bluuebunny/crossref_metadata_2025 huggingface dataset:
Chloroplast Genome Traits Correlate With Organismal Complexity and Ecological Traits in Chlorophyta
Authors: Fang Jiao , Chen Yangliang , Liu Guoxiang , Verbruggen Heroen , Zhu Huan
Published: December 2021

A positive relationship between cell size and chloroplast genome size within chloroplast-bearing protists has been hypothesized in the past and shown in some case studies, but other factors influencing chloroplast genome size during the evolution of chlorophyte algae have been less studied. We study chloroplast genome size and GC content as a function of habitats and cell size of chlorophyte algae. The chloroplast genome size of green algae in freshwater, marine and terrestrial habitats was differed significantly, with terrestrial algae having larger chloroplast genome sizes in general. The most important contributor to these enlarged genomes in terrestrial species was the length of intergenic regions. There was no clear difference in the GC content of chloroplast genomes from the three habitats categories. Functional morphological categories also showed differences in chloroplast genome size, with filamentous algae having substantially larger genomes than other forms of algae, and foliose algae had lower GC content than other groups. Chloroplast genome size showed no significant differences among the classes Ulvophyceae, Trebouxiophyceae, and Chlorophyceae, but the GC content of Chlorophyceae chloroplast genomes was significantly lower than that of Ulvophyceae and Trebouxiophyceae. There was a certain positive relationship between chloroplast genome size and cell size for the Chlorophyta as a whole and within each of three major classes. Our data also confirmed previous reports that ancestral quadripartite architecture had been lost many times independently in Chlorophyta. Finally, the comparison of the phenotype of chlorophytes algae harboring plastids uncovered that most of the investigated Chlorophyta algae housed a single plastid per cell.
Transcriptome Analysis of Eucalyptus grandis Implicates Brassinosteroid Signaling in Defense Against Myrtle Rust (Austropuccinia psidii)
Authors: Swanepoel Shae , Oates Caryn N. , Shuey Louise S. , Pegg Geoff S. , Naidoo Sanushka
Published: December 2021

Eucalyptus grandis, in its native Australian range, varies in resistance to Austropuccinia psidii (syn. Puccinia psidii). The biotrophic rust fungus, A. psidii is the causal agent of myrtle rust and poses a serious threat to Australian biodiversity. The pathogen produces yellow pustules of urediniospores on young leaves and shoots, resulting in shoot tip dieback, stunted growth, and death. Dissecting the underlying mechanisms of resistance against this pathogen will contribute to improved breeding and control strategies to mitigate its devastating effects. The aim of this study was to determine the molecular dialogue between E. grandis and A. psidii, using an RNA-sequencing approach. Resistant and susceptible E. grandis seedlings grown from seed collected across its natural range were inoculated with the pandemic biotype of A. psidii. The leaf tissue was harvested at 12-h post inoculation (hpi), 1-day post inoculation (dpi), 2-dpi and 5-dpi and subjected to RNA-sequencing using Illumina 50 bp PE reads to a depth of 40 million reads per sample. Differential gene expression and gene ontology enrichment indicated that the resistant seedlings showed controlled, coordinated responses with a hypersensitive response, while the susceptible seedlings showed no systemic response against myrtle rust. Brassinosteroid signaling was apparent as an enriched term in the resistant interaction at 2-dpi, suggesting an important role of this phytohormone in defense against the pathogen. Brassinosteroid mediated signaling genes were also among the candidate genes within two major disease resistance loci (Puccinia psidii resistance), Ppr3 and Ppr5. While brassinosteroids have been tagged as positive regulators in other plant disease resistance interactions, this is the first report in the Eucalyptus – Austropuccinia psidii interaction. Furthermore, several putative resistance genes, underlying known resistance loci and implicated in the interaction have been identified and highlighted for future functional studies. This study provided further insights into the molecular interactions between E. grandis and A. psidii, contributing to our understanding of this pathosystem.
Absence of PEXEL-Dependent Protein Export in Plasmodium Liver Stages Cannot Be Restored by Gain of the HSP101 Protein Translocon ATPase
Authors: Kreutzfeld Oriana , Grützke Josephine , Ingmundson Alyssa , Müller Katja , Matuschewski Kai
Published: December 2021

Host cell remodeling is critical for successful Plasmodium replication inside erythrocytes and achieved by targeted export of parasite-encoded proteins. In contrast, during liver infection the malarial parasite appears to avoid protein export, perhaps to limit exposure of parasite antigens by infected liver cells. HSP101, the force-generating ATPase of the protein translocon of exported proteins (PTEX) is the only component that is switched off during early liver infection. Here, we generated transgenic Plasmodium berghei parasite lines that restore liver stage expression of HSP101. HSP101 expression in infected hepatocytes was achieved by swapping the endogenous promoter with the ptex150 promoter and by inserting an additional copy under the control of the elongation one alpha (ef1α) promoter. Both promoters drive constitutive and, hence, also pre-erythrocytic expression. Transgenic parasites were able to complete the life cycle, but failed to export PEXEL-proteins in early liver stages. Our results suggest that PTEX-dependent early liver stage export cannot be restored by addition of HSP101, indicative of alternative export complexes or other functions of the PTEX core complex during liver infection.
Tissue-Specific Expression Pattern in Ancherythroculter nigrocauda, a Sexually Size Dimorphic Fish
Authors: Sun Yanhong , Wei Huijie , Chen Jian , Li Pei , Yang Qing , Wang Guiying , Li Qing
Published: December 2021

