bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory effect and mechanism of action of juniper essential oil on gray mold in cherry tomatoes
Authors: Wu Yu-Xuan , Zhang Yun-Di , Li Na , Wu De-Dong , Li Qi-Meng , Chen Yun-Ze , Zhang Guo-Cai , Yang Jing
Published: September 2022

Juniper essential oil (JEO), which is mostly known as an immune system booster and effective detoxifier, has substantial antimicrobial activity. A comparison of the inhibitory effects of three plant essential oils from juniper (Juniperus rigida), cedarwood (Juniperus virginiana), and cypress (Crupressus sempervirens) on four plant pathogenic fungi indicated that JEO was the most effective at inhibiting the growth of gray mold (Botrytis cinerea). Additional studies were subsequently conducted to explore the in vivo and in vitro antifungal activity and possible mechanism of JEO against B. cinerea. The results show that JEO inhibited the germination of spores and mycelial growth of B. cinerea in a concentration-dependent manner and exhibited strong inhibition when its concentration exceeded 10 μL/mL. JEO also significantly inhibited the incidence of disease and diameters of gray mold lesions on cherry tomato fruit (Solanum lycopersicum). After 12 h of treatment with JEO, the extracellular conductivity, and the contents of soluble protein, malondialdehyde, and hydrogen peroxide were 3.1, 1.2, 7.2, and 4.7 folds higher than those of the control group, respectively (P < 0.05), which indicated that JEO can damage membranes. Scanning electron microscopy observations revealed that JEO affected the morphology of mycelia, causing them to shrivel, twist and distort. Furthermore, JEO significantly improved the activities of the antioxidant-related enzymes superoxide dismutase and catalase but reduced the pathogenicity-related enzymes polygalacturonase (PG), pectin lyase and endoglucanase of B. cinerea (P < 0.05). In particular, PG was reduced by 93% after treatment with JEO for 12 h. Moreover, the 18 constituents of JEO were identified by gas chromatography/mass spectrometry (GC-MS) analysis, mainly limonene (15.17%), γ-terpinene (8.3%), β-myrcene (4.56%), terpinen-4-ol (24.26%), linalool (8.73%), α-terpineol (1.03%), o-cymene (8.35%) and other substances with antimicrobial activity. Therefore, JEO can be an effective alternative to prevent and control gray mold on cherry tomato fruit.
Metabolomic profiling of polymyxin-B in combination with meropenem and sulbactam against multi-drug resistant Acinetobacter baumannii
Authors: Zhu Shixing , Zhang Jiayuan , Song Chu , Liu Yuwei , Oo Charles , Heinrichs M. Tobias , Lv Zhihua , Zhu Yuanqi , Sy Sherwin K. B. , Deng Pan , Yu Mingming
Published: September 2022

Empirical therapies using polymyxins combined with other antibiotics are recommended in the treatment of Acinetobacter baumannii infections. In the present study, the synergistic activities of polymyxin-B, meropenem, and sulbactam as combination therapy were investigated using metabolomic analysis. The metabolome of A. baumannii was investigated after treatment with polymyxin-B alone (2 mg/l), meropenem (2 mg/l) alone, combination of polymyxin-B/meropenem at their clinical breakpoints, and triple-antibiotic combination of polymyxin-B/meropenem and 4 mg/l sulbactam. The triple-antibiotic combination significantly changed the metabolite levels involved in cell outer membrane and cell wall biosynthesis, including fatty acid, glycerophospholipid, lipopolysaccharide, peptidoglycan, and nucleotide within 15 min of administration. In contrast, significant changes in metabolome were observed after 1 h in sample treated with either meropenem or polymyxin-B alone. After 1 h of administration, the double and triple combination therapies significantly disrupted nucleotide and amino acid biosynthesis pathways as well as the central carbon metabolism, including pentose phosphate and glycolysis/gluconeogenesis pathways, and tricarboxylic acid cycle. The addition of sulbactam to polymyxin-B and meropenem combination appeared to be an early disruptor of A. baumannii metabolome, which paves the way for further antibiotic penetration into bacteria cells. Combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can effectively confer susceptibility to A. baumannii harboring OXA-23 and other drug resistant genes. Metabolomic profiling reveals underlying mechanisms of synergistic effects of polymyxin-B combined with meropenem and sulbactam against multi-drug resistant A. baumannii.
High replacement of fishmeal by Chlorella meal affects intestinal microbiota and the potential metabolic function in largemouth bass (Micropterus salmoides)
Authors: Zhang Zhimin , Xi Longwei , Liu Haokun , Jin Junyan , Yang Yunxia , Zhu Xiaoming , Han Dong , Xie Shouqi
Published: September 2022

