± 0.05 g/dL, respectively, with anemia observed in 16.2 (2.4)% and 7.8 (0.8)%, respectively. A 19% decrease in DR risk was found with a 1.0-g/dL increase in hemoglobin level. DR risk exhibited a decreasing trend with increasing hemoglobin levels (P for trend <0.0001). The adjusted odds ratio of DR was significantly lower in the highest hemoglobin quartile. Our findings indicate that high hemoglobin levels are significantly related to a decreased DR risk in Korean type 2 diabetes.
Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids
Authors: Klecka Martin , Thybo Christina , Macaubas Claudia , Solov’yov Ilia , Simard Julia , Balboni Imelda Maria , Fox Emily , Voss Anne , Mellins Elizabeth D. , Astakhova Kira
Published: March 2018

Autoantibodies to nuclear components of cells (antinuclear antibodies, ANA), including DNA (a-DNA), are widely used in the diagnosis and subtyping of certain autoimmune diseases, including systemic lupus erythematosus (SLE). Despite clinical use over decades, precise, reproducible measurement of a-DNA titers remains difficult, likely due to the substantial sequence and length heterogeneity of DNA purified from natural sources. We designed and tested a panel of synthetic nucleic acid molecules composed of native deoxyribonucleotide units to measure a-DNA. ELISA assays using these antigens show specificity and reproducibility. Applying the ELISA tests to serological studies of pediatric and adult SLE, we identified novel clinical correlations. We also observed preferential recognition of a specific synthetic antigen by antibodies in SLE sera. We determined the probable basis for this finding using computational analyses, providing valuable structural information for future development of DNA antigens. Synthetic nucleic acid molecules offer the opportunity to standardize assays and to dissect antibody-antigen interactions.
Earliest Animal Cranial Surgery: from Cow to Man in the Neolithic
Authors: Ramirez Rozzi Fernando , Froment Alain
Published: March 2018

The earliest cranial surgery (trepanation) has been attested since the Mesolithic period. The meaning of such a practice remains elusive but it is evident that, even in prehistoric times, humans from this period and from the Neolithic period had already achieved a high degree of mastery of surgical techniques practiced on bones. How such mastery was acquired in prehistoric societies remains an open question. The analysis of an almost complete cow cranium found in the Neolithic site of Champ-Durand (France) (3400-3000 BC) presenting a hole in the right frontal bone reveals that this cranium underwent cranial surgery using the same techniques as those used on human crania. If bone surgery on the cow cranium was performed in order to save the animal, Champ-Durant would provide the earliest evidence of veterinary surgical practice. Alternatively, the evidence of surgery on this cranium can also suggest that Neolithic people practiced on domestic animals in order to perfect the technique before applying it to humans.
Uptake of plant-derived specific alkaloids allows males of a butterfly to copulate
Authors: Honda Keiichi , Matsumoto Junya , Sasaki Ken , Tsuruta Yoshiaki , Honda Yasuyuki
Published: March 2018

Certain butterflies utilize plant-acquired alkaloids for their own chemical defense and/or for producing male sex pheromone; a trait known as pharmacophagy. Males of the danaine butterfly, Parantica sita, have been reported to ingest pyrrolizidine alkaloids (PAs) as adults to produce two PA-derived sex pheromone components, viz. danaidone (major) and 7R-hydroxydanaidal. We found, however, that not all PAs that can be precursors for the pheromone serve for mating success of males. Here we show that although the sex pheromone is regarded as a requisite for successful mating, uptake of specific PA(s) (lycopsamine-type PAs) is also imperative for the males to achieve copulation. The increase in the levels of two biogenic amines, octopamine and/or serotonin, in the brain and thoracic ganglia of males fed with specific PA(s) suggested that these alkaloids most likely enhance male mating activity. The results can present new evidence for the evolutionary provenance of pharmacophagous acquisition of PAs in PA-adapted insects.
A high nutrient dense diet alters hypothalamic gene expressions to influence energy intake in pigs born with low birth weight
Authors: Liu Jingbo , Cao Shanchuan , Liu Ming , Chen Liang , Zhang Hongfu
Published: March 2018

The low birth weight (LBW) individual had greater risk of developing metabolic dysfunction in adulthood. The aim of this study was to test whether the LBW individual is more prone to glucose intolerance on a high nutrient dense (HND) diet, and to investigate the associated hypothalamic gene expressions using pigs as model. The intake of digestible energy intake, if calculated on a body weight basis, was greater in LBW pigs than that of normal birth weight (NBW) pigs. The LBW pigs fed the HND diet had greater digestible energy intake than those fed the NND diet at adulthood, which did not occur for NBW pigs. Notably, up-regulated hypothalamic toll-like receptor 4, interleukin 6 and phospho-NFκB p65 expressions, and the altered expressions of hypothalamic leptin receptor, suppressor of cytokine signaling 3, agouti-related protein and proopiomelanocortin predicted the overconsumption of energy intake and development of glucose intolerance in LBW pigs fed the HND diet. Collectively, pigs born with LBW had a distinct hypothalamic leptin signaling to a high nutrient dense diet, which contributed to greater energy intake and glucose intolerance.
Metacognitive ability predicts learning cue-stimulus associations in the absence of external feedback
Authors: Hainguerlot Marine , Vergnaud Jean-Christophe , de Gardelle Vincent
Published: March 2018

