bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of Organization of Subcompartments in DSB Repair Foci
Authors: Abate Natnael G. , Hendzel Michael J.
Published: July 2022

Cells assemble compartments around DNA double-strand breaks (DSBs). The assembly of this compartment is dependent on the phosphorylation of histone H2AX, the binding of MDC1 to phosphorylated H2AX, and the assembly of downstream signaling and repair components. The decision on whether to use homologous recombination or nonhomologous end-joining repair depends on competition between 53BP1 and BRCA1. A major point of control appears to be DNA replication and associated changes in the epigenetic state. This includes dilution of histone H4 dimethylation and an increase in acetylation of lysine residues on H2A and H4 that impair 53BP1 binding. In this article, we examined more closely the spatial relationship between 53BP1 and BRCA1 within the cell cycle. We find that 53BP1 can associate with early S-phase replicated chromatin and that the relative concentration of BRCA1 in DSB-associated compartments correlates with increased BRCA1 nuclear abundance as cells progress into and through S phase. In most cases during S phase, both BRCA1 and 53BP1 are recruited to these compartments. This occurs for both IR-induced DSBs and breaks targeted to an integrated LacO array through a LacI-Fok1-mCherry fusion protein. Having established that the array system replicates this heterogeneity, we further examined the spatial relationship between DNA repair components. This enabled us to precisely locate the DNA containing the break and map other proteins relative to that DNA. We find evidence for at least three subcompartments. The damaged DNA, single-stranded DNA generated from end resection of the array, and nuclease CtIP all localized to the center of the compartment. BRCA1 and 53BP1 largely occupied discrete regions of the focus. One of BRCA1 or 53BP1 overlaps with the array, while the other is more peripherally located. The array-overlapping protein occupied a larger volume than the array, CtIP, or single-stranded DNA (ssDNA). Rad51 often occupied a much larger volume than the array itself and was sometimes observed to be depleted in the array volume where the ssDNA exclusively localizes. These results highlight the complexity of molecular compartmentalization within DSB repair compartments.
Variable Clinical Features in a Large Family With Diamond Blackfan Anemia Caused by a Pathogenic Missense Mutation in RPS19
Authors: Cole Sarah , Giri Neelam , Alter Blanche P. , Gianferante D. Matthew
Published: July 2022

Introduction:Diamond Blackfan anemia (DBA) is an autosomal dominant ribosomopathy caused predominantly by pathogenic germline variants in ribosomal protein genes. It is characterized by failure of red blood cell production, and common features include congenital malformations and cancer predisposition. Mainstays of treatment are corticosteroids, red blood cell transfusions, and hematologic stem cell transplantation (HSCT). Despite a better understanding of the genotype of DBA, the biological mechanism resulting in the clinical phenotype remains poorly understood, and wide heterogeneity can be seen even within a single family as depicted here.

Case Description:Thirty family members enrolled in the National Cancer Institute inherited bone marrow failure syndromes study were evaluated with detailed medical questionnaires and physical examinations, including 22 in the family bloodline and eight unrelated partners. Eight participants had been previously told they had DBA by clinical criteria. Targeted germlineRPS19testing was done on all family members. A pathogenic heterozygous missense mutation inRPS19(p.R62Q, c.185G > A) was detected in ten family members, including one person previously presumed unaffected. Eight family members presented with macrocytic anemia in infancy; all of whom were responsive to prednisone. Four family members became treatment independent; however, one individual became transfusion-dependent 36 years later following an episode of pneumonia. One prednisone responsive individual electively discontinued steroid treatment, and lives with severe anemia. One prednisone responsive individual died at age 28 from a stroke. Two family members developed colorectal cancer in their fifties; one had never required treatment for anemia. None had major congenital anomalies.

Discussion:This large family with DBA demonstrates the heterogeneity of phenotypes that can be seen within the same genotype. Most family members presented with steroid-responsive anemia in infancy and subtle congenital malformations, findings consistent with recent genotype-phenotype studies ofRPSDBA. However, two family members were relatively unaffected, underscoring the importance of further studies to assess modifier genes, and epigenetic and/or environmental factors which may result in normal erythropoiesis despite underlying ribosome dysfunction. This large, multigenerational family highlights the need for individualized treatment, the importance of early cancer surveillance even in individuals with clinically mild phenotypes, and the benefit of long-term follow-up to identify late complications.
Genome-wide identification, characterization and expression analysis of the BMP family associated with beak-like teeth in Oplegnathus
Authors: Ma Yuting , Xiao Yongshuang , Xiao Zhizhong , Wu Yanduo , Zhao Haixia , Gao Guang , Wu Lele , Wang Tao , Zhao Ning , Li Jun
Published: July 2022

