bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solitonic State in Microscopic Dynamic Failures
Authors: Ghaffari H. O. , Griffith W. A. , Pec M. 
Published: February 2019

AbstractOnset of permanent deformation in crystalline materials under a sharp indenter tip is accompanied by nucleation and propagation of defects. By measuring the spatio-temporal strain field near the indenter tip during indentation tests, we demonstrate that the dynamic strain history at the moment of a displacement burst carries characteristics of the formation and interaction of local excitations, or solitons. We show that dynamic propagation of multiple solitons is followed by a short time interval where the propagating fronts can accelerate suddenly. As a result of such abrupt local accelerations, duration of the fast-slip phase of a failure event is shortened. Our results show that formation and annihilation of solitons mediate the microscopic fast weakening phase, during which extreme acceleration and collision of solitons lead to non-Newtonian behavior and Lorentz contraction, i.e., shortening of solitons’ characteristic length. The results open new horizons for understanding dynamic material response during failure and, more generally, complexity of earthquake sources.
Towards functional restoration for persons with limb amputation: A dual-stage implementation of regenerative agonist-antagonist myoneural interfaces
Authors: Srinivasan Shriya S. , Diaz Maurizio , Carty Matthew , Herr Hugh M. 
Published: February 2019

AbstractWhile amputation has traditionally been viewed as a failure of therapy, recent developments in amputation surgery and neural interfacing demonstrate improved functionality and bidirectional communication with prosthetic devices. The agonist antagonist myoneural interface (AMI) is one such bi-directional neural communication model comprised of two muscles, an agonist and an antagonist, surgically connected in series within the amputated residuum such that contraction of one muscle stretches the other. By preserving agonist-antagonist muscle dynamics, the AMI allows proprioceptive signals from mechanoreceptors within both muscles to be communicated to the central nervous system. Preliminary human evidence suggests that AMIs have the capacity to provide high fidelity control of a prosthetic device, force feedback, and natural proprioception. However, AMIs have been implemented only in planned amputations and require healthy distal tissues, whereas the majority of amputations occur in patients who do not have healthy distal tissues. Through the use of a dual-stage surgical procedure which leverages existent tissues, this study proposes a revision model for implementation of the AMI in patients who are undergoing traumatic amputation or have already undergone a standard amputation. This paper validates the resulting AMI’s physiology, revealing robust viability and mechanical and electrophysiological function. We demonstrate the presence of H-waves in regenerative grafts, indicating the incorporation of the AMI into physiological reflexive loops.
Comparative studies of catalytic pathways for Streptococcus pneumoniae sialidases NanA, NanB and NanC
Authors: Xiao Kela , Wang Xingyong , Yu Haibo 
Published: February 2019

AbstractStreptococcus pneumoniae (S. pneumoniae) is a leading human pathogen, which takes large responsibility for severe otitis media, acute meningitis and septicaemia. It encodes up to three distinct sialidases: NanA, NanB and NanC, which are promising drug targets. Recent experimental studies have shown that these three sialidases might work together up to the ultimate step, where NanA and NanB produce N-acetylneuraminic acid (Neu5Ac) and 2,7-anhydro-Neu5Ac following the functions of sialidase and intramolecular trans-sialidase, whilst NanC carries on a ping-pong mechanism that produces or removes 2-deoxy-2,3-didehydro-Neu5AC. It is intriguing that these sialidases have similar active sites but operate via three distinct reaction pathways. To clarify this issue, herein we present the first systematic computational investigation on the catalytic pathways for S. pneumoniae NanA, NanB and NanC based on combined quantum mechanics/molecular mechanics simulations, and propose the most preferred routes for the three S. pneumoniae sialidases. Our findings support the mechanisms of NanA and NanC that were proposed by previous experimental studies, whereas the role of water in NanB was found to differ slightly from our current understandings. The mechanistic insights obtained from this work are expected to assist in the design of potent inhibitors targeting these key enzymes for therapeutic applications.
Structural analysis of a calix[4]arene-based Platonic Micelle
Authors: Mylonas Efstratios , Yagi Naoto , Fujii Shota , Ikesue Kodai , Ueda Tomoya , Moriyama Hideaki , Sanada Yusuke , Uezu Kazuya , Sakurai Kazuo , Okobira Tadashi 
Published: February 2019

