bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a remote mutation from the contact paratope on the structure of CDR-H3 in the anti-HIV neutralizing antibody PG16
Authors: Kondo Hiroko X. , Kiribayashi Ryo , Kuroda Daisuke , Kohda Jiro , Kugimiya Akimitsu , Nakano Yasuhisa , Tsumoto Kouhei , Takano Yu
Published: December 2019

PG16 is a broadly neutralizing antibody to the human immunodeficiency virus (HIV). A crystal structure of PG16 revealed that the unusually long 28-residue complementarity determining region (CDR) H3 forms a unique subdomain, referred to as a “hammerhead”, that directly contacts the antigen. The hammerhead apparently governs the function of PG16 while a previous experimental assay showed that the mutation of TyrH100Q to Ala, which does not directly contact the antigen, decreased the neutralization ability of PG16. However, the molecular mechanism by which a remote mutation from the hammerhead or contact paratope affects the neutralization potency has remained unclear. Here, we performed molecular dynamics simulations of the wild-type and variants (TyrH100Q to Ala, and TyrH100Q to Phe) of PG16, to clarify the effects of these mutations on the dynamics of CDR-H3. Our simulations revealed that the structural rigidity of the CDR-H3 in PG16 is attributable to the hydrogen bond interaction between TyrH100Q and ProH99, as well as the steric support by TyrH100Q. The loss of both interactions increases the intrinsic fluctuations of the CDR-H3 in PG16, leading to a conformational transition of CDR-H3 toward an inactive state.
Small molecule allosteric uncoupling of microtubule depolymerase activity from motility in human Kinesin-5 during mitotic spindle assembly
Authors: Kim Catherine D. , Kim Elizabeth D. , Liu Liqiong , Buckley Rebecca S. , Parameswaran Sreeja , Kim Sunyoung , Wojcik Edward J.
Published: December 2019

Human Kinesin-5 (Eg5) has a large number of known allosteric inhibitors that disrupt its mitotic function. Small-molecule inhibitors of Eg5 are candidate anti-cancer agents and important probes for understanding the cellular function. Here we show that Eg5 is capable of more than one type of microtubule interaction, and these activities can be controlled by allosteric agents. While both monastrol and S-trityl-L-cysteine inhibit Eg5 motility, our data reveal an unexpected ability of these loop5 targeting inhibitors to differentially control a novel Eg5 microtubule depolymerizing activity. Remarkably, small molecule loop5 effectors are able to independently modulate discrete functional interactions between the motor and microtubule track. We establish that motility can be uncoupled from the microtubule depolymerase activity and argue that loop5-targeting inhibitors of Kinesin-5 should not all be considered functionally synonymous. Also, the depolymerizing activity of the motor does not contribute to the genesis of monopolar spindles during allosteric inhibition of motility, but instead reveals a new function. We propose that, in addition to its canonical role in participating in the construction of the three-dimensional mitotic spindle structure, Eg5 also plays a distinct role in regulating the dynamics of individual microtubules, and thereby impacts the density of the mitotic spindle.
Recursive patterns in online echo
chambers
Authors: Brugnoli Emanuele , Cinelli Matteo , Quattrociocchi Walter , Scala Antonio
Published: December 2019

Despite their entertainment oriented purpose, social
media changed the way users access information, debate, and form
their opinions. Recent studies, indeed, showed that users online
tend to promote their favored narratives and thus to form polarized
groups around a common system of beliefs. Confirmation bias helps to
account for users’ decisions about whether to spread content, thus
creating informational cascades within identifiable communities. At
the same time, aggregation of favored information within those
communities reinforces selective exposure and group polarization.
Along this path, through a thorough quantitative analysis we
approach connectivity patterns of 1.2 M Facebook users engaged with
two very conflicting narratives: scientific and conspiracy news.
Analyzing such data, we quantitatively investigate the effect of two
mechanisms (namely challenge avoidance and reinforcement seeking)
behind confirmation bias, one of the major drivers of human behavior
in social media. We find that challenge avoidance mechanism triggers
the emergence of two distinct and polarized groups of users (i.e.,
echo chambers) who also tend to be surrounded by friends having
similar systems of beliefs. Through a network based approach, we
show how the reinforcement seeking mechanism limits the influence of
neighbors and primarily drives the selection and diffusion of
contents even among like-minded users, thus fostering the formation
of highly polarized sub-clusters within the same echo chamber.
Finally, we show that polarized users reinforce their preexisting
beliefs by leveraging the activity of their like-minded neighbors,
and this trend grows with the user engagement suggesting how peer
influence acts as a support for reinforcement seeking.
Electromagnetic field quantization and quantum optical input-output relation for grating
Authors: Wang Tiecheng
Published: December 2019