Microalgae have beneficial effects on the performance of fish as additives and they are becoming a promising alternative to fishmeal as macronutrient ingredients. However, the impact on the fish intestinal microbiome and the function, caused by microalgae as protein sources in diets, remains unclear. This study aimed to determine the composition and potential function of the intestinal microbial community of largemouth bass (Micropterus salmoides) fed diets at five replacement levels (0, 25, 50, 75 and 100%) of fishmeal by Chlorella meal in a basal diet (400 g kg−1) after 8 weeks. The results showed significant decreases in unique amplicon sequence variants in the intestine at the higher levels of fishmeal replacement. At 50% of fishmeal replacement, dietary inclusions of Chlorella meal had no impact on species richness and Shannon diversity and the community structure of the intestinal microbiota. However, high levels of fishmeal replacement (75 and 100%) significantly induced intestinal community disturbance and diversity loss in largemouth bass. Responding to the high fishmeal replacement level, the dominant genus Cetobacterium and Pleslomonas sharply increased and several taxa from Lactobacillus decreased significantly. Functional data predicted by PICRUSt revealed that nutrition-related metabolism was dominant in the intestinal microbiota of fish fed all the five diets, although some potential functions, particularly amino acid and lipid metabolisms, and energy metabolism, were upregulated firstly, and then downregulated in fish fed diets with the increase of dietary Chlorella meal. Meanwhile, certain pathways were not enriched in intestinal microbiome until up to 75% of fishmeal replacement, such as carbohydrate metabolism, and cofactors and vitamins metabolism. To conclude, this study reveals that fishmeal replacement (50%) by Chlorella meal at the level of 237 g kg−1 in diets is feasible for largemouth bass without impairing the microbiome structure and the metabolism function, providing an alternative strategy for evaluating the possibility of fishmeal replacement by microalgae in aquafeeds.
Characteristics of denitrification and microbial community in respect to various H2 pressures and distances to the gas supply end in H2-based MBfR
Authors: Li Haixiang , Sun Ruize , Zhang Xuehong , Lin Hua , Xie Yi , Han Yu , Pan Yongxing , Wang Dunqiu , Dong Kun
Published: September 2022

The hydrogen-based hollow fiber membrane biofilm reactor (H2-based MBfR) has shown to be a promising technology for nitrate (NO3––N) reduction. Hollow fiber membranes (HFM) operating in a closed mode in an H2-based MBfR often suffer from reverse gas diffusion, taking up space for the effective gas substrate and resulting in a reduction in the HFM diffusion efficiency, which in turn affects denitrification performance. In this work, we developed a laboratory-scale H2-based MBfR, which operated in a closed mode to investigate the dynamics of denitrification performance and biofilm microbial community analysis at different H2 supply pressures. A faster formation of biofilm on the HFM and a shorter start-up period were found for a higher H2 supply pressure. An increase in the H2 pressure under 0.08 MPa could significantly promote denitrification, while a minor increase in denitrification was observed once the H2 pressure was over 0.08 MPa. Sequencing analysis of the biofilm concluded that (i) the dominant phylum-level bacteria in the reactor during the regulated hydrogen pressure phase were Gammaproteobacteria and Alphaproteobacteria; (ii) when the hydrogen pressure was 0.04–0.06 MPa, the dominant bacteria in the MBfR were mainly enriched on the hollow fiber membrane near the upper location (Gas inlet). With a gradual increase in the hydrogen pressure, the enrichment area of the dominant bacteria in MBfR gradually changed from the upper location to the distal end of the inlet. When the hydrogen pressure was 0.10 MPa, the dominant bacteria were mainly enriched on the hollow fiber membrane in the down location of the MBfR.
Antifungal Activity of Sodium New Houttuyfonate Against Aspergillus fumigatus in vitro and in vivo
Authors: Zhang Qian , Liu Fangyan , Zeng Meng , Zhang Jinping , Liu Yanfei , Xin Caiyan , Mao Yingyu , Song Zhangyong
Published: September 2022

Aspergillus fumigatus is an important pathogen causing invasive aspergillosis, which is associated with high morbidity and mortality in immunocompromised people. However, the treatment of A. fumigatus infection is a growing challenge, owing to the limited availability antifungal agents and the continual emergence of drug-resistant strains. Drug repurposing is a potential strategy to solve this current problem. Sodium new houttuyfonate (SNH), derived from houttuynin, extracted from Houttuynia cordata, has anti-bacterial and anti-Candida albicans effects. However, whether it has anti-A. fumigatus activity had not been reported. In this study, the antifungal properties of SNH against A. fumigatus, including the standard strain AF293, itraconazole resistant clinical strains, and voriconazole resistant clinical strains, were evaluated in vitro and in vivo. Moreover, the potential mechanism of SNH was characterized. SNH exhibited significant fungicidal activity toward various A. fumigatus strains. SNH also inhibited fungal growth, sporulation, conidial germination and pigment formation, and biofilm formation. Further investigations revealed that SNH interfered with the A. fumigatus cell steroid synthesis pathway, as indicated by transcriptomic and quantitative real-time polymerase chain reaction analyses, and inhibited ergosterol synthesis, as indicated by cell membrane stress assays and ergosterol quantification. Moreover, daily gastric gavage of SNH significantly decreased the fungal burden in mice with disseminated infection (kidney, liver, and lung) and local tissue damage. In addition, the application of SNH downregulated the production of IL-6 and IL-17A. Together, these findings provided the first confirmation that SNH may be a promising antifungal agent for the treatment of A. fumigatus infection.
Discovery of Natural Products With Antifungal Potential Through Combinatorial Synergy
Authors: Augostine Catheryn R. , Avery Simon V.
Published: September 2022