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor beta (TGF-β) family, are critical for the control of developmental processes such as dorsal-ventral axis formation, somite and tooth formation, skeletal development, and limb formation. Despite Oplegnathus having typical healing beak-like teeth and tooth development showing a trend from discrete to healing, the potential role of BMPs in the development of the beak-like teeth is incompletely understood. In the present study, 19 and 16 BMP genes were found in O. fasciatus and O. punctatus, respectively, and divided into the BMP2/4/16, BMP5/6/7/8, BMP9/10, BMP12/13/14, BMP3/15 and BMP11 subfamilies. Similar TGFb and TGF_β gene domains and conserved protein motifs were found in the same subfamily; furthermore, two common tandem repeat genes (BMP9 and BMP3a-1) were identified in both Oplegnathus fasciatus and Oplegnathus punctatus. Selection pressure analysis revealed 13 amino acid sites in the transmembrane region of BMP3, BMP7, and BMP9 proteins of O. fasciatus and O. punctatus, which may be related to the diversity and functional differentiation of genes within the BMP family. The qPCR-based developmental/temporal expression patterns of BMPs showed a trend of high expression at 30 days past hatching (dph), which exactly corresponds to the ossification period of the bones and beak-like teeth in Oplegnathus. Tissue-specific expression was found for the BMP4 gene, which was upregulated in the epithelial and mesenchymal tissues of the beak-like teeth, suggesting that it also plays a regulatory role in the development of the beak-like teeth in O. punctatus. Our investigation not only provides a scientific basis for comprehensively understanding the BMP gene family but also helps screen the key genes responsible for beak-like tooth healing in O. punctatus and sheds light on the developmental regulatory mechanism.
Development of a High-Density 665 K SNP Array for Rainbow Trout Genome-Wide Genotyping
Authors: Bernard Maria , Dehaullon Audrey , Gao Guangtu , Paul Katy , Lagarde Henri , Charles Mathieu , Prchal Martin , Danon Jeanne , Jaffrelo Lydia , Poncet Charles , Patrice Pierre , Haffray Pierrick , Quillet Edwige , Dupont-Nivet Mathilde , Palti Yniv , Lallias Delphine , Phocas Florence
Published: July 2022

Single nucleotide polymorphism (SNP) arrays, also named « SNP chips », enable very large numbers of individuals to be genotyped at a targeted set of thousands of genome-wide identified markers. We used preexisting variant datasets from USDA, a French commercial line and 30X-coverage whole genome sequencing of INRAE isogenic lines to develop an Affymetrix 665 K SNP array (HD chip) for rainbow trout. In total, we identified 32,372,492 SNPs that were polymorphic in the USDA or INRAE databases. A subset of identified SNPs were selected for inclusion on the chip, prioritizing SNPs whose flanking sequence uniquely aligned to the Swanson reference genome, with homogenous repartition over the genome and the highest Minimum Allele Frequency in both USDA and French databases. Of the 664,531 SNPs which passed the Affymetrix quality filters and were manufactured on the HD chip, 65.3% and 60.9% passed filtering metrics and were polymorphic in two other distinct French commercial populations in which, respectively, 288 and 175 sampled fish were genotyped. Only 576,118 SNPs mapped uniquely on both Swanson and Arlee reference genomes, and 12,071 SNPs did not map at all on the Arlee reference genome. Among those 576,118 SNPs, 38,948 SNPs were kept from the commercially available medium-density 57 K SNP chip. We demonstrate the utility of the HD chip by describing the high rates of linkage disequilibrium at 2–10 kb in the rainbow trout genome in comparison to the linkage disequilibrium observed at 50–100 kb which are usual distances between markers of the medium-density chip.
Looking for the Genes Related to Lung Cancer From Nasal Epithelial Cells by Network and Pathway Analysis
Authors: Qureshi Noman , Chi Jincheng , Qian Yanan , Huang Qianwen , Duan Shaoyin
Published: July 2022

Previous studies have indicated that the airway epithelia of lung cancer-associated injury can extend to the nose and it was associated with abnormal gene expression. The aim of this study was to find the possible lung cancer-related genes from the nasal epithelium as bio-markers for lung cancer detection. WGCNA was performed to calculate the module–trait correlations of lung cancer based on the public microarray dataset, and their data were processed by statistics of RMA and t-test. Four specific modules associated with clinical features of lung cancer were constructed, including blue, brown, yellow, and light blue. Of which blue or brown module showed strong connection to genetic connectivity. From the brown module, it was found that HCK, NCF1, TLR8, EMR3, CSF2RB, and DYSF are the hub genes, and from the blue module, it was found that SPEF2, ANKFN1, HYDIN, DNAH5, C12orf55, and CCDC113 are the pivotal genes corresponding to the grade. These genes can be taken as the bio-markers to develop a noninvasive method of diagnosing early lung cancer.
Case Report: Post-COVID-19 Vaccine Recurrence of Guillain–Barré Syndrome Following an Antecedent Parainfectious COVID-19–Related GBS
Authors: Bellucci Margherita , Germano Francesco , Grisanti Stefano , Castellano Chiara , Tazza Francesco , Mobilia Emanuela Maria , Visigalli Davide , Novi Giovanni , Massa Federico , Rossi Silvia , Durando Paolo , Cabona Corrado , Schenone Angelo , Franciotta Diego , Benedetti Luana
Published: July 2022