A quantization scheme is developed for the radiation and higher order electromagnetic fields in one dimensional periodic, dispersive and absorbing dielectric medium. For this structure, the Green function is solved based on the plane wave expansion method, thus the photon operators, commutation relations and quantum Langevin equations are given and studied based on the Green function approach, moreover, the input-output relations are also derived. It is proved that this quantum theory can be reduced back to that of the predecessors’ study on the homogenous dielectric. Based on this method, we find that the transformation of the photon state through the lossy grating is non-unitary and that the notable non-unitary transformation can be obtained by tuning the imaginary part of the permittivity, we also discussed the excellent quantum optical properties for the grating which are similar to the classical optical phenomena. We believe our work is very beneficial for the control and regulation of the quantum light based on gratings.
Relationship of extracellular volume assessed on cardiac magnetic resonance and serum cardiac troponins and natriuretic peptides with heart failure outcomes
Authors: Yang Eric Y. , Khan Mohammad A. , Graviss Edward A. , Nguyen Duc T. , Bhimaraj Arvind , Nambi Vijay , Hoogeveen Ron C. , Ballantyne Christie M. , Zoghbi William A. , Shah Dipan J.
Published: December 2019

Measures of serum cardiac troponins and natriuretic peptides have become established as prognostic heart failure risk markers. In addition to detecting myocardial fibrosis through late gadolinium enhancement (LGE), extracellular volume fraction (ECV) measures by cardiac magnetic resonance (CMR) have emerged as a phenotypic imaging risk marker for incident heart failure outcomes. We sought to examine the relationship between cardiac troponins, natriuretic peptides, ECV and their associations with incident heart failure events in a CMR referral base. Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured >30%, the upper 95% bounds of a reference healthy group without known cardiac disease (n = 28). Patients were dichotomized by presence of elevated ECV. High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal B-type natriuretic peptide (NT-proBNP) were measured using serum samples acquired and stored at time of CMR scan, and patients were categorized into 3 groups for each blood marker based on recommended cutoff values. Subsequent heart failure admission and any death were ascertained. Relationships with ECV, hs-cTnT, and NT-proBNP were examined separately and as a composite with Cox proportional hazard models. Of 1,604 serial patients referred for a clinical CMR with myocardial T1 maps, 331 were eligible after exclusions and had blood available and were followed over a median 25.0 [interquartile range 21.8, 31.7] months. After adjustments for age (mean 57.3 [standard deviation (SD) 15.1 years), gender (61% male), and ethnicity (12.7% black), elevated ECV remained a predictor of a first composite heart failure outcome for patients with high levels of hs-cTnT (≥14 ng/L; hazard ratio [HR] 2.42 [95% confidence interval (CI) 1.17, 5.03]; p = 0.02) and NT-proBNP (≥300 pg/mL; HR 2.28 [95% CI 1.24, 4.29]; p = 0.01). Similar trends were seen for lower category levels of blood markers, but did not persist with minimal covariate adjustments. Elevated measures of ECV by CMR are associated with incident heart failure outcomes in patients with high hs-cTnT and NT-proBNP levels. This imaging marker may have a role for additional heart failure risk stratification.
Acute pancreatitis promotes the generation of two different exosome populations
Authors: Jiménez-Alesanco A. , Marcuello M. , Pastor-Jiménez M. , López-Puerto L. , Bonjoch L. , Gironella M. , Carrascal M. , Abian J. , de-Madaria E. , Closa D.
Published: December 2019

Exosomes are small extracellular vesicles that act as intercellular messengers. Previous studies revealed that, during acute pancreatitis, circulating exosomes could reach the alveolar compartment and activate macrophages. However, proteomic analysis suggested that the most likely origin of these exosomes could be the liver instead of the pancreas. The present study aimed to characterize the exosomes released by pancreas to pancreatitis-associated ascitic fluid (PAAF) as well as those circulating in plasma in an experimental model of taurocholate-induced acute pancreatitis in rats. We provide evidence that during acute pancreatitis two different populations of exosomes are generated with relevant differences in cell distribution, protein and microRNA content as well as different implications in their physiological effects. During pancreatitis plasma exosomes, but not PAAF exosomes, are enriched in the inflammatory miR-155 and show low levels of miR-21 and miR-122. Mass spectrometry-based proteomic analysis showed that PAAF exosomes contains 10–30 fold higher loading of histones and ribosomal proteins compared to plasma exosomes. Finally, plasma exosomes have higher pro-inflammatory activity on macrophages than PAAF exosomes. These results confirm the generation of two different populations of exosomes during acute pancreatitis. Deep understanding of their specific functions will be necessary to use them as therapeutic targets at different stages of the disease.
Molecular serotype-specific identification of Streptococcus pneumoniae using loop-mediated isothermal amplification
Authors: Takano Chika , Kuramochi Yoko , Seki Mitsuko , Kim Dong Wook , Omagari Daisuke , Sasano Mari , Chang Bin , Ohnishi Makoto , Kim Eun Jin , Fuwa Kazumasa , Kilgore Paul E. , Hoshino Tomonori , Hayakawa Satoshi
Published: December 2019

