bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic Evidence for a Hot Mantle Transition Zone Beneath the Indian Ocean Geoid Low
Authors: Rao B. Padma , Kumar M. Ravi , Saikia Dipankar
Published: June 2020

The Indian Ocean Geoid Low (IOGL) is the most prominent geoid anomaly (−106 m) on the globe, whose origin remains elusive. In the present study, we investigate the mantle transition zone (MTZ) structure beneath the region using P receiver functions (PRFs), to examine its role in the genesis of this feature. Results from 3‐D time to depth migration of PRFs reveal a thin MTZ primarily due to an elevation of the 660 km discontinuity. This is suggestive of anomalously hot temperatures in the mid mantle beneath the IOGL region, possibly sourced from the African Large Low Shear Velocity Province (LLSVP). The combined effect of the hot (low‐density) material in the MTZ proposed in this study and the (high‐density) cold slab graves atop the core‐mantle boundary inferred from previous studies can possibly explain this geoid low.
Modeling Earthquake‐Induced Spring Discharge and Temperature Changes in a Fault Zone Hydrothermal System
Authors: Yan Xin , Shi Zheming , Zhou Pengpeng , Zhang Hui , Wang Guangcai
Published: June 2020

Although different methods have been employed to study the earthquake‐induced changes in aquifer permeability (e.g., tidal/barometric pressure response and analytical models), identification of the mechanism is usually hindered by the limitation of application conditions or multiplicity of solutions. A numerical simulation that couples flow and heat transport is developed in the present study to explain the coseismic responses that followed two large earthquakes (Mw 7.0 Lijiang earthquake on 3 February 1996 and Mw 9.1 Sumatra earthquake on 26 December 2004) at Banglazhang #1 hot spring, China. The results show that decreased spring discharge and temperature are attributable to earthquake‐induced permeability decrease, which can be related to the blocking of narrow fracture apertures. Analysis of the model revealed that seismic waves may have caused heterogeneous changes in permeability within the fault zone hydrothermal system, which led to nonsynchronous changes in spring flow and temperature. Our study contributes to an enhanced understanding of the impact of the evolution of earthquake‐induced permeability in hydrothermal systems.
Present‐Day and Long‐Term Uplift Across the Western Transverse Ranges of Southern California
Authors: Johnson K. M. , Hammond W. C. , Burgette R. J. , Marshall S. T. , Sorlien C. C.
Published: June 2020

It has been known for decades that the present‐day shortening rates across the Western Transverse Ranges (WTR) in Southern California are rapid, reaching 10–15 mm/year near the heavily populated Los Angeles area. However, only recently have geodetic measurements of vertical motion in the WTR been sufficiently dense to resolve a tectonic vertical signal. In this study, we show that much of the geodetically derived vertical velocity field in the WTR can be attributed to the interseismic signal of strain accumulation on reverse faults. We invert geodetic and geologic data for slip rate and interseismic coupling on faults using a kinematic model consisting of faults embedded in an elastic crust over an inviscid mantle. This method allows us to infer the permanent, long‐term component of vertical motions from recoverable, short‐term motions. We infer that much of the geodetically observed 3–4 mm/year of differential vertical motion across the WTR, involving subsidence along the Santa Barbara coastline and uplift of the Santa Ynez Range, can be attributed to recoverable elastic deformation associated with interseismic locking on faults dipping under the WTR. The sum of dip‐slip rates across the WTR decreases from 10.5–14.6 mm/year on the east side near Ventura, California to 5–6.2 mm/year across the western side of the Santa Barbara Channel. The total moment accumulation rate in both the Santa Barbara Channel and the combined San Fernando Valley‐LA Basin regions is equivalent to about two Mw = 7 earthquakes every 100 years.
Optimization of the Match‐Filtering Method for Robust Repeating Earthquake Detection: The Multisegment Cross‐Correlation Approach
Authors: Gao Dawei , Kao Honn
Published: June 2020

Waveform match‐filtering (MF), based on cross‐correlation between an earthquake pair, is a powerful and widely used tool in seismology. However, its performance can be severely affected by several factors, including the length of the cross‐correlation window, the frequency band of the applied digital filter, and the presence of a large‐amplitude phase(s). To optimize the performance of MF, we first systematically examine the effects of different operational parameters and determine the generic rules for selecting the window length and the optimal frequency passband. To minimize the influence of a large‐amplitude phase(s), we then propose a new approach, namely, MF with multisegment cross‐correlation (MFMC). By equally incorporating the contributions from various segments of the waveforms, this new approach is much more sensitive to small separation between two sources compared to the conventional MF method using the entire waveform template. To compare the reliability and effectiveness of both methods in capturing interevent source separation and identifying repeating earthquakes, we systematically conduct experiments with both synthetic data and real observations. The results demonstrate that the conventional MF method can detect the existence of an event but sometimes lacks the resolution to tell whether the template and detected events are co‐located or not, whereas MFMC works in all cases. The far‐reaching implication from this study is that inferring source separation between an earthquake pair based on the conventional MF method, particularly with data from a single channel/station, may not be reliable.
Mixing State of Black Carbon Particles in Asian Outflow Observed at a Remote Site in Taiwan in the Spring of 2017
Authors: Sun Cuizhi , Adachi Kouji , Misawa Kentaro , Cheung Hing Cho , Chou Charles C.‐K. , Takegawa Nobuyuki
Published: June 2020