The growing prevalence of antifungal drug resistance coupled with the slow development of new, acceptable drugs and fungicides has raised interest in natural products (NPs) for their therapeutic potential and level of acceptability. However, a number of well-studied NPs are considered promiscuous molecules. In this study, the advantages of drug–drug synergy were exploited for the discovery of pairwise NP combinations with potentiated antifungal activity and, potentially, increased target specificity. A rational approach informed by previously known mechanisms of action of selected NPs did not yield novel antifungal synergies. In contrast, a high-throughput screening approach with yeast revealed 34 potential synergies from 800 combinations of a diverse NP library with four selected NPs of interest (eugenol, EUG; β-escin, ESC; curcumin, CUR; berberine hydrochloride, BER). Dedicated assays validated the most promising synergies, namely, EUG + BER, CUR + sclareol, and BER + pterostilbene (PTE) [fractional inhibitory concentrations (FIC) indices ≤ 0.5 in all cases], reduced to as low as 35 (BER) and 7.9 mg L–1 (PTE). These three combinations synergistically inhibited a range of fungi, including human or crop pathogens Candida albicans, Aspergillus fumigatus, Zymoseptoria tritici, and Botrytis cinerea, with synergy also against azole-resistant isolates and biofilms. Further investigation indicated roles for mitochondrial membrane depolarization and reactive oxygen species (ROS) formation in the synergistic mechanism of EUG + BER action. This study establishes proof-of-principle for utilizing high-throughput screening of pairwise NP interactions as a tool to find novel antifungal synergies. Such NP synergies, with the potential also for improved specificity, may help in the management of fungal pathogens.
Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs
Authors: Yin Beibei , Wang Xuan , Yuan Fang , Li Yan , Lu Ping
Published: September 2022

Chemotherapy is one of the most effective methods of systemic cancer treatment. Chemotherapy drugs are delivered through the blood circulation system, and they can act at all stages of the cell cycle, and can target DNA, topoisomerase, or tubulin to prevent the growth and proliferation of cancer cells. However, due to the lack of specific targets for chemotherapeutic agents, there are still unavoidable complications of cytotoxic effects. The effect of the microbiome on human health is clear. There is growing evidence of the potential relationship between the microbiome and the efficacy of cancer therapy. Gut microbiota can regulate the metabolism of drugs in several ways. The presence of bacteria in the tumor environment can also affect the response to cancer therapy by altering the chemical structure of chemotherapeutic agents and affecting their activity and local concentration. However, the underlying mechanisms by which the gut and tumor microbiota affect cancer therapeutic response are unclear. This review provides an overview of the effects of gut and tumor microbiota on the efficacy and adverse effects of chemotherapy in cancer patients, thus facilitating personalized treatment strategies for cancer patients.
Effect of experimentally increased nutrient availability on the structure, metabolic activities, and potential microbial functions of a maritime Antarctic microbial mat
Authors: Camacho Antonio , Rochera Carlos , Picazo Antonio
Published: September 2022

The role of competitive interactions based on resource utilisation was explored in a phototrophic microbial mat from Byers Peninsula (Maritime Antarctica). Shotgun metagenomic profiling of the mat showed a taxonomic and functionally diverse microbial community. The heterotrophic bacterial community was dominated by Proteobacteria, where genera typically found in polar habitats, such as Janthinobacterium, Pseudomonas, and Polaromonas, were highly prevalent. Cyanobacteria played the main role as primary producers, accompanied by diatoms and chlorophytes. To test the potential effects of the inorganic nutrient (N and P) availability on this community, a fully factorial nitrate and phosphorus addition experiment was conducted in situ. The mat exhibited a functional and structural response to the nutrient amendments. Compared to the undisturbed mat, phosphorus fertilisation favoured the growth of (non-heterocystous) cyanobacteria relative to that of diatoms, as indicated by changes in the carotenoid pigment biomarkers. Although no mat accretion was visible, fertilisation improved the phototrophic activity, and, mainly, when P was amended, the production of exopolymeric substances was favoured, whereas further changes in the vertical distribution of primary production activity were observed as well. Illumina amplicon sequencing of the 16S rRNA gene also demonstrated changes in the relative abundance of heterotrophic prokaryotes, which were detectable from the phylum to the genus level and mainly related to the amendment of nitrogen. Predictions made on the functional skills of these shifted prokaryotic communities indicated changes in abundance selecting taxa with a metabolic adaptation to the new nutrient scenarios. They mainly consisted of the enhancement of ecological strategies and metabolic regulatory mechanisms related to the uptake and metabolising of either nitrogen or phosphorus, regulated by its availability whether in a balanced way or not. This study is a pioneer in demonstrating how shifts in the regional dynamic of nutrients might alter the metabolic equilibrium of these initially considered homeostatic benthic communities. They can be accordingly considered as taxonomically diverse microbiomes with a functional repertoire still inclined to respond to the biogeochemical alteration of nutrient cycles, although occurring in a cold extreme environment where biological activity is partially restricted by environmental harshness.
Fungi Occurrence in Ready-to-Eat Hazelnuts (Corylus avellana) From Different Boreal Hemisphere Areas
Authors: Lombardi Silvia Jane , Pannella Gianfranco , Tremonte Patrizio , Mercurio Ida , Vergalito Franca , Caturano Costantino , Maiuro Lucia , Iorizzo Massimo , Succi Mariantonietta , Sorrentino Elena , Coppola Raffaele
Published: September 2022