Guillain–Barré syndrome (GBS) is an autoimmune neurological disorder often preceded by viral illnesses or, more rarely, vaccinations. We report on a unique combination of postcoronavirus disease 2019 (COVID-19) vaccine GBS that occurred months after a parainfectious COVID-19–related GBS. Shortly after manifesting COVID-19 symptoms, a 57-year-old man developed diplopia, right-side facial weakness, and gait instability that, together with electrophysiology and cerebrospinal fluid examinations, led to a diagnosis of post-COVID-19 GBS. The involvement of cranial nerves and IgM seropositivity for ganglioside GD1b were noteworthy. COVID-19 pneumonia, flaccid tetraparesis, and autonomic dysfunction prompted his admission to ICU. He recovered after therapy with intravenous immunoglobulins (IVIg). Six months later, GBS recurred shortly after the first dose of the Pfizer/BioNTech vaccine. Again, the GBS diagnosis was confirmed by cerebrospinal fluid and electrophysiology studies. IgM seropositivity extended to multiple gangliosides, namely for GM3/4, GD1a/b, and GT1b IgM. An IVIg course prompted complete recovery. This case adds to other previously reported observations suggesting a possible causal link between SARS-CoV-2 and GBS. Molecular mimicry and anti-idiotype antibodies might be the underlying mechanisms. Future COVID-19 vaccinations/revaccinations in patients with previous para-/post-COVID-19 GBS deserve a reappraisal, especially if they are seropositive for ganglioside antibodies.
Clinical Investigations of CAR-T Cell Therapy for Solid Tumors
Authors: Chen Kun , Wang Shuhang , Qi Dan , Ma Peiwen , Fang Yuan , Jiang Ning , Wu Erxi , Li Ning
Published: July 2022

Cell therapy is a distinguished targeted immunotherapy with great potential to treat solid tumors in the new era of cancer treatment. Cell therapy products include genetically engineered cell products and non-genetically engineered cell products. Several recent cell therapies, especially chimeric antigen receptor (CAR)-T cell therapies, have been approved as novel treatment strategies for cancer. Many clinical trials on cell therapies, in the form of cell therapy alone or in combination with other treatments, in solid tumors, have been conducted or ongoing. However, there are still challenges since adverse events and the limited efficacy of cell therapies have also been observed. Here, we concisely summarize the clinical milestones of the conducted and ongoing clinical trials of cell therapy, introduce the evolution of CARs, discuss the challenges and limitations of these therapeutic modalities taking CAR-T as the main focus, and analyze the disparities in the regulatory policies in different countries.
The Complement System in Metabolic-Associated Kidney Diseases
Authors: Xu Ziyu , Tao Li , Su Hua
Published: July 2022

Metabolic syndrome (MS) is a group of clinical abnormalities characterized by central or abdominal obesity, hypertension, hyperuricemia, and metabolic disorders of glucose or lipid. Currently, the prevalence of MS is estimated about 25% in general population and is progressively increasing, which has become a challenging public health burden. Long-term metabolic disorders can activate the immune system and trigger a low-grade chronic inflammation named “metaflammation.” As an important organ involved in metabolism, the kidney is inevitably attacked by immunity disequilibrium and “metaflammation.” Recently, accumulating studies have suggested that the complement system, the most important and fundamental component of innate immune responses, is actively involved in the development of metabolic kidney diseases. In this review, we updated and summarized the different pathways through which the complement system is activated in a series of metabolic disturbances and the mechanisms on how complement mediate immune cell activation and infiltration, renal parenchymal cell damage, and the deterioration of renal function provide potential new biomarkers and therapeutic options for metabolic kidney diseases.
Macrophage Polarization, Metabolic Reprogramming, and Inflammatory Effects in Ischemic Heart Disease
Authors: Sun Xiaoqian , Li Yanqin , Deng Qiong , Hu Yueyao , Dong Jianteng , Wang Wei , Wang Yong , Li Chun
Published: July 2022

Macrophages are highly plastic cells, and the polarization-activating actions that represent their functional focus are closely related to metabolic reprogramming. The metabolic reprogramming of macrophages manifests itself as a bias toward energy utilization, transforming their inflammatory phenotype by changing how they use energy. Metabolic reprogramming effects crosstalk with the biological processes of inflammatory action and are key to the inflammatory function of macrophages. In ischemic heart disease, phenotypic polarization and metabolic shifts in circulating recruitment and tissue-resident macrophages can influence the balance of inflammatory effects in the heart and determine disease regression and prognosis. In this review, we present the intrinsic link between macrophage polarization and metabolic reprogramming, discussing the factors that regulate macrophages in the inflammatory effects of ischemic heart disease. Our aim is to estabilsh reliable regulatory pathways that will allow us to better target the macrophage metabolic reprogramming process and improve the symptoms of ischemic heart disease.
Numerical Simulation of the Locality of Erosional Damages by Storm Waves in Searching for Measures to Conserve Bonggil Beach, Korea
Authors: Do Jong Dae , Jin Jae-Youll , Lee Byunggil , Jeong Weon Mu , Choi Jin Yong , Hyun Sang Kwon , Kim Kihyun , Chang Yeon S.
Published: July 2022

