bluuebunny/crossref_metadata_2025 huggingface dataset:
Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity
Authors: Urciuoli Enrica , D’Oria Valentina , Petrini Stefania , Peruzzi Barbara
Published: September 2021

Besides its structural properties in the nucleoskeleton, Lamin A/C is a mechanosensor protein involved in perceiving the elasticity of the extracellular matrix. In this study we provide evidence about Lamin A/C-mediated regulation of osteosarcoma cell adhesion and spreading on substrates with tissue-specific elasticities. Our working hypothesis is based on the observation that low-aggressive and bone-resident SaOS-2 osteosarcoma cells express high level of Lamin A/C in comparison to highly metastatic, preferentially to the lung, osteosarcoma 143B cells, thereby suggesting a role for Lamin A/C in tumor cell tropism. Specifically, LMNA gene over-expression in 143B cells induced a reduction in tumor cell aggressiveness in comparison to parental cells, with decreased proliferation rate and reduced migration capability. Furthermore, LMNA reintegration into 143B cells changed the adhesion properties of tumor cells, from a preferential tropism toward the 1.5 kPa PDMS substrate (resembling normal lung parenchyma) to the 28 kPa (resembling pre-mineralized bone osteoid matrix). Our study suggests that Lamin A/C expression could be involved in the organ tropism of tumor cells, thereby providing a rationale for further studies focused on the definition of cancer mechanism of metastatization.
Lipid Droplet-Organelle Contact Sites as Hubs for Fatty Acid Metabolism, Trafficking, and Metabolic Channeling
Authors: Renne Mike F. , Hariri Hanaa
Published: September 2021

Cells prepare for fluctuations in nutrient availability by storing energy in the form of neutral lipids in organelles called Lipid Droplets (LDs). Upon starvation, fatty acids (FAs) released from LDs are trafficked to different cellular compartments to be utilized for membrane biogenesis or as a source of energy. Despite the biochemical pathways being known in detail, the spatio-temporal regulation of FA synthesis, storage, release, and breakdown is not completely understood. Recent studies suggest that FA trafficking and metabolism are facilitated by inter-organelle contact sites that form between LDs and other cellular compartments such as the Endoplasmic Reticulum (ER), mitochondria, peroxisomes, and lysosomes. LD-LD contact sites are also sites where FAs are transferred in a directional manner to support LD growth and expansion. As the storage site of neutral lipids, LDs play a central role in FA homeostasis. In this mini review, we highlight the role of LD contact sites with other organelles in FA trafficking, channeling, and metabolism and discuss the implications for these pathways on cellular lipid and energy homeostasis.
Membrane-Based Processes to Obtain High-Quality Water From Brewery Wastewater
Authors: Toran Marc Sauchelli , Labrador Patricia Fernández , Ciriza Juan Francisco , Asensio Yeray , Reigersman André , Arevalo Juan , Rogalla Frank , Monsalvo Victor M.
Published: September 2021

Water reuse is a safe and often the least energy-intensive method of providing water from non-conventional sources in water stressed regions. Although public perception can be a challenge, water reuse is gaining acceptance. Recent advances in membrane technology allow for reclamation of wastewater through the production of high-quality treated water, including potable reuse. This study takes an in-depth evaluation of a combination of membrane-based tertiary processes for its application in reuse of brewery wastewater, and is one of the few studies that evaluates long-term membrane performance at the pilot-scale. Two different advanced tertiary treatment trains were tested with secondary wastewater from a brewery wastewater treatment plant (A) ultrafiltration (UF) and reverse osmosis (RO), and (B) ozonation, coagulation, microfiltration with ceramic membranes (MF) and RO. Three specific criteria were used for membrane comparison: 1) pilot plant optimisation to identify ideal operating conditions, 2) Clean-In-Place (CIP) procedures to restore permeability, and 3) final water quality obtained. Both UF and Micro-Filtration membranes were operated at increasing fluxes, filtration intervals and alternating phases of backwash (BW) and chemically enhanced backwash (CEB) to control fouling. Operation of polymeric UF membranes was optimized at a flux of 25–30 LMH with 15–20 min of filtration time to obtain longer production periods and avoid frequent CIP membrane cleaning procedures. Combination of ozone and coagulation with ceramic MF membranes resulted in high flux values up to 120 LMH with CEB:BW ratios of 1:4 to 1:10. Coagulation doses of 3–6 ppm were required to deal with the high concentrations of polyphenols (coagulation inhibitors) in the feed, but higher concentrations led to increasing fouling resistance of the MF membrane. Varying the ozone concentration stepwise from 0 to 25 mg/L had no noticeable effect on coagulation. The most effective cleaning strategy was found to be a combination of 2000 mg/L NaOCl followed by 5% HCl which enabled to recover permeability up to 400 LMH·bar−1. Both polymeric UF and ceramic MF membranes produced effluents that fulfil the limits of the national regulatory framework for reuse in industrial services (RD 1620/2007). Coupling to the RO units in both tertiary trains led to further water polishing and an improved treated water quality.
A Feasibility Study of Photovoltaic—Electrolysis—PEM Hybrid System Integrated Into the Electric Grid System Over the Korean Peninsula
Authors: Kim Chang Ki , Cho Hyun-Seok , Kim Chang-Hee , Cho Wonchul , Kim Hyun-Goo
Published: September 2021

