bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal differentiation induces SNORD115 expression and is accompanied by post-transcriptional changes of serotonin receptor 2c mRNA
Authors: Bratkovič Tomaž , Modic Miha , Camargo Ortega Germán , Drukker Micha , Rogelj Boris
Published: March 2018

The serotonin neurotransmitter system is widespread in the brain and implicated in modulation of neuronal responses to other neurotransmitters. Among 14 serotonin receptor subtypes, 5-HT2cR plays a pivotal role in controlling neuronal network excitability. Serotonergic activity conveyed through receptor 5-HT2cR is regulated post-transcriptionally via two mechanisms, alternative splicing and A-to-I RNA editing. Brain-specific small nucleolar RNA SNORD115 harbours a phylogenetically conserved 18-nucleotide antisense element with perfect complementarity to the region of 5ht2c primary transcript that undergoes post-transcriptional changes. Previous 5ht2c minigene studies have implicated SNORD115 in fine-tuning of both post-transcriptional events. We monitored post-transcriptional changes of endogenous 5ht2c transcripts during neuronal differentiation. Both SNORD115 and 5ht2c were upregulated upon neuronal commitment. We detected increased 5ht2c alternative exon Vb inclusion already at the stage of neuronal progenitors, and more extensive A-to-I editing of non-targeted sites A and B compared to adjacent adenosines at sites E, C and D throughout differentiation. As the extent of editing is known to positively correlate with exon Vb usage while it reduces receptor functionality, our data support the model where SNORD115 directly promotes alternative exon inclusion without the requirement for conversion of key adenosines to inosines, thereby favouring production of full-length receptor isoforms with higher potency.
Methodology challenges in studying human gut microbiota – effects of collection, storage, DNA extraction and next generation sequencing technologies
Authors: Panek Marina , Čipčić Paljetak Hana , Barešić Anja , Perić Mihaela , Matijašić Mario , Lojkić Ivana , Vranešić Bender Darija , Krznarić Željko , Verbanac Donatella
Published: March 2018

The information on microbiota composition in the human gastrointestinal tract predominantly originates from the analyses of human faeces by application of next generation sequencing (NGS). However, the detected composition of the faecal bacterial community can be affected by various factors including experimental design and procedures. This study evaluated the performance of different protocols for collection and storage of faecal samples (native and OMNIgene.GUT system) and bacterial DNA extraction (MP Biomedicals, QIAGEN and MO BIO kits), using two NGS platforms for 16S rRNA gene sequencing (Ilumina MiSeq and Ion Torrent PGM). OMNIgene.GUT proved as a reliable and convenient system for collection and storage of faecal samples although favouring Sutterella genus. MP provided superior DNA yield and quality, MO BIO depleted Gram positive organisms while using QIAGEN with OMNIgene.GUT resulted in greatest variability compared to other two kits. MiSeq and IT platforms in their supplier recommended setups provided comparable reproducibility of donor faecal microbiota. The differences included higher diversity observed with MiSeq and increased capacity of MiSeq to detect Akkermansia muciniphila, [Odoribacteraceae], Erysipelotrichaceae and Ruminococcaceae (primarily Faecalibacterium prausnitzii). The results of our study could assist the investigators using NGS technologies to make informed decisions on appropriate tools for their experimental pipelines.
A wide-band bio-chip for real-time optical detection of bioelectromagnetic interactions with cells
Authors: Merla Caterina , Liberti Micaela , Marracino Paolo , Muscat Adeline , Azan Antoine , Apollonio Francesca , Mir Lluis M.
Published: March 2018

The analytical and numerical design, implementation, and experimental validation of a new grounded closed coplanar waveguide for wide-band electromagnetic exposures of cells and their optical detection in real-time is reported. The realized device fulfills high-quality requirements for novel bioelectromagnetic experiments, involving elevated temporal and spatial resolutions. Excellent performances in terms of matching bandwidth (less than −10 dB up to at least 3 GHz), emission (below 1 × 10−6 W/m2) and efficiency (around 1) have been obtained as revealed by both numerical simulations and experimental measurements. A low spatial electric field inhomogeneity (coefficient of variation of around 10 %) has been achieved within the cell solutions filling the polydimethylsiloxane reservoir of the conceived device. This original bio-chip based on the grounded closed coplanar waveguide concept opens new possibilities for the development of controlled experiments combining electromagnetic exposures and sophisticated imaging using optical spectroscopic techniques.
Propensity Score-Matched Analysis on the Association Between Pregnancy Infections and Adverse Birth Outcomes in Rural Northwestern China
Authors: Guo Leqian , Qu Pengfei , Zhang Ruo , Zhao Doudou , Wang Hongli , Liu Rong , Mi Baibing , Yan Hong , Dang Shaonong
Published: March 2018

