bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide analysis of the WRKY gene family unveil evolutionary history and expression characteristics in tomato and its wild relatives
Authors: Liu Guan , Zhang Dongye , Zhao Tingting , Yang Huanhuan , Jiang Jingbin , Li Jingfu , Zhang He , Xu Xiangyang
Published: September 2022

WRKY transcription factors (WRKYs) are one of the largest plant gene families in plants involved in various biotic and abiotic stress responses. Based on the conservation of WRKY proteins, we identified a total of 642 WRKYs in Amborella trichopoda (33), Vitis vinifera (64), Arabidopsis thaliana (48), Solanum lycopersicoides (88), S. pennellii (77), S. pimpinellifolium (80), S. lycopersicum var. cerasiforme (85), S. lycopersicum cv. Heinz1706 (85), and S. lycopersicum cv. M82 (82) genomes. Phylogenetic analysis clustered WRKYs from nine genomes above into two clusters (Cluster1 and Cluster2). Evolutionary analysis revealed that most of the WRKYs in tomato and its wild relatives were expanded after the whole genome triplication (WGT) event of Solanum ancestor. Effects of tandem duplication (TD) event for WRKYs revealed that several WRKYs have experienced TD event and drove the expansion of the WRKY gene family in tomato and its wild relatives. Comparative analysis of WRKYs derived from WGT and TD events indicated that the WGT event performed a stronger influence on the expansion of the WRKY gene family than the effects of the TD event. Transcriptome profiling of WRKYs in S. lycopersicum cv. Heinz1706 under the biotic stress condition relative to the control condition uncovered a number of up-regulated WRKYs in response to biotic stress. The diversified expression pattern among paralogs derived from TD and WGT implied the impact of gene duplication events on gene functional divergence and diversity in tomato. We hope that this project will supply novel knowledge for studying the evolutionary history and functional characteristics of WRKYs involved in biotic stress in tomato.
Case Report: Necrotizing fasciitis caused by Staphylococcus aureus positive for a new sequence variant of exfoliative toxin E
Authors: Sabat Artur J. , Wouthuyzen-Bakker Marjan , Rondags Angelique , Hughes Laura , Akkerboom Viktoria , Koutsopetra Olga , Friedrich Alexander W. , Bathoorn Erik
Published: September 2022

Objectives: Necrotizing fasciitis (NF) caused by S. aureus is a rare, aggressive and rapidly progressing superficial fascia infection with a high mortality rate. The aim of this study was to identify virulence-related genes from a complete genome sequence of a methicillin-susceptible S. aureus (MSSA) isolate recovered from a monomicrobial case of NF.

Materials and methods: The MSSA isolate UMCG579 was cultured from a pus collection from the subcutis of a patient with NF. The genome of isolate UMCG579 was sequenced using MinION (Oxford Nanopore) and MiSeq (illumina) platforms.

Results: The genome of the UMCG579 isolate was composed of a 2,741,379 bp chromosome and did not harbor any plasmids. Virulence factor profiling identified multiple pore-forming toxin genes in the UMCG579 chromosome, including the Panton-Valentine leukocidin (PVL) genes, and none of the superantigen genes. The UMCG579 isolate harbored a new sequence variant of the recently described ete gene encoding exfoliative toxin (type E). A search in the GenBank database revealed that the new sequence variant (ete2) was exclusively found among isolates (n = 115) belonging to MLST CC152. While the majority of S. aureus ete-positive isolates were recovered from animal sources, S. aureus ete2-positive isolates originated from human carriers and human infections. Comparative genome analysis revealed that the ete2 gene was located on a 8777 bp genomic island.

Conclusion: The combination of two heterogeneously distributed potent toxins, ETE2 and PVL, is likely to enhance the pathogenic ability of S. aureus isolates. Since anti-virulence therapies for the treatment of S. aureus infections continue to be explored, the understanding of specific pathogenetic mechanisms may have an important prophylactic and therapeutic value. Nevertheless, the exact contribution of ETE sequence variants to S. aureus virulence in NF infections must be determined.
Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma
Authors: Wang Yaxuan , Zhu Haixia , Wang Xiaolin
Published: September 2022

Background: Abnormal activation of endoplasmic reticulum (ER) stress sensors and their downstream signalling pathways is a key regulator of tumour growth, tumour metastasis and the response to chemotherapy, targeted therapy and immunotherapy. However, the study of ER stress on the immune microenvironment of bladder urothelial carcinoma (BLCA) is still insufficient.

Methods: Firstly, 23 ER stress genes were selected to analyse their expression differences and prognostic value in BLCA based on the existing BLCA genome atlas data. According to the expression level of ER stress-related genes in BLCA, two independent clusters were identified using consensus cluster analysis. Subsequently, the correlation between these two clusters in terms of the immune microenvironment and their prognostic value was analysed. Finally, we analysed the prognostic value of the key ER stress gene HSP90B1 in BLCA and its corresponding mechanism that affects the immune microenvironment.