Certain members of the Actinopterygii class are known to exhibit sexual dimorphism (SD) that results in major phenotypic differences between male and female fishes of a species. One of the most common differences between the two sexes is in body weight, a factor with a high economic value in aquaculture. In this study, we used RNA sequencing (RNA-seq) to study the liver and brain transcriptomes of Ancherythroculter nigrocauda, a fish exhibiting SD. Females attain about fourfold body weight of males at sexual maturity. Sample clustering showed that both sexes were grouped well with their sex phenotypes. In addition, 2,395 and 457 differentially expressed genes (DEGs) were identified in the liver and brain tissues, respectively. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses predicted the association of PPAR signaling, cytochrome P450, and steroid hormone biosynthesis to the differences in sexual size. In addition, weighted gene co-expression network analyses (WGCNA) were conducted, and the green module was identified to be significantly correlated with sexual size dimorphism (SSD). Altogether, these results improve our understanding of the molecular mechanism underlying SSD in A. nigrocauda.
A Chromosome-Level Genome Assembly of Mozambique Tilapia (Oreochromis mossambicus) Reveals the Structure of Sex Determining Regions
Authors: Tao Wenjing , Cao Jianmeng , Xiao Hesheng , Zhu Xi , Dong Junjian , Kocher Thomas D. , Lu Maixin , Wang Deshou
Published: December 2021

The Mozambique tilapia (Oreochromis mossambicus) is a fascinating taxon for evolutionary and ecological research. It is an important food fish and one of the most widely distributed tilapias. Because males grow faster than females, genetically male tilapia are preferred in aquaculture. However, studies of sex determination and sex control in O. mossambicus have been hindered by the limited characterization of the genome. To address this gap, we assembled a high-quality genome of O. mossambicus, using a combination of high coverage of Illumina and Nanopore reads, coupled with Hi-C and RNA-Seq data. Our genome assembly spans 1,007 Mb with a scaffold N50 of 11.38 Mb. We successfully anchored and oriented 98.6% of the genome on 22 linkage groups (LGs). Based on re-sequencing data for male and female fishes from three families, O. mossambicus segregates both an XY system on LG14 and a ZW system on LG3. The sex-patterned SNPs shared by two XY families narrowed the sex determining regions to ∼3 Mb on LG14. The shared sex-patterned SNPs included two deleterious missense mutations in ahnak and rhbdd1, indicating the possible roles of these two genes in sex determination. This annotated chromosome-level genome assembly and identification of sex determining regions represents a valuable resource to help understand the evolution of genetic sex determination in tilapias.
Testing Gene-Gene Interactions Based on a Neighborhood Perspective in Genome-wide Association Studies
Authors: Guo Yingjie , Cheng Honghong , Yuan Zhian , Liang Zhen , Wang Yang , Du Debing
Published: December 2021

Unexplained genetic variation that causes complex diseases is often induced by gene-gene interactions (GGIs). Gene-based methods are one of the current statistical methodologies for discovering GGIs in case-control genome-wide association studies that are not only powerful statistically, but also interpretable biologically. However, most approaches include assumptions about the form of GGIs, which results in poor statistical performance. As a result, we propose gene-based testing based on the maximal neighborhood coefficient (MNC) called gene-based gene-gene interaction through a maximal neighborhood coefficient (GBMNC). MNC is a metric for capturing a wide range of relationships between two random vectors with arbitrary, but not necessarily equal, dimensions. We established a statistic that leverages the difference in MNC in case and in control samples as an indication of the existence of GGIs, based on the assumption that the joint distribution of two genes in cases and controls should not be substantially different if there is no interaction between them. We then used a permutation-based statistical test to evaluate this statistic and calculate a statistical p-value to represent the significance of the interaction. Experimental results using both simulation and real data showed that our approach outperformed earlier methods for detecting GGIs.
Bioinformatics Analysis of Long Non-coding RNA and Related Diseases: An Overview
Authors: Gong Yuxin , Zhu Wen , Sun Meili , Shi Lei
Published: December 2021

