bluuebunny/crossref_metadata_2025 huggingface dataset:
Enduring rules of care within pairs - how blue tit parents resume provisioning behaviour after experimental disturbance
Authors: Iserbyt Arne , Griffioen Maaike , Eens Marcel , Müller Wendt
Published: February 2019

Sexual conflict over parental investment can result in suboptimal reproductive output. A recent hypothesis suggests that equality in investment, and hence conflict resolution, may be reached via coordination of parental activities like alternating nest visits. However, how robust patterns of care within couples are against temporal disturbances that create asymmetries in parental investment remains as yet to be shown. We here experimentally created such a social disturbance in a wild population of biparental blue tits (Cyanistes caeruleus) when provisioning their nestlings. We randomly caught and subsequently released one of the parents when nestlings were 6 and 12 days old respectively. On average, the parent that was caught did not resume care for nearly two hours. We then compared the levels of individual investment and within-pair coordination before, during and after the absence of the disturbed parent. We show that the remaining parent partially compensated by increasing its provisioning rate, but this compensatory response was strongest in females when nestlings were 6 days old. Once the caught parent returned to feed its nestlings, both parents resumed provisioning at a similar rate as before the disturbance. Likewise, the within-pair alternation level quickly resembled the pre-manipulated level, independent of nestling age or which sex was caught. Thus our experiment highlights the resilience of parental behaviour against temporal disturbances of individual parents.
Influence of obesity, parental history of diabetes, and genes in type 2 diabetes: A case-control study
Authors: Berumen Jaime , Orozco Lorena , Betancourt-Cravioto Miguel , Gallardo Héctor , Zulueta Mirella , Mendizabal Leire , Simon Laureano , Benuto Rosa Elba , Ramírez-Campos Elisa , Marin Melissa , Juárez Eligia , García-Ortiz Humberto , Martínez-Hernández Angélica , Venegas-Vega Carlos , Peralta-Romero Jesús , Cruz Miguel , Tapia-Conyer Roberto
Published: February 2019

Obesity, parental history (PH) of type 2 diabetes (T2D), and genes play an important role in T2D development. However, the influence of each factor on T2D variability is unclear. This study aimed to investigate the influence of obesity (body mass index [BMI], waist/hip ratio), PH, and 16 single-nucleotide polymorphisms (SNPs) associated with T2D on T2D variability in Mexico, comparing 1234 non-diabetic controls and 1219 diabetic patients. To replicate the data, a case-control (n = 2904) and a cross-sectional (n = 1901) study were also included. In a multivariate logistic regression model, all factors accounted for only 27.3% of T2D variability: SNPs (8.4%); PH (11.8%) and obesity (7.1%). These factors contributed more in men (33.2%) than in women (25%), specifically when the disease was diagnosed before the age of 46 (46.7% vs. 30%). Genes played a substantially more important role in men than in women (14.9% vs. 5.5%), while obesity and PH played a similar role in both genders. Genes and PH appeared to play a greater role than obesity in T2D. However, obesity contribution was calculated at the time of recruitment and may be underestimated in patients because the BMI decreased linearly with the number of years with the disease. The data suggest that sexual hormones may play important roles in genes that are associated with T2D.
Analysis of wheat gene expression related to the oxidative stress response and signal transduction under short-term osmotic stress
Authors: Dudziak Karolina , Zapalska Magdalena , Börner Andreas , Szczerba Hubert , Kowalczyk Krzysztof , Nowak Michał
Published: February 2019

Water shortage is a major environmental stress that causes the generation of reactive oxygen species (ROS). The increase in ROS production induces molecular responses, which are key factors in determining the level of plant tolerance to stresses, including drought. The aim of this study was to determine the expression levels of genes encoding MAPKs (MAPK3andMAPK6), antioxidant enzymes (CAT,APXandGPX) and enzymes involved in proline biosynthesis (P5CSandP5CR) inTriticum aestivumL. seedlings in response to short-term drought conditions. A series of wheat intervarietal substitution lines (ISCSLs) obtained by the substitution of single chromosomes from a drought-sensitive cultivar into the genetic background of a drought-tolerant cultivar was used. This source material allowed the chromosomal localization of the genetic elements involved in the response to the analyzed stress factor (drought). The results indicated that the initial plant response to drought stress resulted notably in changes in the expression ofMAPK6andCATand both theP5CSandP5CRgenes. Our results showed that the substitution of chromosomes 3B, 5A, 7B and 7D had the greatest impact on the expression level of all tested genes, which indicates that they contain genetic elements that have a significant function in controlling tolerance to water deficits in the wheat genome.
Crustacean larval factor shares structural characteristics with the insect-specific follicle cell protein
Authors: Ventura Tomer , Nguyen Chan , Fitzgibbon Quinn P. , Abramov Tomer , Smith Gregory G. , Elizur Abigail
Published: February 2019