Results: Consensus clustering showed a worse prognosis and higher expression of immunoassay site-related genes (HAVCR2, PDCD1, CTLA4, CD274, LAG3, TIGIT and PDCD1LG2) in cluster 1 compared with cluster 2. Additionally, both TIMER and CIBERSORT algorithms showed that the expression of immune infiltrating cells in cluster 1 was significantly higher than that in cluster 2. Subsequently, HSP90B1 was identified as a key ER stress gene in BLCA, and its high expression indicated poor prognosis and was closely related to PD1. We also analysed the correlation between HSP90B1 expression and immune-infiltrating cell related biomarkers, which showed positive results. Finally, we verified the prognostic value of HSP90B1 in BLCA using an immunohistochemical assay in a tissue microarray of 100 patients with BLCA, validating the potential of HSP90B1 as a prognostic biomarker in patients with BLCA.

Conclusion: Our work reveals that ER stress genes play a crucial role in the BLCA immunological milieu, and HSP90B1 is a potential prognostic biomarker and therapeutic target for cancer immunotherapy.
A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy
Authors: He Shengfu , Yu Jiawen , Sun Weijie , Sun Yating , Tang Mingyang , Meng Bao , Liu Yanyan , Li Jiabin
Published: September 2022

Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied.

Methods: Expression and clinical data for 33 cancers were obtained from UCSC-Xena. The correlation between RORC expression and clinical parameters was analyzed using the limma software package to assess the prognostic value of RORC. Timer2.0 and DriverDBv3 were used to analyze the RORC mutation and methylation profiles. RORC-associated signaling pathways were identified by GSEA. The correlations of RORC expression with tumor microenvironment factors were further assessed, including immune cell infiltration (obtained by CIBERSORT) and immunomodulators (in pancancer datasets from the Tumor-Immune System Interactions and Drug Bank [TISIDB] database). In addition, the correlations of RORC with four CIT biomarkers (tumor mutational burden, microsatellite instability, programmed death ligand-1, and mismatch repair) were explored. Furthermore, three CIT cohorts (GSE67501, GSE168204, and IMvigor210) from the Gene Expression Omnibus database and a previously published study were used to determine the association between RORC expression and CIT response.

Results: RORC was differentially expressed in many tumor tissues relative to normal tissues (20/33). In a small number of cancers, RORC expression was correlated with age (7/33), sex (4/33), and tumor stage (9/33). Furthermore, RORC expression showed prognostic value in many cancers, especially in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and mesothelioma (MESO). The mutation rate of RORC in most cancer types was low, while RORC was hypermethylated or hypomethylated in multiple cancers. RORC was associated with a variety of biological processes and signal transduction pathways in various cancers. Furthermore, RORC was strongly correlated with immune cell infiltration, immunomodulators, and CIT biomarkers. However, no significant association was found between RORC and CIT response in the three CIT cohorts.

Conclusion Our findings revealed the potential immunotherapeutic value of RORC for various cancers and provides preliminary evidence for the application of RORC in CIT.
From classical mendelian randomization to causal networks for systematic integration of multi-omics
Authors: Yazdani Azam , Yazdani Akram , Mendez-Giraldez Raul , Samiei Ahmad , Kosorok Michael R. , Schaid Daniel J.
Published: September 2022

The number of studies with information at multiple biological levels of granularity, such as genomics, proteomics, and metabolomics, is increasing each year, and a biomedical questaion is how to systematically integrate these data to discover new biological mechanisms that have the potential to elucidate the processes of health and disease. Causal frameworks, such as Mendelian randomization (MR), provide a foundation to begin integrating data for new biological discoveries. Despite the growing number of MR applications in a wide variety of biomedical studies, there are few approaches for the systematic analysis of omic data. The large number and diverse types of molecular components involved in complex diseases interact through complex networks, and classical MR approaches targeting individual components do not consider the underlying relationships. In contrast, causal network models established in the principles of MR offer significant improvements to the classical MR framework for understanding omic data. Integration of these mostly distinct branches of statistics is a recent development, and we here review the current progress. To set the stage for causal network models, we review some recent progress in the classical MR framework. We then explain how to transition from the classical MR framework to causal networks. We discuss the identification of causal networks and evaluate the underlying assumptions. We also introduce some tests for sensitivity analysis and stability assessment of causal networks. We then review practical details to perform real data analysis and identify causal networks and highlight some of the utility of causal networks. The utilities with validated novel findings reveal the full potential of causal networks as a systems approach that will become necessary to integrate large-scale omic data.
Exploration of the underlying biological differences and targets in ovarian cancer patients with diverse immunotherapy response
Authors: Chen Jinjin , Chen Surong , Dai Xichao , Ma Liang , Chen Yu , Bian Weigang , Sun Yunhao
Published: September 2022

Background

Preclinical trials of immunotherapy in ovarian cancer (OC) have shown promising results. This makes it meaningful to prospectively examine the biological mechanisms explaining the differences in response performances to immunotherapy among OC patients.