A photovoltaic–electrolysis–PEM hybrid model was developed for a feasibility study, and simulations of several scenarios in Korea were performed. The solar irradiance was derived from the University of Arizona solar irradiance based on satellite–Korea Institute of Energy Research model which provides the satellite imagery over the Korean peninsula every 15 min. In Korea, the annual average solar irradiance is 1,310 kWh m−2 with a maximum of 1,440 kWh m−2 in 2017. Electricity load and solar irradiance information were used to test the performance model of the photovoltaic–electrolysis–PEM hybrid system for baseload and several peak load shave runs. When the baseload was set at 4200 MW, the total capacity of the Photovoltaic plants was 58.5 GWp. In contrast, the hybrid system reduced the peak load more efficiently during daytime. In particular, the capacity factor of the Proton Exchange Membrane system increased in winter because the solar irradiance is relatively weak in that season. These results provide useful insights for the development of control logic models for the PV–electrolysis–PEM system in micro-grid setups.
Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1
Authors: Kickinger Stefanie , Lie Maria E. K. , Suemasa Akihiro , Al-Khawaja Anas , Fujiwara Koichi , Watanabe Mizuki , Wilhelmsen Kristine S. , Falk-Petersen Christina B. , Frølund Bente , Shuto Satoshi , Ecker Gerhard F. , Wellendorph Petrine
Published: September 2021

The betaine/GABA transporter 1 (BGT1) is a member of the GABA transporter (GAT) family with still elusive function, largely due to a lack of potent and selective tool compounds. Based on modeling, we here present the design, synthesis and pharmacological evaluation of five novel conformationally restricted cyclic GABA analogs related to the previously reported highly potent and selective BGT1 inhibitor (1S,2S,5R)-5-aminobicyclo[3.1.0]hexane-2-carboxylic acid (bicyclo-GABA). Using [3H]GABA radioligand uptake assays at the four human GATs recombinantly expressed in mammalian cell lines, we identified bicyclo-GABA and its N-methylated analog (2) as the most potent and selective BGT1 inhibitors. Additional pharmacological characterization in a fluorescence-based membrane potential assay showed that bicyclo-GABA and 2 are competitive inhibitors, not substrates, at BGT1, which was validated by a Schild analysis for bicyclo-GABA (pKB value of 6.4). To further elaborate on the selectivity profile both compounds were tested at recombinant α1β2γ2 GABAA receptors. Whereas bicyclo-GABA showed low micromolar agonistic activity, the N-methylated 2 was completely devoid of activity at GABAA receptors. To further reveal the binding mode of bicyclo-GABA and 2 binding hypotheses of the compounds were obtained from in silico-guided mutagenesis studies followed by pharmacological evaluation at selected BGT1 mutants. This identified the non-conserved BGT1 residues Q299 and E52 as the molecular determinants driving BGT1 activity and selectivity. The binding mode of bicyclo-GABA was further validated by the introduction of activity into the corresponding GAT3 mutant L314Q (38 times potency increase cf. wildtype). Altogether, our data reveal the molecular determinants for the activity of bicyclic GABA analogs, that despite their small size act as competitive inhibitors of BGT1. These compounds may serve as valuable tools to selectively and potently target BGT1 in order to decipher its elusive pharmacological role in the brain and periphery such as the liver and kidneys.
Total Synthesis and Antimicrobial Evaluation of Pagoamide A
Authors: Wu Cheng-Han , Chu John
Published: September 2021

Natural products are often the starting point for drug development and also the testing ground for synthetic methods. Herein we describe the total synthesis and antimicrobial evaluation of a marine natural product, pagoamide A, which is a macrocyclic depsipeptide with two backbone thiazole units and a dimethylated N-terminus. The two thiazole building blocks were synthesized from commercially available materials in four or fewer steps and employed directly in solid-phase peptide synthesis (SPPS) to afford pagoamide A. The use of SPPS ensured that the synthetic sequence is operationally straightforward and, if needed, permits modular substitution of building blocks to easily access diverse structural analogs. Our antimicrobial assays showed that pagoamide A has moderate activity against Bacillus subtilis.
Facile Synthesis of Cross-linked Hyperbranched Polyamidoamines Dendrimers for Efficient Hg(Ⅱ) Removal From Water
Authors: Geng Xue , Qu Rongjun , Kong Xiangyu , Geng Shengnan , Zhang Ying , Sun Changmei , Ji Chunnuan
Published: September 2021