Long non-coding RNAs (lncRNAs) are usually located in the nucleus and cytoplasm of cells. The transcripts of lncRNAs are >200 nucleotides in length and do not encode proteins. Compared with small RNAs, lncRNAs have longer sequences, more complex spatial structures, and more diverse and complex mechanisms involved in the regulation of gene expression. LncRNAs are widely involved in the biological processes of cells, and in the occurrence and development of many human diseases. Many studies have shown that lncRNAs can induce the occurrence of diseases, and some lncRNAs undergo specific changes in tumor cells. Research into the roles of lncRNAs has covered the diagnosis of, for example, cardiovascular, cerebrovascular, and central nervous system diseases. The bioinformatics of lncRNAs has gradually become a research hotspot and has led to the discovery of a large number of lncRNAs and associated biological functions, and lncRNA databases and recognition models have been developed. In this review, the research progress of lncRNAs is discussed, and lncRNA-related databases and the mechanisms and modes of action of lncRNAs are described. In addition, disease-related lncRNA methods and the relationships between lncRNAs and human lung adenocarcinoma, rectal cancer, colon cancer, heart disease, and diabetes are discussed. Finally, the significance and existing problems of lncRNA research are considered.
Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis
Authors: Menarim Bruno C. , El-Sheikh Ali Hossam , Loux Shavahn C. , Scoggin Kirsten E. , Kalbfleisch Theodore S. , MacLeod James N. , Dahlgren Linda A.
Published: December 2021

Osteoarthritis (OA) may result from impaired ability of synovial macrophages to resolve joint inflammation. Increasing macrophage counts in inflamed joints through injection with bone marrow mononuclear cells (BMNC) induces lasting resolution of synovial inflammation. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of co-expressed gene networks associated with traits from relatedin vivoandin vitrostudies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogen-related gene network. This response was associated with sustained increased expression of two gene networks comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). These networks were common to SF and ISF, but more highly expressed in ISF. Most highly activated pathways in ISF included the mevalonate pathway and PPAR-γ signaling, with pro-resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Lower expression of mevalonate kinase and phospho-PPARγ in synovium from inflamed joints treated with BMNC, and equivalent IL-1β staining between BMNC- and DPBS-treated joints, associates with accomplished resolution in BMNC-treated joints and emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following inflammatory stimulus. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR-γ signaling enhancement for the treatment of arthritic conditions.
Isolation of Primary Mouse Pulmonary Microvascular Endothelial Cells and Generation of an Immortalized Cell Line to Obtain Sufficient Extracellular Vesicles
Authors: Liu Xu , Xia Feiping , Wu Xiao , Tang Ying , Wang Lu , Sun Qin , Xue Ming , Chang Wei , Liu Ling , Guo Fengmei , Yang Yi , Qiu Haibo
Published: December 2021

Pulmonary microvascular endothelial cells (PMECs) and the extracellular vesicles (EVs) derived from PMECs participate in maintaining pulmonary homeostasis and mediating the inflammatory response. However, obtaining a high-purity population of PMECs and their EVs from mouse is still notoriously difficult. Herein we provide a method to isolate primary mouse PMECs (pMPMECs) and to transduce SV40 lentivirus into pMPMECs to establish an immortalized cell line (iMPMECs), which provides sufficient quantities of EVs for further studies. pMPMECs and iMPMECs can be identified using morphologic criteria, a phenotypic expression profile (e.g., CD31, CD144,G. simplicifolialectin binding), and functional properties (e.g., Dil-acetylated low-density protein uptake, Matrigel angiogenesis). Furthermore, pMPMEC–EVs and iMPMEC–EVs can be identified and compared. The characteristics of pMPMEC–EVs and iMPMEC–EVs are ascertained by transmission electron microscopy, nanoparticle tracking analysis, and specific protein markers. iMPMECs produce far more EVs than pMPMECs, while their particle size distribution is similar. Our detailed protocol to isolate and immortalize MPMECs will provide researchers with anin vitromodel to investigate the specific roles of EVs in pulmonary physiology and diseases.
Preliminary Studies for One-Step Fabrication of Metallic Iron-Based Coatings on Magnesium as Temporary Protection in Biodegradable Medical Application
Authors: Yang Yuyun , Shi Zizhong , Cui Xiufang , Liu Yuejun , Jin Guo , Virtanen Sannakaisa , Boccaccini Aldo R. , She Peng
Published: December 2021

Iron and magnesium are being considered as promising candidates for biodegradable materials in medical applications, both materials having their specific advantages and challenges. A hybrid of metallic iron and magnesium in a layered composite is studied in the present work, to combine the merits of both metals. A single-step dip-coating method was employed to prepare the layered composite material. Morphology, composition, crystal structure and corrosion behavior of the Mg/Fe sheet were assessed by SEM, EDX, XRD, and electrochemical measurements. The Mg/Fe layered composite sheet is composed of the magnesium substrate, a 1–2 µm metallic iron coating, and a pompon-like Mg(OH)2/MgO top layer. Long-term open-circuit potential measurements revealed that the Mg/Fe sheet samples exhibit a “self-healing” effect in Dulbecco’s modified Eagle’s medium.
Associations Between the Choroidal Vascularity Index and Malignant Glaucoma After Trabeculectomy for Primary Angle Closure Glaucoma
Authors: Zuo Chengguo , Wang Dingqiao , Guo Xinxing , Xiao Hui , Zheng Shaoyang , Lin Mingkai , Fang Lei , Liu Xing
Published: December 2021

Purpose: To compare the choroidal vasculature characteristics by using the choroidal vascularity index (CVI) in eyes with malignant glaucoma (MG), fellow eyes with non-MG, and eyes with uncomplicated primary angle-closure glaucoma (PACG) after trabeculectomy by spectral-domain optical coherence tomography (SD-OCT).

