bluuebunny/crossref_metadata_2025 huggingface dataset:
Coming to Terms With COVID-19 Reality in the Context of Africa’s Higher Education: Challenges, Insights, and Prospects
Authors: Osabwa Wycliffe
Published: February 2022

This perspective paper aimed at elucidating the effects of the COVID-19 pandemic on African institutions of higher education. With specific reference to Kenya, the paper exposed the state of the country’s unpreparedness in terms of instructional technologies, a situation that had contributed to an almost total shutdown of institutions following the outbreak. It was notable that whereas Kenya—like most African countries—had not borne the brunt of COVID-19 infections in comparison to other countries outside the continent, its education sector was adversely affected. This followed the social distancing requirement that limited in-person gatherings—the low rate of infections notwithstanding—implying that its learning institutions, most of which operated on in-person mode, had to close. Since most universities in Africa had hitherto operated on this mode, the shift to online learning was not easy. Save for a few universities that had digital infrastructure, the rest encountered difficulties in moving to remote learning. Many had to quickly assemble digital curricula, the quality of which could not be guaranteed. Even if an institution managed to do so, not all students could be brought on board. Digital exclusion became more pronounced than ever before, with learners who were economically, technologically, and geographically disadvantaged missing out. Inequalities in education were laid bare and exacerbated. All this notwithstanding, Africa learnt lessons. The whole experience prompted various stakeholders—university management, faculty, and government—to rethink their modes of education delivery, with quality and access in mind. In retrospect, the pandemic could serve as a catalyst for digitalization in Africa’s higher education system.
Evaluating the Impact of Formative Assessment Intervention and Experiences of the Standard 4 Teachers in Teaching Higher-Order-Thinking Skills in Mathematics
Authors: Moyo Sello Editor , Combrinck Celeste , Van Staden Surette
Published: February 2022

Formative assessment may be a useful pedagogical practice to enhance the teaching of HOTS in mathematics. This study explored the impact of a formative assessment intervention on 1) students’ achievements in HOTS mathematics tests (pre-and-post) when their teachers were supported to implement the instructional intervention and 2) Standard 4 (Grade 4) teachers’ formative assessment practices. To explore the effects of 2-day intervention for professional development teacher training, this study employed mixed methods, sequential embedded approach with single-group, pre-test, intervention (training), and post-test instruments. Data were gathered from nine primary schools involving nine teachers and 272 standard 4 students in the southern region of Botswana. Students’ tests scales were used to measure achievement in mathematical HOTS items along with classroom observations and interviewed the teachers’ experiences and reflections. Students’ achievement data were assessed for internal reliability and validity by applying the Rasch Partial Credit Model followed by descriptive analysis and Wilcoxon signed-rank testing. The observed and interviewed teacher data were analyzed by descriptive frequency counts and thematic analysis, respectively. The students’ achievement in mathematically HOTS items was found significantly improved from pre-test to post-testing. Post-intervention classroom observation showed that teachers practised the integration and implementation of some formative assessment strategies. Finally, the teachers’ experience and reflections were found to be favorably inclined to support formative assessment higher-order thinking skills as a strategy to enhance mathematics teaching.
Receptors of Advanced Glycation End Product (RAGE) Suppression Associated With a Preserved Osteogenic Differentiation in Patients With Prediabetes
Authors: Phimphilai Mattabhorn , Pothacharoen Peraphan , Chattipakorn Nipon , Kongtawelert Prachya
Published: February 2022

Type 2 diabetes is widely documented for osteogenic differentiation defect and impaired bone quality, which is related to the skeletal accumulation of advanced glycation end products (AGEs). Prediabetes is a condition in which hyperglycemia is lower than the threshold for the diagnosis of diabetes. Prediabetic animal models consistently demonstrate impaired osteogenic differentiation and deteriorated bone microarchitecture. However, no evidence shows defects in osteoblast development and skeletal effects of AGEs in prediabetic individuals. Therefore, it remains to be elucidated whether impaired osteogenic differentiation ability and altered cellular response to AGEs occur in patients with prediabetes. This cross-sectional study included 28 patients with prediabetes as defined by impaired fasting glucose criteria, fasting plasma glucose (FPG) between 100–125 mg/dl and 17 age-matched normoglycemic controls to elucidate osteogenic differentiation and AGER expression in the PBMC derived from those individuals. The PBMC-isolated from both groups showed similar rates of expression of osteoblast-specific genes, namely, ALPL, BGLAP, COL1A1, and RUNX2/PPAR (89.3% and 88.2%, p = 1.000), and showed comparable levels of expression of those genes. By using age- and pentosidine-matched normoglycemic individuals as references, the PBMC-isolated from prediabetic patients demonstrated lower expression of both AGER and BAX/BCL2. The expression of AGER and BAX/BCL2 significantly correlated to each other (r = 0.986, p <0.0001). The multivariate analysis demonstrated that serum pentosidine is an independent risk factor for AGER expression. With logistic regression analysis, the area under the ROC curve (AUC) for serum pentosidine at the cut-off level of 2.1 ng/ml and FPG at 100 mg/dl, which is a cut-off point for prediabetes, was significantly higher for predicting AGER expression than that of serum pentosidine alone (0.803 vs 0.688, p = 0.048), indicating that serum pentosidine was a good predictor of AGER expression in prediabetic individuals. In conclusion, this study demonstrated a preserved osteogenic differentiation in the PBMC derived from prediabetic individuals. In addition, those PBMC with preserved osteogenic differentiation potential showed the suppression of both cellular RAGE and apoptotic-related signals. Serum pentosidine was an independent risk factor for cellular RAGE expression and is conceivably a good predictor for AGER suppression in prediabetic individuals.
Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development
Authors: Liao Baoying , Qi Xinyu , Yun Chuyu , Qiao Jie , Pang Yanli
Published: February 2022