The purpose of this study is to examine the relationship between infections and birth outcomes in pregnant Chinese women by using propensity score (PS) matching. The data used here was from a large population-based cross-sectional epidemiological survey on birth defects in Shaanxi province, Northwest China. The babies born during 2010–2013 and their mothers were selected with a stratified multistage sampling method. We used PS-matched (1:1) analysis to match participants with infections to participants without infections. Of 22916 rural participants, the overall prevalence of infection was about 39.96%. 5381 pairs were matched. We observed increased risks of birth defects with infections, respiratory infections and genitourinary infections during the pregnancy (OR, 1.59; 95% CI: 1.21–2.08; OR, 1.44; 95% CI: 1.10–1.87; OR, 3.11; 95% CI: 1.75–5.54). There was also a significant increase of low birth weight associated with respiratory infections (1.13(1.01–1.27)). The association of birth defect with the infection could be relatively stable but the effect could be mediated by some important factors such as mother’s age, education level and economic level. The infection during pregnancy is common in Chinese women and might increase the risk of offspring birth defects and low birth weight, especially in younger, lower education, poor pregnant women.
Data-based Decision Rules to Personalize Depression Follow-up
Authors: Lin Ying , Huang Shuai , Simon Gregory E. , Liu Shan
Published: March 2018

Depression is a common mental illness with complex and heterogeneous progression dynamics. Risk grouping of depression treatment population based on their longitudinal patterns has the potential to enable cost-effective monitoring policy design. This paper establishes a rule-based method to identify a set of risk predictive patterns from person-level longitudinal disease measurements by integrating the data transformation, rule discovery and rule evaluation. We further extend the identified rules to create rule-based monitoring strategies to adaptively monitor individuals with different disease severities. We applied the rule-based method on an electronic health record (EHR) dataset of depression treatment population containing person-level longitudinal Patient Health Questionnaire (PHQ)-9 scores for assessing depression severity. 12 risk predictive rules are identified, and the rule-based prognostic model based on identified rules enables more accurate prediction of disease severity than other prognostic models including RuleFit, logistic regression and Support Vector Machine. Two rule-based monitoring strategies outperform the latest PHQ-9 based monitoring strategy by providing higher sensitivity and specificity. The rule-based method can lead to a better understanding of disease dynamics, achieving more accurate prognostics of disease progressions, personalizing follow-up intervals, and designing cost-effective monitoring of patients in clinical practice.
Author Correction: Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients
Authors: Santoru Maria Laura , Piras Cristina , Murgia Antonio , Palmas Vanessa , Camboni Tania , Liggi Sonia , Ibba Ivan , Lai Maria Antonia , Orrù Sandro , Blois Sylvain , Loizedda Anna Lisa , Griffin Julian Leether , Usai Paolo , Caboni Pierluigi , Atzori Luigi , Manzin Aldo
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: Fast, sensitive method for trisaccharide biomarker detection in mucopolysaccharidosis type 1
Authors: Makino Elina , Klodnitsky Helen , Leonard John , Lillie James , Lund Troy C. , Marshall John , Nietupski Jennifer , Orchard Paul J. , Miller Weston P. , Phaneuf Clifford , Tietz Drew , Varban Mariet L. , Donovan Marissa , Belenki Alexey
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Whey protein lowers systolic blood pressure and Ca-caseinate reduces serum TAG after a high-fat meal in mildly hypertensive adults
Authors: Fekete Ágnes A. , Giromini Carlotta , Chatzidiakou Yianna , Givens D. Ian , Lovegrove Julie A.
Published: March 2018

Epidemiological studies show an inverse association between dairy consumption and blood pressure (BP) but there are few data on the postprandial effects of milk proteins. This study examined their effects, compared to maltodextrin, on postprandial BP and other CVD risk markers in volunteers with mild and pre-hypertension over an 8 h period. In this double-blinded, randomised, cross-over, controlled study 27 adults ingested a high-fat, isoenergetic breakfast and lunch with 28 g whey protein, 28 g Ca-caseinate or 27 g maltodextrin. Whey protein reduced systolic BP compared with Ca-caseinate (−15.2 ± 13.6 mmHg) and maltodextrin (−23.4 ± 10.5 mmHg) up to 5 h post-ingestion. There was an improvement in arterial stiffness after whey protein compared with maltodextrin (incremental Area Under the Curve- iAUC0–8h: +14.4 ± 6.2%). Despite similar glucose levels after both whey protein and Ca-caseinate, whey protein induced a higher insulin response than Ca-caseinate (iAUC0–8h: +219.5 ± 54.6 pmol/L). Ca-caseinate induced less suppression of non-esterified fatty acids than whey protein (iAUC0–5h: −58.9 ± 135.5 μmol/L) and maltodextrin (iAUC0–5h: −106.9 ± 89.4 μmol/L) and induced a smaller postprandial triacylglycerol response than whey protein (iAUC0–8h: −1.68 ± 0.6 mmol/L). Milk proteins co-ingestion with high-fat meals may have the potential to maintain or improve CVD risk factors.
Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking
Authors: Coghlan Matthew , Richards Elizabeth , Shaik Sadiq , Rossi Pablo , Vanama Ramesh Babu , Ahmadi Saumel , Petroz Christelle , Crawford Mark , Maynes Jason T.
Published: March 2018

