bluuebunny/crossref_metadata_2025 huggingface dataset:
Source Parameters of Three Moderate Size Earthquakes in Weiyuan, China, and Their Relations to Shale Gas Hydraulic Fracturing
Authors: Sheng Minhan , Chu Risheng , Ni Sidao , Wang Yong , Jiang Liming , Yang Hongfeng
Published: October 2020

On 7 September 2019, an ML5.4 earthquake struck the Weiyuan area in southwestern China. This is the largest and most damaging event in the Weiyuan shale gas field. In the next 4 months, two earthquakes with ML4.3 and ML5.2 rattled the same area. In this study, we obtain source parameters of these earthquakes (e.g., centroid location, focal mechanism, and rupture directivity) to investigate whether they are induced by hydraulic fracturing of shale gas production. We first invert for high‐resolution centroid locations and focal mechanisms of two M ~ 3 earthquakes recorded by a temporary dense seismic array. We then adopt the M ~ 3 events as references to obtain reliable centroid locations and rupture directivity of those moderate‐size earthquakes. The results show that all earthquakes have centroid depths of no more than 3 km and are within 2 km to injection wells of shale gas production, which suggest that these earthquakes may be induced by local hydraulic fracturing. The ML5.2 earthquake has the same rupture directivity to NE as the ML5.4 event and is located in the zone of positive Coulomb stress change caused by the latter. However, the long time lapse of the ML5.2 earthquake and the existence of an injection well within 2 km suggest that it is more likely induced by hydraulic fracturing than triggered statically by the ML5.4 earthquake.
Frictional Strengthening Explored During Non‐Steady State Shearing: Implications for Fault Stability and Slip Event Recurrence Time
Authors: Ikari Matt J. , Carpenter Brett M. , Scuderi Marco M. , Collettini Cristiano , Kopf Achim J.
Published: October 2020

On natural faults that host repeating slip events, the inter‐event loading time is quite large compared to the slip event duration. Since most friction studies focus on steady‐state frictional behavior, the fault loading phase is not typically examined. Here, we employ a method specifically designed to evaluate fault strength evolution during active loading, under shear driving rates as low as 10−10 m/s, on natural fault gouge samples from the Waikukupa Thrust in southern New Zealand. These tests reveal that in the early stages of loading following a slip event, there is a period of increased stability, which fades with accumulated slip. In the framework of rate‐ and state‐dependent friction laws, this temporary stable phase exists as long as slip is less than the critical slip distance and the elapsed time is less than the value of the state variable at steady state. These observations indicate a minimum earthquake recurrence time, which depends on the field value of the critical slip distance and the background slip rate. We compare estimates of minimum earthquake recurrence times with the recurrence times of repeating large earthquakes on the Alpine Fault in southern New Zealand and repeating small‐magnitude earthquakes on the San Andreas Fault system in California. We find that the observed recurrence times are mostly longer than the predicted minimum values, and exceptions in the San Andreas system may be explained by elevated slip rates due to larger earthquakes in this region.
Ocean Access to Zachariæ Isstrøm Glacier, Northeast Greenland, Revealed by OMG Airborne Gravity
Authors: Yang Junjun , Luo Zhicai , Tu Liangcheng
Published: October 2020

Seafloor topography shapes the pathways of ocean currents transporting ocean heat and, thus, is a fundamental boundary condition for modeling ocean‐ice interactions. However, few ship bathymetric data are available on the inner continental shelf of northeast Greenland due to the year‐round presence of sea ice. We infer seafloor topography of this region from airborne gravity anomaly measured by National Aeronautics and Space Administration's Oceans Melting Greenland (OMG) mission through a nonlinear inversion method called simulated annealing and results in a model with 1.95–3.9 km resolution and 52 m accuracy. The model provides a view of the seafloor near Zachariæ Isstrøm and reveals previously unknown topographic features such as a 370–560 m deep trough that enables warm subsurface water to reach Jøkelbugten fjord into which Zachariæ Isstrøm drains. Present bathymetric models do not show deep enough troughs near Jøkelbugten fjord allowing the inflow of warm water.
Temporal and spatial dynamics in the apple flower microbiome in the presence of the phytopathogen Erwinia amylovora
Authors: Cui Zhouqi , Huntley Regan B , Zeng Quan , Steven Blaire
Published: October 2020