Literature on the cuticle formation in larval stages of the diverse group of decapod crustaceans is lacking, as opposed to a wealth of knowledge in several insect groups. Here we provide the first glimpse of the cuticular organisation in larvae of the eastern spiny lobster Sagmariasus verreauxi. A bioinformatic approach applied to S. verreauxi transcriptome through metamorphosis identified for the first time a small secreted protein with multiple isoforms that is highly expressed in crustacean larvae. This protein, named crustacean larval factor (Clf) shares structural characteristics with insect follicle cell protein 3 (FCP3), an insect-specific, rapidly evolving protein, with spatial-temporal regulated expression that is restricted to follicular cells during the production of the vitellin coat. Furthermore, we identified the FCP3 domain in additional structural proteins in multiple arthropod groups. Recombinant Clf inhibited in vitro calcium carbonate crystalline precipitation, in keeping with the finding that the spiny lobster larval cuticle is mainly composed of amorphous calcium carbonate. In addition, the recombinant Clf was shown to bind chitosan. Taken together, this research identifies two novel structural domains with lineage-specific expansion across arthropods. In crustaceans, Clf is found predominantly in larvae and the spatial-temporal regulated FCP3 factor occurs as a domain identified in multiple structural proteins across arthropods. Given the shared ten cysteines backbone between the Clf and FCP domains, a shared evolution is suggested and should be further explored.
Silencing of spinal Trpv1 attenuates neuropathic pain in rats by inhibiting CAMKII expression and ERK2 phosphorylation
Authors: Guo Shao-Hui , Lin Jia-Piao , Huang Ling-Er , Yang Yan , Chen Chao-Qin , Li Na-Na , Su Meng-Yun , Zhao Xian , Zhu Sheng-Mei , Yao Yong-Xing
Published: February 2019

Accumulating evidence suggests a potential role of transient receptor potential vanilloid 1 (TRPV1) channels in inflammatory and cancer-related pain. However, the role of TRPV1 in the maintenance of neuropathic pain remains elusive. The current study investigated the effects of transient Trpv1 gene silencing using a small interference RNA (siRNA) on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Seven days after CCI, the TRPV1 siRNA was intrathecally administered (5 µg/15 µl, once daily for 2 days). TRPV1 and Ca2+/calmodulin-dependent protein kinase II (CAMKII) expression and extracellular signal-regulated kinase (ERK) phosphorylation in the spinal cord were detected using western blotting. The thresholds to mechanical and thermal stimuli were determined before and after intrathecal TRPV1 siRNA administration. TRPV1 and CAMKII expression and ERK2 phosphorylation in the spinal cord were upregulated after CCI. Intrathecal administration of the TRPV1 siRNA not only attenuated behavioural hyperalgesia but also reduced the expression of TRPV1 and CAMKII, as well as ERK2 phosphorylation. Based on these results, silencing of the TRPV1 gene in the spinal cord attenuates the maintenance of neuropathic pain by inhibiting CAMKII/ERK2 activation and suggests that TRPV1 represents a potential target in pain therapy.
Lamellar ordering, droplet formation and phase inversion in exotic active emulsions
Authors: Bonelli F. , Carenza L. N. , Gonnella G. , Marenduzzo D. , Orlandini E. , Tiribocchi A.
Published: February 2019

We study numerically the behaviour of a two-dimensional mixture of a passive isotropic fluid and an active polar gel, in the presence of a surfactant favouring emulsification. Focussing on parameters for which the underlying free energy favours the lamellar phase in the passive limit, we show that the interplay between nonequilibrium and thermodynamic forces creates a range of multifarious exotic emulsions. When the active component is contractile (e.g., an actomyosin solution), moderate activity enhances the efficiency of lamellar ordering, whereas strong activity favours the creation of passive droplets within an active matrix. For extensile activity (occurring, e.g., in microtubule-motor suspensions), instead, we observe an emulsion of spontaneously rotating droplets of different size. By tuning the overall composition, we can create high internal phase emulsions, which undergo sudden phase inversion when activity is switched off. Therefore, we find that activity provides a single control parameter to design composite materials with a strikingly rich range of morphologies.
Deep learning in head & neck cancer outcome prediction
Authors: Diamant André , Chatterjee Avishek , Vallières Martin , Shenouda George , Seuntjens Jan
Published: February 2019

Traditional radiomics involves the extraction of quantitative texture features from medical images in an attempt to determine correlations with clinical endpoints. We hypothesize that convolutional neural networks (CNNs) could enhance the performance of traditional radiomics, by detecting image patterns that may not be covered by a traditional radiomic framework. We test this hypothesis by training a CNN to predict treatment outcomes of patients with head and neck squamous cell carcinoma, based solely on their pre-treatment computed tomography image. The training (194 patients) and validation sets (106 patients), which are mutually independent and include 4 institutions, come from The Cancer Imaging Archive. When compared to a traditional radiomic framework applied to the same patient cohort, our method results in a AUC of 0.88 in predicting distant metastasis. When combining our model with the previous model, the AUC improves to 0.92. Our framework yields models that are shown to explicitly recognize traditional radiomic features, be directly visualized and perform accurate outcome prediction.
Axial electrokinetic trapping of anisotropic particles
Authors: Strubbe Filip , Robben Bavo , Puthenparampil George John , Amer Cid Íngrid , Beunis Filip , Neyts Kristiaan
Published: February 2019

