bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning to Become Smart Radicals: A Regenerative Lens on the Potential for Peace and Reconciliation through Youth and Education Systems
Authors: Lopes Cardozo Mieke T. A.
Published: March 2022

Media coverage and foreign policy around the globe often spread messages of fear about the possible radicalization of the world's growing youth population. More nuance was brought into these debates in 2015 by UN Security Council Resolution 2250 and the subsequent Global Study on Youth, Peace, and Security (Simpson 2018), while specific attention was directed at the potential of education to support young people's agency for peacebuilding. In this reflective piece, I aim to bring a fresh perspective to current education in emergencies thinking and offer insights into how a regenerative approach to education can help reshape it to prepare the younger generations to respond effectively to peacebuilding and to the related "wicked challenges." I bring together two existing conceptual frameworks—the 4Rs (Novelli, Lopes Cardozo, and Smith 2017) and Tomaševski's 4As (2005; see also Shah and Lopes Cardozo 2019)—that are directly relevant to the education in emergencies field. Building on this conceptual work, I adopt a regenerative lens on reconciliation and engage a law of three framework to encourage a deeper understanding of education's transgressive potential to inspire alternative, reconciliatory paths toward peacebuilding. I will invite and encourage you, the reader, to apply these regenerative conceptual explorations to your own experience. The aim of this conceptual exploration is to inspire the development of "smartly radical" questions; to support research, policy, and practice design that is more critically informed and consciousness driven; and, finally, to support the transformative potential of education systems and stakeholders to serve younger generations more effectively and enable them to respond to "glocal" challenges in ways that are mindful, conscious, and effective.
Landscape Analysis of Early Childhood Development and Education in Emergencies
Authors: Ponguta Liliana Angélica , Moore Kathryn , Varghese Divina , Hein Sascha , Ng Angela , Alzaghoul Aseel Fawaz , Benavides Camacho Maria Angélica , Sethi Karishma , Al-Soleiti Majd
Published: March 2022

Despite the vast amount of research that supports investing in early childhood development and education in emergencies (ECDEiE), this area of programming continues to be underprioritized and underfunded. We applied a strategic problem-solving framework to systematically address the challenge of low access to ECDEiE in the global context. Specifically, we addressed three root causes of this problem: low prioritization of ECDEiE across sectors; the lack of a systematic characterization of the ECDEiE institutional and programmatic landscapes; and limited consensus on strategic advocacy for ECDEiE. To address these issues, we applied a mixed methods approach. We administered an online global stocktaking survey to 118 respondents, including those working in humanitarian aid, ECDEiE, government, and academia. We also reviewed the gray literature (N=218 documents). We discuss our six main findings in order to inform strategic initiatives that could be used to increase access to ECDEiE globewide.
Isolation of Extracellular Vesicles From Microalgae: A Renewable and Scalable Bioprocess
Authors: Paterna Angela , Rao Estella , Adamo Giorgia , Raccosta Samuele , Picciotto Sabrina , Romancino Daniele , Noto Rosina , Touzet Nicolas , Bongiovanni Antonella , Manno Mauro
Published: March 2022

Extracellular vesicles (EVs) play a crucial role as potent signal transducers among cells, with the potential to operate cross-species and cross-kingdom communication. Nanoalgosomes are a subtype of EVs recently identified and isolated from microalgae. Microalgae represent a natural bioresource with the capacity to produce several secondary metabolites with a broad range of biological activities and commercial applications. The present study highlights the upstream and downstream processes required for the scalable production of nanoalgosomes from cultures of the marine microalgae Tetraselmis chuii. Different technical parameters, protocols, and conditions were assessed to improve EVs isolation by tangential flow filtration (TFF), aiming to enhance sample purity and yield. The optimization of the overall bioprocess was enhanced by quality control checks operated through robust biophysical and biochemical characterizations. Further, we showed the possibility of recycling by TFF microalgae cells post-EVs isolation for multiple EV production cycles. The present results highlight the potential of nanoalgosome production as a scalable, cost-effective bioprocess suitable for diverse scientific and industrial exploitations.
Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery
Authors: Ajalik Raquel E. , Alenchery Rahul G. , Cognetti John S. , Zhang Victor Z. , McGrath James L. , Miller Benjamin L. , Awad Hani A.
Published: March 2022