Plant microbiomes have important roles in plant health and productivity. However, despite flowers being directly linked to reproductive outcomes, little is known about the microbiomes of flowers and their potential interaction with pathogen infection. Here, we investigated the temporal spatial dynamics of the apple stigma microbiome when challenged with a phytopathogen Erwinia amylovora, the causal agent of fire blight disease. We profiled the microbiome from the stigmas of individual flowers, greatly increasing the resolution at which we can characterize shifts in the composition of the microbiome. Individual flowers harbored unique microbiomes at the operational taxonomic unit level. However, taxonomic analysis of community succession showed a population gradually dominated by bacteria within the families Enterobacteriaceae and Pseudomonadaceae. Flowers inoculated with E. amylovora established large populations of the phytopathogen, with pathogen-specific gene counts of >3.0 × 107 in 90% of the flowers. Yet, only 42% of inoculated flowers later developed fire blight symptoms. This reveals that pathogen abundance on the stigma is not sufficient to predict disease outcome. Our data demonstrate that apple flowers represent an excellent model in which to characterize how plant microbiomes establish, develop, and correlate with biological processes such as disease progression in an experimentally tractable plant organ.
Disruption of Firmicutes and Actinobacteria abundance in tomato rhizosphere causes the incidence of bacterial wilt disease
Authors: Lee Sang-Moo , Kong Hyun Gi , Song Geun Cheol , Ryu Choong-Min
Published: October 2020

Enrichment of protective microbiota in the rhizosphere facilitates disease suppression. However, how the disruption of protective rhizobacteria affects disease suppression is largely unknown. Here, we analyzed the rhizosphere microbial community of a healthy and diseased tomato plant grown <30-cm apart in a greenhouse at three different locations in South Korea. The abundance of Gram-positive Actinobacteria and Firmicutes phyla was lower in diseased rhizosphere soil (DRS) than in healthy rhizosphere soil (HRS) without changes in the causative Ralstonia solanacearum population. Artificial disruption of Gram-positive bacteria in HRS using 500-μg/mL vancomycin increased bacterial wilt occurrence in tomato. To identify HRS-specific and plant-protective Gram-positive bacteria species, Brevibacterium frigoritolerans HRS1, Bacillus niacini HRS2, Solibacillus silvestris HRS3, and Bacillus luciferensis HRS4 were selected from among 326 heat-stable culturable bacteria isolates. These four strains did not directly antagonize R. solanacearum but activated plant immunity. A synthetic community comprising these four strains displayed greater immune activation against R. solanacearum and extended plant protection by 4 more days in comparison with each individual strain. Overall, our results demonstrate for the first time that dysbiosis of the protective Gram-positive bacterial community in DRS promotes the incidence of disease.
Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma
Authors: Pamidimukkala Nidhi , Puts Gemma S. , Kathryn Leonard M. , Snyder Devin , Dabernat Sandrine , De Fabo Edward C. , Noonan Frances P. , Slominski Andrzej , Merlino Glenn , Kaetzel David M.
Published: October 2020

NME1 is a metastasis-suppressor gene (MSG), capable of suppressing metastatic activity in cell lines of melanoma, breast carcinoma and other cancer origins without affecting their growth in culture or as primary tumours. Herein, we selectively ablated the tandemly arranged Nme1 and Nme2 genes to assess their individual impacts on metastatic activity in a mouse model (HGF:p16−/−) of ultraviolet radiation (UVR)-induced melanoma. Metastatic activity was strongly enhanced in both genders of Nme1- and Nme2-null mice, with stronger activity in females across all genotypes. The study ascribes MSG activity to Nme2 for the first time in an in vivo model of spontaneous cancer, as well as a novel metastasis-suppressor function to Nme1 in the specific context of UVR-induced melanoma.
Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth
Authors: Chen Jing-Yi , Li Chien-Feng , Lai You-Syuan , Hung Wen-Chun
Published: October 2020

Background

Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear.

Methods

The expression of KDM2A in CAFs was studied using immunohistochemical staining and its association with clinicopathological features and patient’s survival was tested. Overexpression and knockdown strategies were used to investigate KDM2A-regulated genes in fibroblasts. Senescent cells were detected by using β-galactosidase staining. The in vivo tumour-promoting activity of stromal KDM2A was confirmed by animal study.

Results

Increase of stromal KDM2A is associated with advanced tumour stage and poor clinical outcome in breast cancer patients. Cancer-derived cytokines stimulated KDM2A expression in normal fibroblasts and transformed them into CAFs. Upregulation of KDM2A induced p53-dependent senescence in fibroblasts and enhanced the release of cytokines, which reciprocally promoted cancer cell proliferation. Additionally, KDM2A upregulated programmed death-ligand 1 (PD-L1) expression via transcriptional activation in fibroblasts. Knockdown of KDM2A completely abolished the tumour-promoting activity of CAFs on breast tumour growth in vivo and diminished PD-L1 expression in the stroma of tumour tissues.