Anti-Brownian electrokinetic trapping is a method for trapping single particles in liquid based on particle position measurements and the application of feedback voltages. To achieve trapping in the axial direction, information on the axial particle position is required. However, existing strategies for determining the axial position that are based on measuring the size of the first diffraction ring, theory fitting, advanced optical setups or pre-determined axial image stacks are impractical for anisotropic particles. In this work, axial electrokinetic trapping of anisotropic particles is realized in devices with planar, transparent electrodes. The trapping algorithm uses Fourier-Bessel decomposition of standard microscopy images and is learning from the correlation between applied voltages and changes in the particle appearance. No previous knowledge on the particle appearance, theory fitting or advanced optical setup is required. The particle motion in the trap and the influence of screening of the electric field on this motion are analyzed. The axial trapping method opens new possibilities for measuring properties of anisotropic or isotropic particles and forces acting on such particles.
Pressure Reveals Unique Conformational Features in Prion Protein Fibril Diversity
Authors: Torrent Joan , Martin Davy , Noinville Sylvie , Yin Yi , Doumic Marie , Moudjou Mohammed , Béringue Vincent , Rezaei Human
Published: February 2019

The prion protein (PrP) misfolds and assembles into a wide spectrum of self-propagating quaternary structures, designated PrPSc. These various PrP superstructures can be functionally different, conferring clinically distinctive symptomatology, neuropathology and infectious character to the associated prion diseases. However, a satisfying molecular basis of PrP structural diversity is lacking in the literature. To provide mechanistic insights into the etiology of PrP polymorphism, we have engineered a set of 6 variants of the human protein and obtained PrP amyloid fibrils. We show that pressure induces dissociation of the fibrils, albeit with different kinetics. In addition, by focusing on the generic properties of amyloid fibrils, such as the thioflavin T binding capacities and the PK-resistance, we reveal an unprecedented structure-barostability phenomenological relationship. We propose that the structural diversity of PrP fibrils encompass a multiplicity of packing defects (water-excluded cavities) in their hydrophobic cores, and that the resultant sensitivity to pressure should be considered as a general molecular criterion to accurately define fibril morphotypes. We anticipate that our insights into sequence-dependent fibrillation and conformational stability will shed light on the highly-nuanced prion strain phenomenon and open the opportunity to explain different PrP conformations in terms of volumetric physics.
Proton Magnetic Resonance Spectroscopy of the motor cortex reveals long term GABA change following anodal Transcranial Direct Current Stimulation
Authors: Patel Harshal Jayeshkumar , Romanzetti Sandro , Pellicano Antonello , Nitsche Michael A. , Reetz Kathrin , Binkofski Ferdinand
Published: February 2019

Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been reported to increase the firing rates of neurons and to modulate the gamma-aminobutyric acid (GABA) concentration. To date, knowledge about the nature and duration of these tDCS induced effects is incomplete. We aimed to investigate long-term effects of anodal tDCS over M1 on GABA dynamics in humans. Repeated magnetic resonance spectroscopy (MRS) was employed to measure relative GABA concentration in M1 for approximately 64 minutes after stimulation. The study was performed on 32 healthy subjects. Either anodal or sham tDCS were applied for 10 minutes with the active electrode over the left M1 and the reference electrode over the right supra-orbital region. Pre and post-tDCS MRS scans were performed to acquire GABA-edited spectra using 3 T Prisma Siemens scanner. GABA signals showed no change over time in the sham tDCS group, whereas anodal tDCS resulted in a significant early decrease within 25 minutes after tDCS and then significant late decrease after 66 minutes which continued until the last test measurements. The late changes in GABA concentration might be related to long-term plasticity mechanism. These results contribute to a better understanding of the neurochemical mechanism underlying long-term cortical plasticity following anodal tDCS.
Sleep deprivation and its effects on communication during individual and collaborative tasks
Authors: Holding Benjamin C. , Sundelin Tina , Lekander Mats , Axelsson John
Published: February 2019

Sleep loss has been shown to cause impairments in a number of aspects central for successful communication, ranging from poorer linguistic comprehension to alterations in speech prosody. However, the effect of sleep loss on actual communication is unknown. This study investigated how a night of sleep deprivation affected performance during multiple tasks designed to test verbal communication. Healthy participants (N = 183) spent 8–9 hours per night in bed for three nights and were then randomised to either one night of total sleep deprivation or a fourth night with 8–9 hours in bed. The following day, participants completed two tasks together with another participant: a model-building task and a word-description task. Differences in performance of these tasks were assessed alongside speaking duration, speaking volume, and speaking volume consistency. Additionally, participants individually completed a verbal fluency assessment. Performance on the model-building task was worse if the model-builder was sleep deprived, whereas sleep deprivation in the instruction-giver predicted an improvement. Word-description, verbal fluency, speech duration, speaking volume, and speaking volume consistency were not affected. The results suggest that sleep deprivation leads to changes in communicative performance during instructive tasks, while simpler word-description tasks appear resilient.
Highly efficient coherent conformal projection system based on adaptive fiber optics collimator array
Authors: Zhi Dong , Ma Yanxing , Tao Rumao , Zhou Pu , Wang Xiaolin , Chen Zilun , Si Lei
Published: February 2019

Coherent beam combination (CBC) of fiber laser array, which is a promising approach to overcome the power scaling limitations of the single fiber laser and to achieve high-brightness laser with good beam quality, can be employed in coherent conformal projection system (CCPS) for beam projection and free space laser communication system with enormous potential. To date, all the demonstrated CBC system through several kilometers atmospheric turbulence have employed collimated beams, which significantly decrease the final CBC effect because of the inefficient wavefront overlap. On the other hand, focused CCPS has lots of advantages over collimated projection system since the wave front of the projected beam is closer to that of a convergent spherical wave. In this paper, we design and manufacture focused CCPS based on an adaptive fiber optics collimator array for the first time, which is achieved by introducing controllable spherical aberration through the adaptive fiber optics collimator. A CBC system is setup to evaluate and validate its performance. Results show that compared with the collimated CCPS, the energy portion of the central lobe could be increased by a factor of 44%, which agrees well with the theoretical analysis.
Neutron imaging and modelling inclined vortex driven thin films
Authors: Solheim Timothy E. , Salvemini Filomena , Dalziel Stuart B. , Raston Colin L.
Published: February 2019