In children, the incidence of pneumococcal meningitis has decreased since the introduction of pneumococcal conjugate vaccine (PCV7 and PCV13). However, since the introduction of the vaccine, developed countries have seen the emergence of non-PCV13 serotypes. However, invasive pneumococcal disease (IPD) caused by PCV13-targeted serotypes still represents an important public health problem in resource-limited countries. To develop a rapid, simple, and cost-effective assay to detect serotypes ofStreptococcus pneumoniae, we developed a novel loop-mediated isothermal amplification (LAMP) assay based on the sequences available for the 13 capsular types that are included in PCV13: 1, 3, 4, 5, 6 A, 6B, 7 F, 9 V, 14, 18 C, 19 A, 19 F, and 23 F. We evaluated test reactivity, specificity, sensitivity and performance, and compared the results between established LAMP and conventional PCR assays. To support its clinical use, the detection limits of the LAMP assay were evaluated using bacterial genomic DNA-spiked cerebrospinal fluid (CSF) and blood specimens. We confirmed the specificity of the LAMP assay using 41 serotypes of pneumococcal strains. The sensitivity of the LAMP assay was 10 to 100 copies per reaction, compared to 10 to 104copies per reaction for PCR assays. The detection limits of the LAMP assay were comparable when using DNA-spiked CSF and blood specimens, as compared to using purified DNA as the template. In conclusion, a rapid and simple LAMP-based pneumococcal serotyping method has been developed. This is the first report of a LAMP method for a PCV13 serotype-specific identification assay, which could be a promising step to facilitate epidemiological studies of pneumococcal serotyping.
Extensive recombination challenges the utility of Sugarcane mosaic virus phylogeny and strain typing
Authors: Braidwood Luke , Müller Sebastian Y. , Baulcombe David
Published: December 2019

Sugarcane mosaic virus (SCMV) is distributed worldwide and infects three major crops: sugarcane, maize, and sorghum. The impact of SCMV is increased by its interaction with Maize chlorotic mottle virus which causes the synergistic maize disease maize lethal necrosis. Here, we characterised maize lethal necrosis-infected maize from multiple sites in East Africa, and found that SCMV was present in all thirty samples. This distribution pattern indicates that SCMV is a major partner virus in the East African maize lethal necrosis outbreak. Consistent with previous studies, our SCMV isolates were highly variable with several statistically supported recombination hot- and cold-spots across the SCMV genome. The recombination events generate conflicting phylogenetic signals from different fragments of the SCMV genome, so it is not appropriate to group SCMV genomes by simple similarity.
Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort
Authors: van Laarhoven Constance J. H. C. M. , van Setten Jessica , van Herwaarden Joost A. , Pasterkamp Gerard , de Kleijn Dominique P. V. , de Borst Gert J. , van der Laan Sander W.
Published: December 2019

Recent genome-wide association studies (GWAS) have discovered ten genetic risk variants for abdominal aortic aneurysms (AAA). To what extent these genetic variants contribute to the pathology of aneurysms is yet unknown. The present study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and aneurysm related-symptoms in aortic and peripheral aneurysm patients. Aneurysm tissue of 415 patients included in the Aneurysm-Express biobank was used. A best-fit polygenic risk score (PRS) based on previous GWAS effect estimates was modeled for each clinical phenotype. The best-fit PRS (including 272 variants at PT = 0.01015) showed a significant correlation with aneurysm diameter (R2 = 0.019, p = 0.001). No polygenic association was found with clinical symptoms or artery type. In addition, the ten genome-wide significant risk variants for AAA were tested individually, but no associations were observed with any of the clinical phenotypes. All models were corrected for confounders and data was normalized. In conclusion, a weighted PRS of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in diameter in aneurysm patients. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of susceptibility variants on aneurysmal disease initiation and progression.
Plant-mediated effects of ozone on herbivores depend on exposure duration and temperature
Authors: Duque Laura , Poelman Erik H. , Steffan-Dewenter Ingolf
Published: December 2019

Abiotic stress by elevated tropospheric ozone and temperature can alter plants’ metabolism, growth, and nutritional value and modify the life cycle of their herbivores. We investigated how the duration of exposure of Sinapis arvensis plants to high ozone and temperature levels affect the life cycle of the large cabbage white, Pieris brassicae. Plants were exposed to ozone-clean (control) or ozone-enriched conditions (120 ppb) for either 1 or 5 days and were afterwards kept in a greenhouse with variable temperature conditions. When given the choice, P. brassicae butterflies laid 49% fewer eggs on ozone-exposed than on control plants when the exposure lasted for 5 days, but showed no preference when exposure lasted for 1 day. The caterpillars took longer to hatch on ozone-exposed plants and at lower ambient temperatures. The ozone treatment had a positive effect on the survival of the eggs. Ozone decreased the growth of caterpillars reared at higher temperatures on plants exposed for 5 days, but not on plants exposed for 1 day. Overall, longer exposure of the plants to ozone and higher temperatures affected the life cycle of the herbivore more strongly. With global warming, the indirect impacts of ozone on herbivores are likely to become more common.
In Silico Models of DNA Damage and Repair in Proton Treatment Planning: A Proof of Concept
Authors: Smith Edward A. K. , Henthorn N. T. , Warmenhoven J. W. , Ingram S. P. , Aitkenhead A. H. , Richardson J. C. , Sitch P. , Chadwick A. L. , Underwood T. S. A. , Merchant M. J. , Burnet N. G. , Kirkby N. F. , Kirkby K. J. , Mackay R. I.
Published: December 2019