Human Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of two-dimensional (2D) cell culture systems by mimicking 3D tissue organization and microenvironmental cues that are physiologically and clinically relevant. Unlike animal studies, hMPS models can be configured for high content or high throughput screening in preclinical drug development. Applications in modeling acute and chronic injuries in the musculoskeletal system are slowly developing. However, the complexity and load bearing nature of musculoskeletal tissues and joints present unique challenges related to our limited understanding of disease mechanisms and the lack of consensus biomarkers to guide biological therapy development. With emphasis on examples of modeling musculoskeletal tissues, joints on chips, and organoids, this review highlights current trends of microphysiological systems technology. The review surveys state-of-the-art design and fabrication considerations inspired by lessons from bioreactors and biological variables emphasizing the role of induced pluripotent stem cells and genetic engineering in creating isogenic, patient-specific multicellular hMPS. The major challenges in modeling musculoskeletal tissues using hMPS chips are identified, including incorporating biological barriers, simulating joint compartments and heterogenous tissue interfaces, simulating immune interactions and inflammatory factors, simulating effects of in vivo loading, recording nociceptors responses as surrogates for pain outcomes, modeling the dynamic injury and healing responses by monitoring secreted proteins in real time, and creating arrayed formats for robotic high throughput screens. Overcoming these barriers will revolutionize musculoskeletal research by enabling physiologically relevant, predictive models of human tissues and joint diseases to accelerate and de-risk therapeutic discovery and translation to the clinic.
Hierarchical COK-X Materials for Applications in Catalysis and Adsorptive Separation and Controlled Release
Authors: Pulinthanathu Sree Sreeprasanth , Breynaert Eric , Kirschhock Christine E. A. , Martens Johan A.
Published: March 2022

Over the years, COK has developed a family of silicate materials and metal–organic framework hybrids with hierarchical porosity and functionality, coined zeogrids, zeotiles, and COK-x (stemming from the Flemish name of the laboratory “Centrum voor Oppervlaktechemie en Katalyse”). Several of these materials have unique features relevant to heterogeneous catalysis, molecular separation, and controlled release and found applications in the field of green chemistry, environmental protection, and pharmaceutical formulation. Discovery of a new material typically occurs by serendipity, but the research was always guided by hypothesis. This review provides insight in the process of tuning initial research hypotheses to match material properties to specific applications. This review describes the synthesis, structure, properties, and applications of 12 different materials. Some have simple synthesis protocols, facilitating upscaling and reproduction and rendering them attractive also in this respect.
The Surprisingly Positive Effect of Zinc-Phthalocyanines With High Photodynamic Therapy Efficacy of Melanoma Cancer
Authors: Castro Kelly A. D. F. , Prandini Juliana A. , Biazzotto Juliana Cristina , Tomé João P. C. , da Silva Roberto S. , Lourenço Leandro M. O.
Published: March 2022

Phthalocyanine (Pc) dyes are photoactive molecules that can absorb and emit light in the visible spectrum, especially in the red region of the spectrum, with great potential for biological scopes. For this target, it is important to guarantee a high Pc solubility, and the use of suitable pyridinium units on their structure can be a good strategy to use effective photosensitizers (PSs) for photodynamic therapy (PDT) against cancer cells. Zn(II) phthalocyanines (ZnPcs) conjugated with thiopyridinium units (1–3) were evaluated as PS drugs against B16F10 melanoma cells, and their photophysical, photochemical, and in vitro photobiological properties were determined. The photodynamic efficiency of the tetra- and octa-cationic ZnPcs 1–3 was studied and compared at 1, 2, 5, 10, and 20 µM. The different number of charge units, and the presence/absence of a-F atoms on the Pc structure, contributes for their PDT efficacy. The 3-(4′,5′-dimethylthiazol-2′-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays on B16F10 melanoma cells show a moderate to high capacity to be photoinactivated by ZnPcs 1–3 (ZnPc 1 > ZnPc 2 > ZnPc 3). The best PDT conditions were found at a Pc concentration of 20 μM, under red light (λ = 660 ± 20 nm) at an irradiance of 4.5 mW/cm2 for 667 s (light dose of 3 J/cm2). In these conditions, it is noteworthy that the cationic ZnPc 1 shows a promising photoinactivation ratio, reaching the detection limit of the MTT method. Moreover, these results are comparable to the better ones in the literature.
Mechanochemical Synthesis of Fluorine-Containing Co-Doped Zeolitic Imidazolate Frameworks for Producing Electrocatalysts
Authors: Rautenberg Max , Gernhard Marius , Radnik Jörg , Witt Julia , Roth Christina , Emmerling Franziska
Published: March 2022

Catalysts derived from pyrolysis of metal organic frameworks (MOFs) are promising candidates to replace expensive and scarce platinum-based electrocatalysts commonly used in polymer electrolyte membrane fuel cells. MOFs contain ordered connections between metal centers and organic ligands. They can be pyrolyzed into metal- and nitrogen-doped carbons, which show electrocatalytic activity toward the oxygen reduction reaction (ORR). Furthermore, metal-free heteroatom-doped carbons, such as N-F-Cs, are known for being active as well. Thus, a carbon material with Co-N-F doping could possibly be even more promising as ORR electrocatalyst. Herein, we report the mechanochemical synthesis of two polymorphs of a zeolitic imidazole framework, Co-doped zinc 2-trifluoromethyl-1H-imidazolate (Zn0.9Co0.1(CF3-Im)2). Time-resolved in situ X-ray diffraction studies of the mechanochemical formation revealed a direct conversion of starting materials to the products. Both polymorphs of Zn0.9Co0.1(CF3-Im)2 were pyrolyzed, yielding Co-N-F containing carbons, which are active toward electrochemical ORR.
Current Status of Probiotics as Supplements in the Prevention and Treatment of Infectious Diseases
Authors: Li Xinquan , Wang Qiang , Hu Xiafen , Liu Wanxin
Published: March 2022