Anesthetic agents have been implicated in the causation of neurological and cognitive deficits after surgery, the exacerbation of chronic neurodegenerative disease, and were recently reported to promote the onset of the neurologic respiratory disease Congenital Central Hypoventilation Syndrome (CCHS), related to misfolding of the transcription factor Phox2B. To study how anesthetic agents could affect neuronal function through alterations to protein folding, we created neuronal cell models emulating the graded disease severity of CCHS. We found that the gas anesthetic isoflurane and the opiate morphine potentiated aggregation and mislocalization of Phox2B variants, similar to that seen in CCHS, and observed transcript and protein level changes consistent with activation of the endoplasmic reticulum (ER) unfolded protein response. Attenuation of ER stress pathways did not result in a correction of Phox2B misfolding, indicating a primary effect of isoflurane on protein structure. We also observed that isoflurane hindered the folding and activity of proteins that rely heavily on ER function, like the CFTR channel. Our results show how anesthetic drugs can alter protein folding and induce ER stress, indicating a mechanism by which these agents may affect neuronal function after surgery.
Freestanding photocatalytic materials based on 3D graphene and polyporphyrins
Authors: Ussia Martina , Bruno Elena , Spina Emanuela , Vitalini Daniele , Pellegrino Giovanna , Ruffino Francesco , Privitera Vittorio , Carroccio Sabrina C.
Published: March 2018

A new concept in the formulation of hybrid nanostructured materials combining high quality graphene 3D supported by Nickel foam and polyporphyrins for visible light photocatalytic application is here reported. Our innovative approach involves the development of a freestanding device able to: i) offer a high surface area to bind the photosensitizers by π-π interactions, and ii) enhance stability and photocatalytic efficiency by using cyclic porphyrin polymers. For these purposes, homo- and co-polymerization reactions by using different porphyrin (free or zinc complexed) monomers were performed. The microscopic structures and morphology of graphene polymer nanocomposites were investigated by using Scanning Electron Microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Atomic Force Microscopy (AFM). Finally, photocatalytic activity under visible light irradiation of the obtained nanocomposites was tested, by using methylene blue (MB) as organic pollutant. The obtained data suggested that hindered cyclic polymeric structures stacked on graphene surface by non-covalent interactions, restrict the formation of non photoactive aggregates and, as a consequence, induce an enhancement of photocatalytic activity. Remarkably, our systems show a degradation efficiency in the visible-light range much higher than other similar devices containing nanoporphyrin units reported in literature.
Magnetic field effect on the energy levels of an exciton in a GaAs quantum dot: Application for excitonic lasers
Authors: Jahan K. Luhluh , Boda A. , Shankar I. V. , Raju Ch. Narasimha , Chatterjee Ashok
Published: March 2018

The problem of an exciton trapped in a Gaussian quantum dot (QD) of GaAs is studied in both two and three dimensions in the presence of an external magnetic field using the Ritz variational method, the 1/N expansion method and the shifted 1/N expansion method. The ground state energy and the binding energy of the exciton are obtained as a function of the quantum dot size, confinement strength and the magnetic field and compared with those available in the literature. While the variational method gives the upper bound to the ground state energy, the 1/N expansion method gives the lower bound. The results obtained from the shifted 1/N expansion method are shown to match very well with those obtained from the exact diagonalization technique. The variation of the exciton size and the oscillator strength of the exciton are also studied as a function of the size of the quantum dot. The excited states of the exciton are computed using the shifted 1/N expansion method and it is suggested that a given number of stable excitonic bound states can be realized in a quantum dot by tuning the quantum dot parameters. This can open up the possibility of having quantum dot lasers using excitonic states.
Nature-Inspired Hierarchical Steels
Authors: Cao Shan Cecilia , Liu Jiabin , Zhu Linli , Li Ling , Dao Ming , Lu Jian , Ritchie Robert O.
Published: March 2018

Materials can be made strong, but as such they are often brittle and prone to fracture when under stress. Inspired by the exceptionally strong and ductile structure of byssal threads found in certain mussels, we have designed and manufactured a multi-hierarchical steel, based on an inexpensive austenitic stainless steel, which defeats this “conflict” by possessing both superior strength and ductility. These excellent mechanical properties are realized by structurally introducing sandwich structures at both the macro- and nano-scales, the latter via an isometric, alternating, dual-phase crystal phases comprising nano-band austenite and nano-lamellar martensite, without change in chemical composition. Our experiments (transmission and scanning electron microscopy, electron back-scattered diffraction, nano-indentation and tensile tests) and micromechanics simulation results reveal a synergy of mechanisms underlying such exceptional properties. This synergy is key to the development of vastly superior mechanical properties, and may provide a unique strategy for the future development of new super strong and tough (damage-tolerant), lightweight and inexpensive structural materials.
Predation scars may influence host susceptibility to pathogens: evaluating the role of corallivores as vectors of coral disease
Authors: Nicolet K. J. , Chong-Seng K. M. , Pratchett M. S. , Willis B. L. , Hoogenboom M. O.
Published: March 2018

Infectious diseases not regulated by host density, such as vector-borne diseases, have the potential to drive population declines and extinctions. Here we test the vector potential of the snailDrupellasp. and butterflyfishChaetodon plebeiusfor two coral diseases, black band (BBD) and brown band (BrB) disease.Drupellatransmitted BrB to healthy corals in 40% of cases immediately following feeding on infected corals, and even in 12% of cases 12 and 24 hours following feeding. However,Drupellawas unable to transmit BBD in either transmission treatment. In a field experiment testing the vector potential of naturally-occurring fish assemblages, equivalent numbers of caged and uncaged coral fragments became infected with either BrB, BBD or skeletal eroding band, indicating that corallivorous fish were unlikely to have caused transmission. In aquaria,C.plebeiusdid not transmit either BBD or BrB, even following extended feeding on both infected and healthy nubbins. A literature review confirmed only four known coral disease vectors, all invertebrates, corroborating our conclusion that polyp-feeding fishes are unlikely to be vectors of coral diseases. This potentially because polyp-feeding fishes produce shallow lesions, not allowing pathogens to invade coral tissues. In contrast, corallivorous invertebrates that create deeper feeding scars increase pathogens transmission.
Long term potentiation, but not depression, in interlamellar hippocampus CA1
Authors: Sun Duk-gyu , Kang Hyeri , Tetteh Hannah , Su Junfeng , Lee Jihwan , Park Sung-Won , He Jufang , Jo Jihoon , Yang Sungchil , Yang Sunggu
Published: March 2018

Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.
Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice
Authors: Hedhli Jamila , Slania Stephanie L. L. , Płoska Agata , Czerwinski Andrzej , Konopka Christian J. , Wozniak Marcin , Banach Maciej , Dobrucki Iwona T. , Kalinowski Leszek , Dobrucki Lawrence W.
Published: March 2018

The α
V
 β3 integrin plays an important role in many physiological functions and pathological disorders. α
V
 β3 is minimally expressed in normal quiescent endothelial cells, but significantly upregulated during neovascularization. In this study, we evaluated a 64Cu-labeled dimeric cRGD tracer targeted at α
V
 β3 integrin and report its applicability to assess peripheral angiogenesis in diabetes mellitus (DM). We established a murine model of type-1 DM characterized by elevated glucose, glycated serum protein (GSP), and glycated hemoglobin A1c (HbA1c). We demonstrated that our imaging probe is specific to α
V
 β3 integrin under both normo- and hyperglycemic conditions. We found that the analysis of in vivo PET-CT images correlated well with gamma well counting (GWC). Both GWC and PET-CT imaging demonstrated increased uptake of 64Cu-NOTA-PEG4-cRGD2 in the ischemic hindlimb in contrast to non-ischemic control. GWC of the distal ischemic tissue from DM mice showed significantly lower probe accumulation than in non-DM mice. The immunofluorescence staining of the ischemic tissues showed a 3-fold reduction in CD31 and 4-fold reduction in the α
V
 β3 expression in DM vs. non-DM animals. In conclusion, we successfully demonstrated that diabetes-associated reductions in peripheral angiogenesis can be non-invasively detected with PET-CT imaging using targeted dimeric-cRGD probe.
Effect of live yeast Saccharomyces cerevisiae (Actisaf Sc 47) supplementation on the performance and hindgut microbiota composition of weanling pigs
Authors: Kiros T. G. , Derakhshani H. , Pinloche E. , D’Inca R. , Marshall Jason , Auclair E. , Khafipour E. , Van Kessel A.
Published: March 2018

As an alternative to antibiotic growth promoters, live yeast supplementation has proven useful in reducing weaning stress and improving performance parameters of piglets. Here, we compared the performance and hindgut microbiota of weanling piglets subjected to different pre- and post-weaning yeast supplementation regimens using a live strain of Saccharomyces cerevisiae (Actisaf Sc 47). Average feed intake and average daily weight gain of piglets within Yeast-Control and Yeast-Yeast groups were higher than those in the Control-Control group. Yeast supplementation resulted in development of microbial communities that were phylogenetically more homogenous and less dispersed compared to the microbiota of control piglets. Key bacterial taxa overrepresented in the microbiota of yeast supplemented piglets included phylum Actinobacteria, specifically family Coriobacteriaceae, as well as Firmicutes families Ruminococcaceae, Clostridiaceae, Peptostreptococcaceae, and Peptococcaceae. Correlation network analysis revealed that yeast supplementation was associated with enrichment of positive correlations among proportions of different bacterial genera within the hindgut ecosystem. In particular, within the cecal microbiota of supplemented piglets, higher numbers of positive correlations were observed among potentially beneficial genera of the phyla Actinobacteria and Firmicutes, suggesting a mechanism by which yeast supplementation may contribute to regulation of intestinal homeostasis and improved performance of piglets.
Efficacy and safety of boosted darunavir-based antiretroviral therapy in HIV-1-positive patients: results from a meta-analysis of clinical trials
Authors: Antinori A. , Lazzarin A. , Uglietti A. , Palma M. , Mancusi D. , Termini R.
Published: March 2018

Darunavir/ritonavir (DRV/r) is a second-generation protease inhibitor used in treatment-naïve and -experienced HIV-positive adult patients. To evaluate efficacy and safety in these patient settings, we performed a meta-analysis of randomized controlled trials. We considered eight studies involving 4240 antiretroviral treatment (ART)-naïve patients and 14 studies involving 2684 ART-experienced patients. Regarding efficacy in the ART-naive patients, the virological response rate was not significantly different between DRV/r and the comparator. For the ART-experienced failing patients, the virological response rate was significantly higher with DRV/r than with the comparator (RR 1.45, 95% CI: 1.01–2.08); conversely, no significant differences were found between the treatment-experienced and virologically controlled DRV/r and comparator groups. Regarding safety, the discontinuation rates due to adverse events (AEs) and DRV/r-related serious adverse events (SAEs) did not significantly differ from the rates in the comparator group (RR 0.84, 95% CI: 0.59–1.19 and RR 0.78, 95% CI: 0.57–1.05, respectively). Our meta-analysis indicated that DRV/r-based regimens were effective and tolerable for both types of patients, which was consistent with published data.
Operating length and velocity of human vastus lateralis muscle during walking and running
Authors: Bohm S. , Marzilger R. , Mersmann F. , Santuz A. , Arampatzis A.
Published: March 2018