Conclusions

Stromal KDM2A plays an oncogenic role in breast cancer and inhibition of KDM2A reduces fibroblast senescence and suppresses tumour growth.
LncRNA LL22NC03-N14H11.1 promoted hepatocellular carcinoma progression through activating MAPK pathway to induce mitochondrial fission
Authors: Yi Tingzhuang , Luo Hongcheng , Qin Fengxue , Jiang Qi , He Shougao , Wang Tonghua , Su Jianwei , Song Sien , Qin Xiaoshan , Qin Yueqiu , Zhou Xihan , Huang Zansong
Published: October 2020

Involvement of long non-coding RNAs (lncRNAs) in hepatocarcinogenesis has been largely documented. Mitochondrial dynamics is identified to impact survival and metastasis in tumors including hepatocellular carcinoma (HCC), but the underlying mechanism remains poorly understood. This study planned to explore the regulation of lncRNA LL22NC03-N14H11.1 on HCC progression and mitochondrial fission. Dysregulated lncRNAs in HCC are identified through circlncRNAnet and GEPIA bioinformatics tools. Biological function of LL22NC03-N14H11.1 in HCC was detected by CCK-8 assay, flow cytometry analysis, transwell invasion, and wound healing assays. Molecular interactions were determined by RNA immunoprecipitation, RNA pull-down, and co-immunoprecipitation assays. Results showed that LL22NC03-N14H11.1 was upregulated in HCC tissues and cells. Functionally, LL22NC03-N14H11.1 contributed to cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in HCC. Moreover, LL22NC03-N14H11.1 facilitated mitochondrial fission in HCC cells. Mechanistically, LL22NC03-N14H11.1 recruited Myb proto-oncogene (c-Myb) to repress the transcription of leucine zipper-like transcription regulator 1 (LZTR1), so as to inhibit LZTR1-mediated ubiquitination of H-RAS (G12V), leading to the activation of mitogen-activated protein kinase (MAPK) signaling and induction of p-DRP1 (Serine 616). In conclusion, this study firstly revealed that lncRNA LL22NC03-N14H11.1 promoted HCC progression through activating H-RAS/MAPK pathway to induce mitochondrial fission, indicating LL22NC03-N14H11.1 as a novel potential biomarker for HCC treatment.
A gene expression signature of TREM2hi macrophages and γδ T cells predicts immunotherapy response
Authors: Xiong Donghai , Wang Yian , You Ming
Published: October 2020

Identifying factors underlying resistance to immune checkpoint therapy (ICT) is still challenging. Most cancer patients do not respond to ICT and the availability of the predictive biomarkers is limited. Here, we re-analyze a publicly available single-cell RNA sequencing (scRNA-seq) dataset of melanoma samples of patients subjected to ICT and identify a subset of macrophages overexpressing TREM2 and a subset of gammadelta T cells that are both overrepresented in the non-responding tumors. In addition, the percentage of a B cell subset is significantly lower in the non-responders. The presence of these immune cell subtypes is corroborated in other publicly available scRNA-seq datasets. The analyses of bulk RNA-seq datasets of the melanoma samples identify and validate a signature - ImmuneCells.Sig - enriched with the genes characteristic of the above immune cell subsets to predict response to immunotherapy. ImmuneCells.Sig could represent a valuable tool for clinical decision making in patients receiving immunotherapy.
Origin and adaptation to high altitude of Tibetan semi-wild wheat
Authors: Guo Weilong , Xin Mingming , Wang Zihao , Yao Yingyin , Hu Zhaorong , Song Wanjun , Yu Kuohai , Chen Yongming , Wang Xiaobo , Guan Panfeng , Appels Rudi , Peng Huiru , Ni Zhongfu , Sun Qixin
Published: October 2020

Tibetan wheat is grown under environmental constraints at high-altitude conditions, but its underlying adaptation mechanism remains unknown. Here, we present a draft genome sequence of a Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum Shao) accession Zang1817 and re-sequence 245 wheat accessions, including world-wide wheat landraces, cultivars as well as Tibetan landraces. We demonstrate that high-altitude environments can trigger extensive reshaping of wheat genomes, and also uncover that Tibetan wheat accessions accumulate high-altitude adapted haplotypes of related genes in response to harsh environmental constraints. Moreover, we find that Tibetan semi-wild wheat is a feral form of Tibetan landrace, and identify two associated loci, including a 0.8-Mb deletion region containing Brt1/2 homologs and a genomic region with TaQ-5A gene, responsible for rachis brittleness during the de-domestication episode. Our study provides confident evidence to support the hypothesis that Tibetan semi-wild wheat is de-domesticated from local landraces, in response to high-altitude extremes.
Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
Authors: Pfisterer Ulrich , Petukhov Viktor , Demharter Samuel , Meichsner Johanna , Thompson Jonatan J. , Batiuk Mykhailo Y. , Asenjo-Martinez Andrea , Vasistha Navneet A. , Thakur Ashish , Mikkelsen Jens , Adorjan Istvan , Pinborg Lars H. , Pers Tune H. , von Engelhardt Jakob , Kharchenko Peter V. , Khodosevich Konstantin
Published: October 2020

Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.
In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition
Authors: Mitchel Jennifer A. , Das Amit , O’Sullivan Michael J. , Stancil Ian T. , DeCamp Stephen J. , Koehler Stephan , Ocaña Oscar H. , Butler James P. , Fredberg Jeffrey J. , Nieto M. Angela , Bi Dapeng , Park Jin-Ah
Published: October 2020

The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.
Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma
Authors: Chen Zhaohui , Zhou Lijie , Liu Lilong , Hou Yaxin , Xiong Ming , Yang Yu , Hu Junyi , Chen Ke
Published: October 2020

Although substantial progress has been made in cancer biology and treatment, clinical outcomes of bladder carcinoma (BC) patients are still not satisfactory. The tumor microenvironment (TME) is a potential target. Here, by single-cell RNA sequencing on 8 BC tumor samples and 3 para tumor samples, we identify 19 different cell types in the BC microenvironment, indicating high intra-tumoral heterogeneity. We find that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment. We also find that monocytes undergo M2 polarization in the tumor region and differentiate. Furthermore, the LAMP3 + DC subgroup may be able to recruit regulatory T cells, potentially taking part in the formation of an immunosuppressive TME. Through correlation analysis using public datasets containing over 3000 BC samples, we identify a role for inflammatory cancer-associated fibroblasts (iCAFs) in tumor progression, which is significantly related to poor prognosis. Additionally, we characterize a regulatory network depending on iCAFs. These results could help elucidate the protumor mechanisms of iCAFs. Our results provide deep insight into cancer immunology and provide an essential resource for drug discovery in the future.
Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein
Authors: McAuley Alexander J. , Kuiper Michael J. , Durr Peter A. , Bruce Matthew P. , Barr Jennifer , Todd Shawn , Au Gough G. , Blasdell Kim , Tachedjian Mary , Lowther Sue , Marsh Glenn A. , Edwards Sarah , Poole Timothy , Layton Rachel , Riddell Sarah-Jane , Drew Trevor W. , Druce Julian D. , Smith Trevor R. F. , Broderick Kate E. , Vasan S. S.
Published: October 2020

The ‘D614G’ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.
A cross-country database of COVID-19 testing
Authors: Hasell Joe , Mathieu Edouard , Beltekian Diana , Macdonald Bobbie , Giattino Charlie , Ortiz-Ospina Esteban , Roser Max , Ritchie Hannah
Published: October 2020

Our understanding of the evolution of the COVID-19 pandemic is built upon data concerning confirmed cases and deaths. This data, however, can only be meaningfully interpreted alongside an accurate understanding of the extent of virus testing in different countries. This new database brings together official data on the extent of PCR testing over time for 94 countries. We provide a time series for the daily number of tests performed, or people tested, together with metadata describing data quality and comparability issues needed for the interpretation of the time series. The database is updated regularly through a combination of automated scraping and manual collection and verification, and is entirely replicable, with sources provided for each observation. In providing accessible cross-country data on testing output, it aims to facilitate the incorporation of this crucial information into epidemiological studies, as well as track a key component of countries’ responses to COVID-19.
Addressing the “minimum parking” problem for on-demand mobility
Authors: Kondor Dániel , Santi Paolo , Le Diem-Trinh , Zhang Xiaohu , Millard-Ball Adam , Ratti Carlo
Published: October 2020

Parking infrastructure is pervasive and occupies large swaths of land in cities. However, on-demand (OD) mobility has started reducing parking needs in urban areas around the world. This trend is expected to grow significantly with the advent of autonomous driving, which might render on-demand mobility predominant. Recent studies have started looking at expected parking reductions with on-demand mobility, but a systematic framework is still lacking. In this paper, we apply a data-driven methodology based on shareability networks to address what we call the “minimum parking” problem: what is the minimum parking infrastructure needed in a city for given on-demand mobility needs? While solving the problem, we also identify a critical tradeoff between two public policy goals: less parking means increased vehicle travel from deadheading between trips. By applying our methodology to the city of Singapore we discover that parking infrastructure reduction of up to 86% is possible, but at the expense of a 24% increase in traffic measured as vehicle kilometers travelled (VKT). However, a more modest 57% reduction in parking is achievable with only a 1.3% increase in VKT. We find that the tradeoff between parking and traffic obeys an inverse exponential law which is invariant with the size of the vehicle fleet. Finally, we analyze parking requirements due to passenger pick-ups and show that increasing convenience produces a substantial increase in parking for passenger pickup/dropoff. The above findings can inform policy-makers, mobility operators, and society at large on the tradeoffs required in the transition towards pervasive on-demand mobility.
Human spatial memory implicitly prioritizes high-calorie foods
Authors: de Vries Rachelle , Morquecho-Campos Paulina , de Vet Emely , de Rijk Marielle , Postma Elbrich , de Graaf Kees , Engel Bas , Boesveldt Sanne
Published: October 2020