The vortex fluidic device (VFD) is a thin film microfluidic platform which has a wide range of applications in synthesis and other areas of science, and it is important to understand the nature of the thin film of liquid in its inclined rapidly rotating tube. Neutron imaging has been used to determine the thickness of the film in a quartz tube with its shape modelled mathematically, showing good agreement between the model and experiments. The resultant equations are useful for studying VFD mediated processing in general, for which the optimal tilt angle of the tube is typically 45°. This includes its utility for the intelligent scale-up of organic syntheses, as demonstrated in the present study by the scaling up of an imine and amide synthesis to >1 g/min.
Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
Authors: Musarò Antonio , Dobrowolny Gabriella , Cambieri Chiara , Onesti Emanuela , Ceccanti Marco , Frasca Vittorio , Pisano Annalinda , Cerbelli Bruna , Lepore Elisa , Ruffolo Gabriele , Cifelli Pierangelo , Roseti Cristina , Giordano Carla , Gori Maria Cristina , Palma Eleonora , Inghilleri Maurizio
Published: February 2019

The aim of the study was to verify whether neuromuscular magnetic stimulation (NMMS) improves muscle function in spinal-onset amyotrophic lateral sclerosis (ALS) patients. Twenty-two ALS patients were randomized in two groups to receive, daily for two weeks, NMMS in right or left arm (referred to as real-NMMS, rNMMS), and sham NMMS (sNMMS) in the opposite arm. All the patients underwent a median nerve conduction (compound muscle action potential, CMAP) study and a clinical examination that included a handgrip strength test and an evaluation of upper limb muscle strength by means of the Medical Research Council Muscle Scale (MRC). Muscle biopsy was then performed bilaterally on the flexor carpi radialis muscle to monitor morpho-functional parameters and molecular changes. Patients and physicians who performed examinations were blinded to the side of real intervention. The primary outcome was the change in the muscle strength in upper arms. The secondary outcomes were the change from baseline in the CMAP amplitudes, in the nicotinic ACh currents, in the expression levels of a selected panel of genes involved in muscle growth and atrophy, and in histomorphometric parameters of ALS muscle fibers. The Repeated Measures (RM) ANOVA with a Greenhouse-Geisser correction (sphericity not assumed) showed a significant effect [F(3, 63) = 5.907, p < 0.01] of rNMMS on MRC scale at the flexor carpi radialis muscle, thus demonstrating that the rNMMS significantly improves muscle strength in flexor muscles in the forearm. Secondary outcomes showed that the improvement observed in rNMMS-treated muscles was associated to counteracting muscle atrophy, down-modulating the proteolysis, and increasing the efficacy of nicotinic ACh receptors (AChRs). We did not observe any significant difference in pre- and post-stimulation CMAP amplitudes, evoked by median nerve stimulation. This suggests that the improvement in muscle strength observed in the stimulated arm is unlikely related to reinnervation. The real and sham treatments were well tolerated without evident side effects. Although promising, this is a proof of concept study, without an immediate clinical translation, that requires further clinical validation.
Identifying Windows of Susceptibility by Temporal Gene Analysis
Authors: Bennett Kristin P. , Brown Elisabeth M. , Santos Hannah De los , Poegel Matthew , Kiehl Thomas R. , Patton Evan W. , Norris Spencer , Temple Sally , Erickson John , McGuinness Deborah L. , Boles Nathan C.
Published: February 2019

Increased understanding of developmental disorders of the brain has shown that genetic mutations, environmental toxins and biological insults typically act during developmental windows of susceptibility. Identifying these vulnerable periods is a necessary and vital step for safeguarding women and their fetuses against disease causing agents during pregnancy and for developing timely interventions and treatments for neurodevelopmental disorders. We analyzed developmental time-course gene expression data derived from human pluripotent stem cells, with disease association, pathway, and protein interaction databases to identify windows of disease susceptibility during development and the time periods for productive interventions. The results are displayed as interactive Susceptibility Windows Ontological Transcriptome (SWOT) Clocks illustrating disease susceptibility over developmental time. Using this method, we determine the likely windows of susceptibility for multiple neurological disorders using known disease associated genes and genes derived from RNA-sequencing studies including autism spectrum disorder, schizophrenia, and Zika virus induced microcephaly. SWOT clocks provide a valuable tool for integrating data from multiple databases in a developmental context with data generated from next-generation sequencing to help identify windows of susceptibility.
Tissue Engineered Neural Constructs Composed of Neural Precursor Cells, Recombinant Spidroin and PRP for Neural Tissue Regeneration
Authors: Baklaushev V. P. , Bogush V. G. , Kalsin V. A. , Sovetnikov N. N. , Samoilova E. M. , Revkova V. A. , Sidoruk K. V. , Konoplyannikov M. A. , Timashev P. S. , Kotova S. L. , Yushkov K. B. , Averyanov A. V. , Troitskiy A. V. , Ahlfors J.-E.
Published: February 2019