Probiotics play an important role against infectious pathogens via their effects on the epithelium, the production of antimicrobial compounds, and competitive exclusion. Administration of probiotic supplements may reduce the risk of infectious diseases and the use of antibiotics, hence contributing to a reduction or a delay of the development of multi-resistant bacteria. Infection is a constant concern for people who experience recurrent infections, and antibiotic treatment usually fails due to antibiotic resistance. Therefore, an infection can lead to severe illness and hospitalization if left untreated. A growing number of studies have demonstrated promising results for a variety of probiotic strains used to prevent or treat acute and recurrent infectious diseases, but additional standardized clinical research is needed.
Single Cell Transcriptomes of In Vitro Bradyzoite Infected Cells Reveals Toxoplasma gondii Stage Dependent Host Cell Alterations
Authors: Sugi Tatsuki , Tomita Tadakimi , Kidaka Taishi , Kawai Naoko , Hayashida Kyoko , Weiss Louis M. , Yamagishi Junya
Published: March 2022

Toxoplasma gondii bradyzoites establish chronic infections within their host cells. Recent studies have demonstrated that several parasite effector proteins are translocated to host cells during the bradyzoite stage of chronic infection. To understand the interaction between host cells and bradyzoites at the transcriptomic landscape level, we utilized single-cell RNA-sequencing (scRNA-Seq) to characterize the bradyzoite-induced host cell response. Distinct gene expression profiles were observed in infected host, cells with low parasite mapped reads, and mock (non-exposed) control cells. Gene set enrichment analysis showed that c-Myc and NF-κB signaling and energy metabolic pathways were upregulated by infection. Type I and II interferon response pathways were upregulated in cells with low parasite mapped reads compared to the non-exposed host control cells, and this upregulation effect was reversed in infected cells. Differences were observed in the host cells depending on the differentiation status of the parasites, as determined by BAG1 and SAG1 expression. NF-κB, inflammatory response pathways, and IFN-γ response pathways were downregulated in host cells containing T. gondiiBAG1+/SAG1−, whereas this downregulation effect was reversed in case of T. gondiiBAG1−/SAG1+. We also identified two distinct host cell subsets that contained T. gondiiBAG1+/SAG1−, one of which displayed distinct transcriptomes with upregulated c-Myc expression. Overall, these data clearly demonstrate that host cell transcriptional alteration by bradyzoite infection is different from that of tachyzoite infection, indicating fine-tuning of the host immune response.
Hypertrophic Obstructive Cardiomyopathy: Comparison of Outcomes After Myectomy or Alcohol Ablation
Authors: Meng Xiangbin , Wang Wen-yao , Gao Jun , Zhang Kuo , Zheng Jilin , Wang Jing-jia , Liu YuPeng , Shao Chunli , Tang Yi-Da
Published: March 2022

Introduction and Objectives

The risk of ventricular arrhythmia and heart failure in patients with hypertrophic obstructive cardiomyopathy (HOCM) is much higher than that in the general population. More and more pieces of evidence showed that HOCM is the leading cause of sudden cardiac death in young people. We reported our experience in a study, comparing surgical myectomy, alcohol septal ablation (ASA), and medical therapy.

Methods

The original cohort included 965 consecutive patients with HOCM. The patients were divided into three groups according to treatment strategies: myectomy group (n = 502), ASA group (n = 138), and medical treatment group (n = 325). The median follow-up duration was 42.99 ± 18.32 months, and the primary endpoints were all-cause mortality and heart transplantation.

Results

Both in short- and long-term observations, surgical myectomy reduced the left ventricular outflow tract (LVOT) gradients more effectively (7 days, 16.15 ± 12.07 mmHg vs. 42.33 ± 27.76 mmHg, p < 0.05; 1 year, 14.65 ± 13.18 mmHg vs. 41.17 ± 30.76 mmHg, p < 0.05). Among the three groups, the patients in the medical treatment group were at a higher risk of mortality and cardiac transplantation (vs. the myectomy group, p < 0.001 by log-rank test; vs. the alcohol septal ablation group, p = 0.017 by log-rank test), and the myectomy group shows a lower risk of reaching the primary endpoint than the two other groups. In the multivariate Cox regression analysis, previous atrial fibrillation (AF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and surgical myectomy predicted an HOCM prognosis. However, the impact of surgical myectomy on HOCM prognosis seems to be limited to the <56 years group.