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. Ovarian dysfunction including abnormal steroid hormone synthesis and follicular arrest play a vital role in PCOS pathogenesis. Hyperandrogenemia is one of the important characteristics of PCOS. However, the mechanism of regulation and interaction between hyperandrogenism and ovulation abnormalities are not clear. To investigate androgen-related metabolic state in granulosa cells of PCOS patients, we identified the transcriptome characteristics of PCOS granulosa cells by RNA-seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) revealed that genes enriched in lipid metabolism pathway, fatty acid biosynthetic process and ovarian steroidogenesis pathway were abnormally expressed in PCOS granulosa cells in comparison with that in control. There are close interactions among these three pathways as identified by analysis of the protein-protein interaction (PPI) network of DEGs. Furthermore, in vitro mouse follicle culture system was established to explore the effect of high androgen and its related metabolic dysfunction on follicular growth and ovulation. RT-qPCR results showed that follicles cultured with dehydroepiandrosterone (DHEA) exhibited decreased expression levels of cumulus expansion-related genes (Has2, Ptx3, Tnfaip6 and Adamts1) and oocyte maturation-related genes (Gdf9 and Bmp15), which may be caused by impaired steroid hormone synthesis and lipid metabolism, thus inhibited follicular development and ovulation. Furthermore, the inhibition effect of DHEA on follicle development and ovulation was ameliorated by flutamide, an androgen receptor (AR) antagonist, suggesting the involvement of AR signaling. In summary, our study offers new insights into understanding the role of androgen excess induced granulosa cell metabolic disorder in ovarian dysfunction of PCOS patients.
Uncertainty Analysis of Reactor Structure Material Activation Calculation Induced From Nuclear Data
Authors: Jiebo Wu , Chao Yang , Tao Yu , Zhenping Chen
Published: February 2022

Highly accurate activation calculations are the basis of radiation protection optimization design, and the accuracy of activation calculations depends on nuclear data. Based on the ENDF/B-VIII.0 and JEFF3.3 decay evaluation libraries, the influence of different nuclear data on the reactor structural material activation calculation is analyzed, and the nuclear data-related sensitivity and uncertainty quantification of radioactivity, decay heat and photon sources are carried out by the global sensitivity analysis method and the Latin Hypercube Sampling method. Based on uncertainty data in ENDF/B-VIII.0 and JEFF3.3, quantifying the uncertainty of radioactivity, decay heat and photon source in the shutdown dose calculation of reactor structural materials, the maximum uncertainty of radioactivity and decay heat reach 4.54 and 1.45%, respectively. The half-life and decay energy of 55Fe are the main sources of uncertainty.
Organic Matter Processing on Dry Riverbeds is More Reactive to Water Diversion and Pollution Than on Wet Channels
Authors: Pérez-Calpe Ana Victoria , de Guzman Ioar , Larrañaga Aitor , von Schiller Daniel , Elosegi Arturo
Published: February 2022

Rivers are severely affected by human activities and many are simultaneously impacted by multiple stressors. Water diversion for hydropower generation affects ecosystem functioning of the bypassed reaches, which can alternate between periods with natural discharge and others with reduced flow that increase the surface of dry riverbeds. In parallel, urban pollution contributes a complex mixture of nutrients, organic matter, heavy metals, pesticides, and drugs, thus becoming an important stressor in rivers. However, there is little information on the interaction between both stressors on ecosystem functioning and, particularly, on organic matter processing, a key process linked to the input of energy to food webs. To assess the impact of water diversion and urban pollution on organic matter processing, we selected four rivers in a pollution gradient with a similar diversion scheme and compared reaches upstream and downstream from the diversion weirs. We measured leaf-litter decomposition and carbon dioxide (CO2) fluxes in both the wet channel and the dry riverbed. Water diversion and pollution in the wet channel did not affect CO2 fluxes but reduced microbial decomposition, whereas in the dry riverbed, their interaction reduced total and microbial decomposition and CO2 fluxes. Thus, both stressors affected organic matter processing stronger in dry riverbeds than in the wet channel. These results show that dry riverbeds must be taken into account to assess and manage the impacts of human activities on river ecosystems.
The Legacy of Hurricanes, Historic Land Cover, and Municipal Ordinances on Urban Tree Canopy in Florida (United States)
Authors: Salisbury Allyson B. , Koeser Andrew K. , Hauer Richard J. , Hilbert Deborah R. , Abd-Elrahman Amr H. , Andreu Michael G. , Britt Katie , Landry Shawn M. , Lusk Mary G. , Miesbauer Jason W. , Thorn Hunter
Published: February 2022