All species face the important adaptive problem of efficiently locating high-quality nutritional resources. We explored whether human spatial cognition is enhanced for high-calorie foods, in a large multisensory experiment that covertly tested the location memory of people who navigated a maze-like food setting. We found that individuals incidentally learned and more accurately recalled locations of high-calorie foods – regardless of explicit hedonic valuations or personal familiarity with foods. In addition, the high-calorie bias in human spatial memory already became evident within a limited sensory environment, where solely odor information was available. These results suggest that human minds continue to house a cognitive system optimized for energy-efficient foraging within erratic food habitats of the past, and highlight the often underestimated capabilities of the human olfactory sense.
In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
Authors: Fernandes-Cunha Gabriella Maria , Chen Karen Mei , Chen Fang , Le Peter , Han Ju Hee , Mahajan Leela Ann , Lee Hyun Jong , Na Kyung Sun , Myung David
Published: October 2020

Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy.
Publisher Correction: Gene knockdown via electroporation of short hairpin RNAs in embryos of the marine hydroid Hydractinia symbiolongicarpus
Authors: Quiroga-Artigas Gonzalo , Duscher Alexandrea , Lundquist Katelyn , Waletich Justin , Schnitzler Christine E.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
K-PAM: a unified platform to distinguish Klebsiella species K- and O-antigen types, model antigen structures and identify hypervirulent strains
Authors: Patro L. Ponoop Prasad , Sudhakar Karpagam Uma , Rathinavelan Thenmalarchelvi
Published: October 2020

A computational method has been developed to distinguish theKlebsiellaspecies serotypes to aid in outbreak surveillance. A reliability score (estimated based on the accuracy of a specific K-type prediction against the dataset of 141 distinct K-types) average (ARS) that reflects the specificity between theKlebsiellaspecies capsular polysaccharide biosynthesis and surface expression proteins, and their K-types has been established. ARS indicates the following order of potency in accurate serotyping: Wzx (ARS = 98.5%),Wzy (ARS = 97.5%),WbaP (ARS = 97.2%),Wzc (ARS = 96.4%),Wzb (ARS = 94.3%),WcaJ (ARS = 93.8%),Wza (ARS = 79.9%) and Wzi (ARS = 37.1%). Thus, Wzx, Wzy and WbaP can give more reliable K-typing compared with other proteins. A fragment-based approach has further increased the Wzi ARS from 37.1% to 80.8%. The efficacy of these 8 proteins in accurate K-typing has been confirmed by a rigorous testing and the method has been automated as K-PAM (www.iith.ac.in/K-PAM/). Testing also indicates that the use of multiple genes/proteins helps in reducing the K-type multiplicity, distinguishing the K-types that have identical K-locus (like KN3 and K35) and identifying the ancestral serotypes ofKlebsiellaspp. K-PAM has the facilities to O-type using Wzm (ARS = 85.7%) and Wzt (ARS = 85.7%) and identifies the hypervirulentKlebsiellaspecies by the use ofrmpA, rmpA2,iucA,iroBandpeg-344marker genes. Yet another highlight of the server is the repository of the modeled 11 O- and 79 K- antigen 3D structures.
Establishment of a fluorescence staining method for Schistosoma japonicum miracidia
Authors: Shen Yuanxi , Ji Rongyi , Yang Man , Lin Jiaojiao , Wang Hairong , Zhu Chuangang , Xu Qinkun
Published: October 2020

Currently the diagnosis of schistosomiasis is mainly determined by observing the presence of eggs in host stool samples. Because of the overwhelming number of impurities in the stool, eggs are rarely observed. Therefore, the stool hatching method is used to observe the miracidia in the water. However, the miracidia ofSchistosoma japonicumare small and difficult to detect, and missed detection is likely to occur when the infection level is low. In this study, recombinant streptococcal protein G-enhanced green fluorescent protein (rSPG-EGFP) was expressed, purified, and used as a fluorescence staining reagent for miracidia. A preliminary miracidium fluorescence staining method based on antigen and antibody bindingwas established by combining recombinant protein staining with the stool hatching method. The stool hatching method was used to collect the miracidia ofS. japonicum, andSchistosoma-positive serum and the recombinant protein were mixed to assess the feasibility of fluorescence staining of miracidia. The miracidia ofS. japonicumandSchistosoma turkestanicumwere incubated withS. japonicum-positive serum andS. turkestanicum-positive serum, respectively, to identify miracidia species. When the fluorescence staining method was used to observe living miracidia, the miracidiawere labelled by the recombinant protein, and their motility status was not affected.
Divalent heavy metals and uranyl cations incorporated in calcite change its dissolution process
Authors: Zhang Xiaohang , Guo Jianan , Wu Shijun , Chen Fanrong , Yang Yongqiang
Published: October 2020