The present study evaluated the fungal contamination of ready-to-eat dried hazelnuts considering for the first time the application of the same condition drying process of several hazelnut cultivars from different boreal hemisphere areas. Fifty lots of hazelnuts (Corylus avellana), belonging to eight cultivars from seven regions in four countries, were analyzed for fungal microbiota, describing both load levels and species diversity. For this purpose, a polyphasic approach consisting of morphological examination (optical and scanning electron microscope observation) and molecular characterization [PCR-DGGE analysis and sequence analyses of the internal transcribed spacer (ITS)] was performed. The results show that different fungal populations occur in dried hazelnuts regardless of their geographical area of production. Although some varieties appear to be relatively less susceptible, species related to Aspergillus, such as A. commune and A. ochraceus, Penicillium, including P. commune, P. solitum, and P. expansum, and Rhizopus, for instance, R. stolonifer and R. oryzae, have generally been found. A related character “hazelnut cultivar—fungi” was found for species related to the genera Trichoderma and Fusarium, including F. oxyxporum, F. solani, and F. falciforme. All 14 species found are known to host pathogenic strains. Therefore, their presence in a ready-to-eat product, such as dried hazelnuts, can pose a real danger to the consumer. Based on these considerations, the development of new protective strategies seems highly desirable. The species-level description of the contaminating fungal community acquired through this study is the starting point for the development of tailor-made protective biotechnologies.
Analysis of pit latrine microbiota reveals depth-related variation in composition, and key parameters and taxa associated with latrine fill-up rate
Authors: Ijaz Umer Zeeshan , Gundogdu Ozan , Keating Ciara , Eekert Miriam van , Gibson Walter , Parkhill Julian , Abilahi Faraji , Liseki Benard , Nguyen Viet-Anh , Sudgen Steven , Quince Christopher , Ensink Jeroen H. J. , Torondel Belen , Walker Alan W.
Published: September 2022

Pit latrines are used by billions of people globally, often in developing countries where they provide a low-tech and low-cost sanitation method. However, health and social problems can arise from a lack of emptying or maintenance of these facilities. A better understanding of the biological and environmental parameters within pit latrines could inform attempts to enhance material decomposition rates, and therefore slow fill-up rate. In this study, we have performed a spatial analysis of 35 Tanzanian pit latrines to identify bacteria and environmental factors that are associated with faster or slower pit latrine fill-up rates. Using ordination of microbial community data, we observed a linear gradient in terms of beta diversity with increasing pit latrine sample depth, corresponding to a shift in microbial community structure from gut-associated families in the top layer to environmental- and wastewater-associated taxa at greater depths. We also investigated the bacteria and environmental parameters associated with fill-up rates, and identified pH, volatile solids, and volatile fatty acids as features strongly positively correlated with pit latrine fill-up rates, whereas phosphate was strongly negatively correlated with fill-up rate. A number of pit latrine microbiota taxa were also correlated with fill-up rates. Using a multivariate regression, we identified theLactobacillaceaeandIncertae_Sedis_XIIItaxa as particularly strongly positively and negatively correlated with fill-up rate, respectively. This study therefore increases knowledge of the microbiota within pit latrines, and identifies potentially important bacteria and environmental variables associated with fill-up rates. These new insights may be useful for future studies investigating the decomposition process within pit latrines.
Colony growth and biofilm formation of Aspergillus niger under simulated microgravity
Authors: Cortesão Marta , Holland Gudrun , Schütze Tabea , Laue Michael , Moeller Ralf , Meyer Vera
Published: September 2022

The biotechnology- and medicine-relevant fungus Aspergillus niger is a common colonizer of indoor habitats such as the International Space Station (ISS). Being able to colonize and biodegrade a wide range of surfaces, A. niger can ultimately impact human health and habitat safety. Surface contamination relies on two key-features of the fungal colony: the fungal spores, and the vegetative mycelium, also known as biofilm. Aboard the ISS, microorganisms and astronauts are shielded from extreme temperatures and radiation, but are inevitably affected by spaceflight microgravity. Knowing how microgravity affects A. niger colony growth, in particular regarding the vegetative mycelium (biofilm) and spore production, will help prevent and control fungal contaminations in indoor habitats on Earth and in space. Because fungal colonies grown on agar can be considered analogs for surface contamination, we investigated A. niger colony growth on agar in normal gravity (Ground) and simulated microgravity (SMG) conditions by fast-clinorotation. Three strains were included: a wild-type strain, a pigmentation mutant (ΔfwnA), and a hyperbranching mutant (ΔracA). Our study presents never before seen scanning electron microscopy (SEM) images of A. niger colonies that reveal a complex ultrastructure and biofilm architecture, and provide insights into fungal colony development, both on ground and in simulated microgravity. Results show that simulated microgravity affects colony growth in a strain-dependent manner, leading to thicker biofilms (vegetative mycelium) and increased spore production. We suggest that the Rho GTPase RacA might play a role in A. niger’s adaptation to simulated microgravity, as deletion of ΔracA leads to changes in biofilm thickness, spore production and total biomass. We also propose that FwnA-mediated melanin production plays a role in A. niger’s microgravity response, as ΔfwnA mutant colonies grown under SMG conditions showed increased colony area and spore production. Taken together, our study shows that simulated microgravity does not inhibit A. niger growth, but rather indicates a potential increase in surface-colonization. Further studies addressing fungal growth and surface contaminations in spaceflight should be conducted, not only to reduce the risk of negatively impacting human health and spacecraft material safety, but also to positively utilize fungal-based biotechnology to acquire needed resources in situ.
The source, fate and prospect of antibiotic resistance genes in soil: A review
Authors: Han Binghua , Ma Li , Yu Qiaoling , Yang Jiawei , Su Wanghong , Hilal Mian Gul , Li Xiaoshan , Zhang Shiheng , Li Huan
Published: September 2022