Methods: This case–control study included 53 patients diagnosed with MG after trabeculectomy. Eyes with MG (n = 53) and the fellow eyes with non-MG (n = 50) were included. Eyes with PACG without MG after trabeculectomy (n = 60) were also enrolled as controls. The choroidal parameters, including CVI and the subfoveal choroidal thickness (SFCT), were measured by using SD-OCT images.

Results: Eyes with MG and the fellow eyes showed a significantly lower CVI than eyes with PACG controls (p < 0.001). After adjusting for age, sex, axial length (AL), and intraocular pressure (IOP), eyes with the greater CVI [odds ratio (OR), 0.44] were significantly related to MG. The area under the receiver operating characteristic curve of the CVI was greater than that of the SFCT in the diagnosis of MG (0.911 vs. 0.840, p = 0.034).

Conclusion: Eyes with MG showed a significantly lower macular CVI than eyes with PACG controls. A higher macular CVI was an associated factor of eyes with MG. The CVI serves as a more stable and sensitive indicator for MG than the SFCT in this group of patients with PACG.
Inactivated COVID-19 Vaccine Induces a Low Humoral Immune Response in a Subset of Dermatological Patients Receiving Immunosuppressants
Authors: Seree-aphinan Chutima , Chanprapaph Kumutnart , Rattanakaemakorn Ploysyne , Setthaudom Chavachol , Suangtamai Thanitta , Pomsoong Cherrin , Ratanapokasatit Yanisa , Suchonwanit Poonkiat
Published: December 2021

Inactivated Sinovac-CoronaVac vaccine (Sinovac Life Sciences, Beijing) for coronavirus disease 2019 (COVID-19) has been used in many countries. However, its immunogenicity profile in immunosuppressed dermatological patients is lacking. This prospective observational case-control study compared the humoral immune response between adult dermatological patients receiving systemic immunosuppressive therapies (n = 14) and those who did not (n = 18); excluding patients with HIV infection, cancer, non-dermatological autoimmune conditions, previous COVID-19 infection, and positive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG prior to vaccination. The subjects were advised to withhold methotrexate for 1 week after each vaccine dose while continuing other therapies unadjusted. Anti-SARS-CoV-2 IgG antibody, surrogate neutralizing antibody (sNAb), and seroconversion rates (calculated from the percentages of participants in the group with positive sNAb) were used to assess immunogenicity. We found that participants using azathioprine, cyclosporin, mycophenolate mofetil, or prednisolone ≥ 10 mg/day had a lower level of serum anti-SARS-CoV-2 IgG antibody and sNAb than those received methotrexate ≤ 10 mg/week, prednisolone < 10 mg/day, or biologics (i.e., secukinumab, ixekizumab, omalizumab). Patients who received methotrexate ≤ 10 mg/week, prednisolone < 10 mg/day or the biologics had a similar immunogenicity profile to those without immunosuppressive therapies. Despite the lack of statistical significance, a reduction of humoral immune response was observed among the study participants who used ≥2 immunosuppressants or pemphigus patients. Our findings suggest that a subset of patients with immune-mediated skin conditions respond poorly to the vaccine despite having low-level immunosuppression. These patients could benefit from vaccines that trigger a greater level of immunogenicity or booster doses.
Intimal Arteritis and Microvascular Inflammation Are Associated With Inferior Kidney Graft Outcome, Regardless of Donor-Specific Antibodies
Authors: Novotny Marek , Hruba Petra , Kment Martin , Voska Ludek , Kabrtova Katerina , Slavcev Antonij , Viklicky Ondrej
Published: December 2021

Background: The prognostic role of intimal arteritis of kidney allografts in donor-specific antibody negative (DSA–) antibody-mediated rejection (ABMR) remains unclear.

Methods: Seventy-two out of 881 patients who had undergone kidney transplantation from 2014 to 2017 exhibited intimal arteritis in biopsies performed during the first 12 months. In 26 DSA negative cases, the intimal arteritis was accompanied by tubulointerstitial inflammation as part of T cell-mediated vascular rejection (TCMRV, N = 26); intimal arteritis along with microvascular inflammation occurred in 29 DSA negative (ABMRV/DSA–) and 19 DSA positive cases (ABMRV, DSA+, N = 17). In 60 (83%) patients with intimal arteritis, the surveillance biopsies after antirejection therapy were performed. Hundred and two patients with non-vascular ABMR with DSA (ABMR/DSA+, N = 55) and without DSA (ABMR/DSA–, N = 47) served as controls. Time to transplant glomerulopathy (TG) and graft failure were the study endpoints.