Due to the high capacity of impurities in its structure, calcite is regarded as one of the most attractive minerals to trap heavy metals (HMs) and radionuclides via substitution during coprecipitation/crystal growth. As a high-reactivity mineral, calcite may release HMs via dissolution. However, the influence of the incorporated HMs and radionuclides in calcite on its dissolution is unclear. Herein, we reported the dissolution behavior of the synthesized calcite incorporated with cadmium (Cd), cobalt (Co), nickel (Ni), zinc (Zn), and uranium (U). Our findings indicated that the HMs and U in calcite could significantly change the dissolution process of calcite. The results demonstrated that the incorporated HMs and U had both inhibiting and enhancing effects on the solubility of calcite, depending on the type of metals and their content. Furthermore, secondary minerals such as smithsonite (ZnCO3), Co-poor aragonite, and U-rich calcite precipitated during dissolution. Thus, the incorporation of metals into calcite can control the behavior of HMs/uranium, calcite, and even carbon dioxide.
Detection of tuberculosis in cynomolgus macaques (Macaca fascicularis) using a supplementary Monkey Interferon Gamma Releasing Assay (mIGRA)
Authors: Warit S. , Billamas P. , Makhao N. , Jaitrong S. , Juthayothin T. , Yindeeyoungyeon W. , Dokladda K. , Smittipat N. , Kemthong T. , Meesawat S. , Kongsombat N. , Kraitat C. , Prammananan T. , Palaga T. , Chaiprasert A. , Malaivijitnond S.
Published: October 2020

Cynomolgus monkeys (Macaca fascicularis; MF) are commonly used as nonhuman primate models for pharmaceutical product testing. In their habitat range, monkeys have close contact with humans, allowing the possibility of bidirectional transmission of tuberculosis (TB) between the two species. Although the intradermal tuberculin skin test (TST) is used for TB detection in MF, it has limitations. Herein, we established the mIGRA, combining human QuantiFERON-TB Gold-Plus and monkey IFN-γ ELISApro systems, and used it to investigate 39 captive MF who were cage-mates or lived in cages located near a monkey who died from the naturally TB infection. During a 12-month period of study, 14 (36%), 10 (26%), and 8 (21%) monkeys showed TB-positive results using the mIGRA, the TST, and TB culture, respectively. Among the 14 mIGRA-positive monkeys, 8 (57.1%) were TST-positive and 7 (50%) were culture-positive, indicating early TB detection in the latent and active TB stages with the mIGRA. Interestingly, 3 (37.5%) of the TST-negative monkeys were culture-positive. Our study showed that the mIGRA offers many advantages, including high sensitivity and high throughput, and it requires only one on-site visit to the animals. The assay may be used as a supplementary tool for TB screening in MF.
Synaptic transistors with aluminum oxide dielectrics enabling full audio frequency range signal processing
Authors: Bolat Sami , Torres Sevilla Galo , Mancinelli Alessio , Gilshtein Evgeniia , Sastre Jordi , Cabas Vidani Antonio , Bachmann Dominik , Shorubalko Ivan , Briand Danick , Tiwari Ayodhya N. , Romanyuk Yaroslav E.
Published: October 2020

The rapid evolution of the neuromorphic computing stimulates the search for novel brain-inspired electronic devices. Synaptic transistors are three-terminal devices that can mimic the chemical synapses while consuming low power, whereby an insulating dielectric layer physically separates output and input signals from each other. Appropriate choice of the dielectric is crucial in achieving a wide range of operation frequencies in these devices. Here we report synaptic transistors with printed aluminum oxide dielectrics, improving the operation frequency of solution-processed synaptic transistors by almost two orders of magnitude to 50 kHz. Fabricated devices, yielding synaptic response for all audio frequencies (20 Hz to 20 kHz), are employed in an acoustic response system to show the potential for future research in neuro-acoustic signal processing with printed oxide electronics.
Cerebello-thalamo-cortical network is intrinsically altered in essential tremor: evidence from a resting state functional MRI study
Authors: Nicoletti Valentina , Cecchi Paolo , Pesaresi Ilaria , Frosini Daniela , Cosottini Mirco , Ceravolo Roberto
Published: October 2020

Cerebello-thalamo-cortical network is suggested to be involved in the pathophysiology of Essential Tremor (ET). 23 patients with ET and 23 matched HC underwent a 3T-MRI with acquisition of a resting state sequence. Connectivity was investigated using a seed-based regression analyses approach. In ET patients were observed:

Reduced connectivity between left primary motor cortex (M1) seed and right premotor cortex and cerebellum and bilateral premotor, parietal areas, supplementary motor area (SMA);

Increased connectivity between left somatosensory cortex (S1) seed and parietal areas, M1, premotor cortex, SMA; reduced connectivity of this seed with cerebellum.