Antibiotic resistance genes (ARGs), environmental pollutants of emerging concern, have posed a potential threat to the public health. Soil is one of the huge reservoirs and propagation hotspot of ARGs. To alleviate the potential risk of ARGs, it is necessary to figure out the source and fate of ARGs in the soil. This paper mainly reviewed recent studies on the association of ARGs with the microbiome and the transmission mechanism of ARGs in soil. The compositions and abundance of ARGs can be changed by modulating microbiome, soil physicochemical properties, such as pH and moisture. The relationships of ARGs with antibiotics, heavy metals, polycyclic aromatic hydrocarbons and pesticides were discussed in this review. Among the various factors mentioned above, microbial community structure, mobile genetic elements, pH and heavy metals have a relatively more important impact on ARGs profiles. Moreover, human health could be impacted by soil ARGs through plants and animals. Understanding the dynamic changes of ARGs with influencing factors promotes us to develop strategies for mitigating the occurrence and dissemination of ARGs to reduce health risks.
Culture dependent and independent characterization of endophytic bacteria in the seeds of highland barley
Authors: Chen Yulan , Liang Jinpeng , Zia Alina , Gao Xue , Wang Yong , Zhang Lingzi , Xiang Quanju , Zhao Ke , Yu Xiumei , Chen Qiang , Penttinen Petri , Nyima Tashi , Gu Yunfu
Published: September 2022

Endophytes in the seeds of plants have shown plant growth promoting (PGP) properties. Highland barley is an economically important crop and a major part of the local diet in the Tibetan Plateau, China, with potential health benefits. We applied culture-dependent and culture-independent methods to study endophytic bacteria in the seeds of eight Highland barley varieties. Based on the seed properties, the variety Ali was clearly separated from the other varieties except the variety CM. Most of the 86 isolates were assigned into genus Bacillus. Approximately half of the isolates showed PGP properties in vitro. Compared to the not-inoculated plants, inoculation with the isolate Bacillus tequilensis LZ-9 resulted in greater length and number of roots, and in bigger aboveground and root weights. Based on the 16S rRNA gene sequencing, the seed microbiome was majorly affiliated with the phylum Proteobacteria and the family Enterobacteriaceae. Overall, the bacterial community compositions in the different varieties were different from each other, yet the between variety differences in community composition seemed relatively small. The differences in community compositions were associated with differences in the total and reducing sugar contents and viscosity of the seeds, thus possibly connected to differences in the osmotic pressure tolerance of the endophytes. The results suggested that the seed endophytes are likely to promote the growth of Highland barley since germination.
Development of a rapid neutralization testing system for Rhinovirus C15 based on the enzyme-linked immunospot assay
Authors: Zhou Zhenhong , Zhu Rui , Yang Hongwei , Xu Longfa , Chen Hao , Wu Yuanyuan , Yin Zhichao , Huang Qiongzi , Zhang Dongqing , Liu Che , Que Yuqiong , Zhang Jun , Xia Ningshao , Cheng Tong
Published: September 2022

Human Rhinoviruses (RVs) are dominant pathogens causing a wide range of respiratory tract diseases, posing a huge threat to public health worldwide. Viruses belonging to the RV-C species are more likely to cause severe illnesses and are strongly associated with asthma onset or exacerbations than RV-A or RV-B. Rapid and sensitive detection of neutralizing antibodies (NAbs) against RV-C can promote the development of vaccines and antiviral drugs and help in the diagnosis of viral infection. In this study, a rapid neutralization testing system for RV-C15, based on an enzyme-linked immunospot assay (Nt-ELISPOT) was developed. A monoclonal antibody (MAb), named 9F9, with high binding efficacy for RV-C15 conjugated to horseradish peroxidase (HRP), was used to detect RV-C15-infected cells at a concentration of 2 μg/ml. The optimal infectious dose of RV-C15 was set at 1 × 104 TCID50/well and the cells were fixed with 0.5% formaldehyde diluted in PBS after incubation for 20 h. Compared with the traditional cytopathic effect (CPE)-based neutralization assay (Nt-CPE), Nt-ELISPOT significantly shortened the detection period and showed good consistency with the detection of neutralizing titers of both sera and NAbs. Using Nt-ELISPOT, three anti-RV-C15 NAbs were obtained with IC50 values of 0.16, 0.27, and 11.8 μg/ml, respectively. Moreover, 64 human serum samples collected from a wide range of age groups were tested for NAb against RV-C15 by Nt-ELISPOT. The total seroprevalence was 48.4% (31/64) and the positive rate was lowest in the group under 6 years old. Thus, the Nt-ELISPOT established in this study can be used as a high-throughput and rapid neutralization assay for the screening of NAbs and for seroepidemiological investigation against RV-C15.
Transcriptome analysis of the response of Hypomyces chrysospermus to cadmium stress
Authors: Wang Yunan , Mao Chunze , Shi Yujia , Fan Xuejing , Sun Liping , Zhuang Yongliang
Published: September 2022