Coastal erosion caused by extreme storms can reduce the value of beaches. Under the scenario of climate change, the storm intensity may increase and the resulting severe erosion can lead to disastrous damages on the beaches. Therefore, it is crucial to find appropriate measures and adaptation plans to conserve the beach from storm attacks. In this study, numerical models were applied to analyze the dune erosion in Boggil Beach, Korea, occurred by Typhoon Tapah in September 2019. Two models were used as Telemac-2D was run in larger domains for producing forcing conditions. XBeach was then applied to simulate the 2019 dune erosion after validation using observational data from a post-event field experiment performed in 2020. The model results showed reasonable agreement with the observational data except for the overestimation of erosion that was likely caused by characteristic pattern of sediment that was a mixture of sand and gravel and the accuracy of model results decreased due to the existence of gravel. The results also confirmed the locality of erosional damage by which the dune erosion was severest in the southern part of the beach. This locality was caused because the water depth was steeper in this area, which kept the wave energy in this area higher than that in the northern part. The uneven distribution of depth was induced by natural and anthropogenic causes. Three cases of model tests were performed to determine an appropriate measure to preserve the beach from future storm attacks – two were to place a submerged breakwater (SB), and one to place a submerged groin(SG). Although the SBs could directly protect the shore from erosion in the lee of the SBs, they could cause additional erosions at unexpected seabed areas. Although the SG was not the best in protecting the beach from the dune erosion, it could minimize the side effect. This measure was also environmentally friendly by keeping the sediments within the coastal cell around the SG so that the beach maintenance could be feasible through replenishment. In addition, the SG could also save the initial cost by reducing its size, and would be more effective, if the recovery process considered, because the SBs would disturb the onshore sediment motions under milder wave conditions. The results of this study can be applied for decision-making to establish future adaptation plans from storm impacts in Bonggil Beach.
The Dynamics of 0-Group Herring Clupea harengus and Sprat Sprattus sprattus Populations Along the Norwegian Skagerrak Coast
Authors: Berg Florian , Kvamme Cecilie , Nash Richard D. M.
Published: July 2022

Coastal areas are important habitats for early life stages of many fish species. These habitats are used as nursery grounds and can provide a significant contribution to the recruitment of a fish population. In 1919, standardized sampling with a beach seine along the Norwegian Skagerrak coastline was established mainly to target 0-group fish. Here, we focus on Atlantic herring and European sprat to explore whether inter-annual variability in the abundance of these species is indicative of variability in recruitment. We investigated if the abundance of 0-group herring and sprat are affected by environmental factors. Further, the beach seine abundance indices were compared with recruitment estimates of neighboring stocks. There was a clear correlation between herring and sprat abundance in the beach seine samples. While sprat abundance was mainly affected by environmental factors such as temperature and current drift, herring abundance was positively affected by the recruitment of the neighboring stock of western Baltic spring spawners. One plausible explanation could be that sprat recruit to a more local component, while herring of the neighboring stock utilize the Skagerrak coastline as nursery grounds. This study demonstrates the importance of long time series and can provide new insight into the dynamics and structure of multiple fish species.
The Application of DNA Barcoding in Crustacean Larvae Identification from the Zhongsha Islands, South China Sea
Authors: Xu Lei , Wang Xuehui , Huang Delian , Wang Lianggen , Ning Jiajia , Li Yafang , Liu Shuangshuang , Du Feiyan
Published: July 2022

Marine crustaceans are known as a group with high morphological diversity and great economic value. Most species have planktonic larval stages that are difficult to identify to species level using traditional approaches because of insufficient morphological diagnostic characters or taxonomic descriptions. We used DNA barcoding and molecular species identification to investigate the species diversity and distribution of crustacean larvae in the Zhongsha Islands waters, South China Sea. In total, 108 sequences were obtained from crustacean larvae collected in the Zhongsha Islands waters in 2019 using vertical hauls between the depths of 5 and 200 m. The molecular classification approach confirmed that 108 sequences represented crustaceans typical to the South China Sea, with 70 species identified, representing 43 genera, 23 families, and 4 orders. However, the cytochrome c oxidase subunit I gene sequences of only 27 species identified from the larval samples matched with available sequences taken from adults in GenBank. The comparison of K2P distances yielded a notable gap of 3.5–10.7% between intraspecific and interspecific distances across the sequence dataset. More than 80% of the crustacean larvae species belonged to the order Decapoda, and they displayed marked differences in their distributionsin the Zhongshan Islands waters. The orders Calanoida and Amphipoda were represented by the fewest species, which were recorded only at the edge of the Zhongsha Atoll.
Bearing behavior of high-performance concrete-filled high-strength steel tube composite columns subjected to eccentrical load
Authors: Jiang Liangqin , Wang Weichen , Ji Jing , Ren Hongguo , Wang Qingqin , Sun Ruohan , Yu Chenyu , Zhang Huiling , Luo Gan
Published: July 2022