Conclusions

The patients with medical treatments seemed to suffer from the highest risk of achieving an all-cause mortality and the endpoint of heart transplantation. In the long-term survival and clinical outcome, myectomy seemed better than alcohol septal ablation, especially the younger patients. Due to the less-controllable degree, periprocedural complication frequency after alcohol septal ablation was higher, compared with myectomy. Furthermore, gradients after myectomy are lower at late follow-up. To sum up, when selecting treatment strategies, the patients should be individually evaluated by a multidisciplinary team of cardiologists and surgeons.
Comprehensive Analysis of Key m6A Modification Related Genes and Immune Infiltrates in Human Aortic Dissection
Authors: Yin Fanxing , Zhang Hao , Guo Panpan , Wu Yihao , Zhao Xinya , Li Fangjun , Bian Ce , Chen Chen , Han Yanshuo , Liu Kun
Published: March 2022

Objective

To identify the feature of N6-methyladenosine (m6A) methylation modification genes in acute aortic dissection (AAD) and explore their relationships with immune infiltration.

Methods

The GSE52093 dataset including gene expression data from patients with AAD and healthy controls was downloaded from Gene Expression Omnibus (GEO) database in order to obtain the differentially expressed genes (DEGs). The differentially methylated m6A genes were obtained from the GSE147027 dataset. The differentially expressed m6A-related genes were obtained based on the intersection results. Meanwhile, the protein-protein interaction (PPI) network of differentially expressed m6A-related genes was constructed, and hub genes with close relationships in the network were selected. Later, hub genes were verified by using the GSE153434 dataset. Thereafter, the relationships between these genes and immune cells infiltration were analyzed.

Results

A total of 279 differentially expressed m6A-related genes were identified in the GSE52093 and GSE147027 datasets. Among them, 94 genes were up-regulated in aortic dissection (AD), while the remaining 185 were down-regulated. As indicated by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, these genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs). The seven hub genes, namely, DDX17, CTGF, FLNA, SPP1, MYH11, ITGA5 and CACNA1C, were all confirmed as the potential biomarkers for AD. According to immune infiltration analysis, it was found that hub genes were related to some immune cells. For instance, DDX17, FLNA and MYH11 were correlated with Macrophages M2.

Conclusion

Our study identifies hub genes of AD that may serve as the potential biomarkers, illustrates of the molecular mechanism of AD, and provides support for subsequent research and treatment development.
Immune Cells in Thermogenic Adipose Depots: The Essential but Complex Relationship
Authors: Agueda-Oyarzabal Marina , Emanuelli Brice
Published: March 2022

Brown adipose tissue (BAT) is a unique organ in mammals capable of dissipating energy in form of heat. Additionally, white adipose tissue (WAT) can undergo browning and perform thermogenesis. In recent years, the research community has aimed to harness thermogenic depot functions for new therapeutic strategies against obesity and the metabolic syndrome; hence a comprehensive understanding of the thermogenic fat microenvironment is essential. Akin to WAT, immune cells also infiltrate and reside within the thermogenic adipose tissues and perform vital functions. As highly plastic organs, adipose depots rely on crucial interplay with these tissue resident cells to conserve their healthy state. Evidence has accumulated to show that different immune cell populations contribute to thermogenic adipose tissue homeostasis and activation through complex communicative networks. Furthermore, new studies have identified -but still not fully characterized further- numerous immune cell populations present in these depots. Here, we review the current knowledge of this emerging field by describing the immune cells that sway the thermogenic adipose depots, and the complex array of communications that influence tissue performance.
Heavy Metal Contamination (Cu, Pb, Zn, Fe, and Mn) in Urban Dust and its Possible Ecological and Human Health Risk in Mexican Cities
Authors: Aguilera Anahi , Cortés José Luis , Delgado Carmen , Aguilar Yameli , Aguilar Daniel , Cejudo Ruben , Quintana Patricia , Goguitchaichvili Avto , Bautista Francisco
Published: March 2022

Cities occupy a relatively small percentage of the Earth’s surface. However, they influence the entire biosphere, affect biodiversity and environmental conditions, which end up affecting human health and well-being. Therefore, it is necessary to evaluate the level of contamination by heavy metals in urban environments, as well as the possible ecological and human health risks. In this study, the urban dust of six Mexican cities was analyzed and it was found that all studied cities were contaminated, except for Mérida, when soil world background value was used as reference. In contrast, Mérida and Morelia were the most contaminated when a local background was used (decile 1). The concentrations in the cities for the metals Cu, Pb and Zn, decreased in the order CDMX > San Luis Potosí > Toluca > Morelia-Ensenada > Mérida. In the particular case of Cu and Pb, SLP accompanied CDMX as the most polluted city. For Mn and Fe concentrations, the order was CDMX > Toluca > Ensenada > SLP > Morelia-Mérida. No potential ecological risk was found due to contamination by Cu, Pb, and Zn, in the urban dust of the studied cities. However, the higher metal contribution to the potential ecological risk in all the cities was from Pb; and it represented a moderate ecological risk of more than 25% on CDMX, SLP, and Toluca sites. Pb can also be a potential risk for children’s health. In addition, chronic exposure to Fe and Mn could trigger many ailments. In the future, it is important to identify the main sources of Pb in cities and seek mitigation strategies to reduce the possible adverse effects that this metal may be causing.
Development of Resistance in Escherichia coli Against Repeated Water Disinfection
Authors: Daer Sahar , Rehmann Emily , Rehmann Jessica , Ikuma Kaoru
Published: March 2022