Anthropogenic emissions of aerosols and trace gases from East Asia have significant impacts on air quality and climate on regional and global scales. We conducted intensive measurements of aerosols at a remote site (Cape Fuguei; 25.30°N, 121.54°E) in Taiwan in the spring of 2017, focusing on the chemical composition and mixing state of aerosols in Asian outflow. A laser‐induced incandescence–mass spectrometric analyzer (LII‐MS) was used to measure the chemical composition of aerosols internally or externally mixed with black carbon (BC). Offline analysis by transmission electron microscopy (TEM) was used to characterize the mixing state of aerosols. The observation period was classified into long‐range transport (LRT) periods and local pollution periods on the basis of cluster analysis of 3‐day backward trajectories. LII‐MS data showed that the average mass fractions of sulfate and nitrate internally mixed with BC were 7% ± 13% and 11% ± 15%, respectively, for high‐pollution episodes during LRT periods. By TEM analysis of selected samples from LRT periods, the number fraction of aerosol particles internally mixed with BC was estimated to be 5%–36% for core–shell types and 5%–23% for attached types. Factors affecting the differences between LII‐MS and TEM measurements are discussed. TEM data indicated the presence of a variety of aerosol mixing states in widespread regional pollution transported 500–1,000 km downwind of emission sources. Our results provide new constraints for three‐dimensional models that might resolve the mixing state of aerosol particles, which are critical for accurately estimating the radiative impact of BC.
SUMOylation stabilizes hSSB1 and enhances the recruitment of NBS1 to DNA damage sites
Authors: Zhou Liwen , Zheng Lisi , Hu Kaishun , Wang Xin , Zhang Ruhua , Zou Yezi , Zhong Li , Wang Shang , Wu Yuanzhong , Kang Tiebang
Published: June 2020

Human single-stranded DNA-binding protein 1 (hSSB1) is required for the efficient recruitment of the MRN complex to DNA double-strand breaks and is essential for the maintenance of genome integrity. However, the mechanism by which hSSB1 recruits NBS1 remains elusive. Here, we determined that hSSB1 undergoes SUMOylation at both K79 and K94 under normal conditions and that this modification is dramatically enhanced in response to DNA damage. SUMOylation of hSSB1, which is specifically fine-tuned by PIAS2α, and SENP2, not only stabilizes the protein but also enhances the recruitment of NBS1 to DNA damage sites. Cells with defective hSSB1 SUMOylation are sensitive to ionizing radiation, and global inhibition of SUMOylation by either knocking out UBC9 or adding SUMOylation inhibitors significantly enhances the sensitivity of cancer cells to etoposide. Our findings reveal that SUMOylation, as a novel posttranslational modification of hSSB1, is critical for the functions of this protein, indicating that the use of SUMOylation inhibitors (e.g., 2-D08 and ML-792) may be a new strategy that would benefit cancer patients being treated with chemo- or radiotherapy.
Correction: Exploration of surgical blood pressure management and expected motor recovery in individuals with traumatic spinal cord injury
Authors: Ehsanian Reza , Haefeli Jenny , Quach Nhung , Kosarchuk Jacob , Torres Dolores , Stuck Ellen D. , Endo Jessica , Crew James D. , Dirlikov Benjamin , Bresnahan Jacqueline C. , Beattie Michael S. , Ferguson Adam R. , McKenna Stephen L.
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Symmetries and cluster synchronization in multilayer networks
Authors: Della Rossa Fabio , Pecora Louis , Blaha Karen , Shirin Afroza , Klickstein Isaac , Sorrentino Francesco
Published: June 2020

Real-world systems in epidemiology, social sciences, power transportation, economics and engineering are often described as multilayer networks. Here we first define and compute the symmetries of multilayer networks, and then study the emergence of cluster synchronization in these networks. We distinguish between independent layer symmetries, which occur in one layer and are independent of the other layers, and dependent layer symmetries, which involve nodes in different layers. We study stability of the cluster synchronous solution by decoupling the problem into a number of independent blocks and assessing stability of each block through a Master Stability Function. We see that blocks associated with dependent layer symmetries have a different structure to the other blocks, which affects the stability of clusters associated with these symmetries. Finally, we validate the theory in a fully analog experiment in which seven electronic oscillators of three kinds are connected with two kinds of coupling.
Climate change will affect global water availability through compounding changes in seasonal precipitation and evaporation
Authors: Konapala Goutam , Mishra Ashok K. , Wada Yoshihide , Mann Michael E.
Published: June 2020

Both seasonal and annual mean precipitation and evaporation influence patterns of water availability impacting society and ecosystems. Existing global climate studies rarely consider such patterns from non-parametric statistical standpoint. Here, we employ a non-parametric analysis framework to analyze seasonal hydroclimatic regimes by classifying global land regions into nine regimes using late 20th century precipitation means and seasonality. These regimes are used to assess implications for water availability due to concomitant changes in mean and seasonal precipitation and evaporation changes using CMIP5 model future climate projections. Out of 9 regimes, 4 show increased precipitation variation, while 5 show decreased evaporation variation coupled with increasing mean precipitation and evaporation. Increases in projected seasonal precipitation variation in already highly variable precipitation regimes gives rise to a pattern of “seasonally variable regimes becoming more variable”. Regimes with low seasonality in precipitation, instead, experience increased wet season precipitation.
Using arterial–venous analysis to characterize cancer metabolic consumption in patients
Authors: Xiong Nanxiang , Gao Xiaofei , Zhao Hongyang , Cai Feng , Zhang Fang-cheng , Yuan Ye , Liu Weichao , He Fangping , Zacharias Lauren G. , Lin Hong , Vu Hieu S. , Xing Chao , Yao Dong-Xiao , Chen Fei , Luo Benyan , Sun Wenzhi , DeBerardinis Ralph J. , Xu Hao , Ge Woo-ping
Published: June 2020