In order to study the bearing capacity of high-performance concrete-filled high-strength steel tube (HCHST) composite stub columns subjected to eccentrical load, 22 HCHST composite stub columns, 4 concrete-filled steel tube (CFST) composite stub columns and 8 high-performance concrete-filled steel tube (HCST) composite stub columns were designed with the cubic compressive strength of concrete (fcu), the yield strength of steel tube (fy), the thickness of tube wall (t), the eccentricity (e) and slenderness ratio (λ) as the main parameters. Considering the nonlinear constitutive model of concrete and simplified constitutive model of steel, the finite element (FE) model of HCHST composite stub columns was established by ABAQUS software. By comparison with the existing test results, the rationality of the constitutive model and boundary conditions was verified. The variation of ultimate bearing capacity and the typical failure modes of HCHST composite stub columns under different parameters was analyzed. The results show that the specimens exhibit obvious bulge outward at the end of the steel tube and shear failure at the end of concrete. High-performance concrete (HPC) can significantly improve the ultimate eccentrical compression bearing capacity of composite columns, and high-strength steel tubes have better restraint effect on HPC. With the increasing of t, the ultimate eccentrical compression bearing capacity and the load-holding capacity of HCHST columns increases gradually, while the ultimate eccentrical compression bearing capacity decreases gradually with the increasing of λ and e. By introducing the reduction coefficient of eccentricity (φ1) and the reduction coefficient of slenderness ratio (φ2), the calculation formula of the eccentric bearing capacity of HCHST columns is proposed by statistical regression, which can lay a foundation for the application of HCHST columns in practical engineering.
Tardigrade Community Microbiomes in North American Orchards Include Putative Endosymbionts and Plant Pathogens
Authors: Tibbs-Cortes Laura E. , Tibbs-Cortes Bienvenido W. , Schmitz-Esser Stephan
Published: July 2022

The microbiome of tardigrades, a phylum of microscopic animals best known for their ability to survive extreme conditions, is poorly studied worldwide and completely unknown in North America. An improved understanding of tardigrade-associated bacteria is particularly important because tardigrades have been shown to act as vectors of the plant pathogen Xanthomonas campestris in the laboratory. However, the potential role of tardigrades as reservoirs and vectors of phytopathogens has not been investigated further. This study analyzed the microbiota of tardigrades from six apple orchards in central Iowa, United States, and is the first analysis of the microbiota of North American tardigrades. It is also the first ever study of the tardigrade microbiome in an agricultural setting. We utilized 16S rRNA gene amplicon sequencing to characterize the tardigrade community microbiome across four contrasts: location, substrate type (moss or lichen), collection year, and tardigrades vs. their substrate. Alpha diversity of the tardigrade community microbiome differed significantly by location and year of collection but not by substrate type. Our work also corroborated earlier findings, demonstrating that tardigrades harbor a distinct microbiota from their environment. We also identified tardigrade-associated taxa that belong to genera known to contain phytopathogens (Pseudomonas, Ralstonia, and the Pantoea/Erwinia complex). Finally, we observed members of the genera Rickettsia and Wolbachia in the tardigrade microbiome; because these are obligate intracellular genera, we consider these taxa to be putative endosymbionts of tardigrades. These results suggest the presence of putative endosymbionts and phytopathogens in the microbiota of wild tardigrades in North America.
Identification and Characterization of a New Serratia proteamaculans Strain That Naturally Produces Significant Amount of Extracellular Laccase
Authors: Ali Nadia Sufdar , Huang Fang , Qin Wensheng , Yang Trent Chunzhong
Published: July 2022

Natural biodegradation processes hold promises for the conversion of agro-industrial lignocellulosic biomaterials into biofuels and fine chemicals through lignin-degrading enzymes. The high cost and low stability of these enzymes remain a significant challenge to economic lignocellulosic biomass conversion. Wood-degrading microorganisms are a great source for novel enzyme discoveries. In this study, the decomposed wood samples were screened, and a promising γ-proteobacterial strain that naturally secreted a significant amount of laccase enzyme was isolated and identified as Serratia proteamaculans AORB19 based on its phenotypic and genotypic characteristics. The laccase activities in culture medium of strain AORB19 were confirmed both qualitatively and quantitatively. Significant cultural parameters for laccase production under submerged conditions were identified following a one-factor-at-a-time (OFAT) methodology: temperature 30°C, pH 9, yeast extract (2 g/l), Li+, Cu2+, Ca2+, and Mn2+ (0.5 mM), and acetone (5%). Under the selected conditions, a 6-fold increase (73.3 U/L) in laccase production was achieved when compared with the initial culturing conditions (12.18 U/L). Furthermore, laccase production was enhanced under alkaline and mesophilic growth conditions in the presence of metal ions and organic solvents. The results of the study suggest the promising potential of the identified strain and its enzymes in the valorization of lignocellulosic wastes. Further optimization of culturing conditions to enhance the AORB19 strain laccase secretion, identification and characterization of the purified enzyme, and heterologous expression of the specific enzyme may lead to practical industrial and environmental applications.
Whole-genome single nucleotide polymorphism analysis for typing the pandemic pathogen Fusarium graminearum sensu stricto
Authors: Kulik Tomasz , Molcan Tomasz , Fiedorowicz Grzegorz , van Diepeningen Anne , Stakheev Alexander , Treder Kinga , Olszewski Jacek , Bilska Katarzyna , Beyer Marco , Pasquali Matias , Stenglein Sebastian
Published: July 2022