Hypomyces chrysospermus is a fungal parasite that grows on Boletus species. One isolated strain of H. chrysospermus from B. griseus was obtained and proved of strong ability to tolerate and absorb cadmium (Cd) by previous research. However, the molecular mechanisms of underlying the resistance of H. chrysospermus to Cd stress have not been investigated. This study aimed to assess the effect of Cd stress on the global transcriptional regulation of H. chrysospermus. A total of 1,839 differentially expressed genes (DEGs) were identified under 120 mg/l Cd stress. Gene ontology (GO) enrichment analysis revealed that large amounts of DEGs were associated with cell membrane components, oxidoreductase activity, and transport activity. KEGG enrichment analysis revealed that these DEGs were mainly involved in the translation, amino acid metabolism, transport and catabolism, carbohydrate metabolism, and folding/sorting and degradation pathways under Cd stress. Moreover, the expression of DEGs encoding transporter proteins, antioxidant enzymes, nonenzymatic antioxidant proteins, detoxification enzymes, and transcription factors was associated with the Cd stress response. These results provide insights into the molecular mechanisms underlying Cd tolerance in H. chrysospermus and serve as a valuable reference for further studies on the detoxification mechanisms of heavy metal-tolerant fungi. Our findings may also facilitate the development of new and improved fungal bioremediation strategies.
Novel iron chelator SK4 demonstrates cytotoxicity in a range of tumour derived cell lines
Authors: Abdelaal Gina , Carter Andrew , Panayiotides Mihalis I. , Tetard David , Veuger Stephany
Published: September 2022

Iron is an essential micronutrient due to its involvement in many cellular processes including DNA replication and OXPHOS. Tumors overexpress iron metabolism linked proteins which allow for iron accumulation driving high levels of proliferation. Our group has designed novel iron chelator SK4 which targets cancer’s “iron addiction.” SK4 comprises of two key moieties: an iron chelation moiety responsible for cytotoxicity and an amino acid moiety which allows entry through amino acid transporter LAT1. We selected LAT1 as a route of entry as it is commonly overexpressed in malignant tumors. SK4 has previously demonstrated promising results in an in vitro model for melanoma. We hypothesized SK4 would be effective against a range of tumor types. We have screened a panel of tumor-derived cell lines from different origins including breast, prostate, ovarian and cervical cancer for SK4 sensitivity and we have found a range of differential sensitivities varying from 111.3 to >500 μM. We validated the iron chelation moiety as responsible for inducing cytotoxicity through control compounds; each lacking a key moiety. Following the screen, we conducted a series of assays to elucidate the mechanism of action behind SK4 cytotoxicity. SK4 was shown to induce apoptosis in triple negative breast cancer cell line MDA MB 231 but not ovarian cancer cell line SKOV3 suggesting SK4 may induce different modes of cell death in each cell line. As MDA MB 231 cells harbor a mutation in p53, we conclude SK4 is capable of inducing apoptosis in a p53-independent manner. SK4 upregulated NDRG1 expression in MDA MB 231 and SKOV3 cells. Interestingly, knockdown of NDRG1 antagonized SK4 in MDA MB 231 cells but not SKOV3 cells suggesting SK4’s mechanism of action may be mediated through NDRG1 in MDA MB 231 cells. In conclusion, we have shown tagging iron chelators with an amino acid moiety to allow entry through the LAT1 transporter represents a double pronged approach to cancer therapy, targeting “iron addiction” and amino acid metabolism dysregulation.
Investigation of bioactive compounds from Bacillus sp. against protein homologs CDC42 of Colletotrichum gloeosporioides causing anthracnose disease in cassava by using molecular docking and dynamics studies
Authors: Papathoti Narendra Kumar , Mendam Kishore , Sriram Kanduri Bala Hanumath , Thepbandit Wannaporn , Sangpueak Rungthip , Saengchan Chanon , Hoang Nguyen Huy , Megavath Vineela Sai , Kurakula Madhuri , Le Thanh Toan , Buensanteai Natthiya
Published: September 2022