There is strong in vitro cell survival evidence that the relative biological effectiveness (RBE) of protons is variable, with dependence on factors such as linear energy transfer (LET) and dose. This is coupled with the growing in vivo evidence, from post-treatment image change analysis, of a variable RBE. Despite this, a constant RBE of 1.1 is still applied as a standard in proton therapy. However, there is a building clinical interest in incorporating a variable RBE. Recently, correlations summarising Monte Carlo-based mechanistic models of DNA damage and repair with absorbed dose and LET have been published as the Manchester mechanistic (MM) model. These correlations offer an alternative path to variable RBE compared to the more standard phenomenological models. In this proof of concept work, these correlations have been extended to acquire RBE-weighted dose distributions and calculated, along with other RBE models, on a treatment plan. The phenomenological and mechanistic models for RBE have been shown to produce comparable results with some differences in magnitude and relative distribution. The mechanistic model found a large RBE for misrepair, which phenomenological models are unable to do. The potential of the MM model to predict multiple endpoints presents a clear advantage over phenomenological models.
Up-regulated fibronectin in 3D culture facilitates spreading of triple negative breast cancer cells on 2D through integrin β-5 and Src
Authors: Park Hwa -Jeong , Helfman David M.
Published: December 2019

Using MDA-MB-231 cells as a model of triple negative breast cancer (TNBC) and its metastatic sub-cell lines that preferentially metastasize to lung, bone or brain, we found that the mRNA and protein levels of fibronectin (FN) are increased in MDA-MB-231 cells and its lung metastatic derivative, when cultivated in three-dimensional (3D) suspension cultures. The increase of FN expression in 3D was dependent on p38 mitogen-activated protein kinase (MAPK) because it was prevented by treatment of cells with SB203580, an inhibitor of p38MAPK. The up-regulated FN was converted into fibrils, and it enhanced cell spreading when cells cultured in 3D were transferred to two-dimensional (2D) culture. The arginine-glycine-aspartate (RGD) peptides and siRNAs targeting of integrin β-5 inhibited spreading of cells regardless of the presence of FN on 2D culture dishes. In addition, the levels of phosphorylated Src were found to be increased in 3D and the treatment of cells with SU6656, an inhibitor of Src, decreased the rate of cell spreading on FN. Collectively, these studies demonstrate that increased cellular FN in 3D suspension culture facilitates cancer cell attachment and spreading via integrin β-5 and Src, suggesting that the increased FN promotes initial attachment of cancer cells to secondary organs after circulation during metastasis.
Fungal and bacterial diversity of Svalbard subglacial ice
Authors: Perini L. , Gostinčar C. , Gunde-Cimerman N.
Published: December 2019

The composition of fungal and bacterial communities in three polythermal glaciers and associated aquatic environments in Kongsfjorden, Svalbard was analysed using a combination of cultivation and amplicon sequencing. 109 fungal strains belonging to 30 mostly basidiomycetous species were isolated from glacial samples with counts up to 103CFU/100 ml.Glaciozyma-related taxon andPhenoliferia psychrophenolicawere the dominant species. Unexpectedly, amplicon sequencing uncovered sequences of Chytridiomycota in all samples and Rozellomycota in sea water, lake water, and tap water. Sequences ofMalassezia restrictaand of the extremely halotolerantHortaea werneckiiwere also found in subglacial habitats for the first time. Overall, the fungal communities within a glacier and among glaciers were diverse and spatially heterogenous. Contrary to this, there was a large overlap between the bacterial communities of different glaciers, withFlavobacteriumsp. being the most frequently isolated. In amplicon sequencing Actinobacteria and Proteobacteria sequences were the most abundant.
Inhibitory cell populations depend on age, sex, and prior experience across a neural network for Critical Period learning
Authors: Gogola Joseph V. , Gores Elisa O. , London Sarah E.
Published: December 2019

In many ways, the complement of cell subtypes determines the information processing that a local brain circuit can perform. For example, the balance of excitatory and inhibitory (E/I) signaling within a brain region contributes to response magnitude and specificity in ways that influence the effectiveness of information processing. An extreme example of response changes to sensory information occur across Critical Periods (CPs). In primary mammalian visual cortex, GAD65 and parvalbumin inhibitory cell types in particular control experience-dependent responses during a CP. Here, we test how the density of GAD65- and parvalbumin-expressing cells may inform on a CP for complex behavioral learning. Juvenile male zebra finch songbirds (females cannot sing) learn to sing through coordinated sensory, sensorimotor, and motor learning processes distributed throughout a well-defined neural network. There is a CP for sensory learning, the process by which a young male forms a memory of his “tutor’s” song, which is then used to guide the young bird’s emerging song structure. We quantified the effect of sex and experience with a tutor on the cell densities of GAD65- and parvalbumin-expressing cells across major nodes of the song network, using ages that span the CP for tutor song memorization. As a resource, we also include whole-brain mapping data for both genes. Results indicate that inhibitory cell populations differ across sex, age, and experiential conditions, but not always in the ways we predicted.
The spectraplakin Dystonin antagonizes YAP activity and suppresses tumourigenesis
Authors: Jain Praachi B. , Guerreiro Patrícia S. , Canato Sara , Janody Florence
Published: December 2019