We have designed a novel two-component matrix (SPRPix) for the encapsulation of directly reprogrammed human neural precursor cells (drNPC). The matrix is comprised of 1) a solid anisotropic complex scaffold prepared by electrospinning a mixture of recombinant analogues of the spider dragline silk proteins – spidroin 1 (rS1/9) and spidroin 2 (rS2/12) - and polycaprolactone (PCL) (rSS-PCL), and 2) a “liquid matrix” based on platelet-rich plasma (PRP). The combination of PRP and spidroin promoted drNPC proliferation with the formation of neural tissue organoids and dramatically activated neurogenesis. Differentiation of drNPCs generated large numbers of βIII-tubulin and MAP2 positive neurons as well as some GFAP-positive astrocytes, which likely had a neuronal supporting function. Interestingly the SPRPix microfibrils appeared to provide strong guidance cues as the differentiating neurons oriented their processes parallel to them. Implantation of the SPRPix matrix containing human drNPC into the brain and spinal cord of two healthy Rhesus macaque monkeys showed good biocompatibility: no astroglial and microglial reaction was present around the implanted construct. Importantly, the human drNPCs survived for the 3 month study period and differentiated into MAP2 positive neurons. Tissue engineered constructs based on SPRPix exhibits important attributes that warrant further examination in spinal cord injury treatment.
Cardiovascular responses to leg muscle loading during head-down tilt at rest and after dynamic exercises
Authors: Alessandro Cristiano , Sarabadani Tafreshi Amirehsan , Riener Robert
Published: February 2019

The physiological processes underlying hemodynamic homeostasis can be modulated by muscle activity and gravitational loading. The effects of leg muscle activity on cardiovascular regulation have been observed during orthostatic stress. Here, we evaluated such effects during head-down tilt (HDT). In this posture, the gravitational gradient along the body is different than in upright position, leading to increased central blood volume and reduced venous pooling. We compared the cardiovascular signals obtained with and without leg muscle loading during HDT in healthy human subjects, both at rest and during recovery from leg-press exercises using a robotic device. Further, we compared such cardiovascular responses to those obtained during upright position. Loading leg muscles during HDT at rest led to significantly higher values of arterial blood pressure than without muscle loading, and restored systolic values to those observed during upright posture. Maintaining muscle loading post-exercise altered the short-term cardiovascular responses, but not the values of the signals five minutes after the exercise. These results suggest that leg muscle activity modulates cardiovascular regulation during HDT. This modulation should therefore be considered when interpreting cardiovascular responses to conditions that affect both gravity loading and muscle activity, for example bed rest or microgravity.
Ordinal regression models for zero-inflated and/or over-dispersed count data
Authors: Valle Denis , Ben Toh Kok , Laporta Gabriel Zorello , Zhao Qing
Published: February 2019

Count data commonly arise in natural sciences but adequately modeling these data is challenging due to zero-inflation and over-dispersion. While multiple parametric modeling approaches have been proposed, unfortunately there is no consensus regarding how to choose the best model. In this article, we propose a ordinal regression model (MN) as a default model for count data given that this model is shown to fit well data that arise from several types of discrete distributions. We extend this model to allow for automatic model selection (MN-MS) and show that the MN-MS model generates superior inference when compared to using the full model or more traditional model selection approaches. The MN-MS model is used to determine how human biting rate of mosquitoes, known to be able to transmit malaria, are influenced by environmental factors in the Peruvian Amazon. The MN-MS model had one of the best fit and out-of-sample predictive skill amongst all models. WhileA. darlingiis strongly associated with highly anthropized landscapes, all the other mosquito species had higher mean biting rates in landscapes with a lower fraction of exposed soil and urban area, revealing a striking shift in species composition. We believe that the MN and MN-MS models are valuable additions to the modelling toolkit employed by environmental modelers and quantitative ecologists.
Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis
Authors: Okura Toshiaki , Ohkawara Bisei , Takegami Yasuhiko , Ito Mikako , Masuda Akio , Seki Taisuke , Ishiguro Naoki , Ohno Kinji
Published: February 2019

Aberrant activation of the Wnt/β-catenin signaling pathway promotes the progression of osteoarthritis (OA). We previously reported that R-spondin 2 (Rspo2), an activator of the Wnt/β-catenin signaling, facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification. However, the role of Rspo2 in OA remains elusive. Here, we showed that the amounts of Rspo2 protein in synovial fluid were increased in OA patients. We searched for a preapproved drug that suppresses Rspo2-induced Wnt/β-catenin signaling in chondrogenic cells and reduces joint pathology in a rat model of OA. In Rspo2-treated ATDC5 cells, mianserin, a tetracyclic antidepressant, inhibited Wnt/β-catenin signaling, increased proteoglycan production, and upregulated chondrogenic marker genes. Mianserin suppressed Rspo2-induced accumulation of β-catenin and phosphorylation of Lrp6. We identified that mianserin blocked binding of Rspo2 to its receptor Lgr5. We also observed that intraarticular administration of mianserin suppressed β-catenin accumulation and prevented OA progression in a rat model of OA. We conclude that mianserin suppresses abnormally activated Wnt/β-catenin signaling in OA by inhibiting binding of Rspo2 to Lgr5.
Optimizing environmental DNA sampling effort for fish inventories in tropical streams and rivers
Authors: Cantera Isabel , Cilleros Kévin , Valentini Alice , Cerdan Axel , Dejean Tony , Iribar Amaia , Taberlet Pierre , Vigouroux Régis , Brosse Sébastien
Published: February 2019