Understanding tumor metabolism holds the promise of new insights into cancer biology, diagnosis and treatment. To assess human cancer metabolism, here we report a method to collect intra-operative samples of blood from an artery directly upstream and a vein directly downstream of a brain tumor, as well as samples from dorsal pedal veins of the same patients. After performing targeted metabolomic analysis, we characterize the metabolites consumed and produced by gliomas in vivo by comparing the arterial supply and venous drainage. N-acetylornithine, D-glucose, putrescine, and L-acetylcarnitine are consumed in relatively large amounts by gliomas. Conversely, L-glutamine, agmatine, and uridine 5-monophosphate are produced in relatively large amounts by gliomas. Further we verify that D-2-hydroxyglutarate (D-2HG) is high in venous plasma from patients with isocitrate dehydrogenases1 (IDH1) mutations. Through these paired comparisons, we can exclude the interpatient variation that is present in plasma samples usually taken from the cubital vein.
TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis
Authors: Aguilar-Briseño José A. , Upasani Vinit , Ellen Bram M. ter , Moser Jill , Pauzuolis Mindaugas , Ruiz-Silva Mariana , Heng Sothy , Laurent Denis , Choeung Rithy , Dussart Philippe , Cantaert Tineke , Smit Jolanda M. , Rodenhuis-Zybert Izabela A.
Published: June 2020

Vascular permeability and plasma leakage are immune-pathologies of severe dengue virus (DENV) infection, but the mechanisms underlying the exacerbated inflammation during DENV pathogenesis are unclear. Here, we demonstrate that TLR2, together with its co-receptors CD14 and TLR6, is an innate sensor of DENV particles inducing inflammatory cytokine expression and impairing vascular integrity in vitro. Blocking TLR2 prior to DENV infection in vitro abrogates NF-κB activation while CD14 and TLR6 block has a moderate effect. Moreover, TLR2 block prior to DENV infection of peripheral blood mononuclear cells prevents activation of human vascular endothelium, suggesting a potential role of the TLR2-responses in vascular integrity. TLR2 expression on CD14 + + classical monocytes isolated in an acute phase from DENV-infected pediatric patients correlates with severe disease development. Altogether, these data identify a role for TLR2 in DENV infection and provide insights into the complex interaction between the virus and innate receptors that may underlie disease pathogenesis.
Ultra-large chemical libraries for the discovery of high-affinity peptide binders
Authors: Quartararo Anthony J. , Gates Zachary P. , Somsen Bente A. , Hartrampf Nina , Ye Xiyun , Shimada Arisa , Kajihara Yasuhiro , Ottmann Christian , Pentelute Bradley L.
Published: June 2020

High-diversity genetically-encoded combinatorial libraries (108−1013 members) are a rich source of peptide-based binding molecules, identified by affinity selection. Synthetic libraries can access broader chemical space, but typically examine only ~ 106 compounds by screening. Here we show that in-solution affinity selection can be interfaced with nano-liquid chromatography-tandem mass spectrometry peptide sequencing to identify binders from fully randomized synthetic libraries of 108 members—a 100-fold gain in diversity over standard practice. To validate this approach, we show that binders to a monoclonal antibody are identified in proportion to library diversity, as diversity is increased from 106–108. These results are then applied to the discovery of p53-like binders to MDM2, and to a family of 3–19 nM-affinity, α/β-peptide-based binders to 14-3-3. An X-ray structure of one of these binders in complex with 14-3-3σ is determined, illustrating the role of β-amino acids in facilitating a key binding contact.
The mutREAD method detects mutational signatures from low quantities of cancer DNA
Authors: Perner Juliane , Abbas Sujath , Nowicki-Osuch Karol , Devonshire Ginny , Eldridge Matthew D. , Tavaré Simon , Fitzgerald Rebecca C.
Published: June 2020

Mutational processes acting on cancer genomes can be traced by investigating mutational signatures. Because high sequencing costs limit current studies to small numbers of good-quality samples, we propose a robust, cost- and time-effective method, called mutREAD, to detect mutational signatures from small quantities of DNA, including degraded samples. We show that mutREAD recapitulates mutational signatures identified by whole genome sequencing, and will ultimately allow the study of mutational signatures in larger cohorts and, by compatibility with formalin-fixed paraffin-embedded samples, in clinical settings.
Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
Authors: Morris Elizabeth R. , Caswell Sarah J. , Kunzelmann Simone , Arnold Laurence H. , Purkiss Andrew G. , Kelly Geoff , Taylor Ian A.
Published: June 2020