AbstractWe have recently introduced the concept of “Platonic micelles”, the preference of spherical micelles to specific aggregation numbers mostly coinciding with the number of faces of platonic solids. This effect was observed on bulky, mostly calix[4]arene-based surfactant systems with small aggregation numbers. The preferred aggregation numbers result in better sphere coverage, highliting the packing and the “protection” of hydrophobic cores from the aqueous solvent as the most important factor for this preference. In the present study we further explore the interactions that drive the packing of the highly charged PACaL3 surfactant into highly symmetrical hexameric micelles. We performed a series of molecular dynamics simulations that yielded a large set of structures and an ensemble in good agreement with the experimental Small Angle X-ray Scattering data was selected. The geometry and the rigidity of the calix[4]arene group with proper tail length and headgroup volume are the driving forces for the high symmetry and monodispersity of the micelle. The charge of the headgroups is mainly responsible for inhibiting the formation of higher order structures. Sodium, shown to be important for the stability of the micelle, is not directly interacting with the micelle implying that the calix[4]arene ring is a C2ν symmetry conformation.
Single molecule tracking reveals functions for RarA at replication forks but also independently from replication during DNA repair in Bacillus subtilis
Authors: Romero Hector , Rösch Thomas C. , Hernández-Tamayo Rogelio , Lucena Daniella , Ayora Silvia , Alonso Juan C. , Graumann Peter L. 
Published: February 2019

AbstractRarA is a widely conserved protein proposed to be involved in recombination-dependent replication. We present a cell biological approach to identify functional connections between RarA and other proteins using single molecule tracking. We found that 50% of RarA molecules were static, mostly close to replication forks and likely DNA-bound, while the remaining fraction was highly dynamic throughout the cells. RarA alternated between static and dynamic states. Exposure to H2O2 increased the fraction of dynamic molecules, but not treatment with mitomycin C or with methyl methanesulfonate, which was exacerbated by the absence of RecJ, RecD2, RecS and RecU proteins. The ratio between static and dynamic RarA also changed in replication temperature-sensitive mutants, but in opposite manners, dependent upon inhibition of DnaB or of DnaC (pre)primosomal proteins, revealing an intricate function related to DNA replication restart. RarA likely acts in the context of collapsed replication forks, as well as in conjunction with a network of proteins that affect the activity of the RecA recombinase. Our novel approach reveals intricate interactions of RarA, and is widely applicable for in vivo protein studies, to underpin genetic or biochemical connections, and is especially helpful for investigating proteins whose absence does not lead to any detectable phenotype.
Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application
Authors: Ito Emiko , Miyagawa Shigeru , Takeda Maki , Kawamura Ai , Harada Akima , Iseoka Hiroko , Yajima Shin , Sougawa Nagako , Mochizuki-Oda Noriko , Yasuda Satoshi , Sato Yoji , Sawa Yoshiki 
Published: February 2019

AbstractTransplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.
Basic Units of Inter-Individual Variation in Resting State Connectomes
Authors: Sripada Chandra , Angstadt Mike , Rutherford Saige , Kessler Daniel , Kim Yura , Yee Mike , Levina Elizaveta 
Published: February 2019

AbstractResting state functional connectomes are massive and complex. It is an open question, however, whether connectomes differ across individuals in a correspondingly massive number of ways, or whether most differences take a small number of characteristic forms. We systematically investigated this question and found clear evidence of low-rank structure in which a modest number of connectomic components, around 50–150, account for a sizable portion of inter-individual connectomic variation. This number was convergently arrived at with multiple methods including estimation of intrinsic dimensionality and assessment of reconstruction of out-of-sample data. In addition, we show that these connectomic components enable prediction of a broad array of neurocognitive and clinical symptom variables at levels comparable to a leading method that is trained on the whole connectome. Qualitative observation reveals that these connectomic components exhibit extensive community structure reflecting interrelationships between intrinsic connectivity networks. We provide quantitative validation of this observation using novel stochastic block model-based methods. We propose that these connectivity components form an effective basis set for quantifying and interpreting inter-individual connectomic differences, and for predicting behavioral/clinical phenotypes.
L-PGDS-produced PGD2 in premature, but not in mature, adipocytes increases obesity and insulin resistance
Authors: Fujimori Ko , Aritake Kosuke , Oishi Yo , Nagata Nanae , Maehara Toko , Lazarus Michael , Urade Yoshihiro 
Published: February 2019

AbstractLipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD2 in adipocytes and is selectively induced by a high-fat diet (HFD) in adipose tissue. In this study, we investigated the effects of HFD on obesity and insulin resistance in two distinct types of adipose-specific L-PGDS gene knockout (KO) mice: fatty acid binding protein 4 (fabp4, aP2)-Cre/L-PGDSflox/flox and adiponectin (AdipoQ)-Cre/L-PGDSflox/flox mice. The L-PGDS gene was deleted in adipocytes in the premature stage of the former strain and after maturation of the latter strain. The L-PGDS expression and PGD2 production levels decreased in white adipose tissue (WAT) under HFD conditions only in the aP2-Cre/L-PGDSflox/flox mice, but were unchanged in the AdipoQ-Cre/L-PGDSflox/flox mice. When fed an HFD, aP2-Cre/L-PGDSflox/flox mice significantly reduced body weight gain, adipocyte size, and serum cholesterol and triglyceride levels. In WAT of the HFD-fed aP2-Cre/L-PGDSflox/flox mice, the expression levels of the adipogenic, lipogenic, and M1 macrophage marker genes were decreased, whereas those of the lipolytic and M2 macrophage marker genes were enhanced or unchanged. Insulin sensitivity was improved in the HFD-fed aP2-Cre/L-PGDSflox/flox mice. These results indicate that PGD2 produced by L-PGDS in premature adipocytes is involved in the regulation of body weight gain and insulin resistance under nutrient-dense conditions.
Trans-pairing between osteoclasts and osteoblasts shapes the cranial base during development
Authors: Edamoto Mio , Kuroda Yukiko , Yoda Masaki , Kawaai Katsuhiro , Matsuo Koichi 
Published: February 2019

AbstractBone growth is linked to expansion of nearby organs, as is the case for the cranial base and the brain. Here, we focused on development of the mouse clivus, a sloping surface of the basioccipital bone, to define mechanisms underlying morphological changes in bone in response to brain enlargement. Histological analysis indicated that both endocranial and ectocranial cortical bone layers in the basioccipital carry the osteoclast surface dorsally and the osteoblast surface ventrally. Finite element analysis of mechanical stress on the clivus revealed that compressive and tensile stresses appeared mainly on respective dorsal and ventral surfaces of the basioccipital bone. Osteoclastic bone resorption occurred primarily in the compression area, whereas areas of bone formation largely coincided with the tension area. These data collectively suggest that compressive and tensile stresses govern respective localization of osteoclasts and osteoblasts. Developmental analysis of the basioccipital bone revealed the clivus to be angled in early postnatal wild-type mice, whereas its slope was less prominent in Tnfsf11−/− mice, which lack osteoclasts. We propose that osteoclast-osteoblast “trans-pairing” across cortical bone is primarily induced by mechanical stress from growing organs and regulates shape and size of bones that encase the brain.
Changes in overall and regional body fatness from childhood to early adolescence
Authors: Santos Leonardo Pozza , Santos Ina S. , Matijasevich Alicia , Barros Aluísio J. D. 
Published: February 2019

AbstractChildren weight gain is mostly due to fat-free mass than fat mass, but the changes in body composition dynamics related to child growth can be attributed to the obesity epidemic. We aimed to assess changes in measures of body composition from 6 to 11 years of age according to sex, and to examine whether changes in these measures are associated with sociodemographic characteristics. A longitudinal study using data from the 2004 Pelotas Birth Cohort was conducted, and assessed body composition and fat distribution through measures of BMI, fat mass index, fat-free mass index, and android and gynoid fat mass percentages from DXA. Changes in body fatness were calculated as the difference between measures collected at 6 and 11 years of age, and linear regression models were used to assess changes in body composition according to sociodemographic characteristics. An increase in mean BMI z-score from 6 to 11 years was observed only in boys and obesity prevalence reached one out of four boys and one out of five girls. There was an increase in fat mass percentage, fat mass index and android fat mass, with this effect more accentuated in boys when compared to girls. Maternal BMI was the most consistent factor associated with change in body fatness. Children from mothers with obesity showed larger increases in fat mass percentage, fat mass index and android fat mass. There was an increase in body fatness and a centralisation of body shape, mostly associated with male sex and maternal obesity. These results may indicate an early risk of non-communicable diseases in children from the Pelotas 2004 Birth Cohort.
Exploring cold quarantine to mango fruit against fruit fly using artificial ripening
Authors: Patil Abhinandan S. , Maurer Dalia , Feygenberg Oleg , Alkan Noam 
Published: February 2019

AbstractMango quarantine is based mainly on heat treatment, with a possible deterioration of fruit quality. We studied the effects of cold quarantine (19 days storage at 2 °C) on fruit quality of commercial mango cvs. Keitt and Shelly for three consecutive years. Chilling injury (CI) occurs in mango fruit stored at temperatures lower than 12 °C. By reanalysing our previous transcriptome, we found that under sub-optimal temperature storage (5 °C), the fruit increases its ethylene biosynthesis and osmolarity by activating sugar metabolism, thereby probably reducing its freezing point. Similarly, ripe fruit with higher sugar concentration should be more resistant to cold-storage stress. Here, mango fruit was artificially ripened with 150 ppm ethylene. The control group, stored at 2 °C, suffered from severe CI, whereas the combined treatment of artificial ripening, modified atmosphere (fruit were enclosed in perforated bags) and subsequent low-temperature conditioning resulted in a significant reduction in CI to satisfactory levels for consumer acceptance (taste, aroma and texture). The combined treatment reduced lipid peroxidation and maintained flavour, leading to a novel cold-quarantine treatment for mango fruit. Thus, by reversing the supply chain and storing ripe and ready-to-eat fruit, cold quarantine was enabled for mango, and possibly other chilling-susceptible fruits.
Ambient and controlled exposures to particulate air pollution and acute changes in heart rate variability and repolarization
Authors: Breitner Susanne , Peters Annette , Zareba Wojciech , Hampel Regina , Oakes David , Wiltshire Jelani , Frampton Mark W. , Hopke Philip K. , Cyrys Josef , Utell Mark J. , Kane Cathleen , Schneider Alexandra , Rich David Q. 
Published: February 2019