Dendrimers as commonly used metal ions adsorption materials have the advantages of good adsorption performance and high reuse rate, but the high cost limits its extensive use. Compared with dendrimers, hyperbranched dendrimers have similar physical and chemical properties and are more economical. Therefore, hyperbranched dendrimers are more suitable for industrial large-scale adsorption. The hyperbranched polyamidoamine (HPAMAM) gels were prepared by cross-linking hyperbranched polyamidoamine (HPAMAM-ECH-x and HPAMAM-EGDE-x) with different amounts of epichlorohydrin (ECH) and ethylene glycol diglycidyl ether (EGDE), respectively. The as-synthesized adsorbents were characterized by FT-IR, SEM and XPS. The prepared adsorbents were used to adsorb Hg(Ⅱ) in aqueous solution, and the effects of solution pH, contact time, temperature and initial concentration of metal ion on the adsorption capacity were investigated. The effect of solution pH indicated that the optimum condition to Hg(Ⅱ) removing was at pH 5.0. The adsorption kinetic curves of the two kinds of materials were in accordance with the pseudo-second-order model. For the HPAMAM-ECH samples, the adsorption thermodynamic curves fitted the Langmuir model, while for the HPAMAM-EGDE samples, both Langmuir and Freundlich equations fitted well. The maximum adsorption capacity of HPAMAM-ECH-3 obtained from Langmuir model toward Hg(Ⅱ) was 3.36 mmol/g at pH 5.0 and 35°C.
Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection
Authors: Sinclair Jane E. , Bloxham Conor J. , Chiu Han , Chew Keng Yih , Russell Jake , Yoshikawa Yusuke , Bielefeldt-Ohmann Helle , Steele Lauren E. , Hulme Katina D. , Verzele Nathalie AJ. , Noye Ellesandra C. , Wu Melanie , Reichelt Melissa E. , Thomas Walter G. , Gallo Linda A. , Redd Meredith A. , Short Kirsty R.
Published: September 2021

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.
Wnt Signaling in Vascular Calcification
Authors: Bundy Kaylee , Boone Jada , Simpson C. LaShan
Published: September 2021

Cardiovascular disease is a worldwide epidemic and considered the leading cause of death globally. Due to its high mortality rates, it is imperative to study the underlying causes and mechanisms of the disease. Vascular calcification, or the buildup of hydroxyapatite within the arterial wall, is one of the greatest contributors to cardiovascular disease. Medial vascular calcification is a predictor of cardiovascular events such as, but not limited to, hypertension, stiffness, and even heart failure. Vascular smooth muscle cells (VSMCs), which line the arterial wall and function to maintain blood pressure, are hypothesized to undergo a phenotypic switch into bone-forming cells during calcification, mimicking the manner by which mesenchymal stem cells differentiate into osteoblast cells throughout osteogenesis. RunX2, a transcription factor necessary for osteoblast differentiation and a target gene of the Wnt signaling pathway, has also shown to be upregulated when calcification is present, implicating that the Wnt cascade may be a key player in the transdifferentiation of VSMCs. It is important to note that the phenotypic switch of VSMCs from a healthy, contractile state to a proliferative, synthetic state is necessary in response to the vascular injury surrounding calcification. The lingering question, however, is if VSMCs acquire this synthetic phenotype through the Wnt pathway, how and why does this signaling occur? This review seeks to highlight the potential role of the canonical Wnt signaling pathway within vascular calcification based on several studies and further discuss the Wnt ligands that specifically aid in VSMC transdifferentiation.
Time-Dependent Dynamics Required for the Degradation and Restoration of the Vascular Endothelial Glycocalyx Layer in Lipopolysaccharide-Treated Septic Mice
Authors: Shinohara Akane , Ushiyama Akira , Iijima Takehiko
Published: September 2021