SAMHD1 regulates cellular 2′-deoxynucleoside-5′-triphosphate (dNTP) homeostasis by catalysing the hydrolysis of dNTPs into 2′-deoxynucleosides and triphosphate. In CD4+ myeloid lineage and resting T-cells, SAMHD1 blocks HIV-1 and other viral infections by depletion of the dNTP pool to a level that cannot support replication. SAMHD1 mutations are associated with the autoimmune disease Aicardi–Goutières syndrome and hypermutated cancers. Furthermore, SAMHD1 sensitises cancer cells to nucleoside-analogue anti-cancer therapies and is linked with DNA repair and suppression of the interferon response to cytosolic nucleic acids. Nevertheless, despite its requirement in these processes, the fundamental mechanism of SAMHD1-catalysed dNTP hydrolysis remained unknown. Here, we present structural and enzymological data showing that SAMHD1 utilises an active site, bi-metallic iron-magnesium centre that positions a hydroxide nucleophile in-line with the Pα-O5′ bond to catalyse phosphoester bond hydrolysis. This precise molecular mechanism for SAMHD1 catalysis, reveals how SAMHD1 down-regulates cellular dNTP and modulates the efficacy of nucleoside-based anti-cancer and anti-viral therapies.
Klenkia terrae resistant to DNA extraction in germ-free mice stools illustrates the extraction pitfall faced by metagenomics
Authors: Andreani Julien , Million Matthieu , Baudoin Jean-Pierre , Ominami Yusuke , Khalil Jacques Yaacoub Bou , Frémond Cécile , Khelaifia Saber , Levasseur Anthony , Raoult Didier , La Scola Bernard
Published: June 2020

Over the past decade, metagenomics has become the preferred method for exploring complex microbiota such as human gut microbiota. However, several bias affecting the results of microbiota composition, such as those due to DNA extraction, have been reported. These bias have been confirmed with the development of culturomics technique. In the present study, we report the contamination of a gnotobiotic mice unit with a bacterium first detected by gram staining. Scanning electron microscopy and transmission electron microscopy permitted to detect a bacterium with a thick cell wall. However, in parallel, the first attempt to identify and culture this bacterium by gene amplification and metagenomics of universal 16S rRNA failed. Finally, the isolation in culture of a fastidious bacterium not detected by using universal PCR was successfully achieved by using a BCYE agar plate with CO2 atmosphere at 30 °C. We performed genome sequencing of this bacterium using a strong extraction procedure. The genomic comparison allowed us to classify this bacterium as Klenkia terrae. And finally, it was also detected in the stool and kibble that caused the contamination by using specific qPCR against this bacterium. The elucidation of this contamination provides additional evidence that DNA extraction could be a bias for the study of the microbiota. Currently, most studies that strive to analyze and compare the gut microbiota are based on metagenomics. In a gnotobiotic mice unit contaminated with the fastidious Actinobacteria Klenkia terrae, standard culture, 16S rRNA gene amplification and metagenomics failed to identify the micro-organism observed in stools by gram-staining. Only a procedure based on culturomics allowed us to identify this bacterium and to elucidate the mode of contamination of the gnotobiotic mice unit through diet.
Environmental Remediation of the difficult-to-return zone in Tomioka Town, Fukushima Prefecture
Authors: Cui Limeng , Taira Yasuyuki , Matsuo Masahiko , Orita Makiko , Yamada Yumiko , Takamura Noboru
Published: June 2020

Temporal variations in ambient dose rates in a restricted area designated as “difficult-to-return” for residents of Tomioka Town, Fukushima Prefecture were evaluated in a car-borne survey during 2018–2019. The median dose rates in the “Decontaminated area” in the difficult-to-return zone decreased rapidly from 1.0 μSv/h to 0.32 μSv/h; however, the median dose rates in the “Non-decontaminated area” and “Radioactive waste storage area” fluctuated between 1.1–1.4 μSv/h and 0.46–0.61 μSv/h, respectively. The detected rate of the cesium-137 (137Cs) (137Cs-detected points per all measuring points) in the “Decontaminated area” also decreased rapidly from 64% to 6.7%, accompany with decreasing in ambient dose rates. On the other hand, the detection of 137Cs in the “Radioactive waste storage area” and “Non-decontaminated area” decreased from 53% to 17% and 93% to 88%, respectively. We confirmed that the dose rates in the Decontaminated area dramatically decreased due to decontamination work aiming to help residents return home. Moreover, the estimated external exposure dose of workers during the present survey was 0.66 mSv/y in the Decontaminated area and 0.55 mSv/y in the Radioactive waste storage area, respectively. This case of Tomioka Town within the “difficult-to-return zone” may be the first reconstruction model for evaluating environmental contamination and radiation exposure dose rates due to artificial radionuclides derived from the nuclear disaster.
Symbiotic bacterial communities in rainforest fungus-farming ants: evidence for species and colony specificity
Authors: Ronque Mariane U. V. , Lyra Mariana L. , Migliorini Gustavo H. , Bacci Maurício , Oliveira Paulo S.
Published: June 2020