Environmental DNA (eDNA) metabarcoding is a promising tool to estimate aquatic biodiversity. It is based on the capture of DNA from a water sample. The sampled water volume, a crucial aspect for efficient species detection, has been empirically variable (ranging from few centiliters to tens of liters). This results in a high variability of sampling effort across studies, making comparisons difficult and raising uncertainties about the completeness of eDNA inventories. Our aim was to determine the sampling effort (filtered water volume) needed to get optimal inventories of fish assemblages in species-rich tropical streams and rivers using eDNA. Ten DNA replicates were collected in six Guianese sites (3 streams and 3 rivers), resulting in sampling efforts ranging from 17 to 340 liters of water. We show that sampling 34 liters of water detected more than 64% of the expected fish fauna and permitted to distinguish the fauna between sites and between ecosystem types (stream versus rivers). Above 68 liters, the number of detected species per site increased slightly, with a detection rate higher than 71%. Increasing sampling effort up to 340 liters provided little additional information, testifying that filtering 34 to 68 liters is sufficient to inventory most of the fauna in highly diverse tropical aquatic ecosystems.
Trophoblast-Specific Expression of Hif-1α Results in Preeclampsia-Like Symptoms and Fetal Growth Restriction
Authors: Albers Renee E. , Kaufman Melissa R. , Natale Bryony V. , Keoni Chanel , Kulkarni-Datar Kashmira , Min Sarah , Williams Clintoria R. , Natale David R. C. , Brown Thomas L.
Published: February 2019

The placenta is an essential organ that is formed during pregnancy and its proper development is critical for embryonic survival. While several animal models have been shown to exhibit some of the pathological effects present in human preeclampsia, these models often do not represent the physiological aspects that have been identified. Hypoxia-inducible factor 1 alpha (Hif-1α) is a necessary component of the cellular oxygen-sensing machinery and has been implicated as a major regulator of trophoblast differentiation. Elevated levels of Hif-1α in the human placenta have been linked to the development of pregnancy-associated disorders, such as preeclampsia and fetal growth restriction. As oxygen regulation is a critical determinant for placentogenesis, we determined the effects of constitutively active Hif-1α, specifically in trophoblasts, on mouse placental development in vivo. Our research indicates that prolonged expression of trophoblast-specific Hif-1α leads to a significant decrease in fetal birth weight. In addition, we noted significant physiological alterations in placental differentiation that included reduced branching morphogenesis, alterations in maternal and fetal blood spaces, and failure to remodel the maternal spiral arteries. These placental alterations resulted in subsequent maternal hypertension with parturitional resolution and maternal kidney glomeruloendotheliosis with accompanying proteinuria, classic hallmarks of preeclampsia. Our findings identify Hif-1α as a critical molecular mediator of placental development and indicate that prolonged expression of Hif-1α, explicitly in placental trophoblasts causes maternal pathology and establishes a mouse model that significantly recapitulates the physiological and pathophysiological characteristics of preeclampsia with fetal growth restriction.
How to measure the local Dzyaloshinskii-Moriya Interaction in Skyrmion Thin-Film Multilayers
Authors: Baćani Mirko , Marioni Miguel A. , Schwenk Johannes , Hug Hans J.
Published: February 2019

The current-driven motion of skyrmions in MnSi and FeGe thinned single crystals could be initiated at current densities of the order of 106 A/m2, five orders of magnitude smaller than for magnetic domain walls. The technologically crucial step of replicating these results in thin films has not been successful to-date, but the reasons are not clear. Elucidating them requires analyzing system characteristics at scales of few nm where the key Dzyaloshinskii-Moriya (DM) interactions vary, and doing so in near-application conditions, i.e. in systems at room temperature, capped with additional layers for oxidation protection. In this work’s magnetic force microscopy (MFM) studies of magnetron-sputtered Ir/Co/Pt-multilayers we show skyrmions that are smaller than previously observed, are not circularly symmetric, and are pinned to 50-nm wide areas where the DM interaction is higher than average. This finding matches our measurement of inhomogeneity of the magnetic moment areal density, which amounts to a standard deviation of the Co layer thickness of 0.3 monolayers in our 0.6 nm thick Co layers. This likely originates in small Co layer thickness variation and alloying. These film characteristics must be controlled with greater precision to preclude skyrmion pinning.
Single-shot deflectometry for dynamic 3D surface profile measurement by modified spatial-carrier frequency phase-shifting method
Authors: Nguyen Manh The , Ghim Young-Sik , Rhee Hyug-Gyo
Published: February 2019

We propose a new concept of single-shot deflectometry for real-time measurement of three-dimensional surface profile using a single composite pattern. To retrieve an accurate phase from one-frame composite pattern, we adapt the Fourier Transform (FT) method and the spatial carrier-frequency phase-shifting (SCPS) technique to our proposed deflectometry. Based on Lissajous figure and ellipse fitting method, we also correct the phase extraction error in SCPS technique by reducing the effect of background and modulation variations. The proposed technique is verified by comparing our measurement results with phase-shifting deflectometry, and the maximum difference between two measurement results is less than 30 nm rms. We also test the robustness to vibration and the measurement capability for dynamic object.
Generation of microalga Chlamydomonas reinhardtii expressing shrimp antiviral dsRNA without supplementation of antibiotics
Authors: Charoonnart Patai , Worakajit Nichakorn , Zedler Julie A. Z. , Meetam Metha , Robinson Colin , Saksmerprome Vanvimon
Published: February 2019