The endothelial glycocalyx (GCX) plays a key role in the development of organ failure following sepsis. Researchers have investigated GCX degradation caused by pathological conditions. Nonetheless, the GCX restoration process remains poorly understood. Herein, we developed a model in which GCX restoration could be reproduced in mice using in vivo imaging and a dorsal skinfold chamber (DSC). The severity of sepsis was controlled by adjusting the dose of lipopolysaccharide (LPS) used to trigger GCX degradation in BALB/c mice. We evaluated the GCX thickness, leukocyte-endothelial interactions, and vascular permeability using in vivo imaging through DSC under intravital microscopy. The plasma concentration of syndecan-1(Sdc-1), a GCX structural component, was also determined as a marker of GCX degradation. Thus, we developed a reproducible spontaneous GCX recovery model in mice. Degraded GCX was restored within 24 h by the direct visualization of the endothelial GCX thickness, and leukocyte-endothelial interactions. In contrast, indirectly related indicators of recovery from sepsis, such as body weight and blood pressure, required a longer recovery time. This model can be used to study intractable angiopathy following sepsis.
Digital Support for Renal Patients Before and During the COVID-19 Pandemic: Examining the Efforts of Singapore Social Service Agencies in Facebook
Authors: Tan Junjie , Sesagiri Raamkumar Aravind , Wee Hwee Lin
Published: September 2021

During the coronavirus disease 2019 (COVID-19) pandemic, social service agencies (SSAs) play a crucial role in supporting renal patients, who are particularly vulnerable to infections. Social media platforms such as Facebook, serves as an effective medium for these SSAs to disseminate information. Content analysis of the SSAs’ Facebook posts can provide insights on whether Facebook has been adequately utilized during the COVID-19 pandemic and enable SSAs to improve their social media use in future pandemics. This study aimed to compare renal-related SSAs’ Facebook post content before and during the COVID-19 pandemic. Facebook posts of three SSAs National Kidney Foundation (NKF), Kidney Dialysis Foundation (KDF), and Muslim Kidney Action Association (MKAC), posted during the pre-COVID-19 period (January 23, 2019 to June 2, 2019) and the peri-COVID-19 period (January 23, 2020 to June 1, 2020) were extracted. A classification scheme was developed by two coders with themes derived inductively and deductively. Each Facebook post was assigned with a theme. Quantitative analyses indicate that the number of Facebook posts increased from 115 in the pre-COVID-19 period to 293 in the peri-COVID-19 period. During peri-COVID-19, posts regarding lifestyle changes, donations and infectious disease surfaced. While the proportion of posts about encouraging kindness increased from one to 77 posts, the proportion of posts about community-based events and psychosocial support decreased from 44 to 15 posts and 17 to 10 posts respectively during the two periods. Facebook was found to be well-utilized by two of the three renal SSAs in engaging their beneficiaries during the pandemic. During future pandemics, renal SSAs should place emphasis on posts related to psychosocial support and encouraging kindness. Further studies are required to ascertain the impact of COVID-19 from the perspective of renal patients and also to validate the classification scheme which was developed in this study. The study’s methodology and classification scheme can be used to guide future studies for evaluating the social media outreach performance of renal health support groups.
Hybrid Power Electronic Transformer Model for System-Level Benefits Quantification in Energy Distribution Systems
Authors: Prystupczuk Federico , Rigoni Valentín , Nouri Alireza , Ali Ramy , Keane Andrew , O’Donnell Terence
Published: September 2021

The Hybrid Power Electronic Transformer (HPET) has been proposed as an efficient and economical solution to some of the problems caused by Distributed Energy Resources and new types of loads in existing AC distribution systems. Despite this, the HPET has some limitations on the control it can exert due to its fractionally-rated Power Electronic Converter. Various HPET topologies with different capabilities have been proposed, being necessary to investigate the system benefits that they might provide in possible future scenarios. Adequate HPET models are needed in order to conduct such system-level studies, which are still not covered in the current literature. Consequently, this article presents a methodology to develop power flow models of HPET that facilitate the quantification of controllability requirements for voltage, active power and reactive power. A particular HPET topology composed of a three-phase three-winding Low-Frequency Transformer coupled with a Back-to-Back converter is modeled as an example. The losses in the Back-to-Back converter are represented through efficiency curves that are assigned individually to the two modules. The model performance is illustrated through various power flow simulations that independently quantify voltage regulation and reactive power compensation capabilities for different power ratings of the Power Electronic Converter. In addition, a set of daily simulations were conducted with the HPET supplying a real distribution network modeled in OpenDSS. The results show the HPET losses to be around 1.3 times higher than the conventional transformer losses over the course of the day. The proposed methodology offers enough flexibility to investigate different HPET features, such as power ratings of the Power Electronic Converter, losses, and various strategies for the controlled variables. The contribution of this work is to provide a useful tool that can not only assess and quantify some of the system-level benefits that the HPET can provide, but also allow a network-tailored design of HPETs. The presented model along with the simulation platform were made publicly available.
Helicobacter cyclurae sp. Nov., Isolated From Endangered Blue Iguanas (Cyclura lewisi)
Authors: Chan Nathan , Shen Zeli , Mannion Anthony , Kurnick Susanna , Popescu Ioana S. , Burton Frederic J. , Calle Paul P. , Fox James G.
Published: September 2021