Pathogen resistance against common disinfectants in drinking water treatment could have serious public health implications, particularly in potable water reuse. Frequent disinfection in potable water reuse has a potential to facilitate resistance development. This study investigated resistance development in Escherichia coli against repeated monochloramine and ferrate disinfection. E. coli cultures repeatedly treated with monochloramine developed resistance after 12 + treatment rounds, whereas repeated ferrate disinfection did not lead to resistance development. Monochloramine induced cells into the viable but nonculturable (VBNC) state in initial disinfection rounds; however, repeated monochloramine treatment caused increases in culturability, which corresponded to decreases in the fraction of VBNC cells post-disinfection. The cumulative number of disinfection episodes (∼12 times) rather than treatment frequency (e.g., every 48, 96, or 144 h) played a critical role in resistance development against monochloramine. In addition to preventing resistance, ferrate effectively inactivated (>3-log10) the evolved monochloramine-stressed cultures, suggesting that the evolutionary adaptations against monochloramine were ineffective against ferrate. The lack of resistance against ferrate renders it a promising disinfection agent that deserves further assessment. This work’s findings demonstrate that repeated disinfection coupled with the type of applied disinfectant can influence bacterial resistance development. Therefore, current and future water disinfection schemes, especially within potable water reuse, need regular monitoring to evaluate the resistance profile of pathogenic bacteria.
Trade-Offs in the Water-Energy-Ecosystem Nexus for Cascade Hydropower Systems: A Case Study of the Yalong River, China
Authors: Wu Xiufeng , Yu Lei , Wu Shiqiang , Jia Benyou , Dai Jiangyu , Zhang Yu , Yang Qianqian , Zhou Zehui
Published: March 2022

The hydropower system’s water-energy-ecosystem nexus (WEEN) has gained particular focus in the last years. The water-use trade-offs between hydropower and ecosystem maintenance are complex and variable for cascade hydropower systems, leading to challenges in water resources management and sustainable development of hydropower. To understand the trade-off in the WEEN of cascade hydropower systems and their changes, a WEEN model using the multi-objective optimization approach is developed in this study, including maximizing cascade power generation, minimizing reservoir water footprint, and minimizing amended annual proportional flow deviation. These optimization objectives characterize the nexus’s water, energy, and ecosystem sectors. And the Pareto non-inferiority solutions are obtained by the third edition of the Non-dominated Sorting Genetic Algorithm. Also, we novelly propose an evaluation index called the Multi-objective Trade-off Index (MTI), a quantitative method with clear physical meaning to explore the trade-offs as revealed between different objectives by the solutions. A case study of the Yalong River, China, has shown that: 1) the larger the incoming water is, the more beneficial to the power generation and ecological benefits of the hydropower system; and 2) the trade-off degrees of the water sector with respect to energy-ecosystem and energy sector with respect to water-ecosystem decreases when the hydrological condition changes from wet to dry, while the degree of ecosystem sector with respect to water-energy increases. In general, the proposed MTI that quantifies trade-offs in the WEEN of cascade hydropower systems is efficient and feasible. Meanwhile, the MTI is also generic and can be applied to other multi-objective optimization problems.
Multi-Temporal Landslide Inventory-Based Statistical Susceptibility Modeling Associated With the 2017 Mw 6.5 Jiuzhaigou Earthquake, Sichuan, China
Authors: Luo Luguang , Pei Xiangjun , Zhong Chuangui , Yang Qingwen , Fan Xuanmei , Zhu Ling , Huang Runqiu
Published: March 2022

The 2017 Mw 6.5 Jiuzhaigou earthquake (Sichuan, China) is the first strong ground motion that struck the famous world heritage site, causing widespread landslides and severe rock mass damage effects and landscapes undergoing rapid evolution in the Jiuzhaigou National Geopark. However, the understanding of the variability of pre- and post-earthquake landslide susceptibility and landslide conditioning factor effects over time remains limited. This study aims to carry out multi-temporal statistical landslide susceptibility modeling at the slope-unit level related to this event. To achieve this, we initially used a set of remote sensing imageries in GIS to obtain systematic landslide inventories across the pre-, co-, and post-seismic periods. Based on three landslide inventory datasets, we developed three statistical models by incorporating 14 landslide conditioning (seismic, topographic, and geologic) factors into a binary logistic regression (BLR) model. Finally, we utilized the area under the receiver operating characteristic (AUC) (QA) curve to assess each model’s calibration and validation performance. The results show that the BLR model has good prediction applicability for both normal and seismic landslides in the study area with outstanding to excellent predictive accuracy for Mod1 (pre-seismic, AUC = 0.801), Mod2 (co-seismic, AUC = 0.942), and Mod3 (post-seismic, AUC = 0.880) periods. There are variations in both the importance of landslide conditioning factors and susceptibility maps through time, and the number of slope units with a mean probability over 0.8 from only one (pre-seismic) increased to 21 (post-seismic). The dynamic susceptibility maps are of great significance for identifying potentially unstable slopes and providing references for hazard and risk assessment, which could provide new insights into geo-environmental protection and regional landslide evaluation in scenery spots, even for those world heritage sites in the tectonic active mountainous region. Moreover, more frequent or extended observation periods could contribute a further understanding of the post-seismic landslide developments in the Jiuzhaigou area.
Identification of QTLs/ Candidate Genes for Seed Mineral Contents in Common Bean (Phaseolus vulgaris L.) Through Genotyping-by-Sequencing
Authors: Nazir Muslima , Mahajan Reetika , Mansoor Sheikh , Rasool Sheezan , Mir Rakeeb Ahmad , Singh Ravinder , Thakral Vandana , Kumar Virender , Sofi Parvaze A. , El-Serehy Hamed A. , Hefft Daniel Ingo , Zargar Sajad Majeed
Published: March 2022