Urban Tree Canopy (UTC) greatly enhances the livability of cities by reducing urban heat buildup, mitigating stormwater runoff, and filtering airborne particulates, among other ecological services. These benefits, combined with the relative ease of measuring tree cover from aerial imagery, have led many cities to adopt management strategies based on UTC goals. In this study, we conducted canopy analyses for 300 cities in Florida to assess the impacts of development practices, urban forest ordinances, and hurricanes on tree cover. Within the cities sampled, UTC ranged from 5.9 to 68.7% with a median canopy coverage of 32.3% Our results indicate that the peak gust speeds recorded during past hurricanes events were a significant predictor of canopy coverage (P = 0.001) across the sampled cities. As peak gust speeds increased from 152 km/h (i.e., a lower-intensity Category 1 storm) to 225 km/h (lower-intensity Category 4 and the maximum gusts captured in our data), predicted canopy in developed urban areas decreased by 7.7%. Beyond the impacts of hurricanes and tropical storms, we found that historic landcover and two out of eight urban forest ordinances were significant predictors of existing canopy coverage (P-landcover < 0.001; P-tree preservation ordinance = 0.02, P-heritage tree ordinance = 0.03). Results indicate that some local policies and tree protections can potentially impact urban tree canopy, even in the face of rapid development and periodic natural disturbances.
Relating the Growth Phenology and Biomass Allocation in Seedlings of 13 Acadian Tree Species With Their Drought Tolerance
Authors: Pearson Erin , D’Orangeville Loïc
Published: February 2022

Climate models predict an increase in the frequency and intensity of drought events in the Acadian Forest Region, with higher risk of tree growth decline and mortality. To accurately predict future species response, we need to better compare drought-coping traits between Acadian tree species, especially at early life stages as young trees tend to display increased sensitivity to small environmental changes than mature trees. Here, we compared the seasonal growth phenology and biomass allocation in seedlings of 13 Acadian tree species in a controlled environment to assess their ability to predict species drought tolerance rankings. We focused on two traits associated with drought tolerance, namely biomass allocation to root systems, which affects water uptake, and phenology of seasonal growth, where earlier growth can avoid the peak drought period in late summer. We find an earlier onset of height growth in drought-tolerant species (P < 0.05), supporting the late-summer drought avoidance hypothesis. The observed biomass allocation patterns did not support the hypothesis of a higher allocation to roots with drought tolerance. In fact, we report an initially higher shoot-to-root ratio in drought tolerant species (P < 0.05), which becomes non-significant as the season progresses. Our results highlight the complexity of drought response strategies, as the developmental traits reported here only account for a fraction of each species overall drought tolerance. Yet, the important differences in growth phenology observed here between species, and their linkage with drought tolerance indices, could help predict species response to future drought regime.
Genomic Reporter Constructs to Monitor Pathway-Specific Repair of DNA Double-Strand Breaks
Authors: van de Kooij Bert , van Attikum Haico
Published: February 2022

Repair of DNA Double-Strand Breaks (DSBs) can be error-free or highly mutagenic, depending on which of multiple mechanistically distinct pathways repairs the break. Hence, DSB-repair pathway choice directly affects genome integrity, and it is therefore of interest to understand the parameters that direct repair towards a specific pathway. This has been intensively studied using genomic reporter constructs, in which repair of a site-specific DSB by the pathway of interest generates a quantifiable phenotype, generally the expression of a fluorescent protein. The current developments in genome editing with targetable nucleases like Cas9 have increased reporter usage and accelerated the generation of novel reporter constructs. Considering these recent advances, this review will discuss and compare the available DSB-repair pathway reporters, provide essential considerations to guide reporter choice, and give an outlook on potential future developments.
Evaluation of CircRNA Sequence Assembly Methods Using Long Reads
Authors: Zhang Jingjing , Hossain Md. Tofazzal , Liu Weiguo , Peng Yin , Pan Yi , Wei Yanjie
Published: February 2022

The functional study on circRNAs has been increasing in the past decade due to its important roles in micro RNA sponge, protein coding, the initiation, and progression of diseases. The study of circRNA functions depends on the full-length sequences of circRNA, and current sequence assembly methods based on short reads face challenges due to the existence of linear transcript. Long reads produced by long-read sequencing techniques such as Nanopore technology can cover full-length sequences of circRNA and therefore can be used to evaluate the correctness and completeness of circRNA full sequences assembled from short reads of the same sample. Using long reads of the same samples, one from human and the other from mouse, we have comprehensively evaluated the performance of several well-known circRNA sequence assembly algorithms based on short reads, including circseq_cup, CIRI_full, and CircAST. Based on the F1 score, the performance of CIRI-full was better in human datasets, whereas in mouse datasets CircAST was better. In general, each algorithm was developed to handle special situations or circumstances. Our results indicated that no single assembly algorithm generated better performance in all cases. Therefore, these assembly algorithms should be used together for reliable full-length circRNA sequence reconstruction. After analyzing the results, we have introduced a screening protocol that selects out exonic circRNAs with full-length sequences consisting of all exons between back splice sites as the final result. After screening, CIRI-full showed better performance for both human and mouse datasets. The average F1 score of CIRI-full over four circRNA identification algorithms increased from 0.4788 to 0.5069 in human datasets, and it increased from 0.2995 to 0.4223 in mouse datasets.
PHLDA1 Suppresses TLR4-Triggered Proinflammatory Cytokine Production by Interaction With Tollip
Authors: Peng Hui , Wang Juping , Song Xuhong , Huang Jiangni , Hua Haoming , Wang Fanlu , Xu Ziyun , Ma Jing , Gao Jie , Zhao Jing , Nong Anna , Huang Dongyang , Liang Bin
Published: February 2022