Recent improvements in microbiology and molecular epidemiology were largely stimulated by whole- genome sequencing (WGS), which provides an unprecedented resolution in discriminating highly related genetic backgrounds. WGS is becoming the method of choice in epidemiology of fungal diseases, but its application is still in a pioneer stage, mainly due to the limited number of available genomes. Fungal pathogens often belong to complexes composed of numerous cryptic species. Detecting cryptic diversity is fundamental to understand the dynamics and the evolutionary relationships underlying disease outbreaks. In this study, we explore the value of whole-genome SNP analyses in identification of the pandemic pathogen Fusarium graminearum sensu stricto (F.g.). This species is responsible for cereal diseases and negatively impacts grain production worldwide. The fungus belongs to the monophyletic fungal complex referred to as F. graminearum species complex including at least sixteen cryptic species, a few among them may be involved in cereal diseases in certain agricultural areas. We analyzed WGS data from a collection of 99 F.g. strains and 33 strains representing all known cryptic species belonging to the FGSC complex. As a first step, we performed a phylogenomic analysis to reveal species-specific clustering. A RAxML maximum likelihood tree grouped all analyzed strains of F.g. into a single clade, supporting the clustering-based identification approach. Although, phylogenetic reconstructions are essential in detecting cryptic species, a phylogenomic tree does not fulfill the criteria for rapid and cost-effective approach for identification of fungi, due to the time-consuming nature of the analysis. As an alternative, analysis of WGS information by mapping sequence data from individual strains against reference genomes may provide useful markers for the rapid identification of fungi. We provide a robust framework for typing F.g. through the web-based PhaME workflow available at EDGE bioinformatics. The method was validated through multiple comparisons of assembly genomes to F.g. reference strain PH-1. We showed that the difference between intra- and interspecies variability was at least two times higher than intraspecific variation facilitating successful typing of F.g. This is the first study which employs WGS data for typing plant pathogenic fusaria.
A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Bordetella pertussis Carrying ptxP3 Alleles in China
Authors: Wu Xiaoying , Du Qianqian , Li Dongfang , Yuan Lin , Meng Qinghong , Fu Zhou , Xu Hongmei , Yao Kaihu , Zhao Ruiqiu
Published: July 2022

Background

Previous limited studies have identified that Bordetella pertussis (B. pertussis) isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention.

Methods

The present cross-sectional study involved 311 non-duplicate and unrelated B. pertussis strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both E-test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (ptxA, ptxC, ptxP, prn, fim2, fim3, and tcfA2) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.

Results

A total of 311 B. pertussis strains were isolated from children with a median age of 4 months (interquartile range: 2–9 months). Strains carrying the ptxP1 allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to ptxA1/ptxC1/prn1 alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the ptxP3 allele, mainly harboring the ptxA1/ptxC2/prn2 alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER-ptxP3 isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the ptxP3 allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by E-test strips.

Conclusion

The present results reveal that B. pertussis strains with the ptxP1-ER profile still dominate in China, and a few strains carrying the ptxP3 allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of B. pertussis is necessary for all countries, and the KB disk method can be adopted as a screening test.
The Changes in Microbiotic Composition of Different Intestinal Tracts and the Effects of Supplemented Lactobacillus During the Formation of Goose Fatty Liver
Authors: Wen Kang , Liu Long , Zhao Minmeng , Geng Tuoyu , Gong Daoqing
Published: July 2022

Intestinal bacteria play an important role in the formation of fatty liver in animals by participating in the digestion and degradation of nutrients, producing various metabolites, and altering the barrier effect of the intestine. However, changes in the gut microbiota during the formation of goose fatty liver are unclear. In this study, 80 healthy Landes geese with similar body weights at 70 days of age were randomly divided into two groups: the control group (n = 48; fed ad libitum) and the overfeeding group (n = 32; overfed). The intestinal contents were collected at 0, 12, and 24 days of overfeeding. The 16S rRNA and metagenomic sequencing analyses showed that the dominant phyla were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. At the genus level, Phyllobacterium, Bacteroides, Helicobacter, Lactobacillus, Enterococcus, and Romboutsia were the dominant genera in the goose intestine, and most of them were probiotics. In the control group, the relative abundance of Firmicutes in the jejunum and ileum gradually decreased with time, while that of Proteobacteria increased, whereas in the overfeeding group, the relative abundance of Firmicutes in the jejunum and ileum decreased and then increased with time, while that of Proteobacteria showed an opposite trend. In addition, supplementing Lactobacillus to the diet reduced body weight and fatty liver weight in overfed geese, but increased the weight of abdominal fat, suggesting that Lactobacillus supplementation might affect the transport of nascent fat from the liver to abdominal fat. In conclusion, the species of intestinal-dominant bacteria in the geese are relatively stable, but their relative abundance and function are affected by a number of factors. Overfeeding promotes the metabolism of nutrients in the jejunum and ileum and increases bacterial adaptability to environmental changes by enhancing their ability to process environmental and genetic information more efficiently. These findings suggest that the effect of overfeeding on the composition of intestinal microbiota may indirectly influence the formation of goose fatty liver through the gut/liver axis.
The Composition of Placental Microbiota and Its Association With Adverse Pregnancy Outcomes
Authors: La Xuena , Wang Yuezhu , Xiong Xu , Shen Liandi , Chen Weiyi , Zhang Lifeng , Yang Fengyun , Cai Xushan , Zheng Huajun , Jiang Hong
Published: July 2022