Throughout the ages, the common bean has been consumed by humanity as an important food staple crop and source of nutrition on a global scale. Since its domestication, a wide spectrum of phenotypic and genotypic investigations have been carried out to unravel the potential of this crop and to understand the process of nutrient accumulation along with other desirable characteristics. The common bean is one of the essential legume crops due to its high protein and micronutrient content. The balance in micronutrients is critical for the growth and development of plants as well as humans. Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn), Magnesium (Mg), Calcium (Ca), and Molybdenum (Mo) are some of the important micronutrients present in legumes. Thus, we aimed to investigate the quantitative trait loci’s (QTLs)/single nucleotide polymorphisms (SNPs) to identify the candidate genes associated with micronutrients through genotyping by sequencing (GBS). In our investigation, through GBS we identified SNPs linked with traits and assessed seven micronutrients in 96 selected common bean genotypes for screening nutritionally rich genotypes. Among 96399 SNPs total identified through GBS, 113 SNPs showed significant phenotypic variance, ranging from 13.50 to 21.74%. SNPs associated with most of the seed micronutrients (Mg, Mn, Fe, Ca, Cu) were found on chr3 & chr11 (Mg, Mn, Mo, Ca, Zn). The findings from this study could be used for haplotype-based selection of nutritionally rich genotypes and for marker-assisted genetic enhancement of the common bean. Further, the identified SNPs for candidate genes/transporters associated with micronutrient content may pave the way for the enrichment of seeds by employing genomics-assisted breeding programs.
Whole Genome Sequencing Analysis to Identify Candidate Genes Associated With the rib eye Muscle Area in Hu Sheep
Authors: Zhao Yuan , Zhang Xiaoxue , Li Fadi , Zhang Deyin , Zhang Yukun , Li Xiaolong , Song Qizhi , Zhou Bubo , Zhao Liming , Wang Jianghui , Xu Dan , Cheng Jiangbo , Li Wenxin , Lin Changchun , Yang Xiaobin , Zeng Xiwen , Wang Weimin
Published: March 2022

In sheep meat production, the rib eye area is an important index to evaluate carcass traits. However, conventional breeding programs have led to slow genetic progression in rib eye muscle area. Operationalizing molecular marker assisted breeding is an optimized breeding method that might improve this situation. Therefore, the present study used whole genome sequencing data to excavate candidate genes associated with the rib eye muscle. Male Hu lambs (n = 776) with pedigrees and 274 lambs with no pedigree were included. The genetic parameters of the rib eye area were estimated using a mixed linear mixed model. The rib eye area showed medium heritability (0.32 ± 0.13). Whole-genome sequencing of 40 large rib eye sheep [17.97 ± 1.14, (cm2)] and 40 small rib eye sheep [7.89 ± 0.79, (cm2)] was performed. Case-control genome-wide association studies and the fixation index identified candidate rib eye-associated genes. Seven single nucleotide polymorphisms (SNPs) in six genes (ALS2, ST6GAL2, LOC105611989, PLXNA4, DPP6, and COL12A1) were identified as candidates. The study population was expanded to 1050 lambs to perform KASPar genotyping on five SNPs, which demonstrated that SNPs in LOC105611989, DPP6, and COL12A1 correlated significantly with the rib eye area, which could be used as genetic markers for molecular breeding of the rib eye area. The results provided genetic parameters estimated on the rib eye area and information for breeding based on carcass traits in Hu sheep.
B Cell IL-4 Drives Th2 Responses In Vivo, Ameliorates Allograft Rejection, and Promotes Allergic Airway Disease
Authors: Song Zhixing , Yuan Wenjia , Zheng Leting , Wang Xingan , Kuchroo Vijay K. , Mohib Kanishka , Rothstein David M.
Published: March 2022