Results: Transplant glomerulopathy -free survival at 36 months was 100% in TCMRV, 85% in ABMR/DSA–, 65% in ABMRV/DSA-, 54% in ABMR/DSA+ and 31% in ABMRV/DSA+ (log rank p < 0.001). Death-censored graft survival at 36 months was 98% in ABMR/DSA-, 96% in TCMRV, 86% in ABMRV/DSA–, 79% in ABMR/DSA+, and 64% in ABMRV/DSA+ group (log rank p = 0.001). In surveillance biopsies, the resolution of rejection was found in 19 (90%) TCMRV, 14 (58%) ABMRV/DSA–, and only 4 (27%) ABMRV/DSA+ patients (p = 0.006). In the multivariable model, intimal arteritis as part of ABMR represented a significant risk for TG development (HR 2.1, 95% CI 1.2–3.8; p = 0.012) regardless of DSA status but not for graft failure at 36 months.

Conclusions: Intimal arteritis as part of ABMR represented a risk for early development of TG regardless of the presence or absence of DSA. Intimal arteritis in DSA positive ABMR represented the high-risk phenotype.
Diversity Scaling Analysis of Chinese Gut Microbiomes Across Ethnicities and Lifestyles
Authors: Xiao Wanmeng , Gao Depei , Chen Hongju (Daisy) , Qiao Yuting , Ma Zhanshan (Sam) , Duan Lincan
Published: December 2021

Diversity scaling (changes) of human gut microbiome is important because it measures the inter-individual heterogeneity of diversity and other important parameters of population-level diversity. Understanding the heterogeneity of microbial diversity can be used as a reference for the personalized medicine of microbiome-associated diseases. Similar to diversity per se, diversity scaling may also be influenced by host factors, especially lifestyles and ethnicities. Nevertheless, this important topic regarding Chinese populations has not been addressed, to our best knowledge. Here, we fill the gap by applying a recent extension to the classic species–area relationship (SAR), i.e., diversity–area relationship (DAR), to reanalyze a large dataset of Chinese gut microbiomes covering the seven biggest Chinese ethnic groups (covering > 95% Chinese) living rural and urban lifestyles. Four DAR profiles were constructed to investigate the diversity scaling, diversity overlap, potential maximal diversity, and the ratio of local to global diversity of Chinese gut microbiomes. We discovered the following: (i) The diversity scaling parameters (z) at various taxon levels are little affected by either ethnicity or lifestyles, as exhibited by less than 0.5% differences in pairwise comparisons. (ii) The maximal accrual diversity (potential diversity) exhibited difference in only about 5% of pairwise comparisons, and all of the differences occurred in ethnicity comparisons (i.e., lifestyles had no effects). (iii) Ethnicity seems to have stronger effects than lifestyles across all taxon levels, and this may reflect the reality that China has been experiencing rapid urbanization in the last few decades, while the ethnic-related genetic background may change relatively little during the same period.
Lactic Acid Bacteria Fermentation and Endopeptidase Treatment Improve the Functional and Nutritional Features of Arthrospira platensis
Authors: Verni Michela , Dingeo Cinzia , Rizzello Carlo Giuseppe , Pontonio Erica
Published: December 2021

This study aimed at investigating the effect of fermentation and enzymatic treatment on the degree of proteolysis of wet (WB), dried at low temperature (DB), and freeze-dried Spirulina (LB) proteins that affect the nutritional (e.g., amino acid content and profiles, and protein digestibility) and functional (e.g., antioxidant and antimicrobial activities) properties. The desiccation treatments influenced the unprocessed Spirulina characteristics because, compared with that in WB, peptides and free amino acids content was 73% lower in DB and 34% higher in LB. An integrated approach, including chromatographic and electrophoresis analyses, was used to evaluate the effect of the different bioprocessing options on protein profiles, release of peptides and amino acids, and the overall protein digestibility. Compared with the application of fermentation with the selected Lactiplantibacillus plantarum T0A10, the treatment with the endopeptidase Alcalase®, alone or combined, determined the most intense proteolysis. Moreover, the treatment with Alcalase® of LB allowed the release of potentially bioactive compounds that are able to inhibit Penicillium roqueforti growth, whereas the combination of fermentation with L. plantarum T0A10 and Alcalase® treatment increased Spirulina antioxidant properties, as determined by the scavenging activity toward ABTS radical (up to 60%) and antimicrobial activity against food pathogen Escherichia coli.
Viral Evasion of Innate Immune Defense: The Case of Resistance of Pandemic H1N1 Influenza A Virus to Human Mannose-Binding Proteins
Authors: White Mitchell R. , Nikolaidis Nikolaos M. , McCormack Francis , Crouch Erika C. , Hartshorn Kevan L.
Published: December 2021