Methods

Open-accessed data was obtained from the Cancer Genome Atlas and Gene Expression Omnibus database. All the analysis was conducted using the R software.

Results

We firstly performed the TIDE analysis to evaluate the immunotherapy response rate of OC patients. The machine learning algorithm LASSO logistic regression and SVM-RFE were used to identify the characteristic genes. The genes DPT, RUNX1T1, PTPRN, LSAMP, FDCSP and COL6A6 were selected for molecular typing. Our result showed that the patients in Cluster1 might have a better prognosis and might be more sensitive to immunotherapy, including PD-1 and CTLA4 therapy options. Pathway enrichment analysis showed that in Cluster2, the pathway of EMT, TNFα/NF-kB signaling, IL2/STAT5 signaling, inflammatory response, KRAS signaling, apical junction, complement, interferon-gamma response and allograft rejection were significantly activated. Also, genomic instability analysis was performed to identify the underlying genomic difference between the different Cluster patients. Single-cell analysis showed that the DPT, COL6A6, LSAMP and RUNX1T1 were mainly expressed in the fibroblasts. We then quantified the CAFs infiltration in the OC samples. The result showed that patients with low CAFs infiltration might have a lower TIDE score and a higher proportion of immunotherapy responders. Also, we found all the characteristic genes DPT, RUNX1T1, PTPRN, LSAMP, FDCSP and COL6A6 were upregulated in the patients with high CAFs infiltration. Immune infiltration analysis showed that the patients in Cluster2 might have a higher infiltration of naive B cells, activated NK cells and resting Dendritic cells.

Conclusions

In summary, our study provides new insights into ovarian cancer immunotherapy. Meanwhile, specific targets DPT, RUNX1T1, PTPRN, LSAMP, FDCSP, COL6A6 and CAFs were identified for OC immunotherapy.
Tumor necrosis factor receptor regulation of peripheral node addressin biosynthetic components in tumor endothelial cells
Authors: Rodriguez Anthony B. , Parriott Geoffrey , Engelhard Victor H.
Published: September 2022

Tumor-associated tertiary lymphoid structures are ectopic lymphoid aggregates that have considerable morphological, cellular, and molecular similarity to secondary lymphoid organs, particularly lymph nodes. Tumor vessels expressing peripheral node addressin (PNAd) are hallmark features of these structures. Previous work from our laboratory demonstrated that PNAd is displayed on intratumoral vasculature of murine tumors, and its expression is controlled by the engagement of lymphotoxin-α3, secreted by effector CD8 T cells, with tumor necrosis factor receptors (TNFR) on tumor endothelial cells (TEC). The goals of the present work were: 1) to identify differences in expression of genes encoding the scaffolding proteins and glycosyl transferases associated with PNAd biosynthesis in TEC and lymph node blood endothelial cells (LN BEC); and 2) to determine which of these PNAd associated components are regulated by TNFR signaling. We found that the same genes encoding scaffolding proteins and glycosyl transferases were upregulated in PNAd+ LN BEC and PNAd+ TEC relative to their PNAdneg counterparts. The lower level of PNAd expression on TEC vs LN BEC was associated with relatively lower expression of these genes, particularly the carbohydrate sulfotransferase Chst4. Loss of PNAd on TEC in the absence of TNFR signaling was associated with lack of upregulation of these same genes. A small subset of PNAd+ TEC remaining in the absence of TNFR signaling showed normal upregulation of a subset of these genes, but reduced upregulation of genes encoding the scaffolding proteins podocalyxin and nepmucin, and carbohydrate sulfotransferase Chst2. Lastly, we found that checkpoint immunotherapy augmented both the fraction of TEC expressing PNAd and their surface level of this ligand. This work points to strong similarities in the regulation of PNAd expression on TEC by TNFR signaling and on LN BEC by lymphotoxin-β receptor signaling, and provides a platform for the development of novel strategies that manipulate PNAd expression on tumor vasculature as an element of cancer immunotherapy.
D-tagatose protects against oleic acid-induced acute respiratory distress syndrome in rats by activating PTEN/PI3K/AKT pathway
Authors: Huang Jian , Wang Bingjie , Tao Shaoyi , Hu Yuexia , Wang Ning , Zhang Qiaoyun , Wang Chunhui , Chen Chen , Gao Bingren , Cheng Xingdong , Li Yongnan
Published: September 2022

Acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar–capillary barrier, resulting in severe alveolar edema and inflammation. D-tagatose (TAG) is a low-calorie fructose isomer with diverse biological activities whose role in ARDS has never been explored. We found that TAG protects lung tissues from injury in the oleic acid-induced rat model of ARDS. Seventeen male Sprague–Dawley rats were randomly assigned to 3 groups: Sham (n = 5), ARDS (n = 6), and TAG + ARDS (n = 6). The treatment groups were injected with oleic acid to induce ARDS, and the TAG + ARDS group was given TAG 3 days before the induction. After the treatments, the effect of TAG was evaluated by blood gas analysis and observing the gross and histological structure of the lung. The results showed that TAG significantly improved the oxygenation function, reduced the respiratory acidosis and the inflammatory response. TAG also improved the vascular permeability in ARDS rats and promoted the differentiation of alveolar type II cells, maintaining the stability of the alveolar structure. This protective effect of TAG on the lung may be achieved by activating the PTEN/PI3K/AKT pathway. Thus, TAG protects against oleic acid-induced ARDS in rats, suggesting a new clinical strategy for treating the condition.
Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?
Authors: Corona-Sanchez Esther Guadalupe , Martínez-García Erika Aurora , Lujano-Benítez Andrea Verónica , Pizano-Martinez Oscar , Guerra-Durán Ivette Alejandra , Chavarria-Avila Efrain , Aguilar-Vazquez Andrea , Martín-Márquez Beatriz Teresita , Arellano-Arteaga Kevin Javier , Armendariz-Borunda Juan , Perez-Vazquez Felipe , García-De la Torre Ignacio , Llamas-García Arcelia , Palacios-Zárate Brenda Lucía , Toriz-González Guillermo , Vazquez-Del Mercado Monica
Published: September 2022

Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies’ production.
CSE/H2S ameliorates colitis in mice via protection of enteric glial cells and inhibition of the RhoA/ROCK pathway
Authors: Wang Song , Ding Yanyu , Jiang Wenjun
Published: September 2022

The enteric glial cells (EGCs) participate in the homeostasis of the gastrointestinal tract, and RhoA/ROCK signaling pathway plays a vital role in colonic tight junctions. Hydrogen sulfide (H2S) has been reported to alleviate colitis. However, the effect and mechanism of endogenous H2S on colitis remain unclear. This study established a Cystathionine-γ-lyase (CSE) knockout mouse model, a significant source of H2S production in the gut. The role of CSE-produced H2S on EGCs and the RhoA/ROCK signaling pathway was investigated in experimental colitis using CSE knockout (KO) and wild-type (WT) mice. CSE gene knockout animals presented with disease progression, more deteriorated clinical scores, colon shortening, and histological damage. EGCs dysfunction, characterized by decreased expression of the glial fibrillary acidic protein (GFAP), C3, and S100A10, was observed in the colon of WT and KO mice, especially in KO mice. RhoA/ROCK pathway was significantly upregulated in colon of colitis mice, which was more evident in KO mice. Pretreatment with NaHS, an exogenous H2S donor, significantly ameliorated mucosal injury and inhibited the expression of proinflammatory factors. Furthermore, we found that NaHS promoted the transformation of EGCs from “A1” to “A2” type, with decreased expression of C3 and increased expression of S100A10. These findings suggest that CSE/H2S protects mice from colon inflammation, which may be associated with preserving EGCs function by promoting EGCs transformation and inhibiting the RhoA/ROCK pathway.
The expanding impact of T-regs in the skin
Authors: Hajam Edries Yousaf , Panikulam Patricia , Chu Chung-Ching , Jayaprakash Haarshadri , Majumdar Amitabha , Jamora Colin
Published: September 2022

As the interface between the body and the environment, the skin functions as the physical barrier against external pathogens and toxic agents. In addition, the skin is an immunologically active organ with a plethora of resident adaptive and innate immune cells, as well as effector molecules that provide another layer of protection in the form of an immune barrier. A major subpopulation of these immune cells are the Foxp3 expressing CD4 T cells or regulatory T cells (T-regs). The canonical function of T-regs is to keep other immune cells in check during homeostasis or to dissipate a robust inflammatory response following pathogen clearance or wound healing. Interestingly, recent data has uncovered unconventional roles that vary between different tissues and we will highlight the emerging non-lymphoid functions of cutaneous T-regs. In light of the novel functions of other immune cells that are routinely being discovered in the skin, their regulation by T-regs implies that T-regs have executive control over a broad swath of biological activities in both homeostasis and disease. The blossoming list of non-inflammatory functions, whether direct or indirect, suggests that the role of T-regs in a regenerative organ such as the skin will be a field ripe for discovery for decades to come.
Single-cell RNA sequencing combined with whole exome sequencing reveals the landscape of the immune pathogenic response to chronic mucocutaneous candidiasis with STAT1 GOF mutation
Authors: Lu Xiaodi , Zhang Keming , Jiang Weiwei , Li Hang , Huang Yue , Du Mingwei , Wan Jian , Cao Yanyun , Du Lin , Liu Xiaogang , Pan Weihua
Published: September 2022