B cells can be polarized to express various cytokines. The roles of IFNγ and IL-10, expressed respectively by B effector 1 (Be1) and Bregs, have been established in pathogen clearance, tumor growth, autoimmunity and allograft rejection. However, thein vivorole of B cell IL-4, produced by Be2 cells, remains to be established. We developed B-IL-4/13 iKO mice carrying a tamoxifen-inducible B cell-specific deletion of IL-4 and IL-13. After alloimmunization, B-IL-4/13 iKO mice exhibited decreased IL-4+Th2 cells and IL-10+Bregs without impact on Th1, Tregs, or CD8 T cell responses. B-IL-4/13 iKO mice rejected islet allografts more rapidly, even when treated with tolerogenic anti-TIM-1 mAb. In ovalbumin-induced allergic airway disease (AAD), B-IL-4/13 iKO mice had reduced inflammatory cells in BAL, and preserved lung histology with markedly decreased infiltration by IL-4+and IL-5+CD4+T cells. Hence, B cell IL-4 is a major driver of Th2 responsesin vivowhich promotes allograft survival, and conversely, worsens AAD.
The COVID Complex: A Review of Platelet Activation and Immune Complexes in COVID-19
Authors: Jevtic Stefan D. , Nazy Ishac
Published: March 2022

Coronavirus disease 2019 (COVID-19) is a highly prothrombotic viral infection that primarily manifests as an acute respiratory syndrome. However, critically ill COVID-19 patients will often develop venous thromboembolism with associated increases in morbidity and mortality. The cause for this prothrombotic state is unclear but is likely related to platelet hyperactivation. In this review, we summarize the current evidence surrounding COVID-19 thrombosis and platelet hyperactivation. We highlight the fact that several studies have identified a soluble factor in COVID-19 patient plasma that is capable of altering platelet phenotypein vitro. Furthermore, this soluble factor appears to be an immune complex, which may be composed of COVID-19 Spike protein and related antibodies. We suggest that these Spike-specific immune complexes contribute to COVID-19 platelet activation and thrombosis in a manner similar to heparin-induced thrombocytopenia. Understanding this underlying pathobiology will be critical for advancement of future research and therapeutic options.
Isoforms of the Papillomavirus Major Capsid Protein Differ in Their Ability to Block Viral Spread and Tumor Formation
Authors: Hasche Daniel , Ahmels Melinda , Braspenning-Wesch Ilona , Stephan Sonja , Cao Rui , Schmidt Gabriele , Müller Martin , Rösl Frank
Published: March 2022

Notably, the majority of papillomaviruses associated with a high cancer risk have the potential to translate different isoforms of the L1 major capsid protein. In an infection model, the cutaneous Mastomys natalensis papillomavirus (MnPV) circumvents the humoral immune response of its natural host by first expressing a 30 amino acid extended L1 isoform (L1LONG). Although inducing a robust seroconversion, the raised antibodies are not neutralizing in vitro. In contrast, neutralizing antibodies induced by the capsid-forming isoform (L1SHORT) appear delayed by several months. We now provide evidence that, although L1LONG vaccination showed a strong seroconversion, these antibodies were not protective. As a consequence, virus-free animals subsequently infected with MnPV still accumulated high numbers of transcriptionally active viral genomes, ultimately leading to skin tumor formation. In contrast, vaccination with L1SHORT was completely protective. This shows that papillomavirus L1LONG expression is a unique strategy to escape from antiviral immune surveillance.
IDO1 Inhibition Reduces Immune Cell Exclusion Through Inducing Cell Migration While PD-1 Blockage Increases IL-6 and -8 Secretion From T Cells in Head and Neck Cancer
Authors: Sieviläinen Meri , Saavalainen Jordan , Adnan-Awad Shady , Salo Tuula , Al-Samadi Ahmed
Published: March 2022

Background

Immune checkpoint inhibitors (ICIs), primarily anti-PD-1, are currently used to treat patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, only a minority of patients benefit from these costly therapies. Therefore, there is an unmet need to better understand the effect of ICIs on immune effector cells. This study aimed to investigate the effect of a PD-1 antibody and an IDO1 inhibitor on different lymphocyte populations (NK, CD4+, and CD8+ T cells) in term of migration, cytotoxicity, and cytokine release in the presence of HNSCC cells.

Methods

Using a microfluidic chip, we injected HSC-3 cells (an oral tongue squamous cell carcinoma cell line) embedded in a human tumor-derived matrix “myogel/fibrin” together with NK, CD4+, and CD8+ T cells in separate channels. The two channels were connected with microchannels. The PD-1 antibody nivolumab and IDO1 inhibitor epacadostat were added to the microfluidic chips. Lymphocyte migration and cytotoxicity were examined under fluorescent microscopy and cytokine release was measured using a FirePlex Human Discovery Cytokines Immunoassay.

Results

Epacadostat significantly increased the migration and infiltration of NK and CD4+ T cells, but not CD8+ T cells, towards the cancer cells. Nivolumab did not exhibit a similar effect. While CD8+ T cells alone showed near to no migration, adding CD4+ T cells enhanced migration towards the cancer cells. There was a mild nonsignificant increase in apoptosis of HSC-3 cells after adding epacadostat to lymphocytes. In contrast, HSC-3 proliferation was not affected by lymphocytes regardless of ICIs. Nivolumab significantly increased release of MIP1-α, IL-6, and IL-8 from NK, CD4+, and CD8+ T cells, respectively.

