bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compositional and mechanical properties of growing cortical bone tissue: a study of the human fibula
Authors: Lefèvre Emmanuelle , Farlay Delphine , Bala Yohann , Subtil Fabien , Wolfram Uwe , Rizzo Sébastien , Baron Cécile , Zysset Philippe , Pithioux Martine , Follet Hélène 
Published: November 2019

AbstractHuman cortical bone contains two types of tissue: osteonal and interstitial tissue. Growing bone is not well-known in terms of its intrinsic material properties. To date, distinctions between the mechanical properties of osteonal and interstitial regions have not been investigated in juvenile bone and compared to adult bone in a combined dataset. In this work, cortical bone samples obtained from fibulae of 13 juveniles patients (4 to 18 years old) during corrective surgery and from 17 adult donors (50 to 95 years old) were analyzed. Microindentation was used to assess the mechanical properties of the extracellular matrix, quantitative microradiography was used to measure the degree of bone mineralization (DMB), and Fourier transform infrared microspectroscopy was used to evaluate the physicochemical modifications of bone composition (organic versus mineral matrix). Juvenile and adult osteonal and interstitial regions were analyzed for DMB, crystallinity, mineral to organic matrix ratio, mineral maturity, collagen maturity, carbonation, indentation modulus, indicators of yield strain and tissue ductility using a mixed model. We found that the intrinsic properties of the juvenile bone were not all inferior to those of the adult bone. Mechanical properties were also differently explained in juvenile and adult groups. The study shows that different intrinsic properties should be used in case of juvenile bone investigation.
Stitchless support-free 3D printing of free-form micromechanical structures with feature size on-demand
Authors: Jonušauskas Linas , Baravykas Tomas , Andrijec Dovilė , Gadišauskas Tomas , Purlys Vytautas 
Published: November 2019

AbstractFemtosecond laser based 3D nanolithography is a powerful tool for fabricating various functional micro- and nano-objects. In this work we present several advances needed to push it from the laboratory level use to the industrial production lines. First, linear stage and galvo-scanners synchronization is employed to produce stitch-free mm-sized structures. Furthermore, it is shown that by varying objective numerical apertures (NA) from 1.4 NA to 0.45 NA, voxel size can be tuned in the range from sub μm to tens of mm, resulting in structuring rates between 1809 μm3/s and 313312 μm3/s at 1 cm/s translation velocity achieved via simultaneous movement of linear stages and scanners. Discovered voxel/throughput scaling peculiarities show good agreement to ones acquired with numerical modeling. Furthermore, support-free 3D printing of complex structures is demonstrated. It is achieved by choosing pre-polymer that is in hard gel form during laser writing and acts as a dissolvable support during manufacturing. All of this is combined to fabricate micromechanical structures. First, 1:40 aspect ratio cantilever and 1.5 mm diameter single-helix spring capable of sustaining extreme deformations for prolonged movement times (up to 10000 deformation cycles) are shown. Then, free-movable highly articulated intertwined micromechanical spider and squids (overall size up to 10 mm) are printed and their movement is tested. The presented results are discussed in the broader sense, touching on the stitching/throughput dilemma and comparing it to the standard microstereolithography. It is shown where multiphoton polymerization can outpace standard stereolithography in terms of throughput while still maintaining superior resolution and higher degree of freedom in terms of printable geometries.
Widespread Sexual Dimorphism in the Transcriptome of Human Airway Epithelium in Response to Smoking
Authors: Yang Chen Xi , Shi Henry , Ding Irving , Milne Stephen , Hernandez Cordero Ana I. , Yang Cheng Wei Tony , Kim Edward Kyoo-Hoon , Hackett Tillie-Louise , Leung Janice , Sin Don D. , Obeidat Ma’en 
Published: November 2019

AbstractEpidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females, as well the sex-by-smoking interaction. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n = 68; current smokers n = 143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules’ level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosomes. The two modules were enriched in autophagy (up-regulated in female smokers) and response to virus and type 1 interferon signaling pathways which were down-regulated in female smokers compared to males. The results offer insights into the molecular mechanisms of the sexually dimorphic effect of smoking, potentially enabling a precision medicine approach to smoking related lung diseases.
Marine fog inputs appear to increase methylmercury bioaccumulation in a coastal terrestrial food web
Authors: Weiss-Penzias Peter S. , Bank Michael S. , Clifford Deana L. , Torregrosa Alicia , Zheng Belle , Lin Wendy , Wilmers Christopher C. 
Published: November 2019