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IAVin vitroandin vivo, and to inhibit pandemic H1N1in vitro, failed to protect mice from pandemic H1N1in vivoin the current study. We attempted a variety of maneuvers to improve the activity of the mutant NCRDs vs. the 2009 pandemic H1N1, including the formation of full-length SP-D molecules containing the mutant NCRD, cross-linking of NCRDs through the use of antibodies, combining SP-D or NCRDs with alpha-2-macroglobulin, and introducing an additional mutation to the double mutant NCRD. None of these substantially increased the antiviral activity for the pandemic H1N1. We also tested the activity of bacterial and algal mannose-binding lectins, cyanovirin, and griffithsin, against IAV. These had strong activity against seasonal IAV, which was largely retained against pandemic H1N1. We propose mechanisms to account for differences in activity of SP-D constructs against pandemic H3N2 and H1N1, and for differences in activity of cyanovirin vs. SP-D constructs.
Clonal Spread and Intra- and Inter-Species Plasmid Dissemination Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales During a Hospital Outbreak in Barcelona, Spain
Authors: Marí-Almirall Marta , Ferrando Núria , Fernández Mariana José , Cosgaya Clara , Viñes Joaquim , Rubio Elisa , Cuscó Anna , Muñoz Laura , Pellice Martina , Vergara Andrea , Campo Irene , Rodríguez-Serna Laura , Santana Gemina , Del Río Ana , Francino Olga , Ciruela Pilar , Ballester Frederic , Marco Francesc , Martínez José Antonio , Soriano Álex , Pitart Cristina , Vila Jordi , Roca Ignasi ,   MERCyCAT Study Group
Published: December 2021

Objectives: The study aimed to characterize the clonal spread of resistant bacteria and dissemination of resistance plasmids among carbapenem-resistant Enterobacterales at a tertiary hospital in Catalonia, Spain.

Methods: Isolates were recovered from surveillance rectal swabs and diagnostic samples. Species identification was by matrix-assisted laser desorption ionization-time time of flight mass spectrometry (MALDI-TOF MS). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Antimicrobial susceptibility was assessed by gradient-diffusion and carriage of bla genes was detected by PCR. Plasmid typing, conjugation assays, S1-PFGE studies and long-read sequencing were used to characterize resistance plasmids.

Results: From July 2018 to February 2019, 125 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were recovered from 101 inpatients from surveillance (74.4%) or clinical samples (25.6%), in a tertiary hospital in Barcelona. Clonality studies identified a major clone of Klebsiella pneumoniae belonging to sequence type ST15 and additional isolates of K. pneumoniae, Escherichia coli and Enterobacter sp. from different STs. All isolates but one carried the blaKPC–2 allelic variant. The blaKPC–2 gene was located in an IncFIIk plasmid of circa 106 Kb in a non-classical Tn4401 element designated NTEKPC-pMC-2-1. Whole-genome sequencing revealed different rearrangements of the 106 Kb plasmid while the NTEKPC-pMC-2-1 module was highly conserved.

Conclusion: We report a hospital outbreak caused by the clonal dissemination of KPC-producing ST15 K. pneumoniae but also the intra- and inter-species transmission of the blaKPC–2 gene associated with plasmid conjugation and/or transposon dissemination. To our knowledge, this is the first report of an outbreak caused by KPC-producing Enterobacterales isolated from human patients in Catalonia and highlights the relevance of surveillance studies in the early detection and control of antibiotic resistant high-risk clones.
Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders
Authors: Johnson Jill L.
Published: December 2021

The Hsp90 molecular chaperone, along with a set of approximately 50 cochaperones, mediates the folding and activation of hundreds of cellular proteins in an ATP-dependent cycle. Cochaperones differ in how they interact with Hsp90 and their ability to modulate ATPase activity of Hsp90. Cochaperones often compete for the same binding site on Hsp90, and changes in levels of cochaperone expression that occur during neurodegeneration, cancer, or aging may result in altered Hsp90-cochaperone complexes and client activity. This review summarizes information about loss-of-function mutations of individual cochaperones and discusses the overall association of cochaperone alterations with a broad range of diseases. Cochaperone mutations result in ciliary or muscle defects, neurological development or degeneration disorders, and other disorders. In many cases, diseases were linked to defects in established cochaperone-client interactions. A better understanding of the functional consequences of defective cochaperones will provide new insights into their functions and may lead to specialized approaches to modulate Hsp90 functions and treat some of these human disorders.
Association Between Sleep Disorders and Cognitive Impairment in Middle Age and Older Adult Hemodialysis Patients: A Cross-Sectional Study
Authors: Tian Ru , Bai Yun , Guo Yidan , Ye Pengpeng , Luo Yang
Published: December 2021

Objective: The aims of the current study were to (1) explore the features of overall poor sleep and specific sleep disorders in Chinese middle age and older adult hemodialysis patients; (2) examine the association between sleep disorders and cognitive impairment (CI) in middle age and older patients undergoing hemodialysis in China.

Methods: Data of patients undergoing maintenance hemodialysis were collected from the prospective cohort study of CI in Chinese patients undergoing hemodialysis (Registered in Clinical Trials.gov, ID: NCT03251573). We included 613 patients (mean age = 63.7; SD = 7.8) in this study. We assessed sleep conditions using the Pittsburgh Sleep Quality Index (PSQI) questionnaire and cognitive function by the Chinese Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) scale. Then the association between sleep disorders and CI was evaluated using multivariate logistic regression analysis.