Animals may host diverse bacterial communities that can markedly affect their behavioral physiology, ecology, and vulnerability to disease. Fungus-farming ants represent a classical example of mutualism that depends on symbiotic microorganisms. Unraveling the bacterial communities associated with fungus-farming ants is essential to understand the role of these microorganisms in the ant-fungus symbiosis. The bacterial community structure of five species of fungus-farmers (non-leaf-cutters; genera Mycocepurus, Mycetarotes, Mycetophylax, and Sericomyrmex) from three different environments in the Brazilian Atlantic rainforest (lowland forest, restinga forest, and sand dunes) was characterized with amplicon-based Illumina sequencing of 16 S ribosomal RNA gene. Possible differences in bacterial communities between ants internal to the nest (on the fungus garden) and external foragers were also investigated. Our results on the richness and diversity of associated bacteria provide novel evidence that these communities are host- and colony-specific in fungus-farming ants. Indeed, the bacterial communities associated with external foragers differ among the five species, and among colonies of the same species. Furthermore, bacterial communities from internal ants vs. foragers do not differ or differ only slightly within each ant species. This study highlights the importance of describing ant-associated bacterial communities to better understand this host-bacterial interaction in the social environment of insect colonies and provides the foundation for future studies on the ecological and evolutionary processes that drive the success of fungus-farming ants.
Short-active photoperiod gestation induces psychiatry-relevant behavior in healthy mice but a resiliency to such effects are seen in mice with reduced dopamine transporter expression
Authors: Kwiatkowski Molly A. , Cope Zackary A. , Lavadia Maria L. , van de Cappelle Chuck J. A. , Dulcis Davide , Young Jared W.
Published: June 2020

A higher incidence of multiple psychiatric disorders occurs in people born in late winter/early spring. Reduced light exposure/activity level impacts adult rodent behavior and neural mechanisms, yet few studies have investigated such light exposure on gestating fetuses. A dysfunctional dopamine system is implicated in most psychiatric disorders, and genetic polymorphisms reducing expression of the dopamine transporter (DAT) are associated with some conditions. Furthermore, adult mice with reduced DAT expression (DAT-HT) were hypersensitive to short active (SA; 19:5 L:D) photoperiod exposure versus their wildtype (WT) littermates. Effects of SA photoperiod exposure during gestation in these mice have not been examined. We confirmed adult females exhibit a heightened corticosterone response when in SA photoperiod. We then tested DAT-HT mice and WT littermates in psychiatry-relevant behavioral tests after SA or normal active (NA; 12:12 L:D) photoperiod exposure during gestation and early life. SA-born WT mice exhibited sensorimotor gating deficits (males), increased reward preference, less immobility, open arm avoidance (females), less motivation to obtain a reward, and reversal learning deficits, vs. NA-born WT mice. DAT-HT mice were largely resilient to these effects, however. Future studies will determine the mechanism(s) by which SA photoperiod exposure influences brain development to predispose toward emergence of psychiatry-relevant behaviors.
Horizontal gene transfer and silver nanoparticles production in a new Marinomonas strain isolated from the Antarctic psychrophilic ciliate Euplotes focardii
Authors: John Maria Sindhura , Nagoth Joseph Amruthraj , Ramasamy Kesava Priyan , Ballarini Patrizia , Mozzicafreddo Matteo , Mancini Alessio , Telatin Andrea , Liò Pietro , Giuli Gabriele , Natalello Antonino , Miceli Cristina , Pucciarelli Sandra
Published: June 2020

We isolated a novel bacterial strain from a prokaryotic consortium associated to the psychrophilic marine ciliate Euplotes focardii, endemic of the Antarctic coastal seawater. The 16S rDNA sequencing and the phylogenetic analysis revealed the close evolutionary relationship to the Antarctic marine bacterium Marinomonas sp. BSw10506 and the sub antarctic Marinomonas polaris. We named this new strain Marinomonas sp. ef1. The optimal growth temperature in LB medium was 22 °C. Whole genome sequencing and analysis showed a reduced gene loss limited to regions encoding for transposases. Additionally, five genomic islands, e.g. DNA fragments that facilitate horizontal gene transfer phenomena, were identified. Two open reading frames predicted from the genomic islands coded for enzymes belonging to the Nitro-FMN-reductase superfamily. One of these, the putative NAD(P)H nitroreductase YfkO, has been reported to be involved in the bioreduction of silver (Ag) ions and the production of silver nanoparticles (AgNPs). After the Marinomonas sp. ef1 biomass incubation with 1 mM of AgNO3 at 22 °C, we obtained AgNPs within 24 h. The AgNPs were relatively small in size (50 nm) and had a strong antimicrobial activity against twelve common nosocomial pathogenic microorganisms including Staphylococcus aureus and two Candida strains. To our knowledge, this is the first report of AgNPs biosynthesis by a Marinomonas strain. This biosynthesis may play a dual role in detoxification from silver nitrate and protection from pathogens for the bacterium and potentially for the associated ciliate. Biosynthetic AgNPs also represent a promising alternative to conventional antibiotics against common pathogens.
Incidence and risk of sepsis following appendectomy: a nationwide population-based cohort study
Authors: Wu Meng-Che , Tsou Hsi-Kai , Lin Cheng-Li , Wei James Cheng-Chung
Published: June 2020

Appendectomy is a frequently performed surgical procedure; however, long-term consequences have not been fully explored. We used a nationwide population-based cohort to determine whether patients undergoing appendectomy are at an increased risk of sepsis. Overall, 252,688 patients undergoing appendectomy and 252,472 matched controls were identified from the National Health Insurance Research Database in Taiwan. A propensity score analysis was used for matching age, sex, index year and comorbidities at a ratio of 1:1. Multiple Cox regression and stratified analyses were used to estimate the adjusted hazard ratio (aHR) of developing sepsis. Patients undergoing appendectomy had a 1.29 times (aHR: 1.29; 95% confidence interval [CI], 1.26–1.33) higher risk of developing sepsis than those not undergoing. Patients aged 20–49 years had a 1.58-fold higher risk of sepsis in the appendectomy cohort (aHR; 95% CI, 1.50–1.68). Also, having undergone appendectomy, patients had a higher likelihood of sepsis, regardless of sex and with or without comorbidities. Patients with <1 year follow-up showed a 1.98-fold risk of sepsis in the appendectomy cohort. Patients with 1–4 and ≥5 years follow-up showed a 1.29 and 1.11-fold risk of sepsis, respectively. Future research is required to elucidate the possible immuno-pathological mechanisms of these associations.
The influence of hydrogen on plasticity in pure iron—theory and experiment
Authors: Gong Peng , Katzarov Ivaylo H. , Nutter John , Paxton Anthony T. , Rainforth W. Mark
Published: June 2020

