Integrative genomic and transcriptomic analysis for pinpointing recurrent alterations of plant homeodomain genes and their clinical significance in breast cancer

A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of patients. Different subtypes of breast cancer had different patterns of copy number and expression for each PHF. We identified a subset of PHF genes that was recurrently altered with high prevalence, including PYGO2 (pygopus family PHD finger 2), ZMYND8 (zinc finger, MYND-type containing 8), ASXL1 (additional sex combs like 1) and CHD3 (chromodomain helicase DNA binding protein 3). Copy number increase and overexpression of ZMYND8 were more prevalent in Luminal B subtypes and were significantly associated with shorter survival of breast cancer patients. ZMYND8 was also involved in a positive feedback circuit of the estrogen receptor (ER) pathway, and the expression of ZMYND8 was repressed by the bromodomain and extra terminal (BET) inhibitor in breast cancer. Our findings suggest a promising avenue for future research—to focus on a subset of PHFs to better understand the molecular mechanisms and to identify therapeutic targets in breast cancer

Epidemiological characteristics analysis of foodborne disease outbreaks caused by takeaway in China’s Mainland from 2010 to 2020

ObjectiveTo analyze the epidemiological characteristics of foodborne disease outbreaks caused by takeaway in China’s Mainland from 2010 to 2020， and put forward relevant regulatory suggestions.MethodsThrough the National Foodborne Disease Outbreak Monitoring System， the data of foodborne disease outbreaks caused by takeaway in China’s Mainland from 2010 to 2020 were collected and analyzed， and descriptive epidemiological characteristics were performed.ResultsA total of 549 foodborne disease outbreaks caused by takeaway were reported in China’s Mainland （except Tibet Autonomous Region） from 2010 to 2020， resulting in 9 285 illnesses and 2 deaths. The largest number of outbreaks and illnesses was in the third quarter， accounting for 41.53% and 44.58% of the total respectively. Except the unknown pathogenic factors， the number of outbreaks and illnesses caused by microbial pathogenic factors were the highest， accounting for 39.16% and 60.26% of the total respectively. Except the unknown suspected food， the number of outbreaks and illnesses caused by mixed food and multiple food were higher， accounting for 21.86% and 15.12% of the outbreaks respectively， and accounting for 20.58% and 13.10% of the number of illnesses respectively. Except the unknown food source， the top 3 food source were school canteens， collective dining delivery units/central kitchens and fast food restaurants， the number of outbreaks accounted for 20.04%， 15.66% and 15.48% respectively， and the number of illnesses accounted for 35.30%， 17.52% and 10.57% respectively. Except the multiple factors and unknown factors， the number of outbreaks caused by improper storage were the highest accounting for 8.74%， and the number of illnesses caused by improper processing accounted for 7.74%.ConclusionMicrobial growth and reproduction due to improper storage and processing is the major cause of foodborne disease outbreaks caused by takeaway. It is suggested that the food safety supervision and administration departments should strengthen the whole process supervision and management of takeaway， establish and ensure catering services strictly abide by the good hygiene operations according to food raw in materials， production， transportation， distribution and other aspects， so as to effectively prevent and control the occurrence foodborne diseases

A Monoselective Sphingosine-1-Phosphate Receptor-1 Agonist Prevents Allograft Rejection in a Stringent Rat Heart Transplantation Model

SummaryFTY720 is an immunomodulator with demonstrated efficacy in a phase II trial of relapsing multiple sclerosis. FTY720-phosphate, the active metabolite generated upon phosphorylation in vivo, acts as a potent agonist on four of the five known sphingosine-1-phosphate (S1P1) receptors. AUY954, an aminocarboxylate analog of FTY720, is a low nanomolar, monoselective agonist of the S1P1 receptor. Due to its selectivity and pharmacokinetic profile, AUY954 is an excellent pharmacological probe of S1P1-dependent phenomena. Oral administration of AUY954 induces a profound and reversible reduction of circulating lymphocytes and, in combination with RAD001 (Certican/Everolimus, an mTOR inhibitor), is capable of prolonging the survival of cardiac allografts in a stringent rat transplantation model. This demonstrates that a selective agonist of the S1P1 receptor is sufficient to achieve efficacy in an animal model of transplantation

Optimization of Membrane Protein TmrA Purification Procedure Guided by Analytical Ultracentrifugation