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.
Harnessing invariant natural killer T cells to control pathological inflammation
Authors: Bharadwaj Nikhila S. , Gumperz Jenny E.
Published: September 2022

Invariant natural killer T (iNKT) cells are innate T cells that are recognized for their potent immune modulatory functions. Over the last three decades, research in murine models and human observational studies have revealed that iNKT cells can act to limit inflammatory pathology in a variety of settings. Since iNKT cells are multi-functional and can promote inflammation in some contexts, understanding the mechanistic basis for their anti-inflammatory effects is critical for effectively harnessing them for clinical use. Two contrasting mechanisms have emerged to explain the anti-inflammatory activity of iNKT cells: that they drive suppressive pathways mediated by other regulatory cells, and that they may cytolytically eliminate antigen presenting cells that promote excessive inflammatory responses. How these activities are controlled and separated from their pro-inflammatory functions remains a central question. Murine iNKT cells can be divided into four functional lineages that have either pro-inflammatory (NKT1, NKT17) or anti-inflammatory (NKT2, NKT10) cytokine profiles. However, in humans these subsets are not clearly evident, and instead most iNKT cells that are CD4+ appear oriented towards polyfunctional (TH0) cytokine production, while CD4- iNKT cells appear more predisposed towards cytolytic activity. Additionally, structurally distinct antigens have been shown to induce TH1- or TH2-biased responses by iNKT cells in murine models, but human iNKT cells may respond to differing levels of TCR stimulation in a way that does not neatly separate TH1 and TH2 cytokine production. We discuss the implications of these differences for translational efforts focused on the anti-inflammatory activity of iNKT cells.
Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates
Authors: Boyarchuk Oksana , Yarema Nataliia , Kravets Volodymyr , Shulhai Oleksandra , Shymanska Ivanna , Chornomydz Iryna , Hariyan Tetyana , Volianska Liubov , Kinash Maria , Makukh Halyna
Published: September 2022

Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T- and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 - from patients with Nijmegen breakage syndrome, 1 – with X-linked agammaglobulinemia, 2 – with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (TlowB+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the method on DNA samples of children with ataxia-telangiectasia and Nijmegen syndrome showed a high sensitivity of TRECs (a total of 95.2% with cut-off 2000 copies per 106 cells) for the detection of these diseases. Thus, the tested method has shown its effectiveness for the detection of T- and B-lymphopenia and can be used for implementation of newborn screening for SCID in Ukraine.
Effect of Sinonovacula constricta on sediment microbial numbers and easily degradable organics in shrimp-crab polyculture systems
Authors: Liu Huiling , Chai Xinru , Zhang Dongxu , Xu Wenjun , He Jie
Published: September 2022

To explore the influence of different densities of Sinonovacula constricta on the composition of easily degradable organic matter and related functional bacteria, four experimental ecosystems were established: three polyculture systems (PMB1, PMB2, and PMB3) of Portunus trituberculatus and Marsupenaeus japonicus with different stocking densities of S. constricta (11.6, 23.1, and 34.7×104 ind./hm2, respectively) and a polyculture system with only P. trituberculatus and M. japonicus (PM). Among the easily degradable organic components in all aquaculture systems, protein content was the highest (0.74%~0.86%), followed by carbohydrates (0.16%~0.21%) and lipids (0.06%~0.13%). In the high-density (34.7×104 ind./hm2) S. constricta mixed culture system, the contents of carbohydrates, lipids, and proteins in the sediment were significantly lower than those of the other polyculture systems. The number of cellulose-decomposing bacteria in PMB3 was 3.79×106 cfu/g, which was significantly higher than that in the other systems. The number of starch-degrading bacteria and glutin-degrading bacteria was the lowest in PMB3, 1.26×104 cfu/g, and 160.00 cfu/g, respectively. The number of lipid-degrading bacteria in PMB3 was 0.77×104 cfu/g, which was significantly lower than that in the other systems. The easily degradable organics content in sediment was significantly positively correlated with the corresponding functional bacteria. The results showed that mixed culture of S. constricta could reduce the content of easily degradable organics in the sediment of mariculture ponds and change the number of functional bacteria in the sediment and the availability of degradable organic sediments may determine the abundance of corresponding degradable bacteria.
Iron oxides impact sulfate-driven anaerobic oxidation of methane in diffusion-dominated marine sediments
Authors: Yorshansky Omer , Liang Lewen , Pellerin André , Wang Fengping , Herut Barak , Sivan Orit
Published: September 2022