Manihot esculenta, commonly called cassava, is an economically valuable crop and important staple food, grown in tropical and subtropical regions of the world. Demand for cassava in the food and fuel industry is growing worldwide. However, anthracnose disease caused by Colletotrichum gloeosporioides severely affects cassava yield and production. The bioactive molecules from Bacillus are widely used to control fungal diseases in several plants. Therefore, in this study, bioactive compounds (erucamide, behenic acid, palmitic acid, phenylacetic acid, and β-sitosterol) from Bacillus megaterium were assessed against CDC42, a key protein for virulence, from C. gloeosporioides. Structure of the CDC42 protein was generated through the comparative homology modeling method. The binding site of the ligands and the stability of the complex were analyzed through docking and molecular dynamics simulation studies, respectively. Furthermore, a protein interaction network was envisaged through the STRING database, followed by enrichment analysis in the WebGestalt tool. From the enrichment analysis, it is apparent that bioactive from B. megaterium chiefly targets the MAP kinase pathway that is essential for filamentous growth and virulence. Further exploration through experimental studies could be advantageous for cassava improvement as well as to combat against C. gloeosporioides pathogen.
In silico analysis of the HSP90 chaperone system from the African trypanosome, Trypanosoma brucei
Authors: Jamabo Miebaka , Bentley Stephen John , Macucule-Tinga Paula , Tembo Praise , Edkins Adrienne Lesley , Boshoff Aileen
Published: September 2022

African trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei (T. brucei) and spread by the tsetse fly in sub-Saharan Africa. The trypanosome relies on heat shock proteins for survival in the insect vector and mammalian host. Heat shock protein 90 (HSP90) plays a crucial role in the stress response at the cellular level. Inhibition of its interactions with chaperones and co-chaperones is being explored as a potential therapeutic target for numerous diseases. This study provides an in silico overview of HSP90 and its co-chaperones in both T. brucei brucei and T. brucei gambiense in relation to human and other trypanosomal species, including non-parasitic Bodo saltans and the insect infecting Crithidia fasciculata. A structural analysis of T. brucei HSP90 revealed differences in the orientation of the linker and C-terminal domain in comparison to human HSP90. Phylogenetic analysis displayed the T. brucei HSP90 proteins clustering into three distinct groups based on subcellular localizations, namely, cytosol, mitochondria, and endoplasmic reticulum. Syntenic analysis of cytosolic HSP90 genes revealed that T. b. brucei encoded for 10 tandem copies, while T. b. gambiense encoded for three tandem copies; Leishmania major (L. major) had the highest gene copy number with 17 tandem copies. The updated information on HSP90 from recently published proteomics on T. brucei was examined for different life cycle stages and subcellular localizations. The results show a difference between T. b. brucei and T. b. gambiense with T. b. brucei encoding a total of twelve putative HSP90 genes, while T. b. gambiense encodes five HSP90 genes. Eighteen putative co-chaperones were identified with one notable absence being cell division cycle 37 (Cdc37). These results provide an updated framework on approaching HSP90 and its interactions as drug targets in the African trypanosome.
eIF4G1 N-terminal intrinsically disordered domain is a multi-docking station for RNA, Pab1, Pub1, and self-assembly
Authors: Chaves-Arquero Belén , Martínez-Lumbreras Santiago , Sibille Nathalie , Camero Sergio , Bernadó Pau , Jiménez M. Ángeles , Zorrilla Silvia , Pérez-Cañadillas José Manuel
Published: September 2022

Yeast eIF4G1 interacts with RNA binding proteins (RBPs) like Pab1 and Pub1 affecting its function in translation initiation and stress granules formation. We present an NMR and SAXS study of the N-terminal intrinsically disordered region of eIF4G1 (residues 1–249) and its interactions with Pub1, Pab1 and RNA. The conformational ensemble of eIF4G11-249 shows an α-helix within the BOX3 conserved element and a dynamic network of fuzzy π-π and π-cation interactions involving arginine and aromatic residues. The Pab1 RRM2 domain interacts with eIF4G1 BOX3, the canonical interaction site, but also with BOX2, a conserved element of unknown function to date. The RNA1 region interacts with RNA through a new RNA interaction motif and with the Pub1 RRM3 domain. This later also interacts with eIF4G1 BOX1 modulating its intrinsic self-assembly properties. The description of the biomolecular interactions involving eIF4G1 to the residue detail increases our knowledge about biological processes involving this key translation initiation factor.
Stmol: A component for building interactive molecular visualizations within streamlit web-applications
Authors: Nápoles-Duarte J.M. , Biswas Avratanu , Parker Mitchell I. , Palomares-Baez J.P. , Chávez-Rojo M. A. , Rodríguez-Valdez L. M.
Published: September 2022

Streamlit is an open-source Python coding framework for building web-applications or “web-apps” and is now being used by researchers to share large data sets from published studies and other resources. Here we present Stmol, an easy-to-use component for rendering interactive 3D molecular visualizations of protein and ligand structures within Streamlit web-apps. Stmol can render protein and ligand structures with just a few lines of Python code by utilizing popular visualization libraries, currently Py3DMol and Speck. On the user-end, Stmol does not require expertise to interactively navigate. On the developer-end, Stmol can be easily integrated within structural bioinformatic and cheminformatic pipelines to provide a simple means for user-end researchers to advance biological studies and drug discovery efforts. In this paper, we highlight a few examples of how Stmol has already been utilized by scientific communities to share interactive molecular visualizations of protein and ligand structures from known open databases. We hope Stmol will be used by researchers to build additional open-sourced web-apps to benefit current and future generations of scientists.
Correlation between retinal vessel rarefaction and psychometric measures in an older Southern Italian population
Authors: Giuliani Gianluigi , Sborgia Giancarlo , Niro Alfredo , Castellana Fabio , Lampignano Luisa , Puzo Pasquale , Pascale Angelo , Pastore Valentina , Buonamassa Rosa , Galati Roberta , Bordinone Marco , Cassano Flavio , Clemente Arcangelo , Landini Luca , Scotti Giacomo , Gaudiomonte Marida , Guglielmi Antonella , Semeraro Roberto , Santoro Michele , Alessio Giovanni , Sardone Rodolfo , Boscia Francesco
Published: September 2022

Objective

To explore the linear association between inner retinal layers thickness and macular capillary density compared to variations of global cognition evaluated by psychometric measures in a cohort of Mediterranean subjects aged 65+ years.