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) has been reported to be expressed in many mammalian tissues and cells. However, the functions and exact mechanisms of PHLDA1 remain unclear. In this study, we found that PHLDA1 expression was significantly altered in macrophages after exposure to lipopolysaccharide (LPS) in vitro, suggesting that PHLDA1 may be involved in the regulation of TLR4 signaling pathway activated by LPS. PHLDA1 attenuated the production of LPS-stimulated proinflammatory cytokines (TNF-α, IL-6, and IL-1β). Further research showed that the phosphorylation levels of some important signal molecules in TLR4/MyD88-mediated MAPK and NF-κB signaling pathways were reduced by PHLDA1, which in turn impaired the transcription factors NF-κB and AP1 nuclear translocation and their responsive element activities. Furthermore, we found that PHLDA1 repressed LPS-induced proinflammatory cytokine production via binding to Tollip which restrained TLR4 signaling pathway. A mouse model of endotoxemia was established to confirm the above similar results. In brief, our findings demonstrate that PHLDA1 is a negative regulator of LPS-induced proinflammatory cytokine production by Tollip, suggesting that PHLDA1 plays an anti-inflammatory role through inhibiting the TLR4/MyD88 signaling pathway with the help of Tollip. PHLDA1 may be a novel therapeutic target in treating endotoxemia.
Crosstalk Between Pyroptosis and Apoptosis in Hepatitis C Virus-induced Cell Death
Authors: Wallace Hannah L. , Wang Lingyan , Gardner Cassandra L. , Corkum Christopher P. , Grant Michael D. , Hirasawa Kensuke , Russell Rodney S.
Published: February 2022

Extensive inflammation in the liver is known to contribute to the pathogenesis of hepatitis C virus (HCV) infection. Apoptosis has, for a long time, been known to act as a mechanism of hepatocyte death, but our previous research also identified inflammasome-mediated pyroptosis in infected and uninfected bystander cells as an additional mechanism of HCV-induced cytopathicity. The purpose of this study was to investigate the mechanism of HCV-induced cell death and to determine the timing and relative contributions of apoptosis and pyroptosis during HCV infection. In a model employing a cell culture-adapted strain of JFH-1 HCV and Huh-7.5 hepatocyte-like cells, we found that pyroptosis occurred earlier than did apoptosis during infection. CRISPR knockout of NLRP3 resulted in decreased caspase-1 activation, but not complete elimination, indicating multiple sensors are likely involved in HCV-induced pyroptosis. Knockout of gasdermin-D resulted in increased activation of apoptosis-related caspase-3, suggesting potential crosstalk between the two cell death pathways. An unexpected decrease in activated caspase-1 levels was observed when caspase-3 was knocked out, implying that caspase-3 may have a role in the initiation of pyroptosis, at least in the context of HCV infection. Lower viral titres in culture fluids and increased ratios of intracellular to extracellular levels of infectious virus were observed in knockout versus wild-type Huh-7.5 cells, suggesting that HCV may induce programmed cell death in order to enhance virus release from infected cells. These results contribute to the understanding of HCV pathogenesis and add to the increasing volume of literature suggesting various programmed cell death pathways are not mutually exclusive.
Interaction of Mycobacteria With Host Cell Inflammasomes
Authors: Rastogi Shivangi , Briken Volker
Published: February 2022

The inflammasome complex is important for host defense against intracellular bacterial infections. Mycobacterium tuberculosis (Mtb) is a facultative intracellular bacterium which is able to survive in infected macrophages. Here we discuss how the host cell inflammasomes sense Mtb and other related mycobacterial species. Furthermore, we describe the molecular mechanisms of NLRP3 inflammasome sensing of Mtb which involve the type VII secretion system ESX-1, cell surface lipids (TDM/TDB), secreted effector proteins (LpqH, PPE13, EST12, EsxA) and double-stranded RNA acting on the priming and/or activation steps of inflammasome activation. In contrast, Mtb also mediates inhibition of the NLRP3 inflammasome by limiting exposure of cell surface ligands via its hydrolase, Hip1, by inhibiting the host cell cathepsin G protease via the secreted Mtb effector Rv3364c and finally, by limiting intracellular triggers (K+ and Cl- efflux and cytosolic reactive oxygen species production) via its serine/threonine kinase PknF. In addition, Mtb inhibits the AIM2 inflammasome activation via an unknown mechanism. Overall, there is good evidence for a tug-of-war between Mtb trying to limit inflammasome activation and the host cell trying to sense Mtb and activate the inflammasome. The detailed molecular mechanisms and the importance of inflammasome activation for virulence of Mtb or host susceptibility have not been fully investigated.
Machine Learning Algorithms Identify Clinical Subtypes and Cancer in Anti-TIF1γ+ Myositis: A Longitudinal Study of 87 Patients
Authors: Zhao Lijuan , Xie Shuoshan , Zhou Bin , Shen Chuyu , Li Liya , Pi Weiwei , Gong Zhen , Zhao Jing , Peng Qi , Zhou Junyu , Peng Jiaqi , Zhou Yan , Zou Lingxiao , Song Liang , Zhu Honglin , Luo Hui
Published: February 2022

Background

Anti-TIF1γ antibodies are a class of myositis-specific antibodies (MSAs) and are closely associated with adult cancer-associated myositis (CAM). The heterogeneity in anti-TIF1γ+ myositis is poorly explored, and whether anti-TIF1γ+ patients will develop cancer or not is unknown at their first diagnosis. Here, we aimed to explore the subtypes of anti-TIF1γ+ myositis and construct machine learning classifiers to predict cancer in anti-TIF1γ+ patients based on clinical features.