Microbial iron (Fe) reduction by naturally abundant iron minerals has been observed in many anoxic aquatic sediments in the sulfidic and methanic zones, deeper than it is expected based on its energetic yield. However, the potential consequence of this “deep” iron reduction on microbial elemental cycles is still unclear in sediments where diffusion is the dominant transport process. In this contribution, we experimentally quantify the impact of iron oxides on sulfate-driven anaerobic oxidation of methane (S-AOM) within the sulfate methane transition zone (SMTZ) of marine diffusive controlled sediments. Sediments were collected from the oligotrophic Southeastern (SE) Mediterranean continental shelf and were incubated with 13C-labeled methane. We followed the conversion of 13C-labeled methane as a proxy of S-AOM and monitored the sediment response to hematite addition. Our study shows microbial hematite reduction as a significant process in the SMTZ, which appears to be co-occurring with S-AOM. Based on combined evidence from sulfur and carbon isotopes and functional gene analysis, the reduction of hematite seems to slow down S-AOM. This contrasts with methane seep environments, where iron oxides appear to stimulate S-AOM and hence attenuate the release of the greenhouse gas methane from the sediments. In the deep methanic zone, the addition of iron oxides inhibits the methanogenesis process and hence methane gas production. The inhibition effect deeper in the sediment is not related to Fe-AOM as a competing process on the methane substrate, since Fe-AOM was not observed throughout the methanic sediments with several iron oxides additions.
A statistical assessment of the density of Antarctic krill based on “chaotic” acoustic data collected by a commercial fishing vessel
Authors: Zhao Yunxia , Wang Xinliang , Zhao Xianyong , Ying Yiping
Published: September 2022

With the development of acoustic data processing technology, it is possible to make full use of the “chaotic” acoustic data obtained by fishing vessels. The purpose of this study is to explore a feasible statistical approach to assess the Antarctic krill density rationally and scientifically based on the acoustic data collected during routine fishing operations. The acoustic data used in this work were collected from the surveys conducted by the Chinese krill fishing vessel F/V Fu Rong Hai since the 2015/16 fishing season in the Bransfield Strait. We first processed acoustic data into small units of 0.1 nm, then selected the location of the central fishing ground for grid processing. Because of many zero and low values, we established a Regional Gridding and Extended Delta-distribution (RGED) model to evaluate the acoustic density of the krill. We defined the selection coefficient of grid size by using the coefficient of variation (CV) of the mean density and the weight of the effective covered area of the grids. Through the comparison of selection indexes, cells of 5′S × 10′W were selected as a computational grid and applied to the hotspot in the Bransfield Strait. Acoustic data reveal the distribution of krill density to be spatially heterogeneous. The CV of the mean density for 4 months converges at ~15% for cells of 5′S × 10′W. Simulations estimate krill resource densities in February to be ~1990 m2 nm−2 and to increase to ~8760 m2 nm−2 in May (4.4 times higher). We deem the RGED model to be useful to explore dynamic changes in krill resources in the hotspot. It is not only of great significance for guiding krill fishery, but it also provides krill density data for studying the formation mechanism of the resource hotspots.
Seasonal distribution of an opportunistic apex predator (Tursiops truncatus) in marine coastal habitats of the Western Mediterranean Sea
Authors: Pace Daniela Silvia , Panunzi Greta , Arcangeli Antonella , Moro Stefano , Jona-Lasinio Giovanna , Martino Sara
Published: September 2022

Assessing the distribution of marine apex–predators is pivotal to understanding community interactions and defining management goals. However, several challenges arise in both estimates and predictions considering the distinctive and mutable biological/ecological requirements of these species and the influence of human activities. Thus, efforts to study apex–predators’ spatial distribution patterns must deal with inherent uncertainty. Relying on different data sources (research programs and social media reports), physiographic and environmental covariates (depth, slope, surface temperature and chlorophyll–a), and specific source–related detection functions, this study selected a Spatial Log–Gaussian Cox Process to model the distribution patterns of an opportunistic apex–predator, the common bottlenose dolphin (Tursiops truncatus), over 14 years (2008−2021) in the Mediterranean Sea (Italy) using a total of 955 encounters. Both depth and slope showed a significant (95% significance) reduction effect in the encounters when deeper and steeper, respectively. Temperature (parabolic) shows a positive effect (90% significance), while chlorophyll–a values did not seem to have a significant effect on encounter intensities within each season. The estimated posterior mean and the coefficient of variation surfaces for the intensity by season showed higher intensity in summer near the Tiber River estuary than other regions. Almost homogeneous predictions were observed in winter, with marginal greater intensities where lower temperatures and higher chlorophyll–a concentration were observed. The relatively low variance was predicted in the more coastal parts of the study area within each season, while higher uncertainty was instead revealed in the southernmost offshore area. This study highlighted the persistent presence of the common bottlenose dolphin in the investigated area both winter and summer, with a coherent distribution within each season, and rare transient occurrences in deeper waters (where uncertainty increases). Thanks to its versatile characteristics, the species seems to well adapt to different seasonal conditions and maintain its distributional range.
Worldwide analysis of reef surveys sorts coral taxa by associations with recent and past heat stress
Authors: Selmoni Oliver , Lecellier Gaël , Berteaux-Lecellier Véronique , Joost Stéphane
Published: September 2022