Materials and methods

We performed a cross-sectional analysis of 574 participants aged 65 years+ drawn from a population-based Southern Italian study. All subjects underwent neurological evaluations, including global cognitive screening, the Mini-Mental State Examination (MMSE) and frontal assessment battery (FAB), together with an ophthalmic examination including optical coherence tomography (OCT) and OCT-Angiography. We assessed the average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL), the foveal avascular zone area, and vascular density (VD) of superficial (SVD) and deep (DVD) capillary plexi at the foveal and parafoveal area. Linear regression was applied to assess associations of ocular measurements with MMSE and FAB scores.

Results

In the linear regression model, foveal DVD (beta = 0.01, 95% CI:0.004–0.052), whole DVD (beta = 0.04, 95% CI:0.02–0.08), and whole SVD (beta = 0.04, 95% CI:0.02–0.07) showed a positive association with MMSE. In addition, foveal SVD (beta = 0.01, 95% CI:0.003–0.05) and whole SVD (beta = 0.03, 95% CI:0.004–0.08) were positively associated with the FAB score. We found no further significant association between the MMSE score or the FAB score and the average thickness of the GCC and RNFL, and FAZ area.

Conclusion

A direct linear association between the VD of the macular capillary plexi with global and frontal cognitive functions was observed in elderly subjects.
Identification of glucocorticoid receptors as potential modulators of parasympathetic and sympathetic neurons within rat intracardiac ganglia
Authors: Mousa Shaaban A. , Dehe Lukas , Aboryag Noureddin , Shaqura Mohammed , Beyer Antje , Schäfer Michael , Treskatsch Sascha
Published: September 2022

Background

Emerging evidences indicate that glucocorticoid receptors (GR) play a regulatory role in cardiac function, particularly with regard to the autonomic nervous system. Therefore, this study aimed to demonstrate the expression and the precise anatomical location of GR in relation to the parasympathetic and sympathetic innervations of the heart.

Methods

The present study used tissue samples from rat heart atria to perform conventional reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, and double immunofluorescence confocal analysis of GR with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) as well as the mineralocorticoid receptor (MR).

Results

Double immunofluorescence labeling revealed that GRs were co-expressed with VAChT in parasympathetic principal neuronal somata and nerve terminals innervating atrium. Also, GR colocalized with the sympathetic neuronal marker TH in a cluster of small intensely fluorescent (SIF) cells, on intracardiac nerve terminals and in the atrial myocardium. GR immunoreactivity was scarcely identified on CGRP-immunoreactive sensory nerve terminals. Approximately 20% of GR immunoreactive neuronal somata co-localized with MR. Finally, conventional RT-PCR and Western blot confirmed the presence of GR and MR in rat heart atria.

Conclusion

This study provides evidence for the existence of GR predominantly on cardiac parasympathetic neurons and TH-immunoreactive SIF cells suggesting a functional role of cardiac GR on cardiovascular function by modulation of the cardiac autonomic nervous system.
Acute sleep deprivation disrupts emotion, cognition, inflammation, and cortisol in young healthy adults
Authors: Thompson Kayla I. , Chau Minh , Lorenzetti Margaret S. , Hill Lauren D. , Fins Ana I. , Tartar Jaime L.
Published: September 2022

Chronic sleep deprivation has been demonstrated to diminish cognitive performance, alter mood states, and concomitantly dysregulate inflammation and stress hormones. At present, however, there is little understanding of how an acute sleep deprivation may collectively affect these factors and alter functioning. The present study aimed to determine the extent to which 24-h of sleep deprivation influences inflammatory cytokines, stress hormones, cognitive processing across domains, and emotion states. To that end, 23 participants (mean age = 20.78 years, SD = 2.87) filled out clinical health questionnaires measured by the Pittsburgh Sleep Quality Index, Morningness Eveningness Questionnaire, and Center for Epidemiological Studies Depression Scale. Actigraph was worn for seven days across testing to record sleep duration. At each session participants underwent a series of measures, including saliva and blood samples for quantification of leptin, ghrelin, IL-1β, IL-6, CRP, and cortisol levels, they completed a cognitive battery using an iPad, and an emotion battery. We found that an acute sleep deprivation, limited to a 24 h period, increases negative emotion states such as anxiety, fatigue, confusion, and depression. In conjunction, sleep deprivation results in increased inflammation and decreased cortisol levels in the morning, that are accompanied by deficits in vigilance and impulsivity. Combined, these results suggest that individuals who undergo 24 h sleep deprivation will induce systemic alterations to inflammation and endocrine functioning, while concomitantly increasing negative emotions.