Membrane proteins are involved in various cellular processes. However, purification of membrane proteins has long been a challenging task, as membrane protein stability in detergent is the bottleneck for purification and subsequent analyses. Therefore, the optimization of detergent conditions is critical for the preparation of membrane proteins. Here, we utilize analytical ultracentrifugation (AUC) to examine the effects of different detergents (OG, Triton X-100, DDM), detergent concentrations, and detergent supplementation on the behavior of membrane protein TmrA. Our results suggest that DDM is more suitable for the purification of TmrA compared with OG and TritonX-100; a high concentration of DDM yields a more homogeneous protein aggregation state; supplementing TmrA purified with a low DDM concentration with DDM maintains the protein homogeneity and aggregation state, and may serve as a practical and cost-effective strategy for membrane protein purification

A Stable interface based on aryl diazonium salts/SWNTs modified gold electrodes for sensitive detection of hydrogen peroxide

A stable and sensitive hydrogen peroxide (H₂O₂) biosensor based on aryldiazonium salt and SWNTs modified gold electrodes is reported. SWNTs were covalently anchored to the mixed monolayer of phenyl and 4-aminophenyl in molar ratio of 1:1 through aryldiazonium salt reaction to form stable C-C bonding. PEG molecules were introduced to the interface to resist non-specific protein adsorption. Covalent attachment of HRP to SWNTs allowed direct electron transfer to the redox protein with a rate constant of 28.6 ± 1.9 s⁻¹, indicating a specific interaction between SWNTs and HRP. The covalently attached SWNTs facilitate the electrical coupling between protein and electrodes. The covalently immobilized HRP retained its catalytic activity by the enzyme responding to the addition of H₂O₂. The SWNTs/PEG/HRP modified sensing interface can be used for the detection of H₂O₂ in the range of 0.01-24 μM with a detection limit of 10 nM. Comparing to the sensing system in which HRP was physically adsorbed on the interface without the assembly of PEG, the performance of the SWNTs/PEG/HRP sensing interface has been significantly improved. The so fabricated biosensor exhibited high sensitivity, good reproducibility, and long-term stability, and can be used for the detection of H₂O₂ in real samples with good recovery.7 page(s

How does functional distinctiveness affect single species contribution to β diversity? Evidence from a subtropical forest plot in southern China

To biologically interpret β diversity patterns, in terms of species characteristics, needs to quantify how each individual species contributes to overall β diversity (SCBD). However, the lack of studies linking SCBD to functional traits hinders to explore the full potential of the approach in biodiversity conservation. Here, we combined census data, species functional traits, and environmental variables from a 50-ha stem-mapped forest plot in southern China, with the aim to disentangle the relationship among SCBD, species functional traits and niche properties. We used nine functional traits to estimate species functional distinctiveness, and eleven environmental variables were used to compute species niche properties (niche position and niche breadth). Structural equation modeling (SEM) was applied to analyze how functional distinctiveness and niche properties jointly influenced SCBD. Results found that species with more unique trait combinations (higher functional distinctiveness) occupied marginal niche position and maintained smaller niche breadths and thus contributed less to overall β diversity. Meanwhile, functional distinctiveness and niche properties jointly determined SCBD. In addition, we found a negative effect of functional distinctiveness on SCBD, which implies the urgency of developing better biodiversity conservation strategies by unravelling the linkage between SCBD and ecosystem multifunctionality. These findings contribute to a better understanding of how species characteristics affect β diversity and making SCBD more applicable in biodiversity conservation

The Quantification of Bacterial Cell Size: Discrepancies Arise from Varied Quantification Methods

The robust regulation of the cell cycle is critical for the survival and proliferation of bacteria. To gain a comprehensive understanding of the mechanisms regulating the bacterial cell cycle, it is essential to accurately quantify cell-cycle-related parameters and to uncover quantitative relationships. In this paper, we demonstrate that the quantification of cell size parameters using microscopic images can be influenced by software and by the parameter settings used. Remarkably, even if the consistent use of a particular software and specific parameter settings is maintained throughout a study, the type of software and the parameter settings can significantly impact the validation of quantitative relationships, such as the constant-initiation-mass hypothesis. Given these inherent characteristics of microscopic image-based quantification methods, it is recommended that conclusions be cross-validated using independent methods, especially when the conclusions are associated with cell size parameters that were obtained under different conditions. To this end, we presented a flexible workflow for simultaneously quantifying multiple bacterial cell-cycle-related parameters using microscope-independent methods