Coral reefs around the world are under threat from anomalous heat waves that are causing the widespread decline of hard corals. Different coral taxa are known to have different sensitivities to heat, although variation in susceptibilities have also been observed within the same species living in different environments. Characterizing such taxa-specific variations is key to enforcing efficient reef conservation strategies. Here, we combine worldwide-reef-survey data with remote sensed environmental variables to evaluate how local differences in taxa-specific coral cover are associated with past trends of thermal anomalies, as well as of non-heat related conditions. While the association with non-heat related environmental variation was seldom significant, we found that heat stress trends matched local differences in coral cover. Coral taxa were sorted based on the different patterns of associations with recent heat stress (measured the year before the survey) and past heat stress (measured since 1985). For branching, tabular and corymbose Acroporidae, reefs exposed to recent heat stress had lower coral cover than locally expected. Among such reefs, those previously exposed to frequent past heat stress displayed relatively higher coral cover, compared to those less frequently exposed. For massive and encrusting Poritidae, and for meandroid Favidae and Mussidae, we observed a negative association of coral cover with recent heat stress. However, unlike with Acroporidae, these associations were weaker and did not vary with past heat exposure. For Pocilloporidae, we found a positive association between coral cover and recent heat stress for reefs frequently exposed to past heat, while we found a negative association at reefs less frequently exposed to past heat. A similar pattern was observed for the branching Poritidae, although the associations were weaker and not statistically significant. Overall, these results show taxa-specific heat association patterns that might correspond to taxa-specific responses to past heat exposure, such as shifts in the assembly of coral communities, evolutionary adaptation or physiological acclimation.
The corrosion behavior and tensile strength of the 2060 Al-Li alloy with different heat treatments
Authors: Zheng Xingwei , Yin Haohao , Shu Yan , Chu Zhenhua , Liu Zhiwei
Published: September 2022

The structural safety and service life of civil aircraft can be decreased by corrosion damage to their aluminum components caused by long-term service in corrosive conditions. In this work, the effect of heat treatment on corrosion behavior and tensile strength was systematically analyzed for 2060 Al-Li alloy immersed in 3.5 wt% NaCl solution for different corrosion times. The results show that the corrosion depths of the 2060-T4 and 2060-T6 Al-Li alloys immersed for 720 h are 85 and 93 μm, respectively. The ultimate tensile strengths of 2060-T4 and 2060-T6 Al-Li alloys immersed for 720 h were reduced by 5.8 and 6.4%, respectively. Linear relationships between tensile strength and the corrosion depths of 2060-T4 and 2060-T6 Al-Li alloys were established as σres=486−0.33h and σres=547−0.35h respectively.
A phase-field model with irradiation-enhanced diffusion for constituent redistribution in U-10wt%Zr metallic fuels
Authors: Wen Chunyang , Liu Wenbo , Yun Di , Qian Zhengyu
Published: September 2022

Constituent redistribution is a unique phenomenon to metal fuels that threatens the safety of such fuel forms. Therefore, it is imperative to establish models to understand the intrinsic mechanisms and predict the redistribution kinetics. In this work, we derived the conservative field equations of the phase-field model from near-equilibrium thermodynamic theory. A macroscopic constituent redistribution phase-field model was developed by introducing the effect of irradiation on the atom mobility and the effect of temperature on the interface mobility. An expression of phase boundary width, applicable to both microscopic and macroscopic scenarios was proposed. The interfacial parameters of the model and the Zr concentration distribution near the fuel surface were discussed at last. These works may help understand constituent redistribution characteristics and promote the application of the phase-field method in studying constituent redistribution in macroscopic scenarios.
Case report: A case of anti-laminin 332 mucous membrane pemphigoid associated with severe pharyngolaryngeal involvement
Authors: Quattri Eleonora , Zussino Martina , Lauro Wanda , Berti Emilio , Marzano Angelo Valerio , Genovese Giovanni
Published: September 2022

A 74-year-old woman presented with a 30-day history of blisters and erosions in the oral cavity, trunk, and left eye conjunctival mucosa, also reporting a weight loss of 15 kg in the last 3 months. Histopathological examination showed subepidermal blisters and lymphocytic infiltrates with rare eosinophils in the superficial dermis. Direct immunofluorescence showed linear deposits of IgG and C3 along the dermal-epidermal junction and salt-split skin indirect immunofluorescence confirmed the presence of linear deposits of IgG along the blister floor. Indirect immunofluorescence revealed antibodies against laminin 332 using recombinant laminin 332 expressed in human HEK293 cells, and commercial ELISA kits (Euroimmun, Padova, Italy) did not reveal antibodies against BP230 and BP180 antigens. Anti-laminin 332 mucous membrane pemphigoid (MMP), a condition often associated with a hidden neoplasm, was diagnosed. In our case, the paraneoplastic nature of MMP was excluded. Thus, topical treatment with triamcinolone acetonide 0.1% in orabase once daily for 30 days, oral prednisone 0.75 mg/kg/day and rituximab were started to relieve symptoms. Conjunctival, nasal and oral erosions improved, as well as skin lesions, but later the patient was tracheotomized due to respiratory distress linked to the appearance of pharyngolaryngeal synechiae.
Mucoid Acinetobacter baumannii enhances anti-phagocytosis through reducing C3b deposition
Authors: Gong Xiaoxia , Zhao Qian , Wu Yifan , Zhou Hongwei , Ding Shuangyang , Zhu Kui
Published: September 2022