Aberrant expression of the Spectraplakin Dystonin (DST) has been observed in various cancers, including those of the breast. However, little is known about its role in carcinogenesis. In this report, we demonstrate that Dystonin is a candidate tumour suppressor in breast cancer and provide an underlying molecular mechanism. We show that in MCF10A cells, Dystonin is necessary to restrain cell growth, anchorage-independent growth, self-renewal properties and resistance to doxorubicin. Strikingly, while Dystonin maintains focal adhesion integrity, promotes cell spreading and cell-substratum adhesion, it prevents Zyxin accumulation, stabilizes LATS and restricts YAP activation. Moreover, treating DST-depleted MCF10A cells with the YAP inhibitor Verteporfin prevents their growth. In vivo, the Drosophila Dystonin Short stop also restricts tissue growth by limiting Yorkie activity. As the two Dystonin isoforms BPAG1eA and BPAG1e are necessary to inhibit the acquisition of transformed features and are both downregulated in breast tumour samples and in MCF10A cells with conditional induction of the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. Thus, their loss could deem as promising prognostic biomarkers for breast cancer.
Reversibility of membrane permeabilization upon pulsed electric field treatment in Lactobacillus plantarum WCFS1
Authors: Vaessen E. M. J. , Timmermans R. A. H. , Tempelaars M. H. , Schutyser M. A. I. , den Besten H. M. W.
Published: December 2019

Pulsed electric field (PEF) treatment, or electroporation, can be used to load molecules into cells. The permeabilizing effect of the PEF treatment on the cellular membrane can be either reversible or irreversible depending on the severity of the PEF treatment conditions. The influence of PEF on the reversibility of membrane permeabilization in Lactobacillus plantarum WCFS1 by two different fluorescent staining methods was investigated in this study. Whereas staining with propidium iodide (PI) before and after PEF treatment indicated small reversible permeabilized fractions of maximum 14%, the use of a double staining method with PI and SYTOX Green suggested larger reversible permeabilized fractions up to 40% of the population. This difference shows that the choice for a fluorescent staining method affects the conclusions drawn regarding reversibility of membrane permeabilization. Additionally, the effect of PEF treatment conditions on membrane integrity was compared, indicating a relation between critical electric field strength, cell size and membrane permeabilization. Overall this study showed the possibilities and limitations of fluorescent membrane integrity staining methods for PEF studies.
Evaluation of Selected Outcomes of Combination Antiretroviral Therapy: Yemen Cohort Retrospective Descriptive Studies
Authors: Nabih Mayada Faisal , Puteh Sharifa Ezat Wan , Nur Amrizal Muhammad
Published: December 2019

In 2007, HIV treatment services were established in five main governorates out of twenty-two which resulted in low access to services and poor treatment outcomes. The main goal of this study was to evaluate and analyse the selected treatment outcomes of eight cohorts of PLHIV who were treated with cART during 2007–2014. The method used was a retrospective descriptive study of 1,703 PLHIV who initiated cART at five public health facilities. The results: Retention rate was less than 80%, male: female ratio 1.661, with a mean age of 35 years (±9.2 SD), 85% had been infected with HIV via heterosexual contact. 65% of patients presented with clinical stages 3 and 4, and 52% of them were initiated cART at a CD4 T-cell count ≤200 cells/mm. 61% of cART included Tenofovir and Efavirenz. TB treatment started for 5% of PLHIV, and 22% developed HIV-related clinical manifestations after cART initiation. 67% of PLHIV had experienced cART substitution. The mean AIDS-mortality rate was 15% and the mean LTFU rate was 16%. Conclusion: Although cART showed effectiveness in public health, mobilization of resources and formulation of better health policies are important steps toward improving access to cART and achieving the desired treatment outcomes.
Incidence and evolution of venous thrombosis during the first 3 months after irreversible electroporation of malignant hepatic tumours
Authors: Bäumler W. , Sebald M. , Einspieler I. , Wiggermann P. , Schicho A. , Schaible J. , Lürken L. , Dollinger M. , Stroszczynski C. , Beyer L. P.
Published: December 2019

The incidence and evolution of venous thrombosis adjacent to the ablation zone after percutaneous irreversible electroporation (IRE) were evaluated to identify potential risk factors in patients with hepatic malignancies. 205 venous structures (in 87 patients) within a ≤1.0 cm radius of the ablation zone were assessed after IRE of 112 hepatic lesions (74 primary, 38 secondary hepatic malignancies) by pre-interventional and post-interventional (1–3 days, 6 weeks and 3 months after IRE) contrast-enhanced magnetic resonance imaging. The relationships between venous thrombosis and clinical features were analysed using a binary logistic regression model. In 27 of 87 patients (31%), a total of 67 venous complications were noted during the 3 months follow-up. Thrombosis represented the most frequently observed complication (n = 47; 70.1%), followed by vessel narrowing (n = 20; 29.9%). 5 (10.6%) of 47 thromboses showed spontaneous regression 3 months after IRE. A small vessel diameter (p = 0.011) and post-interventional vessel narrowing (p = 0.006) were independently associated with delayed post-ablative thrombosis. Delayed venous thrombosis frequently occurs after IRE of hepatic malignancies. Pre-existing vessel narrowing and a small vessel diameter represent significant risk factors that require further surveillance and potentially therapeutic intervention.
Sex and race differences in J-Tend, J-Tpeak, and Tpeak-Tend intervals
Authors: Hnatkova Katerina , Toman Ondřej , Šišáková Martina , Smetana Peter , Huster Katharina M. , Barthel Petra , Novotný Tomáš , Schmidt Georg , Malik Marek
Published: December 2019