To verify whether the placenta harbors bacteria, and to explore the composition of placental microbiota (if yes) and its association with adverse pregnancy outcomes. The placental microbiota was detected by 16S rRNA gene sequencing technology. In the process of detecting placental samples, exogenous marine bacterial DNA that does not exist in the human body was artificially added to obtain a visible 16S band. At the same time, the sterile samples, such as scissors, sheets, and cotton swabs, in delivery and operating rooms were collected as the environmental control samples. As a result, a total of 2,621,009 sequences were obtained from 71 samples, 88.9% of which came from artificially added exogenous bacterial DNA, suggesting that the placenta contained fewer bacteria. After removing the operational taxonomic units (OTUs) that coexisted in environmental controls, the placenta was annotated with 11 phyla, 22 classes, 43 orders, 79 families, and 157 genera. The β diversity analysis showed that there were significant differences in the placental microbiota between 10 women with gestational diabetes mellitus (GDM) (pAMOVA = 0.01) or 19 women with premature rupture of membranes (PROM) (pAMOVA = 0.004), and 21 women without adverse pregnancy outcomes, respectively. There were higher abundances of genera Bifidobacterium, Duncaniella, and Ruminococcus in the placenta samples of women with GDM. The genera of Bacteroides, Paraprevotella, and Ruminococcus were more enriched in the placental samples of women with PROM. The authors concluded that the placenta may harbor small amounts of microbiota, and significant differences in the dominant microbiota of the placenta were observed between those pregnant women with and without adverse pregnancy outcomes.
Effect of Straw and Wood Ash on Soil Carbon Sequestration and Bacterial Community in a Calcareous Soil
Authors: Zhao Huili , Ahmad Shakeel , Wu Nan , Suo Lizhu , Tian Xiaohong , Zhao Ying , Yu Jinyi , Wang Li , Si Bingcheng
Published: July 2022

Soil fertility can be improved by effectively utilizing agricultural waste. Straw can supply energy and wood ash adds nutrients to improve soil quality. However, few kinds of research have investigated the effect of wood ash and straw on soil carbon sequestration and the soil bacterial population, particularly in calcareous soils. The main goal of this current study was to quantify the impact of a combination of wood ash and straw on the indicators described above using stable δ13C isotope analyses by applying wheat straw to calcareous soil under a long-term C4 crop rotation. The incubation experiment included four treatments as follows: (i) no amendment (Control); (ii) amendment with wood ash (W); (iii) amendment with straw (S); and (iv) a combined amendment of straw and wood ash (SW). Our results showed that sequestration of soil inorganic carbon (SIC) in the SW and W treatments was higher (an average of 7.78%) than that in the S and Control treatments. The sequestered soil organic carbon (SOC) in the SW treatment was 1.25-fold greater than that in the S treatment, while there was no evident effect on the SOC content compared with straw alone. The microbial biomass carbon increased under SW by 143.33%, S by 102.23%, and W by 13.89% relative to control. The dissolved organic carbon increased under SW by 112.0%, S by 66.61%, and W by 37.33% relative to the control. The pH and electrical conductivity were higher in the SW and W treatments than in the S treatment and the control. The SW was conducive to maintaining soil enzymatic activities and bacterial diversity. Bacteroidetes and Actinobacteriota were dominant in SW, while the Acidobacteria phyla were dominant in the S treatment. The diversity of bacteria in the soil and community composition of the bacteria were predominantly assessed by the levels of water-soluble K, pH, and electrical conductivity. The incorporation of straw and wood ash is probably more effective at improving SIC and SOC sequestration and ameliorates the soil microhabitat.
Intestinal Flora-Derived Kynurenic Acid Protects Against Intestinal Damage Caused by Candida albicans Infection via Activation of Aryl Hydrocarbon Receptor
Authors: Wang Zetian , Yin Liping , Qi Yue , Zhang Jiali , Zhu Haiyan , Tang Jianguo
Published: July 2022

Colonization of the intestinal tract by Candida albicans (C. albicans) can lead to invasive candidiasis. Therefore, a functional intestinal epithelial barrier is critical for protecting against invasive C. albicans infections. We collected fecal samples from patients with Candida albicans bloodstream infection and healthy people. Through intestinal flora 16sRNA sequencing and intestinal metabolomic analysis, we found that C. albicans infection resulted in a significant decrease in the expression of the metabolite kynurenic acid (KynA). We used a repeated C. albicans intestinal infection mouse model, established following intake of 3% dextran sulfate sodium salt (DSS) for 9 days, and found that KynA, a tryptophan metabolite, inhibited inflammation, promoted expression of intestinal tight junction proteins, and protected from intestinal barrier damage caused by invasive Candida infections. We also demonstrated that KynA activated aryl hydrocarbon receptor (AHR) repressor in vivo and in vitro. Using Caco-2 cells co-cultured with C. albicans, we showed that KynA activated AHR, inhibited the myosin light chain kinase-phospho-myosin light chain (MLCK-pMLC) signaling pathway, and promoted tristetraprolin (TTP) expression to alleviate intestinal inflammation. Our findings suggest that the metabolite KynA which is differently expressed in patients with C. albicans infection and has a protective effect on the intestinal epithelium, via activating AHR, could be explored to provide new potential therapeutic strategies for invasive C. albicans infections.
Bibliometric Insights of Global Research Landscape in Mitophagy
Authors: Li Guoli , Yin Wei , Yang Yiya , Yang Hongyu , Chen Yinyin , Liang Yumei , Zhang Weiru , Xie Tingting
Published: July 2022

Background: Autophagy is a highly regulated and evolutionarily conserved process in eukaryotes which is responsible for protein and organelle degradation. Although this process was described over 60 years ago, the selective autophagy of mitochondria (mitophagy) was recently coined in 2005. Research on the topic of mitophagy has made rapid progress in the past decade, which proposed to play critical roles in human health and disease. This study aimed to visualize the scientific outputs and research trends of mitophagy.