Learning how certain cues in our environment predict specific states of nature is an essential ability for survival. However learning typically requires external feedback, which is not always available in everyday life. One potential substitute for external feedback could be to use the confidence we have in our decisions. Under this hypothesis, if no external feedback is available, then the agents’ ability to learn about predictive cues should increase with the quality of their confidence judgments (i.e. metacognitive efficiency). We tested and confirmed this novel prediction in an experimental study using a perceptual decision task. We evaluated in separate sessions the metacognitive abilities of participants (N = 65) and their abilities to learn about predictive cues. As predicted, participants with greater metacognitive abilities learned more about the cues. Knowledge of the cues improved accuracy in the perceptual task. Our results provide strong evidence that confidence plays an active role in improving learning and performance.
Recycling Waste Soot from Merchant Ships to Produce Anode Materials for Rechargeable Lithium-Ion Batteries
Authors: Lee Won-Ju , Kim Han Vin , Choi Jae-Hyuk , Panomsuwan Gasidit , Lee Young-Chan , Rho Beom-Seok , Kang Jun
Published: March 2018

In this study, the waste soot generated by ships was recycled to produce an active material for use in lithium-ion batteries (LIBs). Soot collected from a ship was graphitized by a heat treatment process and used as an anode active material. It was confirmed that the graphitized soot was converted into a highly crystalline graphite, and was found to form carbon nano-onions with an average diameter of 70 nm. The graphitized soot showed a high discharge capacity and an excellent cycle life, with a reversible capacity of 260 mAhg−1 even after 150 cycles at a rate of 1 C. This study demonstrates that the annealed soot with a unique graphitic multilayer structure has an electrochemical performance that renders it suitable as a candidate for the production of low-cost anode materials for use in LIBs.
Prognostic value of cancer antigen -125 for lung adenocarcinoma patients with brain metastasis: A random survival forest prognostic model
Authors: Wang Hao , Shen Liuhai , Geng Jianhua , Wu Yitian , Xiao Huan , Zhang Fan , Si Hongwei
Published: March 2018

Using random survival forest, this study was intended to evaluate the prognostic value of serum markers for lung adenocarcinoma patients with brain metastasis (BM), and tried to integrate them into a prognostic model. During 2010 to 2015, the patients were retrieved from two medical centers. Besides the Cox proportional hazards regression, the random survival forest (RSF) were also used to develop prognostic model from the group A (n = 142). In RSF of the group A, the factors, whose minimal depth were greater than the depth threshold or had a negative variable importance (VIMP), were firstly excluded. Subsequently, C-index and Akaike information criterion (AIC) were used to guide us finding models with higher prognostic ability and lower overfitting possibility. These RSF models, together with the Cox, modified-RPA and lung-GPA index were validated and compared, especially in the group B (CAMS, n = 53). Our data indicated that the KSE125 model (KPS, smoking, EGFR-20 (exon 18, 19 and 21) and Ca125) was the best in survival prediction, and performed well in internal and external validation. In conclusions, for lung adenocarcinoma patients with brain metastasis, a validated prognostic nomogram (KPS, smoking, EGFR-20 and Ca125) can more accurately predict 1-year and 2-year survival of the patients.
Fingolimod therapy is not effective in a mouse model of spontaneous autoimmune peripheral polyneuropathy
Authors: Huehnchen Petra , Boehmerle Wolfgang , Endres Matthias
Published: March 2018

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder, which causes progressive sensory and motor deficits and often results in severe disability. Knockout of the co-stimulatory protein CD86 in mice of the non-obese diabetic background (NoD.129S4-Cd86tm1Shr/JbsJ) results in the development of a spontaneous autoimmune peripheral polyneuropathy (SAPP). We used this previously described transgenic model to study the effects of the sphingosine-1-phosphate receptor agonist fingolimod on SAPP symptoms, functional and electrophysiological characteristics. Compared to two control strains, knockout of CD86 in NOD mice (CD86−/−NOD) resulted in progressive paralysis with distinct locomotor deficits due to a severe sensory-motor axonal-demyelinating polyneuropathy as assessed by electrophysiological measurements. We started fingolimod treatment when CD86−/−NOD mice showed signs of unilateral hind limb weakness and continued at a dose of 1 mg/kg/day for eight weeks. We did not observe any beneficial effects of fingolimod regarding disease progression. In addition, fingolimod did not influence the functional outcome of CD86−/−NOD mice compared to vehicle treatment nor any of the electrophysiological characteristics. In summary, we show that fingolimod treatment has no beneficial effects in autoimmune polyneuropathy, which is in line with recent clinical data obtained in CIDP patients.
Tensile behavior of Cu-coated Pd40Cu30Ni10P20 metallic glassy wire
Authors: Hussain I. , Jiang Y. Y. , Jia Y. D. , Wang G. , Zhai Q. J. , Chan K. C. , Yi J.
Published: March 2018