To facilitate the precision of clinical electrocardiographic studies of J-to-Tpeak (JTp) and Tpeak-to-Tend (Tpe) intervals, the study investigated their differences between healthy females and males, and between subjects of African and Caucasian origin. In 523 healthy subjects (254 females; 236 subjects of African origin), repeated Holter recordings were used to measure QT, JT, JTp, and Tpe intervals preceded by both stable and variable heart rates. Subject-specific curvilinear regression models were used to obtain individual QTc, JTc, JTpc and Tpec intervals. Rate hysteresis, i.e., the speed with which the intervals adapted after heart rate changes, was also investigated. In all sex-race groups, Tpe intervals were not systematically heart rate dependent. Similar to QTc intervals, women had JTc, and JTpc intervals longer than males (difference 20–30 ms, p < 0.001). However, women had Tpec intervals (and rate uncorrected Tpe intervals) shorter by approximately 10 ms compared to males (p < 0.001). Subjects of African origin had significantly shorter QTc intervals than Caucasians (p < 0.001). Gradually diminishing race-difference was found for JTc, JTpc and Tpec intervals. JTc and JTpc were moderately increasing with age but Tpe/Tpec were not. Rate hysteresis of JTp was approximately 10% longer compared to that of JT (p < 0.001). In future clinical studies, Tpe interval should not be systematically corrected for heart rate and similar to the QT interval, the differences in JT, JTp and Tpe intervals should be corrected for sex. The differences in QT and JT, and JTp intervals should also be corrected for race.
BACE1 partial deletion induces synaptic plasticity deficit in adult mice
Authors: Lombardo Sylvia , Chiacchiaretta Martina , Tarr Andrew , Kim WonHee , Cao Tingyi , Sigal Griffin , Rosahl Thomas W. , Xia Weiming , Haydon Philip G. , Kennedy Matthew E. , Tesco Giuseppina
Published: December 2019

BACE1 is the first enzyme involved in APP processing, thus it is a strong therapeutic target candidate for Alzheimer’s disease. The observation of deleterious phenotypes in BACE1 Knock-out (KO) mouse models (germline and conditional) raised some concerns on the safety and tolerability of BACE1 inhibition. Here, we have employed a tamoxifen inducible BACE1 conditional Knock-out (cKO) mouse model to achieve a controlled partial depletion of BACE1 in adult mice. Biochemical and behavioural characterization was performed at two time points: 4–5 months (young mice) and 12–13 months (aged mice). A ~50% to ~70% BACE1 protein reduction in hippocampus and cortex, respectively, induced a significant reduction of BACE1 substrates processing and decrease of Aβx-40 levels at both ages. Hippocampal axonal guidance and peripheral nerve myelination were not affected. Aged mice displayed a CA1 long-term potentiation (LTP) deficit that was not associated with memory impairment. Our findings indicate that numerous phenotypes observed in germline BACE1 KO reflect a fundamental role of BACE1 during development while other phenotypes, observed in adult cKO, may be absent when partially rather than completely deleting BACE1. However, we demonstrated that partial depletion of BACE1 still induces CA1 LTP impairment, supporting a role of BACE1 in synaptic plasticity in adulthood.
Light Intensity-dependent Variation in Defect Contributions to Charge Transport and Recombination in a Planar MAPbI3 Perovskite Solar Cell
Authors: Ryu Shinyoung , Nguyen Duc Cuong , Ha Na Young , Park Hui Joon , Ahn Y. H. , Park Ji-Yong , Lee Soonil
Published: December 2019

We investigated operation of a planar MAPbI3 solar cell with respect to intensity variation ranging from 0.01 to 1 sun. Measured J-V curves consisted of space-charge-limited currents (SCLC) in a drift-dominant range and diode-like currents in a diffusion-dominant range. The variation of power-law exponent of SCLC showed that charge trapping by defects diminished as intensity increased, and that drift currents became eventually almost ohmic. Diode-like currents were analysed using a modified Shockley-equation model, the validity of which was confirmed by comparing measured and estimated open-circuit voltages. Intensity dependence of ideality factor led us to the conclusion that there were two other types of defects that contributed mostly as recombination centers. At low intensities, monomolecular recombination occurred due to one of these defects in addition to bimolecular recombination to result in the ideality factor of ~1.7. However, at high intensities, another type of defect not only took over monomolecular recombination, but also dominated bimolecular recombination to result in the ideality factor of ~2.0. These ideality-factor values were consistent with those representing the intensity dependence of loss-current ratio estimated by using a constant internal-quantum-efficiency approximation. The presence of multiple types of defects was corroborated by findings from equivalent-circuit analysis of impedance spectra.
Comparative analysis of cardiac mechano-energetics in isolated hearts supported by pulsatile or rotary blood pumps
Authors: Granegger Marcus , Choi Young , Locher Benedikt , Aigner Philipp , Hubmann Emanuel J. , Lemme Frithjof , Cesarovic Nikola , Hübler Michael , Schweiger Martin
Published: December 2019