Methods

A cohort of 87 anti-TIF1γ+ patients were enrolled and followed up in Xiangya Hospital from June 2017 to June 2021. Sankey diagrams indicating temporal relationships between anti-TIF1γ+ myositis and cancer were plotted. Elastic net and random forest were used to select and rank the most important variables. Multidimensional scaling (MDS) plot and hierarchical cluster analysis were performed to identify subtypes of anti-TIF1γ+ myositis. The clinical characteristics were compared among subtypes of anti-TIF1γ+ patients. Machine learning classifiers were constructed to predict cancer in anti-TIF1γ+ myositis, the accuracy of which was evaluated by receiver operating characteristic (ROC) curves.

Results

Forty-seven (54.0%) anti-TIF1γ+ patients had cancer, 78.7% of which were diagnosed within 0.5 years of the myositis diagnosis. Fourteen variables contributing most to distinguishing cancer and non-cancer were selected and used for the calculation of the similarities (proximities) of samples and the construction of machine learning classifiers. The top 10 were disease duration, percentage of lymphocytes (L%), percentage of neutrophils (N%), neutrophil-to-lymphocyte ratio (NLR), sex, C-reactive protein (CRP), shawl sign, arthritis/arthralgia, V-neck sign, and anti-PM-Scl75 antibodies. Anti-TIF1γ+ myositis patients can be clearly separated into three clinical subtypes, which correspond to patients with low, intermediate, and high cancer risk, respectively. Machine learning classifiers [random forest, support vector machines (SVM), extreme gradient boosting (XGBoost), elastic net, and decision tree] had good predictions for cancer in anti-TIF1γ+ myositis patients. In particular, the prediction accuracy of random forest was >90%, and decision tree highlighted disease duration, NLR, and CRP as critical clinical parameters for recognizing cancer patients.

Conclusion

Anti-TIF1γ+ myositis can be separated into three distinct subtypes with low, intermediate, and high risk of cancer. Machine learning classifiers constructed with clinical characteristics have favorable performance in predicting cancer in anti-TIF1γ+ myositis, which can help physicians in choosing appropriate cancer screening programs.
Dectin-1 Signaling Update: New Perspectives for Trained Immunity
Authors: Mata-Martínez Pablo , Bergón-Gutiérrez Marta , del Fresno Carlos
Published: February 2022

The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by β-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the β-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.
COVID-19 Recovery Patterns Across Alpha (B.1.1.7) and Delta (B.1.617.2) Variants of SARS-CoV-2
Authors: Kumar Nitya , Quadri Suha , AlAwadhi Abdulla Ismaeel , AlQahtani Manaf
Published: February 2022

Background

B.1.1.7 (alpha) and B.1.617.2 (delta) variants of concern for SARS-CoV-2 have been reported to have differential infectivity and pathogenicity. Difference in recovery patterns across these variants and the interaction with vaccination status has not been reported in population-based studies.

Objective

The objective of this research was to study the length of stay and temporal trends in RT-PCR cycle times (Ct) across alpha and delta variants of SARS-CoV-2 between vaccinated and unvaccinated individuals.

Methods

Participants consisted of patients admitted to national COVID-19 treatment facilities if they had a positive RT-PCR test for SARS-CoV-2, and analysis of variants was performed (using whole genome sequencing). Information on vaccination status, age, sex, cycle times (Ct) for four consecutive RT-PCR tests conducted during hospital stay, and total length of hospital stay for each participant were ascertained from electronic medical records.

Results

Patients infected with the delta variant were younger (mean age = 35years vs 39 years for alpha, p<0.001) and had lesser vaccination coverage (54% vs 72% for alpha, p<0.001). RT-PCR Ct values were similar for both variants at the baseline test; however by the fourth test, delta variant patients had significantly lower Ct values (27 vs 29, p=0.05). Length of hospital stay was higher in delta variant patients in vaccinated (3 days vs 2.9 days for alpha variant) as well as in unvaccinated patients (5.2 days vs 4.4 days for alpha variant, p<0.001). Hazards of hospital discharge after adjusting for vaccination status, age, and sex was higher for alpha variant infections (HR=1.2, 95% CI: 1.01–1.41, p=0.029).