Background

Multidrug resistant (MDR) Acinetobacter baumannii causes serious infections in intensive care units and is hard to be eradicated by antibiotics. Many A. baumannii isolates are identified as the mucoid type recently, but the biological characteristics of mucoid A. baumannii and their interactions with host cells remains unclear.

Methods

The mucoid phenotype, antimicrobial susceptibility, biofilm-forming ability, acid resistance ability, peroxide tolerance, and in vivo toxicity of clinical ICUs derived A. baumannii isolates were first investigated. Secondly, the phagocytic resistance and invasive capacity of A. baumannii isolates to macrophages (MH-S, RAW264.7) and epithelial cells (A549) were analyzed. Furthermore, the abundance of C3b (complement factor C3 degradation product) deposition on the surface of A. baumannii was investigated. Last, the relationship between C3b deposition and the abundance of capsule in A. baumannii isolates were analyzed.

Results

These A. baumannii strains showed different mucoid phenotypes including hyper mucoid (HM), medium mucoid (MM), and low mucoid (LM). All tested strains were MDR with high tolerance to either acid or hydrogen peroxide exposure. Notably, these mucoid strains showed the increase of mortality in the Galleria mellonella infection models. Besides, the HM strain exhibited less biofilm abundance, higher molecular weight (MW) of capsule, and greater anti-phagocytic activity to macrophages than the LM strain. Together with the increased abundance of capsule, high expression of tuf gene (associated with the hydrolysis of C3b), the HM strain effectively inhibits C3b deposition on bacterial surface, resulting in the low-opsonization phenotype.

Conclusion

Capsular characteristics facilitate the anti-phagocytic activity in hyper mucoid A. baumannii through the reduction of C3b deposition. Mucoid A. baumannii exhibits high phagocytosis resistance to both macrophages and epithelial cells.
Indications and hemoglobin thresholds for red blood cell transfusion and iron replacement in adults with gastrointestinal bleeding: An algorithm proposed by gastroenterologists and patient blood management experts
Authors: Montoro Miguel , Cucala Mercedes , Lanas Ángel , Villanueva Cándido , Hervás Antonio José , Alcedo Javier , Gisbert Javier P. , Aisa Ángeles P. , Bujanda Luis , Calvet Xavier , Mearin Fermín , Murcia Óscar , Canelles Pilar , García López Santiago , Martín de Argila Carlos , Planella Montserrat , Quintana Manuel , Jericó Carlos , García Erce José Antonio
Published: September 2022

Gastrointestinal (GI) bleeding is associated with considerable morbidity and mortality. Red blood cell (RBC) transfusion has long been the cornerstone of treatment for anemia due to GI bleeding. However, blood is not devoid of potential adverse effects, and it is also a precious resource, with limited supplies in blood banks. Nowadays, all patients should benefit from a patient blood management (PBM) program that aims to minimize blood loss, optimize hematopoiesis (mainly by using iron replacement therapy), maximize tolerance of anemia, and avoid unnecessary transfusions. Integration of PBM into healthcare management reduces patient mortality and morbidity and supports a restrictive RBC transfusion approach by reducing transfusion rates. The European Commission has outlined strategies to support hospitals with the implementation of PBM, but it is vital that these initiatives are translated into clinical practice. To help optimize management of anemia and iron deficiency in adults with acute or chronic GI bleeding, we developed a protocol under the auspices of the Spanish Association of Gastroenterology, in collaboration with healthcare professionals from 16 hospitals across Spain, including expert advice from different specialties involved in PBM strategies, such as internal medicine physicians, intensive care specialists, and hematologists. Recommendations include how to identify patients who have anemia (or iron deficiency) requiring oral/intravenous iron replacement therapy and/or RBC transfusion (using a restrictive approach to transfusion), and transfusing RBC units 1 unit at a time, with assessment of patients after each given unit (i.e., “don’t give two without review”). The advantages and limitations of oral versus intravenous iron and guidance on the safe and effective use of intravenous iron are also described. Implementation of a PBM strategy and clinical decision-making support, including early treatment of anemia with iron supplementation in patients with GI bleeding, may improve patient outcomes and lower hospital costs.