Results: The prevalence of sleep disorders in this group of 613 hemodialysis patients was 77.0%. Patients with CI were more inclined to have sleep disorders in specific aspects of sleep latency, habitual sleep efficiency, sleep disturbances, and daytime dysfunction (p < 0.05). In multivariate logistic regression analyses, every 1-point increase in global PSQI score was associated with a 1.2-fold increased risk of CI (adjusted OR = 1.201; 95%CI = 1.123–1.284, p < 0.001). For each specific PSQI, every 1-point increase in sleep disturbances score was associated with a 2.6-fold increased risk of CI (adjusted OR = 2.624; 95%CI = 1.891–3.640, p < 0.001), and every 1-point increase in daytime dysfunction score was associated with a 3.7-fold increased risk of CI (adjusted OR = 3.709; 95%CI = 2.653–5.184, p < 0.001), whereas every 1-point increase in sleep duration score was associated with a decreased risk of CI (adjusted OR = 0.600; 95%CI = 0.434–0.830, p = 0.002).

Conclusion: Poor sleep quality especially sleep disturbances, daytime dysfunction, and long sleep duration are associated with CI in middle age and older adult hemodialysis patients. Thus, the early detection of sleep disorders may help identify patients with cognitive impairment among hemodialysis individuals.

Clinical Trial Registration: [Clinical Trials.gov], identifier [NCT03251573]
Muscle-Nerve-Nerve Grafting Improves Facial Reanimation in Rats Following Facial Nerve Injury
Authors: Charous Steven J. , Hutz Michael J. , Bialek Samantha E. , Schumacher Jane K. , Foecking Eileen M.
Published: December 2021

Nerve injury resulting in muscle paralysis from trauma or surgery is a major medical problem. Repair of such injuries with existing nerve grafting and reconstructive techniques often results in less than optimal outcomes. After previously demonstrating significant return of function using muscle-nerve-muscle (MNM) grafting in a rat facial nerve model, this study compares a variant of the technique, muscle-nerve-nerve (MNN) neurotization to MNM and interposition (IP) nerve grafting. Thirty male rats were randomized into four groups (1) control with no intervention, (2) repair with IP grafts, (3) MNM grafts and (4) MNN grafts. All groups had the buccal and marginal mandibular branches of the right facial nerve resected. Return of vibrissae movement, orientation, and snout symmetry was measured over 16 weeks. Functional recovery and muscle atrophy were assessed and quantified. All interventions resulted in significant improvement in vibrissae movement and orientation as compared to the control group (p < 0.05). The MNM and MNN groups had significantly less time to forward vibrissae movement as compared to controls (p < 0.05), and a large number of animals in the MNN group had coordinated vibrissae movement at 16 weeks. MNN and IP grafts retained significantly more muscle mass as compared to control (p < 0.05). Thus, MNN grafting is a promising adjuvant or alternative technique for reanimation for patients with unilateral peripheral nerve injury who are not candidates for primary neurorrhaphy.
Altered Expression of Par3, aPKC-λ, and Lgl1 in Hippocampus in Kainic Acid-Induced Status Epilepticus Rat Model
Authors: Zhang Chen , Tian Fafa , Tan Zheren , Du Juan , Long Xiaoyan
Published: December 2021

Introduction: Mossy fiber sprouting (MFS) is a frequent histopathological finding in temporal lobe epilepsy (TLE) and is involved in the pathology of TLE. However, molecular signals underlying MFS remain unclear. Partitioning defective 3(Par3), atypical protein kinase C-λ(aPKC-λ), and lethal giant larvae 1(Lgl1) were involved in the neuronal polarity and axon growth. The potential roles of those proteins in MFS and epileptogenesis of TLE were investigated.

Material and Methods: The epileptic rat models were established by intracerebroventricular injection of kainic acid (KA). The degree of MFS was measured by using Timm staining, Neuronal loss and the expression aPKC-λ, Par3, and Lgl1 in hippocampus were measured by using immunohistochemistry and western blot analysis.

Results: The neuronal loss in CA3 region was observed from 3 days to 8 weeks, while the neuronal loss in the hilar region was observed from 1 to 8 weeks in experimental group. The Timm score in the CA3 region in experimental group was significantly higher than that in the control group from 2 to 8 weeks. Compared with control group, the expressions of Par3 and Lgl1 were upregulated and the expression of aPKC-λ was downregulated in the experimental groups. Positive correlation between the Par3 expression and Timm scores, and the negative correlation between the aPKC-λ expression and Timm scores in CA3 region were discovered in experimental group.

Conclusion: The findings of the present study indicated that aPKC-λ, Par3, and Lgl1 may be involved in MFS and in the epileptogenesis of temporal lobe epilepsy.
Diet, Sports, and Psychological Stress as Modulators of Breast Cancer Risk: Focus on OPRM1 Methylation
Authors: Li Liangliang , Li Shuo , Qin Shidong , Gao Yu , Wang Chao , Du Jinghang , Zhang Nannan , Chen Yanbo , Han Zhen , Yu Yue , Wang Fan , Zhao Yashuang
Published: December 2021

Background: DNA methylation is influenced by environmental factors and contributes to adverse modification of cancer risk and clinicopathological features.