AbstractCoastal marine atmospheric fog has recently been implicated as a potential source of ocean-derived monomethylmercury (MMHg) to coastal terrestrial ecosystems through the process of sea-to-land advection of foggy air masses followed by wet deposition. This study examined whether pumas (Puma concolor) in coastal central California, USA, and their associated food web, have elevated concentrations of MMHg, which could be indicative of their habitat being in a region that is regularly inundated with marine fog. We found that adult puma fur and fur-normalized whiskers in our marine fog-influenced study region had a mean (±SE) total Hg (THg) (a convenient surrogate for MMHg) concentration of 1544 ± 151 ng g−1(N = 94), which was three times higher (P < 0.01) than mean THg in comparable samples from inland areas of California (492 ± 119 ng g−1, N = 18). Pumas in California eat primarily black-tailed and/or mule deer (Odocoileus hemionus), and THg in deer fur from the two regions was also significantly different (coastal 28.1 ± 2.9, N = 55, vs. inland 15.5 ± 1.5 ng g−1, N = 40). We suggest that atmospheric deposition of MMHg through fog may be contributing to this pattern, as we also observed significantly higher MMHg concentrations in lace lichen (Ramalina menziesii), a deer food and a bioindicator of atmospheric deposition, at sites with the highest fog frequencies. At these ocean-facing sites, deer samples had significantly higher THg concentrations compared to those from more inland bay-facing sites. Our results suggest that fog-borne MMHg, while likely a small fraction of Hg in all atmospheric deposition, may contribute, disproportionately, to the bioaccumulation of Hg to levels that approach toxicological thresholds in at least one apex predator. As global mercury levels increase, coastal food webs may be at risk to the toxicological effects of increased methylmercury burdens.
Increased Dynamics of α-Synuclein Fibrils by β-Synuclein Leads to Reduced Seeding and Cytotoxicity
Authors: Yang Xue , Williams Jonathan K. , Yan Run , Mouradian M. Maral , Baum Jean 
Published: November 2019

AbstractAlpha-synuclein (αS) fibrils are toxic to cells and contribute to the pathogenesis and progression of Parkinson’s disease and other synucleinopathies. β-Synuclein (βS), which co-localizes with αS, has been shown to provide a neuroprotective effect, but the molecular mechanism by which this occurs remains elusive. Here we show that αS fibrils formed in the presence of βS are less cytotoxic, exhibit reduced cell seeding capacity and are more resistant to fibril shedding compared to αS fibrils alone. Using solid-state NMR, we found that the overall structure of the core of αS fibrils when co-incubated with βS is minimally perturbed, however, the dynamics of Lys and Thr residues, located primarily in the imperfect KTKEGV repeats of the αS N-terminus, are increased. Our results suggest that amyloid fibril dynamics may play a key role in modulating toxicity and seeding. Thus, enhancing the dynamics of amyloid fibrils may be a strategy for future therapeutic targeting of neurodegenerative diseases.
Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs
Authors: Mahajan Aatish , Sapehia Divika , Thakur Shilpa , Mohanraj Palani Selvam , Bagga Rashmi , Kaur Jyotdeep 
Published: November 2019

AbstractDNA methylation, a central component of the epigenetic network is altered in response to nutritional influences. In one-carbon cycle, folate acts as a one-carbon carrier and vitamin B12 acts as co-factor for the enzyme methionine synthase. Both folate and vitamin B12 are the important regulators of DNA methylation which play an important role in development in early life. Previous studies carried out in this regard have shown the individual effects of these vitamins but recently the focus has been to study the combined effects of both the vitamins during pregnancy. Therefore, this study was planned to elucidate the effect of the altered dietary ratio of folate and B12 on the expression of transporters, related miRNAs and DNA methylation in C57BL/6 mice. Female mice were fed diets with 9 combinations of folate and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks post-weaning. Maternal and fetal (F2) tissues were collected at day 20 of gestation. Deficient state of folate led to an increase in the expression of folate transporters in both F1 and F2 generations, however, B12 deficiency (BDFN) also led to an increase in the expression in both the generations. B12 transporters/proteins were found to be increased with B12 deficiency in F1 and F2 generations except for TC-II in the kidney which was found to be decreased in the F1 generation. miR-483 was found to be increased with all conditions of folate and B12 in both F1 and F2 generations, however, deficient conditions of B12 led to an increase in the expression of miR-221 in both F1 and F2 generations. The level of miR-133 was found to be increased in BDFN group in F1 generation however; in F2 generation the change in expression was tissue and sex-specific. Global DNA methylation was decreased with deficiency of both folate and B12 in maternal tissues (F1) but increased with folate deficiency in placenta (F1) and under all conditions in fetal tissues (F2). DNA methyltransferases were overall found to be increased with deficiency of folate and B12 in both F1 and F2 generations. Results suggest that the dietary ratio of folate and B12 resulted in altered expression of transporters, miRNAs, and genomic DNA methylation in association with DNMTs.
Choroidal and retinal displacements after vitrectomy with internal limiting membrane peeling in eyes with idiopathic macular hole
Authors: Goto Kensuke , Iwase Takeshi , Akahori Tomohiko , Yamamoto Kentaro , Ra Eimei , Terasaki Hiroko 
Published: November 2019