Methods: Articles and reviews related to the topic of mitophagy were retrieved from the Web of Science Core Collection on 30 November 2021. Two kinds of software (CiteSpace and VOSviewer) were used to perform a visualized analysis of countries/regions, institutions, authors, journals, references, and keywords.

Results: From 2005 to 2021, total 5844 publications on mitophagy were identified for final analysis. The annual number of publications grew yearly over the past 17 years. United States (N = 2025) and Chinese Academy of Sciences is the leading country and institute (N = 112) ranked by the number of publications, respectively. The most productive author was Jun Ren (N = 38) and Derek P. Narendra obtained the most co-cited times (2693 times). The journals with the highest output and the highest co-citation frequency were Autophagy (N = 208) and Journal of Biological Chemistry (co-citation: 17226), respectively. Analyses of references and keywords suggested that “mechanism of mitochondrial quality control”, “molecule and signaling pathway in mitophagy”, and “mitophagy related diseases” were research hotspots, and parkin-mediated mitophagy and its roles in skeletal muscle and inflammation-related diseases may be the frontiers of future research.

Conclusion: Although mitophagy research has flourished and attracted attention from all over the world, the regional imbalance in the development of mitophagy research was observed. Our results provided a comprehensive global research landscape of mitophagy from 2005– 2021 from a perspective of bibliometrics, which may serve as a reference for future mitophagy studies.
Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults
Authors: Ho Jean K. , Nation Daniel A.
Published: July 2022

Objective

Validation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed “neuropsychological (NP) decline,” in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum.

Methods

A prospective cohort study utilized 6,794 older adults from the National Alzheimer’s Coordinating Center (NACC) database with a baseline diagnosis of normal cognition, impaired without MCI or with MCI. Operationalization of NP decline over 12-month follow-up used regression-based norms developed in a robustly normal reference sample. The extent to which each participant’s 12-month follow-up score deviated from norm-referenced expectations was quantified and standardized to an NP decline z-score. Cox regression evaluated whether the NP decline metric predicted future dementia.

Results

Participant’s NP decline scores predicted future all-cause dementia in the total sample, χ2 = 110.71, hazard ratio (HR) = 1.989, p < 0.001, and in the subset diagnosed with normal cognition, χ2 = 40.84, HR = 2.006, p < 0.001, impaired without MCI diagnosis, χ2 = 14.89, HR = 2.465, p < 0.001, and impaired with MCI diagnosis, χ2 = 55.78, HR = 1.916, p < 0.001.

Conclusion

Operationalizing NP decline over 12 months with a regression-based norming method allows for further stratification of dementia risk along the cognitively unimpaired-to-MCI spectrum. The use of NP decline as an adjunctive marker of risk beyond standard cognitive diagnostic practices may aid in prognosis and clinical decision-making.
Machine Learning Prediction Models for Postoperative Stroke in Elderly Patients: Analyses of the MIMIC Database
Authors: Zhang Xiao , Fei Ningbo , Zhang Xinxin , Wang Qun , Fang Zongping
Published: July 2022

Objective

With the aging of populations and the high prevalence of stroke, postoperative stroke has become a growing concern. This study aimed to establish a prediction model and assess the risk factors for stroke in elderly patients during the postoperative period.

Methods

ML (Machine learning) prediction models were applied to elderly patients from the MIMIC (Medical Information Mart for Intensive Care)-III and MIMIC-VI databases. The SMOTENC (synthetic minority oversampling technique for nominal and continuous data) balancing technique and iterative SVD (Singular Value Decomposition) data imputation method were used to address the problem of category imbalance and missing values, respectively. We analyzed the possible predictive factors of stroke in elderly patients using seven modeling approaches to train the model. The diagnostic value of the model derived from machine learning was evaluated by the ROC curve (receiver operating characteristic curve).

Results

We analyzed 7,128 and 661 patients from MIMIC-VI and MIMIC-III, respectively. The XGB (extreme gradient boosting) model got the highest AUC (area under the curve) of 0.78 (0.75–0.81), making it better than the other six models, Besides, we found that XGB model with databalancing was better than that without data balancing. Based on this prediction model, we found hypertension, cancer, congestive heart failure, chronic pulmonary disease and peripheral vascular disease were the top five predictors. Furthermore, we demonstrated that hypertension predicted postoperative stroke is much more valuable.

Conclusion

Stroke in elderly patients during the postoperative period can be reliably predicted. We proved XGB model is a reliable predictive model, and the history of hypertension should be weighted more heavily than the results of laboratory tests to prevent postoperative stroke in elderly patients regardless of gender.