Increased connectivity of SMA seed with premotor cortex and decreased with parietal and precentral areas;

Increased connectivity between left thalamus seed and cerebellum;

Reduced connectivity between right cerebellum seeds and other cerebellar areas, precentral and premotor areas.

ET showed altered connectivity within the cortical sensory-motor network and between cerebral cortex and cerebellum. The increased connectivity between cerebellum and thalamus is consistent with their crucial role in tremor generation. These findings support the dynamical entrainment of multiple central oscillators throughout the cerebello-thalamo-cortical network in ET. This evidence is strengthened by the finding that this network is altered also when the core symptom is absent.
Unlocking the mystery of the mid-Cretaceous Mysteriomorphidae (Coleoptera: Elateroidea) and modalities in transiting from gymnosperms to angiosperms
Authors: Peris David , Kundrata Robin , Delclòs Xavier , Mähler Bastian , Ivie Michael A. , Rust Jes , Labandeira Conrad C.
Published: October 2020

The monospecific family Mysteriomorphidae was recently described based on two fossil specimens from the Late Cretaceous Kachin amber of northern Myanmar. The family was placed in Elateriformia incertae sedis without a clear list of characters that define it either in Elateroidea or in Byrrhoidea. We report here four additional adult specimens of the same lineage, one of which was described using a successful reconstruction from a CT-scan analysis to better observe some characters. The new specimens enabled us to considerably improve the diagnosis of Mysteriomorphidae. The family is definitively placed in Elateroidea, and we hypothesize its close relationship with Elateridae. Similarly, there are other fossil families of beetles that are exclusively described from Cretaceous ambers. These lineages may have been evolutionarily replaced by the ecological revolution launched by angiosperms that introduced new co-associations with taxa. These data indicate a macroevolutionary pattern of replacement that could be extended to other insect groups.
Analysis of factors affecting reversal of Hartmann’s procedure and post-reversal complications
Authors: Kang Jae Hyun , Kang Byung Mo , Yoon Sang Nam , Kim Jeong Yeon , Park Jun Ho , Oh Bo Young , Kim Jong Wan
Published: October 2020

Although Hartmann’s procedure (HP) is commonly used as emergency treatment for colorectal disease, the reversal of HP (HR) is infrequently performed. The aims were to evaluate the rate of HR and determine the factors predictive of achieving HR. We retrospectively reviewed the medical records of patients who underwent HP between January 2007 and June 2019 at six Hallym University-affiliated hospitals. Multivariable analysis was performed to identify which factors were independently associated with HR. In the study period, 437 patients underwent HP, and 127 (29.0%) subsequently underwent HR. Of these, 46 (35.9%) patients experienced post-HR complications. In multivariable analysis, an interval between HP and HR of > 6 months was associated with the only lower rate of post-HR complications. Multivariate analysis showed that HR was less likely in patients aged > 70 years, those with American Society of Anesthesiologists (ASA) class III or IV, elective surgery, those experiencing more than two HP-related complications, and those with a malignancy (an indication for HP). One-third of the patients underwent HR. Age > 70 years, ASA class III or IV, elective surgery, more than two HP-related complications, and malignancy were associated with a non-HR rate.
Origin of the biphase nature and surface roughness of biogenic calcite secreted by the giant barnacle Austromegabalanus psittacus
Authors: Checa Antonio G. , Macías-Sánchez Elena , Rodríguez-Navarro Alejandro B. , Sánchez-Navas Antonio , Lagos Nelson A.
Published: October 2020

The calcite grains forming the wall plates of the giant barnacle Austramegabalanus psittacus have a distinctive surface roughness made of variously sized crystalline nanoprotrusions covered by extremely thin amorphous pellicles. This biphase (crystalline-amorphous) structure also penetrates through the crystal’s interiors, forming a web-like structure. Nanoprotrusions very frequently elongate following directions related to the crystallographic structure of calcite, in particular, the <− 441> directions, which are the strongest periodic bond chains (PBCs) in calcite. We propose that the formation of elongated nanoprotrusions happens during the crystallization of calcite from a precursor amorphous calcium carbonate (ACC). This is because biomolecules integrated within the ACC are expelled from such PBCs due to the force of crystallization, with the consequent formation of uninterrupted crystalline nanorods. Expelled biomolecules accumulate in adjacent regions, thereby stabilizing small pellicle-like volumes of ACC. With growth, such pellicles become occluded within the crystal. In summary, the surface roughness of the biomineral surface reflects the complex shape of the crystallization front, and the biphase structure provides evidence for crystallization from an amorphous precursor. The surface roughness is generally explained as resulting from the attachment of ACC particles to the crystal surface, which later crystallised in concordance with the crystal lattice. If this was the case, the nanoprotrusions do not reflect the size and shape of any precursor particle. Accordingly, the particle attachment model for biomineral formation should seek new evidence.
Kynurenic acid is a potential overlapped biomarker between diagnosis and treatment response for depression from metabolome analysis
Authors: Erabi Hisayuki , Okada Go , Shibasaki Chiyo , Setoyama Daiki , Kang Dongchon , Takamura Masahiro , Yoshino Atsuo , Fuchikami Manabu , Kurata Akiko , Kato Takahiro A. , Yamawaki Shigeto , Okamoto Yasumasa
Published: October 2020