According to the force-length-velocity relationships, the muscle force potential during locomotion is determined by the operating fibre length and velocity. We measured fascicle and muscle-tendon unit length and velocity as well as the activity of the human vastus lateralis muscle (VL) during walking and running. Furthermore, we determined the VL force-length relationship experimentally and calculated the force-length and force-velocity potentials (i.e. fraction of maximum force according to the force-length-velocity curves) for both gaits. During the active state of the stance phase, fascicles showed significantly (p < 0.05) smaller length changes (walking: 9.2 ± 4.7% of optimal length (L0); running: 9.0 ± 8.4%L0) and lower velocities (0.46 ± 0.36 L0/s; 0.03 ± 0.83 L0/s) compared to the muscle-tendon unit (walking: 19.7 ± 5.3%L0, −0.94 ± 0.32 L0/s; running: 34.5 ± 5.8%L0, −2.59 ± 0.41 L0/s). The VL fascicles operated close to optimum length (L0 = 9.4 ± 0.11 cm) in both walking (8.6 ± 0.14 cm) and running (10.1 ± 0.19 cm), resulting in high force-length (walking: 0.92 ± 0.08; running: 0.91 ± 0.14) and force-velocity (0.91 ± 0.08; 0.97 ± 0.13) potentials. For the first time we demonstrated that, in contrast to the current general conception, the VL fascicles operate almost isometrically and close to L0 during the active state of the stance phase of walking and running. The findings further verify an important contribution of the series-elastic element to VL fascicle dynamics.
Dual binding in cohesin-dockerin complexes: the energy landscape and the role of short, terminal segments of the dockerin module
Authors: Wojciechowski Michał , Różycki Bartosz , Huy Pham Dinh Quoc , Li Mai Suan , Bayer Edward A. , Cieplak Marek
Published: March 2018

The assembly of the polysaccharide degradating cellulosome machinery is mediated by tight binding between cohesin and dockerin domains. We have used an empirical model known as FoldX as well as molecular mechanics methods to determine the free energy of binding between a cohesin and a dockerin from Clostridium thermocellum in two possible modes that differ by an approximately 180° rotation. Our studies suggest that the full-length wild-type complex exhibits dual binding at room temperature, i.e., the two modes of binding have comparable probabilities at equilibrium. The ability to bind in the two modes persists at elevated temperatures. However, single-point mutations or truncations of terminal segments in the dockerin result in shifting the equilibrium towards one of the binding modes. Our molecular dynamics simulations of mechanical stretching of the full-length wild-type cohesin-dockerin complex indicate that each mode of binding leads to two kinds of stretching pathways, which may be mistakenly taken as evidence of dual binding.
Author Correction: Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy
Authors: Jang Young Kyoung , Kim Hee Jin , Lee Jin San , Kim Yeo Jin , Kim Ko Woon , Kim Yeshin , Jang Hyemin , Lee Juyoun , Lee Jong Min , Kim Seung-Joo , Yu Kyung-Ho , Charidimou Andreas , Werring David J. , Kim Sung Tae , Na Duk L. , Seo Sang Won
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Dynamics of RIF1 SUMOylation is regulated by PIAS4 in the maintenance of Genomic Stability
Authors: Kumar Ramesh , Cheok Chit Fang
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Metal-organic framework and Tenax-TA as optimal sorbent mixture for concurrent GC-MS analysis of C1 to C5 carbonyl compounds
Authors: Dutta Tanushree , Kim Ki-Hyun , Brown Richard J. C. , Kim Yong-Hyun , Boukhvalov Danil
Published: March 2018

We report a multi adsorbent-based method using combinations of metal-organic frameworks (MOFs) and a commercial sorbent Tenax-TA for sampling and thermal desorption (TD) gas chromatography-mass spectrometry (GC-MS) quantification of mixtures of six (C1 to C5) aldehydes. The feasibility of this approach was demonstrated along with the optical analytical conditions for maximum recovery. Optimal TD conditions for adsorption and desorption of aldehydes using MOF-5 (Zn-based MOF)+ Tenax-TA were determined as −25 °C and 150 °C, respectively (purge volume: 100 ml). These conditions yielded good linearity (R2 = 0.997), precision, and high sensitivity. Analysis of the aldehyde mixtures yielded slightly smaller R2 values than the analysis of single species. Additionally, the performance of MOF-5+ Tenax-TA was compared with other combinations comprising of Cu-based MOF-199 and Zr-based MOF of UiO-66 topology. The results of the theoretical modelling analyses propose simultaneous interaction of the C=O group of aldehydes with open metal sites of the studied MOFs and van der Waals interaction of hydrocarbon “tail” of aldehydes with linkers of MOFs. The combined interactions significantly increased the enthalpy (eV/molecule) of formaldehyde adsorption on MOF. Our findings unravel a potential way to extend the application of GC-based detection toward concurrent analysis of organic molecules of variable sizes.
Physical and biological roles of mesoscale eddies in Japanese eel larvae dispersal in the western North Pacific Ocean
Authors: Chang Yu-Lin K. , Miyazawa Yasumasa , Béguer-Pon Mélanie , Han Yu-San , Ohashi Kyoko , Sheng Jinyu
Published: March 2018