Conclusion

Patients infected with the delta variant of SARS-CoV-2 were found to have a slower recovery as indicated by longer length of stay and higher shedding of the virus compared to alpha variant infections, and this trend was consistent in both vaccinated and unvaccinated patients.
Toll-Like Receptor Evolution: Does Temperature Matter?
Authors: Sousa Cármen , Fernandes Stefan A. , Cardoso João C. R. , Wang Ying , Zhai Wanying , Guerreiro Pedro M. , Chen Liangbiao , Canário Adelino V. M. , Power Deborah M.
Published: February 2022

Toll-like receptors (TLRs) recognize conserved pathogen-associated molecular patterns (PAMPs) and are an ancient and well-conserved group of pattern recognition receptors (PRRs). The isolation of the Antarctic continent and its unique teleost fish and microbiota prompted the present investigation into Tlr evolution. Gene homologues of tlr members in teleosts from temperate regions were present in the genome of Antarctic Nototheniidae and the non-Antarctic sister lineage Bovichtidae. Overall, in Nototheniidae apart from D. mawsoni, no major tlr gene family expansion or contraction occurred. Instead, lineage and species-specific changes in the ectodomain and LRR of Tlrs occurred, particularly in the Tlr11 superfamily that is well represented in fish. Positive selective pressure and associated sequence modifications in the TLR ectodomain and within the leucine-rich repeats (LRR), important for pathogen recognition, occurred in Tlr5, Tlr8, Tlr13, Tlr21, Tlr22, and Tlr23 presumably associated with the unique Antarctic microbiota. Exposure to lipopolysaccharide (Escherichia coli O111:B4) Gram negative bacteria did not modify tlr gene expression in N. rossii head–kidney or anterior intestine, although increased water temperature (+4°C) had a significant effect.
Immunological Evidence of Variation in Exposure and Immune Response to Bacillus anthracis in Herbivores of Kruger and Etosha National Parks
Authors: Ochai Sunday O. , Crafford Jan E. , Hassim Ayesha , Byaruhanga Charles , Huang Yen-Hua , Hartmann Axel , Dekker Edgar H. , van Schalkwyk O. Louis , Kamath Pauline L. , Turner Wendy C. , van Heerden Henriette
Published: February 2022

Exposure and immunity to generalist pathogens differ among host species and vary across spatial scales. Anthrax, caused by a multi-host bacterial pathogen,Bacillus anthracis, is enzootic in Kruger National Park (KNP), South Africa and Etosha National Park (ENP), Namibia. These parks share many of the same potential host species, yet the main anthrax host in one (greater kudu (Tragelaphus strepsiceros) in KNP and plains zebra (Equus quagga) in ENP) is only a minor host in the other. We investigated species and spatial patterns in anthrax mortalities,B. anthracisexposure, and the ability to neutralize the anthrax lethal toxin to determine if observed host mortality differences between locations could be attributed to population-level variation in pathogen exposure and/or immune response. Using serum collected from zebra and kudu in high and low incidence areas of each park (18- 20 samples/species/area), we estimated pathogen exposure from anti-protective antigen (PA) antibody response using enzyme-linked immunosorbent assay (ELISA) and lethal toxin neutralization with a toxin neutralization assay (TNA). Serological evidence of pathogen exposure followed mortality patterns within each system (kudus: 95% positive in KNP versus 40% in ENP; zebras: 83% positive in ENP versus 63% in KNP). Animals in the high-incidence area of KNP had higher anti-PA responses than those in the low-incidence area, but there were no significant differences in exposure by area within ENP. Toxin neutralizing ability was higher for host populations with lower exposure prevalence, i.e., higher in ENP kudus and KNP zebras than their conspecifics in the other park. These results indicate that host species differ in their exposure to and adaptive immunity againstB. anthracisin the two parks. These patterns may be due to environmental differences such as vegetation, rainfall patterns, landscape or forage availability between these systems and their interplay with host behavior (foraging or other risky behaviors), resulting in differences in exposure frequency and dose, and hence immune response.
Spatiotemporal Patterns of CRF07_BC in China: A Population-Based Study of the HIV Strain With the Highest Infection Rates
Authors: Gan Mengze , Zheng Shan , Hao Jingjing , Ruan Yuhua , Liao Lingjie , Shao Yiming , Feng Yi , Xing Hui
Published: February 2022

The prevalence of CRF07_BC is 39.7% and has become the most infectious HIV strain in China. To study the transmission and diffusion trajectory of CRF07_BC in China and to prevent further expansion of its transmission. A total of 16,635 sequences of the CRF07_BC pol gene were collected from 1997-2020. We characterized the gene subtypes according to a phylogenetic tree analysis. A 0.50% molecular network was constructed to analyze the transmission relationship among different provinces for CRF07_BC and its two epidemic clusters. Spatial and temporal propagation characteristics were analyzed according to phylogeographic analysis. Finally, we evaluated the differences in transmission of CRF07_BC-O, and CRF07_BC-N. Our dataset included 8,816 sequences of CRF07_BC-N and 7,819 sequences of CRF07_BC-O. There were 7,132 CRF07_BC sequences in the molecular network, and the rate of clustered was 42.9%. Compared to CRF07_BC-O, CRF07_BC-N showed significantly (P<0.001) higher transmission-specific rates. CRF07_BC originated among injecting drug users (IDUs), and spread to men who have sex with men (MSMs) and heterosexual individuals (HETs), while MSMs also transmitted directly to HETs. CRF07_BC-O and CRF07_BC-N were prevalent in Xinjiang and Sichuan, respectively, before spreading interprovincially. In modern China, CRF07_BC-N occurs in five of the major economic zones. The CRF07_BC strain, which has contributed to the highest number of HIV infections in China, is divided into two epidemic clusters. Compared with CRF07_BC-O, risk of transmission is much greater in CRF07_BC-N, which is predominantly prevalent in economically developed provinces, and both MSMs and IDUs have transmitted this epidemic cluster to HETs. High-resolution, large-scale monitoring is a useful tool in assessing the trend and spread of the HIV epidemic. The rapidly developing economy of China requires an equally rapid response to the prevention and control of infectious diseases.
Complement Activation via the Lectin and Alternative Pathway in Patients With Severe COVID-19
Authors: Niederreiter Janina , Eck Christine , Ries Tajana , Hartmann Arndt , Märkl Bruno , Büttner-Herold Maike , Amann Kerstin , Daniel Christoph
Published: February 2022