Tensile stress relaxation is combined with transmission electron microscopy to reveal dramatic changes in dislocation structure and sub structure in pure α-Fe as a result of the effects of dissolved hydrogen. We find that hydrogen charged specimens after plastic deformation display a very characteristic pattern of trailing dipoles and prismatic loops which are absent in uncharged pure metal. We explain these observations by use of a new self consistent kinetic Monte Carlo model, which in fact was initially used to predict the now observed microstructure. The results of this combined theory and experimental study is to shed light on the fundamental mechanism of hydrogen enhanced localised plasticity.
Role of gene signatures combined with pathology in classification of oropharynx head and neck cancer
Authors: Dhawan Andrew , Scott Jacob , Sundaresan Purnima , Veness Michael , Porceddu Sandro , Hau Eric , Harris Adrian L. , Buffa Francesca M. , Gee Harriet E.
Published: June 2020

Treatment personalisation remains an unmet need in oropharynx cancer (OPC). We aimed to determine whether gene expression signatures improved upon clinico-pathological predictors of outcome in OPC. The clinico-pathological predictors, AJCC version 7 (AJCC 7), AJCC 8, and a clinical algorithm, were assessed in 4 public series of OPC (n = 235). Literature review identified 16 mRNA gene expression signatures of radiosensitivity, HPV status, tumour hypoxia, and microsatellite instability. We quality tested signatures using a novelsigQCmethodology, and added signatures to clinico-pathological variables as predictors of survival, in univariate and multivariate analyses. AJCC 7 Stage was not predictive of recurrence-free survival (RFS) or overall survival (OS). AJCC 8 significantly predicted RFS and OS. Gene signature quality was highly variable. Among HPV-positive cases, signatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant underlying inter-tumour biological heterogeneity, but did not show prognostic significance when adjusted for clinical covariates. Surprisingly, among HPV-negative cases, a gene signature for HPV status was predictive of survival, even after adjustment for clinical covariates. Across the whole series, several gene signatures representing HPV and microsatellite instability remained significant in multivariate analysis. However, quality control and independent validation remain to be performed to add prognostic information above recently improved clinico-pathological variables.
Quantifying Perfusion Properties with DCE-MRI Using a Dictionary Matching Approach
Authors: Ghodasara Satyam , Chen Yong , Pahwa Shivani , Griswold Mark A. , Seiberlich Nicole , Wright Katherine L. , Gulani Vikas
Published: June 2020

Perfusion properties can be estimated from pharmacokinetic models applied to DCE-MRI data using curve fitting algorithms; however, these suffer from drawbacks including the local minimum problem and substantial computational time. Here, a dictionary matching approach is proposed as an alternative. Curve fitting and dictionary matching were applied to simulated data using the dual-input single-compartment model with known perfusion property values and 5 in vivo DCE-MRI datasets. In simulation at SNR 60 dB, the dictionary estimate had a mean percent error of 0.4–1.0% for arterial fraction, 0.5–1.4% for distribution volume, and 0.0% for mean transit time. The curve fitting estimate had a mean percent error of 1.1–2.1% for arterial fraction, 0.5–1.3% for distribution volume, and 0.2–1.8% for mean transit time. In vivo, dictionary matching and curve fitting showed no statistically significant differences in any of the perfusion property measurements in any of the 10 ROIs between the methods. In vivo, the dictionary method performed over 140-fold faster than curve fitting, obtaining whole volume perfusion maps in just over 10 s. This study establishes the feasibility of using a dictionary matching approach as a new and faster way of estimating perfusion properties from pharmacokinetic models in DCE-MRI.
Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells
Authors: Allen Ashley , Vaninov Natalie , Li Matthew , Nguyen Sunny , Singh Maneet , Igo Peter , Tilles Arno W. , O’Rourke Brian , Miller Brian L. K. , Parekkadan Biju , Barcia Rita N.
Published: June 2020

Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to effectively maintain ideal MSC function as a single population while also being able to impart an immunoregulatory effect when cultured in tandem with an inflamed lymphocyte population. MSCs were seeded on the extraluminal side of hollow fibers within a bioreactor where they indirectly interact with immune cells flowing within the lumen of the fibers. MSCs showed a stable and predictable metabolite and secreted factor profile during several days of perfusion culture. Exposure of bioreactor-seeded MSCs to inflammatory stimuli reproducibly switched MSC secreted factor profiles and altered microvesicle composition. Furthermore, circulating, activated human peripheral blood mononuclear cells (PBMCs) were suppressed by MSC bioreactor culture confirmed by a durable change in their immunophenotype and function. This platform was useful to study a model of immobilized MSCs and circulating immune cells and showed that monocytes play an important role in MSC driven immunomodulation. This coculture technology can have broad implications for use in studying MSC-immune interactions under flow conditions as well as in the generation of ex vivo derived immune cellular therapeutics.
Transient effects of chemotherapy for testicular cancer on mouse behaviour
Authors: Borbélyová Veronika , Renczés Emese , Chovanec Michal , Mego Michal , Celec Peter
Published: June 2020