Blue iguanas (Cyclura lewisi) are endangered reptiles found only on Grand Cayman. Previously, DNA for a novel Helicobacter species GCBI1 was detected in sick and dead iguanas. In the current study, fecal and cloacal swab samples were obtained from 25 iguanas. Through molecular and microbiological techniques, a novel Helicobacter species was cultured from feces and characterized, for whom we propose the name Helicobacter cyclurae. This novel helicobacter had a prevalence of 56% by PCR and 20% by culture in samples analyzed. The type strain MIT 16-1353 was catalase, oxidase, and gamma-glutamyl transpeptidase positive. By electron microscopy, H. cyclurae has a curved rod morphology and a single sheathed polar flagellum. Phylogenetic analysis using 16S rRNA, gyrB, and hsp60 indicated that these strains were most closely related to Helicobacter sp. 12502256-12 previously isolated from lizards. H. cyclurae has a 1.91-Mb genome with a GC content of 33.37%. There were 1,969 genes with four notable virulence genes: high temperature requirement-A protein-secreted serine protease, gamma-glutamyl transpeptidase, fibronectin/fibrinogen binding protein, and neutrophil-activating protein. Whole-genome phylogeny, average nucleotide identity, and digital DNA–DNA hybridization analysis confirmed that H. cyclurae is a novel species, and the first helicobacter cultured and characterized from blue iguanas.
Freshwater Releases Into Estuarine Wetlands Change the Determinants of Benthic Invertebrate Metacommunity Structure
Authors: Liu Dandan , Yu Hongxian , Lu Kangle , Guan Qiang , Wu Haitao
Published: September 2021

In recent years, the relative importance of the processes driving metacommunity composition has aroused extensive attention and become a powerful approach to identify community patterns and their regulatory mechanisms. We investigated variations in the composition of benthic community in restored wetlands and natural wetlands in the Yellow River Delta (Shandong Province, China). First, spatial structures within each wetland were modeled with Moran eigenvector maps. Next, the variation in community structure among local environmental and spatial variables was partitioned using constrained ordination, and the “elements of metacommunity structure” analysis was used to determine the patterns of best fit for species distributions within metacommunities. Finally, the null model was used to analyze non-random patterns of species co-occurrence. The community structure of benthic invertebrates in restored wetlands and natural wetlands differed significantly. The benthic invertebrate metacommunity structure showed a nested distribution in restored wetlands and a quasi-Clementsian structure in natural wetlands. Pure environmental fractions and pure spatial fractions were critical in regulating benthic invertebrate metacommunities of restored wetlands. In natural wetlands, pure spatial fractions and the interaction between environmental and spatial factors (shared fractions) played a major role in the metacommunity. A species co-occurrence analysis showed that species co-occurred more frequently than expected by chance, demonstrating that biotic interactions were not the main driver of metacommunity structures in both wetland types. Accordingly, the benthic invertebrate metacommunity in estuarine wetlands following freshwater releases was mostly determined by environmental and spatial effects, which resulted in a metacommunity with nested distribution. These results are important for biodiversity protection and ecosystem management of estuarine wetlands in the Yellow River Delta.
Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT
Authors: Jeppesen Line Dahl , Hatt Lotte , Singh Ripudaman , Schelde Palle , Andreasen Lotte , Markholt Sara , Lildballe Dorte L. , Vogel Ida
Published: September 2021

Background: Cell-free NIPT and cell-based NIPT are risk-free testing options using maternal blood samples to screen for fetal aneuploidies, but the methods differ. For cell-free NIPT, the fetal fraction of cell-free DNA in plasma is analyzed with a high background of maternal DNA. In contrast, for cell-based NIPT, a limited number of the rare, intact fetal cells are isolated for the genetic analysis. This case demonstrates the differences regarding testing for fetal sex-chromosomes anomalies (SCAs) between these two tests.

Materials and Methods: A pregnant woman with mosaicism for Turner syndrome opted for NIPT in first trimester. For the cell-free NIPT analysis, DNA extraction, genome-wide massive parallel sequencing, and data analysis were carried out as described by the kit manufacturer (Illumina©, San Diego, CA, USA). For cell-based NIPT, the first sample gave no result, but the woman consented to repeat cell-based NIPT. After whole genome amplification and STR analysis, fetal DNA from three individual fetal cells was subjected to chromosomal microarray (aCGH, Agilent oligoarray, 180 kb).