The physical and biological roles of mesoscale eddies in Japanese eel larvae dispersal are investigated using a three-dimensional (3D) particle-tracking method, with a focus on the Subtropical Counter Current eddies of the western North Pacific Ocean. Virtual eel larvae (v-larvae) movements depends on the 3D ocean currents and active swimming behavior, including vertical swimming (diel vertical migration), horizontal directional swimming toward settlement habitat, and horizontal swimming toward available food. V-larvae are able to remain in eddies passively due to mesoscale eddy nonlinearity and/or actively due to attraction to rich food supplies. Thus, both physical trapping and biological attraction to food contribute to the retention of v-larvae in eddies. Physical trapping dominates the retention of v-larvae whose swimming speeds are slower than the eddy propagation speed, whereas biological food attraction prevails in the retention of v-larvae swimming faster than eddy propagation. Food availability differs between warm (anti-cyclonic) and cold (cyclonic) eddies, with the latter providing a richer food supply. Fish larvae that are retained for longer durations in cold eddies (shorter durations in warm eddies) are able to obtain more food and potentially grow faster, which enhances survival rates.
Machine learning approaches for large scale classification of produce
Authors: Gupta Otkrist , Das Anshuman J. , Hellerstein Joshua , Raskar Ramesh
Published: March 2018

The analysis and identification of different attributes of produce such as taxonomy, vendor, and organic nature is vital to verifying product authenticity in a distribution network. Though a variety of analysis techniques have been studied in the past, we present a novel data-centric approach to classifying produce attributes. We employed visible and near infrared (NIR) spectroscopy on over 75,000 samples across several fruit and vegetable varieties. This yielded 0.90–0.98 and 0.98–0.99 classification accuracies for taxonomy and farmer classes, respectively. The most significant factors in the visible spectrum were variations in the produce color due to chlorophyll and anthocyanins. In the infrared spectrum, we observed that the varying water and sugar content levels were critical to obtaining high classification accuracies. High quality spectral data along with an optimal tuning of hyperparameters in the support vector machine (SVM) was also key to achieving high classification accuracies. In addition to demonstrating exceptional accuracies on test data, we explored insights behind the classifications, and identified the highest performing approaches using cross validation. We presented data collection guidelines, experimental design parameters, and machine learning optimization parameters for the replication of studies involving large sample sizes.
Interpretation of biological experiments changes with evolution of the Gene Ontology and its annotations
Authors: Tomczak Aurelie , Mortensen Jonathan M. , Winnenburg Rainer , Liu Charles , Alessi Dominique T. , Swamy Varsha , Vallania Francesco , Lofgren Shane , Haynes Winston , Shah Nigam H. , Musen Mark A. , Khatri Purvesh
Published: March 2018

Gene Ontology (GO) enrichment analysis is ubiquitously used for interpreting high throughput molecular data and generating hypotheses about underlying biological phenomena of experiments. However, the two building blocks of this analysis — the ontology and the annotations — evolve rapidly. We used gene signatures derived from 104 disease analyses to systematically evaluate how enrichment analysis results were affected by evolution of the GO over a decade. We found low consistency between enrichment analyses results obtained with early and more recent GO versions. Furthermore, there continues to be a strong annotation bias in the GO annotations where 58% of the annotations are for 16% of the human genes. Our analysis suggests that GO evolution may have affected the interpretation and possibly reproducibility of experiments over time. Hence, researchers must exercise caution when interpreting GO enrichment analyses and should reexamine previous analyses with the most recent GO version.
Sequence-dependent catalytic regulation of the SpoIIIE motor activity ensures directionality of DNA translocation
Authors: Chara Osvaldo , Borges Augusto , Milhiet Pierre-Emmanuel , Nöllmann Marcelo , Cattoni Diego I.
Published: March 2018

Transport of cellular cargo by molecular motors requires directionality to ensure proper biological functioning. During sporulation in Bacillus subtilis, directionality of chromosome transport is mediated by the interaction between the membrane-bound DNA translocase SpoIIIE and specific octameric sequences (SRS). Whether SRS regulate directionality by recruiting and orienting SpoIIIE or by simply catalyzing its translocation activity is still unclear. By using atomic force microscopy and single-round fast kinetics translocation assays we determined the localization and dynamics of diffusing and translocating SpoIIIE complexes on DNA with or without SRS. Our findings combined with mathematical modelling revealed that SpoIIIE directionality is not regulated by protein recruitment to SRS but rather by a fine-tuned balance among the rates governing SpoIIIE-DNA interactions and the probability of starting translocation modulated by SRS. Additionally, we found that SpoIIIE can start translocation from non-specific DNA, providing an alternative active search mechanism for SRS located beyond the exploratory length defined by 1D diffusion. These findings are relevant in vivo in the context of chromosome transport through an open channel, where SpoIIIE can rapidly explore DNA while directionality is modulated by the probability of translocation initiation upon interaction with SRS versus non-specific DNA.
Genetic markers for urine haptoglobin is associated with decline in renal function in type 2 diabetes in East Asians
Authors: Gurung Resham Lal , Dorajoo Rajkumar , Liu Sylvia , M Yiamunaa , Liu Jian-Jun , Wang Ling , Guo Lin , Yu Xueqing , Liu Jian-Jun , Lim Su Chi
Published: March 2018