RNA interference (RNAi) is an effective way of combating shrimp viruses by using sequence-specific double-stranded (dsRNA) designed to knock down key viral genes. The aim of this study was to use microalgae expressing antiviral dsRNA as a sustainable feed supplement for shrimp offering viral protection. In this proof of concept, we engineered the chloroplast genome of the green microalga Chlamydomonas reinhardtii for the expression of a dsRNA cassette targeting a shrimp yellow head viral gene. We used a previously described chloroplast transformation approach that allows for the generation of stable, marker-free C. reinhardtii transformants without the supplementation of antibiotics. The generated dsRNA-expressing microalgal strain was then used in a shrimp feeding trial to evaluate the efficiency of the algal RNAi-based vaccine against the virus. Shrimps treated with dsRNA-expressed algal cells prior to YHV infection had 50% survival at 8 day-post infection (dpi), whereas 84.1% mortality was observed in control groups exposed to the YHV virus. RT-PCR using viral specific primers revealed a lower infection rate in dsRNA-expressing algae treated shrimp (55.6 ± 11.1%) compared to control groups (88.9 ± 11.1% and 100.0 ± 0.0%, respectively). Our results are promising for using microalgae as a novel, sustainable alternative as a nutritious, anti-viral protective feedstock in shrimp aquaculture.
Identification of an XRCC1 DNA binding activity essential for retention at sites of DNA damage
Authors: Mok Mac C. Y. , Campalans Anna , Pillon Monica C. , Guarné Alba , Radicella J. Pablo , Junop Murray S.
Published: February 2019

Repair of two major forms of DNA damage, single strand breaks and base modifications, are dependent on XRCC1. XRCC1 orchestrates these repair processes by temporally and spatially coordinating interactions between several other repair proteins. Here we show that XRCC1 contains a central DNA binding domain (CDB, residues 219–415) encompassing its first BRCT domain. In contrast to the N-terminal domain of XRCC1, which has been reported to mediate damage sensing in vitro, we demonstrate that the DNA binding module identified here lacks binding specificity towards DNA containing nicks or gaps. Alanine substitution of residues within the CDB of XRCC1 disrupt DNA binding in vitro and lead to a significant reduction in XRCC1 retention at DNA damage sites without affecting initial recruitment. Interestingly, reduced retention at sites of DNA damage is associated with an increased rate of repair. These findings suggest that DNA binding activity of XRCC1 plays a significant role in retention at sites of damage and the rate at which damage is repaired.
Treatment with maresin 1, a docosahexaenoic acid-derived pro-resolution lipid, protects skin from inflammation and oxidative stress caused by UVB irradiation
Authors: Cezar Talita L. C. , Martinez Renata M. , Rocha Camila da , Melo Cristina P. B. , Vale David L. , Borghi Sergio M. , Fattori Victor , Vignoli Josiane A. , Camilios-Neto Doumit , Baracat Marcela M. , Georgetti Sandra R. , Verri Waldiceu A. , Casagrande Rubia
Published: February 2019

Acute exposure to UVB irradiation causes skin inflammation and oxidative stress, and long-term exposure to UVB irradiation may lead to carcinogenesis. Our organism has endogenous mechanisms to actively limit inflammation. Maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid) is a pro-resolution lipid mediator derived from the docosahexaenoic acid, which presents anti-inflammatory and pro-resolution effects. However, it remains to be determined if treatment with MaR1 can inhibit inflammatory and oxidative alterations in the skin triggered by UVB. The treatment with MaR1 (0.1–10 ng/mice at −10 min relative to the UVB irradiation protocol) reduced UVB-induced skin edema, neutrophil recruitment (MPO; myeloperoxidase activity, and migration of LysM-eGFP+ cells), cytokine production, matrix metalloproteinase-9 activity, keratinocyte apoptosis, epidermal thickening, mast cells counts and degradation of skin collagen in hairless mice. UVB irradiation caused a decrease of GSH (reduced glutathione) levels, activity of the enzyme catalase, ferric reducing ability (FRAP), and ABTS radical scavenging capacity as well as induced lipid hydroperoxide, superoxide anion production, and gp91phox mRNA expression. These parameters that indicate oxidative stress were inhibited by MaR1 treatment. Therefore, these data suggest MaR1 as a promising pharmacological tool in controlling the deleterious effects related to UVB irradiation.
Toads phenotypically adjust their chemical defences to anthropogenic habitat change
Authors: Bókony Veronika , Üveges Bálint , Verebélyi Viktória , Ujhegyi Nikolett , Móricz Ágnes M.
Published: February 2019