Complement plays an important role in the direct defense to pathogens, but can also activate immune cells and the release of pro-inflammatory cytokines. However, in critically ill patients with COVID-19 the immune system is inadequately activated leading to severe acute respiratory syndrome (SARS) and acute kidney injury, which is associated with higher mortality. Therefore, we characterized local complement deposition as a sign of activation in both lungs and kidneys from patients with severe COVID-19. Using immunohistochemistry we investigated deposition of complement factors C1q, MASP-2, factor D (CFD), C3c, C3d and C5b-9 as well as myeloperoxidase (MPO) positive neutrophils and SARS-CoV-2 virus particles in lungs and kidneys from 38 patients who died from COVID-19. In addition, tissue damage was analyzed using semi-quantitative scores followed by correlation with complement deposition. Autopsy material from non-COVID patients who died from cardiovascular causes, cerebral hemorrhage and pulmonary embolism served as control (n=8). Lung injury in samples from COVID-19 patients was significantly more pronounced compared to controls with formation of hyaline membranes, thrombi and edema. In addition, in the kidney tubular injury was higher in these patients and correlated with lung injury (r=0.361*). In autopsy samples SARS-CoV-2 spike protein was detected in 22% of the lungs of COVID-19 patients but was lacking in kidneys. Complement activation was significantly stronger in lung samples from patients with COVID-19 via the lectin and alternative pathway as indicated by deposition of MASP-2, CFD, C3d and C5b9. Deposits in the lung were predominantly detected along the alveolar septa, the hyaline membranes and in the alveolar lumina. In the kidney, complement was significantly more deposited in patients with COVID-19 in peritubular capillaries and tubular basement membranes. Renal COVID-19-induced complement activation occurred via the lectin pathway, while activation of the alternative pathway was similar in both groups. Furthermore, MPO-positive neutrophils were found in significantly higher numbers in lungs and kidneys of COVID-19 patients and correlated with local MASP-2 deposition. In conclusion, in patients who died from SARS-CoV-2 infection complement was activated in both lungs and kidneys indicating that complement might be involved in systemic worsening of the inflammatory response. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury in COVID-19.
Fighting MDR-Klebsiella pneumoniae Infections by a Combined Host- and Pathogen-Directed Therapeutic Approach
Authors: Poerio Noemi , Olimpieri Tommaso , Henrici De Angelis Lucia , De Santis Federica , Thaller Maria Cristina , D’Andrea Marco Maria , Fraziano Maurizio
Published: February 2022

Klebsiella pneumoniae is an opportunistic pathogen that is very difficult to treat mainly due to its high propensity to acquire complex resistance traits. Notably, multidrug resistance (MDR)-Klebsiella pneumoniae (KP) infections are responsible for 22%–72% of mortality among hospitalized and immunocompromised patients. Although treatments with new drugs or with combined antibiotic therapies have some degree of success, there is still the urgency to investigate and develop an efficient approach against MDR-KP infections. In this study, we have evaluated, in an in vitro model of human macrophages, the efficacy of a combined treatment consisting of apoptotic body-like liposomes loaded with phosphatidylinositol 5-phosphate (ABL/PI5P) and φBO1E, a lytic phage specific for the major high-risk clone of KPC-positive MDR-KP. Results show that ABL/PI5P did not affect in a direct manner KKBO-1 viability, being able to reduce only the intracellular KKBO-1 bacterial load. As expected, φBO1E was effective mainly on reducing extracellular bacilli. Importantly, the combination of both treatments resulted in a simultaneous reduction of both intracellular and extracellular bacilli. Moreover, the combined treatment of KKBO-1-infected cells reduced proinflammatory TNF-α and IL-1β cytokines and increased anti-inflammatory TGF-β cytokine production. Overall, our data support the therapeutic value of a combined host- and pathogen-directed therapy as a promising approach, alternative to single treatments, to simultaneously target intracellular and extracellular pathogens and improve the clinical management of patients infected with MDR pathogens such as MDR-KP.
Molecular Prerequisites for Neutrophil Extracellular Trap Formation and Evasion Mechanisms of Staphylococcus aureus
Authors: von Köckritz-Blickwede Maren , Winstel Volker
Published: February 2022