The previously more frequently implanted pulsatile blood pumps (PBPs) showed higher recovery rates than the currently preferred rotary blood pumps (RBPs), with unclear causality. The aim of this study was to comparatively assess the capability of PBPs and RPBs to unload the left ventricle and maintain cardiac energetics as a possible implication for recovery. An RBP and a heartbeat synchronized PBP were alternately connected to isolated porcine hearts. Rotational speed of RBPs was set to different support levels. For PBP support, the start of ejection was phased to different points during the cardiac cycle, prescribed as percentage delays from 0% to 90%. Cardiac efficiency, quantified by the ratio of external work over myocardial oxygen consumption, was determined. For RBP support, higher degrees of RBP support correlated with lower left atrial pressures (LAP) and lower cardiac efficiency (r = 0.91 ± 0.12). In contrast, depending on the phase delay of a PBP, LAP and cardiac efficiency exhibited a sinusoidal relationship with the LAP minimum at 90% and efficiency maximum at 60%. Phasing of a PBP offers the possibility to maintain a high cardiac efficiency and simultaneously unload the ventricle. These results warrant future studies investigating whether optimized cardiac energetics promotes functional recovery with LVAD therapy.
Re-examining the effect of door-to-balloon delay on STEMI outcomes in the context of unmeasured confounders: a retrospective cohort study
Authors: Foo Chee Yoong , Andrianopoulos Nick , Brennan Angela , Ajani Andrew , Reid Christopher M. , Duffy Stephen J. , Clark David J. , Reidpath Daniel D. , Chaiyakunapruk Nathorn
Published: December 2019

Literature studying the door-to-balloon time-outcome relation in coronary intervention is limited by the potential of residual biases from unobserved confounders. This study re-examines the time-outcome relation with further consideration of the unobserved factors and reports the population average effect. Adults with ST-elevation myocardial infarction admitted to one of the six registry participating hospitals in Australia were included in this study. The exposure variable was patient-level door-to-balloon time. Primary outcomes assessed included in-hospital and 30 days mortality. 4343 patients fulfilled the study criteria. 38.0% (1651) experienced a door-to-balloon delay of >90 minutes. The absolute risk differences for in-hospital and 30-day deaths between the two exposure subgroups with balanced covariates were 2.81 (95% CI 1.04, 4.58) and 3.37 (95% CI 1.49, 5.26) per 100 population. When unmeasured factors were taken into consideration, the risk difference were 20.7 (95% CI −2.6, 44.0) and 22.6 (95% CI −1.7, 47.0) per 100 population. Despite further adjustment of the observed and unobserved factors, this study suggests a directionally consistent linkage between longer door-to-balloon delay and higher risk of adverse outcomes at the population level. Greater uncertainties were observed when unmeasured factors were taken into consideration.
Antidepressant–like effects of fish, krill oils and Vit B12 against exposure to stress environment in mice models: current status and pilot study
Authors: Zadeh-Ardabili Parastoo Mojtahed , Rad Sima Kianpour , Rad Soheila Kianpour , Movafagh Abolfazl
Published: December 2019

Oxidative stress has significant role in pathophysiology of any kind of depression through actions of free radicals, non-radical molecules, and unbalancing antioxidant systems in body. In the current study, antidepressant responses of fish oil (FO), Neptune krill oil (NKO), vitamin B12 (Vit B12), and also imipramine (IMP) as the reference were studied. Natural light was employed to induce stress in the animals followed by oral administration of the drugs for 14 days. The antidepressant effect was assessed by tail suspension test (TST) and forced swimming test (FST), antioxidant enzymes and oxidative stress markers were then measured in the brain tissue of the animals. The administration of FO and NKO could significantly reduce the immobility of the animals; while, increasing climbing and swimming time compared to the normal saline in CUS-control group in TST and FST, similarly to IMP but not with Vit B12. Vit B12 could not effect on SOD activity and H2O2 level, but, cause decrease of the malondialdihydric (MDA) level and CAT activity, as well as increased the GPx and GSH activities. The rest treatments led to decrease of MDA, H2O2 levels and CAT activity and increase of GPx, SOD, GSH activities.
Whole-Body Movement during Videogame Play Distinguishes Youth with Autism from Youth with Typical Development
Authors: Ardalan Adel , Assadi Amir H. , Surgent Olivia J. , Travers Brittany G.
Published: December 2019