AbstractIt has been reported that the macular region of the retina is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with macular hole (MH), but the displacements of the deeper layers of the eye, e.g. RPE and choroid are unclear following the surgery. We used optical coherence tomography (OCT) and OCT angiography (OCTA) to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the vitrectomy with internal limiting membrane (ILM) peeling from 22 eyes of 22 patients with a MH. The OCT and OCTA images showed displacements of the fovea and choroidal intermediate vessels postoperatively. The degree of displacement of the choroid was significantly less than that of the retina (P < 0.001). The displacements of the choroidal bifurcations were significantly correlated to their preoperative distance from the optic disc (r = −0.467, P < 0.001) and they were significantly correlated with the retinal displacements (r = 0.535, P < 0.001). The retina was displaced inferiorly and centripetally, but these localized displacements were not observed in the choroid. In conclusion, clinicians need to be aware of these displacements when evaluating the subfoveal choroid following the surgery because the displacement is different between the retina and the choroid.
Online asynchronous decoding of error-related potentials during the continuous control of a robot
Authors: Lopes-Dias Catarina , Sburlea Andreea I. , Müller-Putz Gernot R. 
Published: November 2019

AbstractError-related potentials (ErrPs) are the neural signature of error processing. Therefore, the detection of ErrPs is an intuitive approach to improve the performance of brain-computer interfaces (BCIs). The incorporation of ErrPs in discrete BCIs is well established but the study of asynchronous detection of ErrPs is still in its early stages. Here we show the feasibility of asynchronously decoding ErrPs in an online scenario. For that, we measured EEG in 15 participants while they controlled a robotic arm towards a target using their right hand. In 30% of the trials, the control of the robotic arm was halted at an unexpected moment (error onset) in order to trigger error-related potentials. When an ErrP was detected after the error onset, participants regained the control of the robot and could finish the trial. Regarding the asynchronous classification in the online scenario, we obtained an average true positive rate (TPR) of 70% and an average true negative rate (TNR) of 86.8%. These results indicate that the online asynchronous decoding of ErrPs was, on average, reliable, showing the feasibility of the asynchronous decoding of ErrPs in an online scenario.
The effect of analgesics on stimulus evoked pain-like behaviour in animal models for chemotherapy induced peripheral neuropathy- a meta-analysis
Authors: Hooijmans Carlijn R. , Draper Derk , Ergün Mehmet , Scheffer Gert Jan 
Published: November 2019

AbstractChemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no sufficiently effective pharmacological treatment for CIPN. Although reducing pain is often a focus of CIPN treatment, remarkably few analgesics have been tested for this indication in clinical trials. We conducted a systematic review and meta-analyses regarding the effects of analgesics on stimulus evoked pain-like behaviour during CIPN in animal models. This will form a scientific basis for the development of prospective human clinical trials. A comprehensive search identified forty-six studies. Risk of bias (RoB) analyses revealed that the design and conduct of the included experiments were poorly reported, and therefore RoB was unclear in most studies. Meta-analyses showed that administration of analgesics significantly increases pain threshold for mechanical (SMD: 1.68 [1.41; 1.82]) and cold (SMD: 1. 41 [0.99; 1.83]) evoked pain. Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary.
Profiling microRNAs through development of the parasitic nematode Haemonchus identifies nematode-specific miRNAs that suppress larval development
Authors: Marks Neil D. , Winter Alan D. , Gu Henry Y. , Maitland Kirsty , Gillan Victoria , Ambroz Martin , Martinelli Axel , Laing Roz , MacLellan Rachel , Towne Jessica , Roberts Brett , Hanks Eve , Devaney Eileen , Britton Collette 
Published: November 2019