Since optimal treatment at an early stage leads to remission of symptoms and recovery of function, putative biomarkers leading to early diagnosis and prediction of therapeutic responses are desired. The current study aimed to use a metabolomic approach to extract metabolites involved in both the diagnosis of major depressive disorder (MDD) and the prediction of therapeutic response for escitalopram. We compared plasma metabolites of MDD patients (n = 88) with those in healthy participants (n = 88) and found significant differences in the concentrations of 20 metabolites. We measured the Hamilton Rating Scale for Depression (HRSD) on 62 patients who completed approximately six-week treatment with escitalopram before and after treatment and found that kynurenic acid and kynurenine were significantly and negatively associated with HRSD reduction. Only one metabolite, kynurenic acid, was detected among 73 metabolites for overlapped biomarkers. Kynurenic acid was lower in MDD, and lower levels showed a better therapeutic response to escitalopram. Kynurenic acid is a metabolite in the kynurenine pathway that has been widely accepted as being a major mechanism in MDD. Overlapping biomarkers that facilitate diagnosis and prediction of the treatment response may help to improve disease classification and reduce the exposure of patients to less effective treatments in MDD.
Adaptation to pitch-altered feedback is independent of one’s own voice pitch sensitivity
Authors: Alemi Razieh , Lehmann Alexandre , Deroche Mickael L. D.
Published: October 2020

Monitoring voice pitch is a fine-tuned process in daily conversations as conveying accurately the linguistic and affective cues in a given utterance depends on the precise control of phonation and intonation. This monitoring is thought to depend on whether the error is treated as self-generated or externally-generated, resulting in either a correction or inflation of errors. The present study reports on two separate paradigms of adaptation to altered feedback to explore whether participants could behave in a more cohesive manner once the error is of comparable size perceptually. The vocal behavior of normal-hearing and fluent speakers was recorded in response to a personalized size of pitch shift versus a non-specific size, one semitone. The personalized size of shift was determined based on the just-noticeable difference in fundamental frequency (F0) of each participant’s voice. Here we show that both tasks successfully demonstrated opposing responses to a constant and predictable F0 perturbation (on from the production onset) but these effects barely carried over once the feedback was back to normal, depicting a pattern that bears some resemblance to compensatory responses. Experiencing a F0 shift that is perceived as self-generated (because it was precisely just-noticeable) is not enough to force speakers to behave more consistently and more homogeneously in an opposing manner. On the contrary, our results suggest that the type of the response as well as the magnitude of the response do not depend in any trivial way on the sensitivity of participants to their own voice pitch. Based on this finding, we speculate that error correction could possibly occur even with a bionic ear, typically even when F0 cues are too subtle for cochlear implant users to detect accurately.
Improved cis-Abienol production through increasing precursor supply in Escherichia coli
Authors: Cheng Tao , Zhao Guang , Xian Mo , Xie Congxia
Published: October 2020

cis-Abienol, a natural diterpene-diol isolated from balsam fir (Abies balsamea), can be employed as precursors for the semi-synthesis of amber compounds, which are sustainable replacement for ambergris and widely used in the fragmented industry. This study combinatorially co-expressed geranyl diphosphate synthase, geranylgeranyl diphosphate synthase, Labda-13-en-8-ol diphosphate synthase and diterpene synthase, with the best combination achieving ~ 0.3 mg/L of cis-abienol. An additional enhancement of cis-abienol production (up to 8.6 mg/L) was achieved by introducing an exogenous mevalonate pathway which was divided into the upper pathway containing acetyl-CoA acetyltransferase/HMG-CoA reductase and HMG-CoA synthase and the lower pathway containing mevalonate kinase, phosphomevalonate kinase, pyrophosphate mevalonate decarboxylase and isopentenyl pyrophosphate isomerase. The genetically modified strain carrying chromosomal copy of low genes of the mevalonate with the trc promoter accumulated cis-abienol up to 9.2 mg/L in shake flask. Finally, cis-abienol titers of ~ 220 mg/L could be achieved directly from glucose using this de novo cis-abienol-producing E. coli in high-cell-density fermentation. This study demonstrates a microbial process to apply the E. coli cell factory in the biosynthesis of cis-abienol.