AbstractPrevious studies have reported increased risks of myocardial infarction in association with elevated ambient particulate matter (PM) in the previous hour(s). However, whether PM can trigger mechanisms that act on this time scale is still unclear. We hypothesized that increases in PM are associated with rapid changes in measures of heart rate variability and repolarization. We used data from panel studies in Augsburg, Germany, and Rochester, New York, USA, and two controlled human exposure studies in Rochester. Data included ECG recordings from all four studies, controlled exposures to (concentrated) ultrafine particles (UFP; particles with an aerodynamic diameter <100 nm) and ambient concentrations of UFP and fine PM (PM2.5, aerodynamic diameter <2.5 μm). Factor analysis identified three representative ECG parameters: standard deviation of NN-intervals (SDNN), root mean square of successive differences (RMSSD), and T-wave complexity. Associations between air pollutants and ECG parameters in the concurrent and previous six hours were estimated using additive mixed models adjusting for long- and short-term time trends, meteorology, and study visit number. We found decreases in SDNN in relation to increased exposures to UFP in the previous five hours in both of the panel studies (e.g. Augsburg study, lag 3 hours: −2.26%, 95% confidence interval [CI]: −3.98% to −0.53%; Rochester panel study, lag 1 hour: −2.69%; 95% CI: −5.13% to −0.26%) and one of the two controlled human exposure studies (1-hour lag: −13.22%; 95% CI: −24.11% to −2.33%). Similarly, we observed consistent decreases in SDNN and RMSSD in association with elevated PM2.5 concentrations in the preceding six hours in both panel studies. We did not find consistent associations between particle metrics and T-wave complexity. This study provided consistent evidence that recent exposures to UFP and PM2.5 can induce acute pathophysiological responses.
The cyclic peptide labaditin does not alter the outer membrane integrity of Salmonella enterica serovar Typhimurium
Authors: Barbosa Simone C. , Nobre Thatyane M. , Volpati Diogo , Cilli Eduardo M. , Correa Daniel S. , Oliveira Osvaldo N. 
Published: February 2019

AbstractAntimicrobial peptides are a promising class of new antibiotics with the ability to kill bacteria by disrupting their cell membrane, which is especially difficult for Gram-negative bacteria whose cell wall contains an outer layer of lipopolysaccharides (LPS). Here we show that the cyclic decapeptide Labaditin (Lo), with proven activity against the Gram-positive Staphylococcus aureus and Streptococcus mutans, is not able to kill the Gram-negative Salmonella enterica serovar Typhimurium (S.e.s. Typhimurium). We found that Lo induced significant changes in the surface pressure isotherms of Langmuir monolayers representing the Salmonella enterica serovar Typhimurium inner membrane (S.e.s. Typhimurium IM), and caused leakage in large unilamellar vesicles made with this IM lipid composition. On the basis of these results one should expect bactericidal activity against S.e.s. Typhimurium. However, Lo could not interact with a monolayer of LPS, causing no significant changes in either the surface pressure isotherms or in the polarization-modulated infrared reflection absorption spectra (PM-IRRAS). Therefore, the failure of Lo to kill S.e.s. Typhimurium is associated with the lack of interaction with LPS from the outer bacteria membrane. Our approach with distinct monolayer compositions and combined techniques to investigate molecular-level interactions is useful for drug design to fight antibiotic-resistant bacteria.
The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association
Authors: Cervilha Daniela A. B. , Ito Juliana T. , Lourenço Juliana D. , Olivo Clarice R. , Saraiva-Romanholo Beatriz M. , Volpini Rildo A. , Oliveira-Junior Manoel C. , Mauad Thais , Martins Milton A. , Tibério Iolanda F. L. C. , Vieira Rodolfo P. , Lopes Fernanda D. T. Q. S. 
Published: February 2019

AbstractWe proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in 50 µl of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4+ and CD8+ T cells, Treg cells, and IL-10+ and IL-17+ cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-γ, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4+ and CD8+ T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17+ cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5+ cells corroborated the increased numbers of IL-17+ and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL-10+ cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.