Despite the well-documented effects of human-induced environmental changes on the morphology, physiology, behaviour and life history of wild animals, next to nothing is known about how anthropogenic habitats influence anti-predatory chemical defence, a crucial fitness component of many species. We investigated the amount and composition of defensive toxins in adult common toads (Bufo bufo) captured in natural, agricultural and urban habitats, and in their offspring raised in a common-garden experiment. We found that, compared to toads captured from natural habitats, adults from both types of anthropogenic habitats had larger toxin glands (parotoids) and their toxin secretion contained higher concentrations of bufagenins, the more potent class of bufadienolide toxins. Furthermore, urban toads had lower concentrations of bufotoxins, the compounds with lower toxicity. None of these differences were present in the captive-raised juveniles; instead, toadlets originating from agricultural habitats had smaller parotoids and lower bufotoxin concentrations. These results suggest that toads’ chemical defences respond to the challenges of anthropogenic environments via phenotypic plasticity. These responses may constitute non-adaptive consequences of pollution by endocrine-disrupting chemicals as well as adaptive adjustments to the altered predator assemblages of urban and agricultural habitats.
Spatial contribution of hippocampal BOLD activation in high-resolution fMRI
Authors: Abe Yoshifumi , Tsurugizawa Tomokazu , Le Bihan Denis , Ciobanu Luisa
Published: February 2019

While the vascular origin of the BOLD-fMRI signal is established, the exact neurovascular coupling events contributing to this signal are still incompletely understood. Furthermore, the hippocampal spatial properties of the BOLD activation are not elucidated, although electrophysiology approaches have already revealed the precise spatial patterns of neural activity. High magnetic field fMRI offers improved contrast and allows for a better correlation with the underlying neuronal activity because of the increased contribution to the BOLD signal of small blood vessels. Here, we take advantage of these two benefits to investigate the spatial characteristics of the hippocampal activation in a rat model before and after changing the hippocampal plasticity by long-term potentiation (LTP). We found that the hippocampal BOLD signals evoked by electrical stimulation at the perforant pathway increased more at the radiatum layer of the hippocampal CA1 region than at the pyramidal cell layer. The return to the baseline of the hippocampal BOLD activation was prolonged after LTP induction compared with that before most likely due vascular or neurovascular coupling changes. Based on these results, we conclude that high resolution BOLD-fMRI allows the segregation of hippocampal subfields probably based on their underlying vascular or neurovascular coupling features.
Levels of Systemic Low-grade Inflammation in Pregnant Mothers and Their Offspring are Correlated
Authors: Fink Nadia Rahman , Chawes Bo , Bønnelykke Klaus , Thorsen Jonathan , Stokholm Jakob , Rasmussen Morten Arendt , Brix Susanne , Bisgaard Hans
Published: February 2019

High sensitivity C-reactive protein (hs-CRP) is a marker of systemic low-grade inflammation and associated with chronic inflammatory diseases. It is unknown whether maternal and infant hs-CRP levels are correlated and little is known about risk factors in early childhood. Hs-CRP were measured in mothers during pregnancy week 24 (N = 690), and one-week postpartum (N = 675) and in their children age 6 mo (N = 640) enrolled in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort. The risk factor analysis included anthropometrics, environmental exposures and CRP-Genetic Risk Score (GRS). Mother’s body mass index (BMI), use of antibiotics, smoking, cesarean delivery and season were associated with higher maternal hs-CRP level, whereas higher social circumstances were associated with lower hs-CRP level (p < 0.05). Child’s BMI, siblings, bacterial airway colonization, current infection, CRP-genetic risk score and season were associated with higher hs-CRP at age 6 mo (all p < 0.05). Mother’s hs-CRP level in pregnancy week 24 was associated with hs-CRP level in the child at 6 mo: β-coefficient = 0.11 [95% CI: 0.01–0.20], R2 = 0.22, p = 0.03. The association was unchanged adjusted for all significant risk factors. Systemic low-grade inflammation in pregnant mothers and their offspring is correlated independently of BMI, environmental exposures and genetic risk factors.
Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia
Authors: Kim Wan-Young , Nam Sun Ah , Choi Arum , Kim Yu-Mi , Park Sang Hee , Kim Hong Lim , Kim Hyang , Han Ki-Hwan , Yang Chul Woo , Lee Myung-Shik , Kim Yong Kyun , Kim Jin
Published: February 2019

Prolonged hypokalemia induces a decrease of urinary concentrating ability via down-regulation of aquaporin 2 (AQP2); however, the precise mechanisms remain unknown. To investigate the role of autophagy in the degradation of AQP2, we generated the principal cell-specific Atg7 deletion (Atg7Δpc) mice. In hypokalemic Atg7-floxed (Atg7f/f) mice, huge irregular shaped LC3-positive autophagic vacuoles accumulated mainly in inner medullary collecting duct (IMCD) cells. Total- and pS261-AQP2 were redistributed from apical and subapical domains into these vacuoles, which were not co-localized with RAB9. However, in the IMCD cells of hypokalemic Atg7Δpc mice, these canonical autophagic vacuoles were markedly reduced, whereas numerous small regular shaped LC3-negative/RAB9-positive non-canonical autophagic vacuoles were observed along with diffusely distributed total- and pS261-AQP2 in the cytoplasm. The immunoreactivity of pS256-AQP2 in the apical membrane of IMCD cells was markedly decreased, and no redistribution was observed in both hypokalemic Atg7f/f and Atg7Δpc mice. These findings suggest that AQP2 down regulation in hypokalemia was induced by reduced phosphorylation of AQP2, resulting in a reduction of apical plasma labeling of pS256-AQP2 and degradation of total- and pS261-AQP2 via an LC3/ATG7-dependent canonical autophagy pathway.