Root-centric β diversity reveals functional homogeneity while phylogenetic heterogeneity in a subtropical forest

<p>Root-centric studies have revealed fast taxonomic turnover across root neighborhoods, but how such turnover is accompanied by changes in species functions and phylogeny (i.e. β diversity), which can reflect the degree of community-wide biotic homogenization, remains largely unknown, hindering better inference of below-ground assembly rules, community structuring, and ecosystem processes. We collected 2480 root segments from 625 0–30 cm soil profiles in a subtropical forest in China. Root segments were identified into 143 species with DNA-barcoding with six root morphological and architectural traits measured per species. By using the mean pairwise (Dpw) and mean nearest neighbor distance (Dnn) to quantify species ecological differences, we tested the non-random functional and phylogenetic turnover of root neighborhoods that would lend more support to deterministic over stochastic community assembly processes, examined the distance-decay pattern of β diversity, and finally partitioned β diversity into geographical and environmental components to infer their potential drivers of environmental filtering, dispersal limitation, and biotic interactions. We found that functional turnover was often lower than expected given the taxonomic turnover, whereas phylogenetic turnover was often higher than expected. Both functional and phylogenetic Dpw (e.g. interfamily species) turnover exhibited a distance-decay pattern, likely reflecting limited dispersal or abiotic filtering that leads to the spatial aggregation of specific plant lineages. Conversely, phylogenetic Dnn (e.g. intrageneric species) exhibited an inverted distance-decay pattern, likely reflecting strong biotic interactions among spatially and phylogenetically close species leading to phylogenetic divergence. While the spatial distance was generally a better predictor of β diversity than environmental distance, the joint effect of environmental and spatial distance usually overrode their respective pure effects. These findings suggest that root neighborhood functional homogeneity may somewhat increase forest resilience after disturbance by exhibiting an insurance effect. Likewise, root neighborhood phylogenetic heterogeneity may enhance plant fitness by hindering the transmission of host-specific pathogens through root networks or by promoting interspecific niche complementarity not captured by species functions. Our study highlights the potential role of root-centric β diversity in mediating community structures and functions largely ignored in previous studies.</p><p>These datasets were collected in the Guangdong Heishiding Dynamic Forest Plot in Southern China (2016). Details for each dataset are provided in the README file.</p><p>Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 31925027</p><p>Funding provided by: China Postdoctoral Science Foundation<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100002858<br>Award Number: 2021M70375</p><p>Funding provided by: Basic and Applied Basic Research Foundation of Guangdong Province<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100021171<br>Award Number: 2021A1515110362</p><p>Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 32301341</p&gt

MiR-10a-5p-Mediated Syndecan 1 Suppression Restricts Porcine Hemagglutinating Encephalomyelitis Virus Replication

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a single-stranded RNA coronavirus that causes nervous dysfunction in the infected hosts and leads to widespread alterations in the host transcriptome by modulating specific microRNA (miRNA) levels. MiRNAs contribute to RNA virus pathogenesis by promoting antiviral immune response, enhancing viral replication, or altering miRNA-mediated host gene regulation. Thus, exploration of the virus–miRNA interactions occurring in PHEV-infected host may lead to the identification of novel mechanisms combating the virus life cycle or pathogenesis. Here, we discovered that the expression of miR-10a-5p was constitutively up-regulated by PHEV in both the N2a cells in vitro and mice brain in vivo. Treatment with miR-10a-5p mimics allowed miR-10a-5p enrichment and resulted in a significant restriction in PHEV replication, suggesting widespread negative regulation of the RNA virus infection by miR-10a-5p. The outcomes were also evidenced by miR-10a-5p inhibitor over-expression. Luciferase reporter, quantitative real-time PCR (qRT-PCR), and western blotting analysis further showed that Syndecan 1 (SDC1), a cell surface proteoglycan associated with host defense mechanisms, acts as a target gene of miR-10a-5p during PHEV infection. Naturally, siRNA-mediated knockdown of SDC1 leads to a reduction in viral replication, implying that SDC1 expression is likely a favorable condition for viral replication. Together, the findings demonstrated that the abundant miR-10a-5p leads to downstream suppression of SDC1, and it functions as an antiviral mechanism in the PHEV-induced disease, providing a potential strategy for the prevention and treatment of PHEV infection in the future work