Results: Fetal fraction was 7%, and cell-free NIPT showed 2 copies of chromosomes 13, 18, and 21 and a decreased proportion of chromosome X, suggestive of fetal Turner syndrome. In contrast, the cell-based NIPT result showed no aneuploidy and two X-chromosomes in the fetus.

Conclusion: cell-based NIPT may provide a non-invasive testing option to screen for SCAs in women with mosaicism for monosomy-X in blood, where cell-free NIPT cannot discriminate whether the X-loss is maternal or fetal.
Mouse Models of Antigen Presentation in Hematopoietic Stem Cell Transplantation
Authors: Koyama Motoko , Hill Geoffrey R.
Published: September 2021

Allogeneic stem cell transplantation (alloSCT) is a curative therapy for hematopoietic malignancies. The therapeutic effect relies on donor T cells and NK cells to recognize and eliminate malignant cells, known as the graft-versus-leukemia (GVL) effect. However, off target immune pathology, known as graft-versus-host disease (GVHD) remains a major complication of alloSCT that limits the broad application of this therapy. The presentation of recipient-origin alloantigen to donor T cells is the primary process initiating GVHD and GVL. Therefore, the understanding of spatial and temporal characteristics of alloantigen presentation is pivotal to attempts to separate beneficial GVL effects from detrimental GVHD. In this review, we discuss mouse models and the tools therein, that permit the quantification of alloantigen presentation after alloSCT.
Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations
Authors: Felgentreff Kerstin , Schuetz Catharina , Baumann Ulrich , Klemann Christian , Viemann Dorothee , Ursu Simona , Jacobsen Eva-Maria , Debatin Klaus-Michael , Schulz Ansgar , Hoenig Manfred , Schwarz Klaus
Published: September 2021

DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets.
Confronting Challenges to Enterotoxigenic Escherichia coli Vaccine Development
Authors: Fleckenstein James M.
Published: September 2021

The enterotoxigenic Escherichia coli (ETEC) are a diverse and genetically plastic pathologic variant (pathovar) of E. coli defined by their production of heat-labile (LT) and heat-stable (ST) enterotoxins. These pathogens, which came to recognition more than four decades ago in patients presenting with severe cholera-like diarrhea, are now known to cause hundreds of millions of cases of symptomatic infection annually. Children in low-middle income regions of the world lacking access to clean water and basic sanitation are disproportionately affected by ETEC. In addition to acute diarrheal morbidity, these pathogens remain a significant cause of mortality in children under the age of five years and have also been linked repeatedly to sequelae of childhood malnutrition and growth stunting. Vaccines that could prevent ETEC infections therefore remain a high priority. Despite several decades of effort, a licensed vaccine that protects against the breadth of these pathogens remains an aspirational goal, and the underlying genetic plasticity of E. coli has posed a fundamental challenge to development of a vaccine that can encompass the complete antigenic spectrum of ETEC. Nevertheless, novel strategies that include toxoids, a more complete understanding of ETEC molecular pathogenesis, structural details of target immunogens, and the discovery of more highly conserved antigens essential for virulence should accelerate progress and make a broadly protective vaccine feasible.
Anthropogenic Dispersal of Leishmania (Viannia) braziliensis in the Americas: A Plausible Hypothesis
Authors: Marzochi Mauro Célio de Almeida , Marzochi Keyla Belizia Feldman , Fagundes Aline , Schubach Armando de Oliveira , Miranda Luciana de Freitas Campos , Pacheco Raquel da Silva
Published: September 2021

There are several gaps in our knowledge on the origin and spread ofLeishmania (Viannia) braziliensis, an etiological agent of cutaneous and mucocutaneous or American tegumentary leishmaniasis, to different biomes, hosts, and vectors, with important epidemiological implications, including the possible existence of an anthroponotic component. Historical, biological, and epidemiological evidence suggests thatLeishmania (V.) braziliensisand its variants were preexistent in Amazonia with great genetic variability, where they dispersed with less variability to other regions (clonal expansion). During pre-Columbian times the parasite may have been transported by migrating humans and probably also their dogs, from western Amazonia to the high inter-Andean valleys and from there to other regions of South America. The same thing could have happened later, in the same way, when it spread to non-Amazonian regions of Brazil and other countries of South and Central America, between the late 19th and early 20th centuries, during the so-called Rubber Boom and construction of the Madeira-Mamoré Railway in the Brazilian Amazon, by migrant workers who later returned to their places of origin, transporting the agent. The parasite’s dispersal in genetic correlated clusters, involving unexpectedly distinct ecosystems in Brazil (Amazonian, Cerrado, Caatinga and Atlantic Forest biomes), has continued until the present through human displacement. The infection of certain species of domestic, synanthropic and even wild animals, could be secondary to anthropogenic introduction ofL. (V.) braziliensisin new environments. We admit the same phenomena happening in the probable transference ofLeishmania infantum(visceral leishmaniasis), and of Yersinia pestis (plague) from the Old world to the New world, generating domestic and wild enzotic cycles from these agents. These assumptions associated with human infections, chronicity and parasite persistence with possibility of recovery ofLeishmaniain peripheral blood, skin and scars of cured or asymptomatic patients, (that may provide an alternative blood meal), along with the sand flies’ adaptation to the peri-domicile and the high susceptibility of domestic dogs, horses, mules and cats to the parasite, can reinforce the evidence of anthropogenic spread ofL. (V.) braziliensis.
Characterization of Strength and Quality of Cemented Mine Backfill Made up of Lead-Zinc Processing Tailings
Authors: Akkaya Ufuk Gokhan , Cinku Kenan , Yilmaz Erol
Published: September 2021