Urine haptoglobin (uHP) level prospectively predicts diabetic kidney disease (DKD) progression. Here, we aim to identify genetic determinants of uHP level and evaluate association with renal function in East Asians (EA) with type 2 diabetes (T2D). Genome-wide association study (GWAS) among 805 [236 Chinese (discovery) and 569 (57 Malay and 512 Chinese) (validation)] found that rs75444904/kgp16506790 variant was robustly associated with uHP level (MetaP = 1.21 × 10−60). rs75444904 correlates well with plasma HP protein levels and multimerization in EA but was not in perfect LD (r2 = 0.911 in Chinese, r2 = 0.536 in Malay) and is monomorphic in Europeans (1000 G data). Conditional probability analysis indicated weakening of effects but residual significant associations between rs75444904 and uHP when adjusted on HP structural variant (MetaP = 8.22 × 10−7). The rs75444904 variant was associated with DKD progression (OR = 1.77, P = 0.014) independent of traditional risk factors. In an additional validation-cohort of EA (410 end-stage renal disease (ESRD) cases and 1308 controls), rs75444904 was associated with ESRD (OR = 1.22, P = 0.036). Furthermore, increased risk of DKD progression (OR = 2.09, P = 0.007) with elevated uHP level through Mendelian randomisation analysis provide support for potential causal role of uHP in DKD progression in EA. However, further replication of our findings in larger study populations is warranted.
Modeling the effects of lipid peroxidation during ferroptosis on membrane properties
Authors: Agmon Eran , Solon Jérôme , Bassereau Patricia , Stockwell Brent R.
Published: March 2018

Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid hydroperoxides. There has been significant research on the pathways leading to the accumulation of oxidized lipids, but the downstream effects and how lipid peroxides cause cell death during ferroptosis remain a major puzzle. We evaluated key features of ferroptosis in newly developed molecular dynamics models of lipid membranes to investigate the biophysical consequences of lipid peroxidation, and generated hypotheses about how lipid peroxides contribute to cell death during ferroptosis.
Resonance interaction energy between two entangled atoms in a photonic bandgap environment
Authors: Notararigo Valentina , Passante Roberto , Rizzuto Lucia
Published: March 2018

We consider the resonance interaction energy between two identical entangled atoms, where one is in the excited state and the other in the ground state. They interact with the quantum electromagnetic field in the vacuum state and are placed in a photonic-bandgap environment with a dispersion relation quadratic near the gap edge and linear for low frequencies, while the atomic transition frequency is assumed to be inside the photonic gap and near its lower edge. This problem is strictly related to the coherent resonant energy transfer between atoms in external environments. The analysis involves both an isotropic three-dimensional model and the one-dimensional case. The resonance interaction asymptotically decays faster with distance compared to the free-space case, specifically as 1/r2 compared to the 1/r free-space dependence in the three-dimensional case, and as 1/r compared to the oscillatory dependence in free space for the one-dimensional case. Nonetheless, the interaction energy remains significant and much stronger than dispersion interactions between atoms. On the other hand, spontaneous emission is strongly suppressed by the environment and the correlated state is thus preserved by the spontaneous-decay decoherence effects. We conclude that our configuration is suitable for observing the elusive quantum resonance interaction between entangled atoms.
Lung Topology Characteristics in patients with Chronic Obstructive Pulmonary Disease
Authors: Belchi Francisco , Pirashvili Mariam , Conway Joy , Bennett Michael , Djukanovic Ratko , Brodzki Jacek
Published: March 2018

Quantitative features that can currently be obtained from medical imaging do not provide a complete picture of Chronic Obstructive Pulmonary Disease (COPD). In this paper, we introduce a novel analytical tool based on persistent homology that extracts quantitative features from chest CT scans to describe the geometric structure of the airways inside the lungs. We show that these new radiomic features stratify COPD patients in agreement with the GOLD guidelines for COPD and can distinguish between inspiratory and expiratory scans. These CT measurements are very different to those currently in use and we demonstrate that they convey significant medical information. The results of this study are a proof of concept that topological methods can enhance the standard methodology to create a finer classification of COPD and increase the possibilities of more personalized treatment.
Ion implantation in nanodiamonds: size effect and energy dependence
Authors: Shiryaev Andrey A. , Hinks Jonathan A. , Marks Nigel A. , Greaves Graeme , Valencia Felipe J. , Donnelly Stephen E. , González Rafael I. , Kiwi Miguel , Trigub Alexander L. , Bringa Eduardo M. , Fogg Jason L. , Vlasov Igor I.
Published: March 2018