AbstractParasitic nematodes transition between dramatically different free-living and parasitic stages, with correctly timed development and migration crucial to successful completion of their lifecycle. However little is known of the mechanisms controlling these transitions. microRNAs (miRNAs) negatively regulate gene expression post-transcriptionally and regulate development of diverse organisms. Here we used microarrays to determine the expression profile of miRNAs through development and in gut tissue of the pathogenic nematode Haemonchus contortus. Two miRNAs, mir-228 and mir-235, were enriched in infective L3 larvae, an arrested stage analogous to Caenorhabditis elegans dauer larvae. We hypothesized that these miRNAs may suppress development and maintain arrest. Consistent with this, inhibitors of these miRNAs promoted H. contortus development from L3 to L4 stage, while genetic deletion of C. elegans homologous miRNAs reduced dauer arrest. Epistasis studies with C. elegans daf-2 mutants showed that mir-228 and mir-235 synergise with FOXO transcription factor DAF-16 in the insulin signaling pathway. Target prediction suggests that these miRNAs suppress metabolic and transcription factor activity required for development. Our results provide novel insight into the expression and functions of specific miRNAs in regulating nematode development and identify miRNAs and their target genes as potential therapeutic targets to limit parasite survival within the host.
A framework for identification of on- and off-target transcriptional responses to drug treatment
Authors: Huang Yi , Furuno Masaaki , Arakawa Takahiro , Takizawa Satoshi , de Hoon Michiel , Suzuki Harukazu , Arner Erik 
Published: November 2019

AbstractOwing to safety concerns or insufficient efficacy, few drug candidates are approved for marketing. Drugs already on the market may be withdrawn due to adverse effects (AEs) discovered after market introduction. Comprehensively investigating the on-/off-target effects of drugs can help expose AEs during the drug development process. We have developed an integrative framework for systematic identification of on-/off-target pathways and elucidation of the underlying regulatory mechanisms, by combining promoter expression profiling after drug treatment with gene perturbation of the primary drug target. Expression profiles from statin-treated cells and HMG-CoA reductase knockdowns were analyzed using the framework, allowing for identification of not only reported adverse effects but also novel candidates of off-target effects from statin treatment, including key regulatory elements of on- and off-targets. Our findings may provide new insights for finding new usages or potential side effects of drug treatment.
Effects on milk quantity and composition associated with extruded linseed supplementation to dairy cow diets
Authors: Ariza Juan Manuel , Meignan Thomas , Madouasse Aurélien , Beaudeau François , Bareille Nathalie 
Published: November 2019

AbstractEnhanced milk composition can improve human health. The composition of milk determines its nutritional and market value. Therefore, in almost all pricing schemes the economic benefits obtained from raw milk sales are influenced by the milk yield and composition. The objective of this retrospective study was to quantify the average effects of supplementing extruded linseed, rich in α-linolenic acid, to dairy cows on milk yield and milk fat and protein content under field conditions. The study included test day records performed on cows from 1294 dairy herds during the period from 2008 to 2015 that were supplied at least 4 times with extruded linseed deliveries. Exposure statuses were defined according to the time sequence and the amount of extruded linseed distributed in the herd. The unexposed population was composed of cows being in a herd period when extruded linseed was not offered. In a linear dose-response relationship, every 100 g increase in exposure to EL was associated with an increased milk yield from 0.11 to 0.14 kg/day, decreased milk fat from 0.06 to 0.13 g/kg and decreased milk protein from 0 to 0.02 g/kg, according to the cow parity. This study provides information on the associations between estimated intakes of EL and milk production and composition using a large database obtained from commercial dairy herds.
DNA methylation changes in infants between 6 and 52 weeks
Authors: Wikenius Ellen , Moe Vibeke , Smith Lars , Heiervang Einar R. , Berglund Anders 
Published: November 2019

AbstractInfants undergo extensive developments during their first year of life. Although the biological mechanisms involved are not yet fully understood, changes in the DNA methylation in mammals are believed to play a key role. This study was designed to investigate changes in infant DNA methylation that occurs between 6 and 52 weeks. A total of 214 infant saliva samples from 6 or 52 weeks were assessed using principal component analyses and t-distributed stochastic neighbor-embedding algorithms. Between the two time points, there were clear differences in DNA methylation. To further investigate these findings, paired two-sided student’s t-tests were performed. Differently methylated regions were defined as at least two consecutive probes that showed significant differences, with a q-value < 0.01 and a mean difference > 0.2. After correcting for false discovery rates, changes in the DNA methylation levels were found in 42 genes. Of these, 36 genes showed increased and six decreased DNA methylation. The overall DNA methylation changes indicated decreased gene expression. This was surprising because infants undergo such profound developments during their first year of life. The results were evaluated by taking into consideration the extensive development that occurs during pregnancy. During the first year of life, infants have an overall three-fold increase in weight, while the fetus develops from a single cell into a viable infant in 9 months, with an 875-million-fold increase in weight. It is possible that the findings represent a biological slowing mechanism in response to extensive fetal development. In conclusion, our study provides evidence of DNA methylation changes during the first year of life, representing a possible biological slowing mechanism. We encourage future studies of DNA methylation changes in infants to replicate the findings by using a repeated measures model and less stringent criteria to see if the same genes can be found, as well as investigating whether other genes are involved in development during this period.