Predicting the reactions of the backfill materials exposed to the effects of air and groundwater will eventually ensure an efficient and accurate mine fill system for sustainable mining operations. This paper reveals the effect of the mobility of sulfur ions within lead-zinc processing tailings on strength and quality of cemented mine backfills. Some laboratory tests such as X-ray diffraction, ion chromatography, scanning electron microscopy, combustion tests, chemical analysis, pH and zeta potential measurements were performed to better characterize the backfill’s mechanical and microstructural properties. Moreover, CEM II/A-P Portland pozzolan and CEM IV/A pozzolanic cements as ready-to-use cement products were used for cemented mine backfill preparation. To ensure the carrier of the lead-zinc tailings and to prevent the mobility of the sulfurous components, a binder content ranging from 3 to 7 wt% were employed in mine backfills. The experimental findings demonstrate that the used cement type and proportions were insufficient and some fractures are occurred in the samples due to the sulfur ion mobility. Accordingly, one can state clearly that the elemental analysis through the combustion test method can provide fast and reliable results in the determination of sulfur within lead-zinc processing tailings.
Case Report: Malacoplakia Due to E. coli With Cryptococcus albidus Infection of a Transplanted Kidney in a Patient With Recurrent Urinary Tract Infection
Authors: Yan Ziyan , Deng Wenfeng , Wang Yuchen , Liu Yanna , Sun Hengbiao , Xia Renfei , Zeng Wenli , Geng Jian , Chen Gui , He Xiaolong , Xu Jian , Wu Chin-Lee , Miao Yun
Published: September 2021

Background: Colonization of Cryptococcus rarely occurs in a graft. This study reports a case of malacoplakia and cryptococcoma caused by E. coli and Cryptococcus albidus in a transplanted kidney, with detailed pathology and metagenome sequencing analysis.

Case Presentation: We presented a case of cryptococcoma and malacoplakia in the genitourinary system including the transplant kidney, bladder, prostate, and seminal vesicles caused by Cryptococcus albidus and Escherichia coli in a renal-transplant recipient. Metagenome sequencing was conducted on a series of samples obtained from the patient at three different time points, which we termed Phase I (at the diagnosis of cryptococcoma), Phase II (during perioperative period of graftectomy, 3 months after the diagnosis), and Phase III (2 months after graftectomy). Sequencing study in the Phase I detected two and four sequences of C. albidus respectively in cerebrospinal fluid (CSF) and feces, with resistant Escherichia coli 09-02E presented in urine and renal mass. A 3-month antibiotic treatment yielded a smaller bladder lesion but an enlarged allograft lesion, leading to a nephrectomy. In the Phase II, two sequences of C. albidus were detected in CSF, while the E. coli 09-02E continued as before. In the Phase III, the lesions were generally reduced, with one C. albidus sequence in feces only.

Conclusions: The existence and clearance of Cryptococcus sequences in CSF without central nervous system symptoms may be related to the distribution of infection foci in vivo, the microbial load, and the body's immunity. Overall, this study highlights the need for enhanced vigilance against uncommon types of Cryptococcus infections in immunocompromised populations and increased concern about the potential correlation between E. coli and Cryptococcus infections.
The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China
Authors: Zhang Xiao-Ai , Zhao Rui-Qiu , Chen Jin-Jin , Yuan Yang , Tang Xiang , Zhou Zi-Wei , Ren Luo , Lu Qin-Bin , Wang Yu-Na , Zhang Hai-Yang , Zhang Pan-He , Fang Li-Qun , Zhou Hai-Sheng , Liu En-Mei , Xu Hong-Mei , Liu Wei
Published: September 2021