Nanoparticles are ubiquitous in nature and are increasingly important for technology. They are subject to bombardment by ionizing radiation in a diverse range of environments. In particular, nanodiamonds represent a variety of nanoparticles of significant fundamental and applied interest. Here we present a combined experimental and computational study of the behaviour of nanodiamonds under irradiation by xenon ions. Unexpectedly, we observed a pronounced size effect on the radiation resistance of the nanodiamonds: particles larger than 8 nm behave similarly to macroscopic diamond (i.e. characterized by high radiation resistance) whereas smaller particles can be completely destroyed by a single impact from an ion in a defined energy range. This latter observation is explained by extreme heating of the nanodiamonds by the penetrating ion. The obtained results are not limited to nanodiamonds, making them of interest for several fields, putting constraints on processes for the controlled modification of nanodiamonds, on the survival of dust in astrophysical environments, and on the behaviour of actinides released from nuclear waste into the environment.
Multi-Target Tracking of Human Spermatozoa in Phase-Contrast Microscopy Image Sequences using a Hybrid Dynamic Bayesian Network
Authors: Arasteh Abdollah , Vosoughi Vahdat Bijan , Salman Yazdi Reza
Published: March 2018

Male infertility is mostly related to semen and spermatozoa, and any diagnosis or treatment requires the investigation of the motility patterns of spermatozoa. The movements of spermatozoa are fast and involve collision and occlusion with each other. In order to extract the motility patterns of spermatozoa, multi-target tracking (MTT) of spermatozoa is necessary. One of the most important steps of MTT is data association, in which the newly arrived observations are used to update the previous tracks. Dynamic Bayesian network (DBN) is a powerful tool for modeling and solving various types of problems such as tracking and classification. There can also be a hybrid-DBN (HDBN), in which both continuous and discrete nodes are present. HDBN has a suitable structure for modeling problems that have both discrete and continuous parameters like MTT. In this research, the data association for MTT of human spermatozoa has been studied. The proposed algorithm was tested over hundreds of manually extracted spermatozoa tracks and evaluated using several standard measures. The superior results of the proposed algorithm in comparison to the other well-known algorithms, show that it could be considered as an improved alternative to traditional computer assisted sperm analysis (CASA) algorithms.
Analysis of microsatellites from transcriptome sequences of Phytophthora capsici and applications for population studies
Authors: Parada-Rojas C. H. , Quesada-Ocampo L. M.
Published: March 2018

Phytophthora capsici is a devastating oomycete that affects solanaceous, cucurbitaceous, fabaceous, and other crops in the United States (US) and worldwide. The release of the P. capsici genome allows for design of robust markers for genetic studies. We identified and characterized microsatellites in the P. capsici transcriptome. A subset of 50 microsatellites were assayed in a diverse set of P. capsici isolates and evaluated for polymorphism. Polymorphic microsatellites were confirmed by fragment analysis, and 12 were used for population characterization of 50 P. capsici isolates from different states, hosts, and mating types. Analysis of genetic relationship among isolates revealed significant geographic structure by state. Our findings highlight the usefulness of these 12 microsatellites to characterize the population structure of P. capsici and potential transferability to closely-related Phytophthora spp. since markers are located in coding regions. Our markers will facilitate genetic characterization and complement phenotypic studies of P. capsici populations, which may assist in deployment of disease management strategies.
Increased Levels of Cardiac Troponin I in Subjects with Extremely Low B-type Natriuretic Peptide Levels
Authors: Sugawa Satoshi , Masuda Izuru , Kato Kiminori , Yoshimura Michihiro
Published: March 2018

Because of the lack of studies focused on the biological implications of extremely low B-type natriuretic peptide (BNP) levels, we investigated whether extremely low BNP levels could be harmful to the cardiovascular system due to compromised cardio-protection. By using cardiac troponin I (cTnI) as an indicator of cardiovascular disorder, we assessed whether cTnI was inversely associated with BNP in populations with low BNP levels. A total of 2,001 apparently healthy subjects older than 38 years were included in this study. We defined subgroups from this population by limiting the maximum BNP level with cut-off values ranging from 1 through 20 pg/mL and performed covariance structure analyses by comparing log(BNP) with log(cTnI) in each subgroup. The beta values between log(BNP) and log(cTnI) sharply decreased as the BNP cut-off was reduced from 20 pg/mL (beta = 0.04) to 1 pg/mL (beta = −0.29) and became significant when the BNP cut-off levels were lower than 4 pg/mL (p < 0.005). In subgroups with BNP levels lower than 4 pg/mL, elevation in cTnI level was inversely associated with BNP (p < 0.005), which suggests that insufficient BNP may play a pathogenic role in the occurrence of cardiovascular abnormalities.
Electrocaloric effect in cubic Hubbard nanoclusters
Authors: Szałowski Karol , Balcerzak Tadeusz
Published: March 2018

In the paper a computational study of the electrocaloric effect is presented for a cubic nanocluster consisting of 8 sites. The system of interest is described by means of an extended Hubbard model in external electric field at half filling of the energy levels. The thermodynamic description is obtained within canonical ensemble formalism on the basis of exact numerical diagonalization of the system Hamiltonian. In particular, the entropy and the specific heat are determined as a function of temperature and external electric field. The electrocaloric effect is described quantitatively by isothermal entropy change. The behaviour of this quantity is thoroughly analysed as a function of extended Hubbard model parameters, temperature and electric field variation magnitude. The existence of direct and inverse electrocaloric effect is predicted for some range of model parameters. A high sensitivity to Hubbard model parameters is shown, what paves the way towards controlling and tuning the effect. A non-linear, quadratic dependence of isothermal entropy change on electric field variation magnitude is demonstrated. The potential for applications of electrocaloric effect in strongly correlated nanoclusters is shown.