The treatment of testicular cancer includes unilateral orchiectomy and chemotherapy and is curative for most patients. However, observational studies revealed an association with depression, anxiety and cognitive impairment. It is unclear whether these side effects are caused by chemotherapy, hemicastration or the disease itself. The aim of our study was to analyse the behavioural effects of hemicastration and chemotherapy in adult male mice. The animals were randomly divided into four groups – control, chemotherapy, hemicastration and hemicastration with chemotherapy. After chemotherapy that included three cycles of bleomycin, etoposide, cisplatin mice underwent a battery of behavioural tests. To assess the long-term effects animals were tested also 3 months after the end of treatment. Chemotherapy led to lower locomotor- and exploratory activity, higher anxiety-like behaviour and worse spatial memory immediately after treatment. These behavioural effects were not present three months later. Hemicastration had no effect on most of the observed outcomes. In conclusion, adverse behavioural effects induced by chemotherapy in mice are transient and disappear later in life. Further studies are needed to elucidate the mechanisms responsible for the observed effects.
Auxins and Cytokinins Regulate Phytohormone Homeostasis and Thiol-Mediated Detoxification in the Green Alga Acutodesmus obliquus Exposed to Lead Stress
Authors: Piotrowska-Niczyporuk Alicja , Bajguz Andrzej , Kotowska Urszula , Zambrzycka-Szelewa Elżbieta , Sienkiewicz Aneta
Published: June 2020

Phytohormones, such as auxins and cytokinins, take part in the integration of growth control and stress response, but their role in algal adaptation to heavy metal remains to be elucidated. The current research indicated that lead (Pb), one of the most toxic metals in nature, causes severe depletion of endogenous cytokinins, auxins, and gibberellin and an increase in abscisic acid content in the green alga Acutodesmus obliquus. Exogenous auxins and cytokinins alleviate Pb toxicity through the regulation of the endogenous phytohormones’ levels. Exogenously applied auxins provoked the coordinated activation metal tolerance mechanisms leading to the increase in phytochelatin synthase activity and accumulation of phytochelatins and their precursors, which are essential for Pb sequestration. On the other hand, phytochelatin synthesis decreased in algal cells treated with cytokinins. Significant changes in the levels of low molecular weight metabolites, mainly involved in metal chelation and glutathione synthesis pathway under the influence of phytohormones in algal cells growing in the presence of Pb stress, were observed. This is the first report showing that auxins and cytokinins are important regulatory factors in algal adaptation strategies to heavy metal stress based on thiol-mediated compounds and the maintenance of phytohormone homeostasis.
SB772077B (SB77) Alleviated the Aqueous Outflow Resistance Mediated by Cyclic Mechanical Stress in Perfused Human Cadaveric Eyes
Authors: Ashwinbalaji Soundararajan , Haribalaganesh Ravinarayanan , Krishnadas Subbaiah , Muthukkaruppan Veerappan , Senthilkumari Srinivasan
Published: June 2020

The intraocular pressure lowering property of a new rho kinase inhibitor, SB772077B (SB77) has been previously demonstrated in perfused human cadaveric eyes. In this study, the efficacy of SB77 in alleviating the aqueous outflow resistance mediated by cyclic mechanical stress in perfused human cadaveric eyes was investigated. A human anterior segment perfusion culture model was used to investigate the effect of cyclic intraocular pressure (IOP) on aqueous outflow facility in presence or absence of SB77. The status of RhoA activation and the downstream effector molecule myosin-light chain phosphorylation (p-MLC) was investigated by Western blot. Cyclic mechanical stress resulted in decrease in aqueous outflow facility (–19.79 ± 4.93%; p = 0.019) in perfused human eyes and treatment with SB77 (50 µM) significantly enhanced outflow facility by 15% (p = 0.05). The increase in outflow facility by SB77 was confirmed with the inactivation of RhoA/ROCK signaling and decreased expression of extracellular matrix markers. SB77 effectively reduced the outflow resistance mediated by cyclic IOP and thus may be a potential clinical candidate for the management of glaucoma.
Clinical relevance of B7H3 expression in retinoblastoma
Authors: Ganesan Bhuvaneswari , Parameswaran Sowmya , Sharma Ashwani , Krishnakumar Subramanian
Published: June 2020

Retinoblastoma (RB) is the most common paediatric intraocular tumour. Currently, chemotherapy is widely used to reduce the chance of metastasis as well as for vision salvage. The limitations of chemotherapy for RB include chemoresistance and cytotoxicity. Recently, immunotherapy is considered for treating chemoresistant cancers. Although, several molecular targets are available for immunotherapy in different cancers, we were interested in B7H3, as it was differentially expressed between retinoblastoma and retina in our earlier proteomics study. Hence, in this study we validated the previous finding by Western blotting and immunohistochemistry on primary RB tumor samples. The results suggest significantly increased expression of B7H3 in RB tumor samples compared to retina by western blotting. Immunohistochemistry revealed spatial, inter and intratumoral heterogeneity in the primary RB tumor sections. Correlation of the B7H3 expression with clinical and histopathological data revealed significantly increased expression of B7H3 in poorly differentiated, non-neural invasive tumors and lower expression in neural invasion and severe anaplastic areas of the tumors. B7H3 expression did not significantly vary between low-risk and high-risk tumors. The study also revealed considerably reduced infiltration of T lymphocytes in RB. We conclude that B7H3 is prominently expressed in primary RB tumors and could be used for targeted therapy.
Human salivary Raman fingerprint as biomarker for the diagnosis of Amyotrophic Lateral Sclerosis
Authors: Carlomagno C. , Banfi P. I. , Gualerzi A. , Picciolini S. , Volpato E. , Meloni M. , Lax A. , Colombo E. , Ticozzi N. , Verde F. , Silani V. , Bedoni M.
Published: June 2020