Individuals with autism spectrum disorder struggle with motor difficulties throughout the life span, and these motor difficulties may affect independent living skills and quality of life. Yet, we know little about how whole-body movement may distinguish individuals with autism spectrum disorder from individuals with typical development. In this study, kinematic and postural sway data were collected during multiple sessions of videogame play in 39 youth with autism spectrum disorder and 23 age-matched youth with typical development (ages 7–17 years). The youth on the autism spectrum exhibited more variability and more entropy in their movements. Machine learning analysis of the youths’ motor patterns distinguished between the autism spectrum and typically developing groups with high aggregate accuracy (up to 89%), with no single region of the body seeming to drive group differences. Moreover, the machine learning results corresponded to individual differences in performance on standardized motor tasks and measures of autism symptom severity. The machine learning algorithm was also sensitive to age, suggesting that motor challenges in autism may be best characterized as a developmental motor delay rather than an autism-distinct motor profile. Overall, these results reveal that whole-body movement is a distinguishing feature in autism spectrum disorder and that movement atypicalities in autism are present across the body.
Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms
Authors: Jiménez-Gambín Sergio , Jiménez Noé , Benlloch José M. , Camarena Francisco
Published: December 2019

We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.
Detection and phenotyping of extracellular vesicles by size exclusion chromatography coupled with on-line fluorescence detection
Authors: Kitka Diána , Mihály Judith , Fraikin Jean-Luc , Beke-Somfai Tamás , Varga Zoltán
Published: December 2019

New methods for quantifying extracellular vesicles (EVs) in complex biofluids are critically needed. We report the development of a new technology combining size exclusion chromatography (SEC), a commonly used EV purification technique, with fluorescence detection of specifically labelled EVs. The resulting platform, Flu-SEC, demonstrates a linear response to concentration of specific EVs and could form the basis of a system with phenotyping capability. Flu-SEC was validated using red blood cell derived EVs (REVs), which provide an ideal EV model with monodisperse size distribution and high EV concentration. Microfluidic Resistive Pulse Sensing (MRPS) was used to accurately determine the size distribution and concentration of REVs. Anti-CD235a antibody, specific to glycophorin A, and the more general wheat germ agglutinin (WGA), were selected to label REVs. The results show the quantitative power of Flu-SEC: a highly linear fluorescence response over a wide range of concentrations. Moreover, the Flu-SEC technique reports the ratio of EV-bound and free-antibody molecules, an important metric for determining optimal labelling conditions for other applications. Flu-SEC represents an orthogonal tool to single-particle fluorescent methods such as flow cytometry and fluorescent NTA, for the quantification and phenotyping of EVs.
Seed selection and storage with nano-silver and copper as potential antibacterial agents for the seagrass Zostera marina: implications for habitat restoration
Authors: Xu Shaochun , Zhou Yi , Xu Shuai , Gu Ruiting , Yue Shidong , Zhang Yu , Zhang Xiaomei
Published: December 2019

Globally, seagrass meadows are extremely important marine ecosystems that are disappearing at an alarming rate. Therefore, research into seagrass restoration has become increasingly important. Various strategies have been used in Zostera marina L. (eelgrass) restoration, including planting seeds. To improve the efficiency of restoration by planting seeds, it is necessary to select high-quality seeds. In addition, a suitable antibacterial agent is necessary for wet storage of desiccation sensitive seeds to reduce or inhibit microorganism infection and seed decay. In the present study, an efficient method for selecting for high-quality eelgrass seeds using different specific gravities of salt water was developed, and potential antibacterial agents (nano-silver and copper sulfate) for seed storage were assessed. The results showed that the highest proportion of intact seeds (72.91 ± 0.50%) was recorded at specific gravities greater than 1.20. Therefore, specific gravities greater than 1.20 can be used for selecting high-quality eelgrass seeds. During seed storage at 0 °C, the proportion of intact seeds after storage with nano-silver agent was over 90%, and also higher than 80% with copper sulfate agent, which was significantly higher than control treatments. The findings revealed a potential selection method for high-quality seeds and long-term seed storage conditions for Z. marina, which could facilitate conservation and habitat restoration.
Somatic and visceral effects of word valence, arousal and concreteness in a continuum lexical space
Authors: Vergallito Alessandra , Petilli Marco Alessandro , Cattaneo Luigi , Marelli Marco
Published: December 2019

Although affective and semantic word properties are known to independently influence our sensorimotor system, less is known about their interaction. We investigated this issue applying a data-driven mixed-effects regression approach, evaluating the impact of lexical-semantic properties on electrophysiological parameters, namely facial muscles activity (left corrugator supercilii, zygomaticus major, levator labii superioris) and heartbeat, during word processing. 500 Italian words were acoustically presented to 20 native-speakers, while electrophysiological signals were continuously recorded. Stimuli varied for affective properties, namely valence (the degree of word positivity), arousal (the amount of emotional activation brought by the word), and semantic ones, namely concreteness. Results showed that the three variables interacted in predicting both heartbeat and muscular activity. Specifically, valence influenced activation for lower levels of arousal. This pattern was further modulated by concreteness: the lower the word concreteness, the larger affective-variable impact. Taken together, our results provide evidence for bodily responses during word comprehension. Crucially, such responses were found not only for voluntary muscles, but also for the heartbeat, providing evidence to the idea of a common emotional motor system. The higher impact of affective properties for abstract words supports proposals suggesting that emotions play a central role in the grounding of abstract concepts.