NETosis is a multi-facetted cellular process that promotes the formation of neutrophil extracellular traps (NETs). NETs as web-like structures consist of DNA fibers armed with granular proteins, histones, and microbicidal peptides, thereby exhibiting pathogen-immobilizing and antimicrobial attributes that maximize innate immune defenses against invading microbes. However, clinically relevant pathogens often tolerate entrapment and even take advantage of the remnants of NETs to cause persistent infections in mammalian hosts. Here, we briefly summarize how Staphylococcus aureus, a high-priority pathogen and causative agent of fatal diseases in humans as well as animals, catalyzes and concurrently exploits NETs during pathogenesis and recurrent infections. Specifically, we focus on toxigenic and immunomodulatory effector molecules produced by staphylococci that prime NET formation, and further highlight the molecular and underlying principles of suicidal NETosis compared to vital NET-formation by viable neutrophils in response to these stimuli. We also discuss the inflammatory potential of NET-controlled microenvironments, as excessive expulsion of NETs from activated neutrophils provokes local tissue injury and may therefore amplify staphylococcal disease severity in hospitalized or chronically ill patients. Combined with an overview of adaptation and counteracting strategies evolved by S. aureus to impede NET-mediated killing, these insights may stimulate biomedical research activities to uncover novel aspects of NET biology at the host-microbe interface.
Artificial Attraction: Linking Vessel Monitoring System and Habitat Data to Assess Commercial Exploitation on Artificial Structures in the Gulf of Mexico
Authors: Gardner Christopher , Goethel Daniel R. , Karnauskas Mandy , Smith Matthew W. , Perruso Larry , Walter John F.
Published: February 2022

Marine artificial structures provide important ecosystem benefits, but the extent to which commercially valuable reef fish species and their associated fisheries utilize artificial structures is still undetermined. However, the increasing implementation of onboard Vessel Monitoring Systems (VMS) now enables precise identification of catch and effort locations that can be linked via satellite coordinates to seafloor habitat maps. To better understand the distribution of fishing effort across artificial and natural reef types in the Gulf of Mexico, we present the first attempt to link VMS data from commercial reef fish vessels with high resolution habitat maps for an iconic species, red snapper (Lutjanus campechanus). By allocating landings from VMS-linked individual fishing trips to habitat type (i.e., natural reef, artificial structure, or uncharacterized bottom) and overlaying these with previously developed red snapper biomass distributions, we are able to develop one of the first fine-scale spatial maps of exploitation across the entire Gulf of Mexico. Results indicated that nearly half (46%) of commercial red snapper landings were extracted from artificial structures. The degree of exploitation was highly heterogeneous with several localized hotspots on natural reefs along the continental shelf break and offshore areas of the Northeast Gulf of Mexico. Similarly, there were distinct regional differences in fishing patterns: a majority of the landings from the state of Florida (∼91%) came from natural reefs, whereas ∼75% of landings were from artificial structures from all other Gulf of Mexico states combined. These results indicate that the potential for localized depletion exists for red snapper. The exploitation maps developed here can directly aid fisheries managers by highlighting specific habitats and locations that should be carefully monitored as catch limits continue to increase.
Effect of Greater Duckweed Spirodela polyrhiza Supplemented Feed on Growth Performance, Digestive Enzymes, Amino and Fatty Acid Profiles, and Expression of Genes Involved in Fatty Acid Biosynthesis of Juvenile Common Carp Cyprinus carpio
Authors: Shrivastav Avanish Kumar , Kumar Guddu , Mittal Prabhat , Tocher Douglas R. , Glencross Brett D. , Chakrabarti Rina , Sharma JaiGopal
Published: February 2022

The greater duckweed Spirodela polyrhiza (Lemnaceae) is a free-floating freshwater macrophyte. The effect of dietary inclusion of duckweed in the feed of common carp Cyprinus carpio fry was evaluated. The control feed (SP0) contained soybean meal as the primary protein source. In four experimental feeds, greater duckweed was incorporated at levels of 5% (SP5), 10% (SP10), 15% (SP15), and 20% (SP20) replacing soybean meal. Broken-line regression showed that incorporation of greater duckweed at 10 and 13.4% levels were the breakpoint for final weight and specific growth rate (SGR) of fish, respectively. The final weight and SGR of common carp fed diet SP20 were significantly higher compared with those of others. The feed conversion ratio was lowest in SP20 treatment. The inclusion of greater duckweed in the fish feeds showed linear relationships with amylase, trypsin, chymotrypsin, and lipase activities. The content of crude protein was significantly higher in SP10, SP15, and SP20 treatments compared with that of others. Significantly higher crude lipid and ash contents were found in SP20 diet-fed fish compared with other diet-fed fish. The essential amino acids composition was similar in five different diet-fed fish. The greater duckweed supplemented feeds influenced the fatty acid contents of fish. The monounsaturated fatty acids (MUFA) showed an inverse relationship with the inclusion level of greater duckweed in the feed. The highest MUFA content was found in fish fed SP0 diet. The highest level of linoleic acid was found in SP20 diet fed fish. The n-3 PUFA contents of fish showed an increasing trend with the increasing inclusion of greater duckweed, and a significantly higher level was found in SP20 compared with that of others. A significantly higher expression of fas was found in SP5 and fads2d6 in SP5 and SP10 compared with that of others. The expressions of elovl2 and elovl5 were significantly higher in SP5, SP10, and SP15 diet-fed fish compared with other diet-fed fish. The incorporation of greater duckweed in diets improved the growth performance and nutritional value of common carp.