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34–0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23–4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It’s concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.
Synergistic and Offset Effects of Fungal Species Combinations on Plant Performance
Authors: Hori Yoshie , Fujita Hiroaki , Hiruma Kei , Narisawa Kazuhiko , Toju Hirokazu
Published: September 2021

In natural and agricultural ecosystems, survival and growth of plants depend substantially on residing microbes in the endosphere and rhizosphere. Although numerous studies have reported the presence of plant-growth promoting bacteria and fungi in below-ground biomes, it remains a major challenge to understand how sets of microbial species positively or negatively affect plants’ performance. By conducting a series of single- and dual-inoculation experiments of 13 plant-associated fungi targeting a Brassicaceae plant species (Brassica rapa var. perviridis), we here systematically evaluated how microbial effects on plants depend on presence/absence of co-occurring microbes. The comparison of single- and dual-inoculation experiments showed that combinations of the fungal isolates with the highest plant-growth promoting effects in single inoculations did not have highly positive impacts on plant performance traits (e.g., shoot dry weight). In contrast, pairs of fungi with small/moderate contributions to plant growth in single-inoculation contexts showed the greatest effects on plants among the 78 fungal pairs examined. These results on the offset and synergistic effects of pairs of microbes suggest that inoculation experiments of single microbial species/isolates can result in the overestimation or underestimation of microbial functions in multi-species contexts. Because keeping single-microbe systems under outdoor conditions is impractical, designing sets of microbes that can maximize performance of crop plants is an important step for the use of microbial functions in sustainable agriculture.
Pipeline Embolization Device for the Treatment of Unruptured Intracranial Dissecting Aneurysms
Authors: Chen Jigang , Tao Mushun , Han Jiangli , Feng Xin , Peng Fei , Tong Xin , Niu Hao , Ma Ning , Liu Aihua
Published: September 2021

Background: Intracranial dissecting aneurysms (IDAs) are rare but pose significant challenges to treatment. The pipeline embolization device (PED) has been demonstrated to be an effective treatment option with excellent outcomes. Herein, we report our experience with patients treated with the PED for unruptured IDAs.

Methods: We retrospectively reviewed our hospital database and identified patients who were treated with PEDs for unruptured IDAs between March 2016 and September 2020. Data including demographics, clinical presentation, aneurysm characteristics, procedural details, intra- or peri-procedural complications, and follow-up details were collected.

Results: Eighty patients (61 men, 76.25%) were treated with PED for unruptured IDAs. The most common symptoms were headache (34, 42.5%), dizziness (29, 36.25%), and nausea or vomiting (15, 18.75%). Of these patients, 73 had one aneurysm, and seven harbored two aneurysms. All of them achieved successful PED deployment. Six patients experienced intra- or peri-procedural complications including perforator artery occlusion, thromboembolic, hemorrhagic events, and falling of the stent into the aneurysm sac. Follow-up with digital subtractive angiography was available for 29 patients with a median of 6 months, and 28 (96.56%) patients had aneurysm occlusion. Late thrombosis occurred in four patients, and two of them had unfavorable outcomes. Clinical follow-up showed that a favorable clinical outcome was achieved in 76 (95%) patients, and the mortality rate was 3.75%.

Conclusion: Treating unruptured IDAs is safe and effective with long-term favorable clinical and angiographic outcomes. However, the complications of this treatment should be noted. Careful selection of appropriate patients and individualized antiplatelet therapy might be needed.
An Improvement of Robot Stiffness-Adaptive Skill Primitive Generalization Using the Surface Electromyography in Human–Robot Collaboration
Authors: Guan Yuan , Wang Ning , Yang Chenguang
Published: September 2021

Learning from Demonstration in robotics has proved its efficiency in robot skill learning. The generalization goals of most skill expression models in real scenarios are specified by humans or associated with other perceptual data. Our proposed framework using the Probabilistic Movement Primitives (ProMPs) modeling to resolve the shortcomings of the previous research works; the coupling between stiffness and motion is inherently established in a single model. Such a framework can request a small amount of incomplete observation data to infer the entire skill primitive. It can be used as an intuitive generalization command sending tool to achieve collaboration between humans and robots with human-like stiffness modulation strategies on either side. Experiments (human–robot hand-over, object matching, pick-and-place) were conducted to prove the effectiveness of the work. Myo armband and Leap motion camera are used as surface electromyography (sEMG) signal and motion capture sensors respective in the experiments. Also, the experiments show that the proposed framework strengthened the ability to distinguish actions with similar movements under observation noise by introducing the sEMG signal into the ProMP model. The usage of the mixture model brings possibilities in achieving automation of multiple collaborative tasks.