Catastrophic brittle fracture of monolithic metallic glass (MG) hinders engineering application of MGs. Although many techniques has been tried to enhance tensile ductility of metallic glasses, the enhancement is quite limited. Here, we show the effect of electrodeposited Cu coating on tensile plasticity enhancement of Pd40Cu30Ni10P20 MG wires, with different volume fractions of copper coatings (R), from 0% to 97%. With increasing R, tensile elongation is enhanced to 7.1%. The plasticity enhancement is due to confinement of the Cu coatings, which lead to multiple and secondary shear bands, according to SEM investigations. In addition, the SEM images also show that the patterns on the fracture surface of the Cu-coated MG wires vary with volume fraction of the Cu coatings. The size of shear offset decreases with increasing R. The viscous fingerings on the fracture surface of monolithic MG wire changes into dimples on the fracture surface of Cu coated MG wires with R of 90% and 97%. The electrodeposition technique used in this work provides a useful way to enhance plasticity of monolithic MGs under tensile loading at room temperature.
Aligned laminin core-polydioxanone/collagen shell fiber matrices effective for neuritogenesis
Authors: Song Su-Jin , Shin Yong Cheol , Kim Sung Eun , Kwon Il Keun , Lee Jong-Ho , Hyon Suong-Hyu , Han Dong-Wook , Kim Bongju
Published: March 2018

Neural tissue regeneration is a significant challenge, because severe nerve injury is quite difficult to regenerate spontaneously. Although, many studies have been devoted to promote nerve regeneration, there are still many technical challenges to achieve satisfactory results. In this study, we designed biomimetic matrices composed of aligned laminin core-polydioxanone/collagen shell (Lam-PDO/Col) fibers, which can provide both topographical and biochemical cues for promoting neuritogenesis. The aligned Lam-PDO/Col core-shell fiber matrices were fabricated by magnetic field-assisted electrospinning with the coaxial system, and their potential as biofunctional scaffolds for promoting neuritogenesis was explored. It was demonstrated that the aligned Lam-PDO/Col core-shell fibers were successfully fabricated, and the laminin in the core of fibers was steadily and continuously released from fibers. In addition, the cellular behaviors of hippocampal neuronal cells on the matrices were significantly enhanced. Moreover, the aligned Lam-PDO/Col fiber matrices effectively improved and guided neurite outgrowth as well as the neurogenic differentiation by providing both topographical and biochemical cues through aligned fiber structure and sustained release of laminin. Collectively, it is suggested that the aligned Lam-PDO/Col core-shell fiber matrices are one of the most promising approaches for promoting neuritogenesis and neural tissue regeneration.
Small molecule detection with aptamer based lateral flow assays: Applying aptamer-C-reactive protein cross-recognition for ampicillin detection
Authors: Kaiser Lars , Weisser Julia , Kohl Matthias , Deigner Hans-Peter
Published: March 2018

Aptamer-based lateral flow assays (LFAs) are an emerging field of aptamer applications due to numerous potential applications. When compared to antibodies, potential advantages like cost effectiveness or lower batch to batch variations are evident. The development of LFAs for small molecules, however, is still challenging due to several reasons, primarily linked to target size and accessible interaction sites. In small molecule analysis, however, aptamers in many cases are preferable since immunogenicity is not required and they may exhibit even higher target selectivity. We report the first cross-recognition of a small molecule (ampicillin) and a protein (C-reactive protein), predicted by in-silico analysis, then experimentally confirmed - using two different aptamers. These features can be exploited for developing an aptamer-based LFA for label-free ampicillin detection, functioning also for analysis in milk extract. Most importantly, the principal setup denotes a novel, transferable and versatile general approach for detection of small molecules using competitive LFAs, unlikely to be generally realized by aptamer-DNA-binding otherwise.
Network approach of the conformational change of c-Src, a tyrosine kinase, by molecular dynamics simulation
Authors: Yoon Hyun Jung , Lee Sungmin , Park Sun Joo , Wu Sangwook
Published: March 2018

Non-receptor tyrosine kinase c-Src plays a critical role in numerous cellular signalling pathways. Activation of c-Src from its inactive to the active state involves large-scale conformational changes, and is controlled by the phosphorylation state of two major phosphorylation sites, Tyr416 and Tyr527. A detailed mechanism for the entire conformational transition of c-Src via phosphorylation control of Tyr416 and Tyr527 is still elusive. In this study, we investigated the inactive-to-active conformational change of c-Src by targeted molecular dynamics simulation. Based on the simulation, we proposed a dynamical scenario for the activation process of c-Src. A detailed study of the conformational transition pathway based on network analysis suggests that Lys321 plays a key role in the c-Src activation process.