Conclusions

This study revealed that each subpopulation of lymphocytes respond differently to ICIs. We also revealed the subpopulation of lymphocytes responsible for the increases in specific serum cytokines after ICI treatment.
T Cell Metabolism in Infection
Authors: Wik Jonas Aakre , Skålhegg Bjørn Steen
Published: March 2022

T lymphocytes (T cells) are divided into two functionally different subgroups the CD4+ T helper cells (Th) and the CD8+ cytotoxic T lymphocytes (CTL). Adequate CD4 and CD8 T cell activation to proliferation, clonal expansion and effector function is crucial for efficient clearance of infection by pathogens. Failure to do so may lead to T cell exhaustion. Upon activation by antigen presenting cells, T cells undergo metabolic reprograming that support effector functions. In this review we will discuss how metabolic reprograming dictates functionality during viral infections using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) as examples. Moreover, we will briefly discuss T cell metabolic programs during bacterial infections exemplified byMycobacterium tuberculosis(MT) infection.
Integrated Analysis Highlights the Immunosuppressive Role of TREM2+ Macrophages in Hepatocellular Carcinoma
Authors: Zhou Lisha , Wang Meiling , Guo Hanrui , Hou Jun , Zhang Yingna , Li Man , Wu Xiangwei , Chen Xueling , Wang Lianghai
Published: March 2022

Recently, attention has been focused on the central role of TREM2 in diverse pathologies. However, the role of TREM2 signaling in the tumor microenvironment of hepatocellular carcinoma (HCC) remains poorly understood. Herein, we systematically investigated the single-cell transcriptomes of human HCC tissues and found that TREM2 was predominantly expressed by a macrophage subpopulation enriched in tumor tissues that resemble lipid-associated macrophages (LAMs). The accumulation of TREM2+ LAM-like cells in HCC was confirmed in two additional cohorts using scRNA-seq analysis and immunohistochemistry. High expression of TREM2 correlated with high infiltrating macrophage abundance and poor prognosis. Based on systematic interrogations of transcriptional profiles and cellular interactions, TREM2+ LAM-like cells were identified to mainly originate from S100A8+ monocytes and represented an immunosuppressive state. TREM2+ LAM-like cells recruited suppressive Treg cells, facilitating microenvironment remodeling. Furthermore, gene regulatory analysis and in vitro functional assays indicated that activation of LXR signaling could promote the reprogramming of TREM2+ LAM-like cells. Correlation analysis of bulk RNA-sequencing data demonstrated that the enrichment of TREM2+ LAM-like cells was an independent indicator of adverse clinical outcomes in HCC patients. Our comprehensive analyses provide deeper insights into the immunosuppressive role of TREM2+ LAM-like cells in HCC.
Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens
Authors: Serrano-Villar Sergio , López-Huertas María Rosa , Jiménez Daniel , Galera Carlos , Martínez-Sanz Javier , Moreno Elena , Muriel Alfonso , Gutiérrez Félix , Busca Carmen , Portilla Joaquín , Bisbal Otilia , Iribarren José Antonio , Tejerina Francisco , de los Santos Ignacio , Moreno Santiago
Published: March 2022

Background

Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation.

Methods

Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.

Results

We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG).

Conclusions

In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.
The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study
Authors: Loft Josefine Amalie , Møller Dina Leth , Thudium Rebekka Faber , Knudsen Jenny Dahl , Ostrowski Sisse Rye , Andersen Åse Bengård , Nielsen Susanne Dam
Published: March 2022

Introduction

Infectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.

Methods

This was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.

Results

In total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.

Conclusion

We found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.
Role of the Epigenetic Modifier JMJD6 in Tumor Development and Regulation of Immune Response
Authors: Wang Kai , Yang Chao , Li Haibin , Liu Xiaoyan , Zheng Meiling , Xuan Zixue , Mei Zhiqiang , Wang Haiyong
Published: March 2022

JMJD6 is a member of the Jumonji (JMJC) domain family of histone demethylases that contributes to catalyzing the demethylation of H3R2me2 and/or H4R3me2 and regulating the expression of specific genes. JMJD6-mediated demethylation modifications are involved in the regulation of transcription, chromatin structure, epigenetics, and genome integrity. The abnormal expression of JMJD6 is associated with the occurrence and development of a variety of tumors, including breast carcinoma, lung carcinoma, colon carcinoma, glioma, prostate carcinoma, melanoma, liver carcinoma, etc. Besides, JMJD6 regulates the innate immune response and affects many biological functions, as well as may play key roles in the regulation of immune response in tumors. Given the importance of epigenetic function in tumors, targeting JMJD6 gene by modulating the role of immune components in tumorigenesis and its development will contribute to the development of a promising strategy for cancer therapy. In this article, we introduce the structure and biological activities of JMJD6, followed by summarizing its roles in tumorigenesis and tumor development. Importantly, we highlight the potential functions of JMJD6 in the regulation of tumor immune response, as well as the development of JMJD6 targeted small-molecule inhibitors for cancer therapy.