Methods: A case-control study (402 newly diagnosed cases, 470 controls) was conducted to evaluate the effect of environmental factors and OPRM1 methylation in peripheral blood leukocyte (PBL) DNA on the risk of breast cancer. A case-only study (373 cases) was designed to evaluate the effects of environmental factors on OPRM1 methylation in tumor tissue and the relationship of methylation with clinicopathological features.

Results: We found a significant association between hypermethylation of OPRM1 and the risk of breast cancer (OR = 1.914, 95%CI = 1.357–2.777). OPRM1 hypermethylation in PBL DNA combined with low intake of vegetable, garlic, soybean, poultry, and milk; high pork intake; less regular sports and a high psychological stress index significantly increased the risk of breast cancer. Soybean intake (OR = 0.425, 95%CI: 0.231–0.781) and regular sports (OR = 0.624, 95%CI: 0.399–0.976) were associated with OPRM1 hypermethylation in tumor DNA. OPRM1 hypermethylation in tumor tissue was correlated with estrogen receptor (ER) (OR = 1.945, 95%CI: 1.262–2.996) and progesterone receptor (PR) (OR = 1.611, 95%CI: 1.069–2.427) negative status; in addition, OPRM1 hypermethylation in PBL DNA was associated with human epidermal growth factor receptor 2 (HER-2) negative status (OR = 3.673, 95%CI: 1.411–9.564).

Conclusion: A healthy diet, psychosocial adaptability, and regular sports are very beneficial for breast cancer prevention and progress, especially for OPRM1 hypermethylation carriers. Personalized treatment considering the correlation between OPRM1 hypermethylation and ER and PR status may provide a novel benefit for breast cancer patients.
Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Mild Cognitive Impairment and Alzheimer's Disease: A Meta-Analysis
Authors: Li Xurui , Lv Chang , Song Jinxiao , Li Jianguo
Published: December 2021

Background: Alzheimer's disease (AD) is a progressive and multifactorial neurodegenerative disease accounting for 80% of dementia worldwide.

Objective: To assess the influence of probiotics on cognitive function in patients with mild cognitive impairment (MCI) and AD.

Methods: PubMed, Embase, and Cochrane Library databases were searched for relevant studies.

Results: Six randomized controlled trials involving 462 patients with MCI and AD were included in this meta-analysis. The probiotic administration had favorable effects on homeostasis model assessment–insulin resistance [HOMA-IR; Weighted mean difference (WMD) = −0.34, 95% confidence intervals (95% CI): −0.44 to 0.24, P < 0.001, I2 = 0%], very low–density lipoprotein levels (VLDL; WMD = −3.71, 95% CI: −6.11 to −1.32, P=0.002, I2 = 57.7%), quantitative insulin sensitivity check index (QUICKI; WMD = 0.01, 95% CI: 0.00–0.01, P = 0.003, I2 = 51%), and triglyceride levels (WMD = −15.65, 95% CI: −27.48 to −3.83, P = 0.009, I2 = 63.4%) in patients with AD. However, after Hartung-Knapp adjustment, all effects were non-significant except for HOMA-IR (MD = −0.34, 95%CI = −0.58 to −0.11). The changes in the Mini-Mental State Examination, repeatable battery for the assessment of neuropsychological status, and other biomarkers of oxidative stress, inflammation, and lipid profiles (high-sensitivity C-reactive protein, malondialdehyde, and total cholesterol) were negligible.

Conclusion: The findings suggested that the consumption of probiotics had favorable effects on the HOMA-IR in patients with AD. However, the probiotic treatment did not affect cognitive function, other biomarkers of oxidative stress, and other lipid profiles.
Association of Brain Metastases With Immune Checkpoint Inhibitors Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Yanning , Zhang Qianning , Chen Chuansheng , Hu Yuxuan , Miao Liyun , Zhou Yujie
Published: December 2021

Background

In pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.

Methods

Systematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.

Results

Nine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P <.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).

Conclusions

Immunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.
Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity
Authors: Xiong Zujian , Liu Hongwei , He Chenqi , Li Xuejun
Published: December 2021

Aims

To reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.

Methods

Single-cell RNA-seq data and bulk RNA-seq data were acquired from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Hypoxia status and subtypes of tumor cells were identified based on single-sample Gene Set Enrichment Analysis (ssGSEA). Regulon network analysis of different subtypes under different conditions was conducted by SCENIC. Within tumor microenvironment, biological process activity analysis and cell–cell communication network were conducted to uncover the inner links between each cell subtype under different hypoxia status.

Results

Different types of tumor cell in GBM possessed different hypoxia status, and MES-like subtype was under a more severe hypoxia condition than other subtypes. Hypoxia also induced MES-like signature gene expression within each tumor cell, which could stimulate tumor cell proliferation and invasion by regulating cell–cell communication. Additionally, hypoxia inhibited immune cell activity in the tumor microenvironment by inducing macrophage phenotype polarization and upregulating immune-inhibited cell–cell interaction within immune cells. Interactions between tumor cells and immune cells under hypoxia status also promoted tumor progression.

Conclusions

Hypoxia was a poor prognostic marker for primary IDH-wt GBM patients. Meanwhile, it could induce tumor cells’ MES-like transformation trend and inhibit antitumor function of immune cells.