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to progressive and irreversible muscle atrophy. The diagnosis of ALS is time-consuming and complex, with the clinical and neurophysiological evaluation accompanied by monitoring of progression and a long procedure for the discrimination of similar neurodegenerative diseases. The delayed diagnosis strongly slows the potential development of adequate therapies and the time frame for a prompt intervention. The discovery of new biomarkers could improve the disease diagnosis, as well as the therapeutic and rehabilitative effectiveness and monitoring of the pathological progression. In this work saliva collected from 19 patients with ALS, 10 affected by Parkinson’s disease, 10 affected by Alzheimer’s disease and 10 healthy subjects, was analysed using Raman spectroscopy, optimizing the parameters for detailed and reproducible spectra. The statistical multivariate analysis of the data revealed a significant difference between the groups, allowing the discrimination of the disease onset. Correlation of Raman data revealed a direct relationship with paraclinical scores, identifying multifactorial biochemical modifications related to the pathology. The proposed approach showed a promising accuracy in ALS onset discrimination, using a fast and sensitive procedure that can make more efficient the diagnostic procedure and the monitoring of therapeutic and rehabilitative processes in ALS.
TGFβ activity released from platelet-rich fibrin adsorbs to titanium surface and collagen membranes
Authors: Di Summa Francesca , Kargarpour Zahra , Nasirzade Jila , Stähli Alexandra , Mitulović Goran , Panić-Janković Tanja , Koller Veronika , Kaltenbach Cosima , Müller Heinz , Panahipour Layla , Gruber Reinhard , Strauss Franz-Josef
Published: June 2020

Platelet-rich fibrin (PRF) contains a broad spectrum of bioactive molecules that can trigger several cellular responses. However, these molecules along with their upstream responses remain mostly uninvestigated. By means of proteomics we revealed that PRF lysates contain more than 650 proteins, being TGF-β one of the few growth factors found. To uncover the major target genes regulated by PRF lysates, gingival fibroblasts were exposed to lysates obtained from PRF membranes followed by a whole genome array. We identified 51 genes strongly regulated by PRF including IL11, NOX4 and PRG4 which are characteristic TGF-β target genes. RT-PCR and immunoassay analysis confirmed the TGF-β receptor I kinase-dependent increased expression of IL11, NOX4 and PRG4. The PRF-derived TGF-β activity was verified by the translocation of Smad2/3 into the nucleus along with the increased phosphorylation of Smad3. Considering that PRF is clinically used in combination with dental implants and collagen membranes, we showed here that PRF-derived TGF-β activity adsorbs to titanium implants and collagen membranes indicated by the changes in gene expression and immunoassay analysis. Our study points towards TGF-β as major target of PRF and suggest that TGF-β activity released by PRF adsorbs to titanium surface and collagen membranes
Different distribution of malaria parasite in left and right extremities of vertebrate hosts translates into differences in parasite transmission
Authors: Pigeault Romain , Isaïa Julie , Yerbanga Rakiswendé S. , Dabiré Kounbobr R. , Ouédraogo Jean-Bosco , Cohuet Anna , Lefèvre Thierry , Christe Philippe
Published: June 2020

Malaria, a vector-borne disease caused byPlasmodium spp., remains a major global cause of mortality. Optimization of disease control strategies requires a thorough understanding of the processes underlying parasite transmission. While the number of transmissible stages (gametocytes) ofPlasmodiumin blood is frequently used as an indicator of host-to-mosquito transmission potential, this relationship is not always clear. Significant effort has been made in developing molecular tools that improve gametocyte density estimation and therefore prediction of mosquito infection rates. However a significant level of uncertainty around estimates remains. The weakness in the relationship between gametocyte burden, measured from a blood sample, and the mosquito infection rate could be explained by a non-homogeneous distribution of gametocytes in the bloodstream. The estimated gametocyte density would then only be a single snapshot that does not reflect the host infectivity. This aspect ofPlasmodiuminfection, however, remains largely neglected. In both humans and birds, we found here that the gametocyte densities differed depending on which side of the body the sample was taken, suggesting that gametocytes are not homogeneously distributed within the vertebrate host. We observed a fluctuating asymmetry, in other words, the extremity of the body with the highest density of parasites is not always the same from one individual to another. An estimation of gametocyte density from only one blood sample, as is commonly measured, could, therefore, over- or underestimated the infectivity of gametocyte carriers. This might have important consequences on the epidemiology of the disease since we show that this variation influences host-to-mosquito transmission. Vectors fed on the least infected body part had a lower parasite burden than those fed on the most infected part. The heterogeneous distribution of gametocytes in bloodstream should be considered to improve diagnosis and test new malaria control strategies.