Phenotypic Characteristics Research Articles

Comprehensive analysis of genotypic and phenotypic characteristics of biotinidase deficiency patients in the eastern region of Türkiye

Background. Biotin is a water-soluble vitamin that plays a key role in carboxylation. The formation of free biotin is impaired in biotinidase deficiency (BD), resulting in impaired biotin-dependent carboxylase functions. Based on the percentage of residual serum enzyme activity, BD is classified as partial and profound. Methods. Retrospective data including gender, age, parental consanguinity, family history, biotinidase activity analyses, type of deficiency (partial-profound), physical examination, treatment, and genotypes were evaluated in patients diagnosed with biotinidase deficiency in a single center in the eastern region of Türkiye. Patients whose biotinidase enzyme activity was below 30% with biallelic variants in the BTD gene were diagnosed as BD. Results. A total of 302 patients were included in the study. Parental consanguinity was present in 135 (44.7%) of them. Two hundred eighty-six (94.7%) were diagnosed by neonatal screening, 14 (4.6%) by family screening and two (0.06%) by clinical symptoms. Ninety-two (30.5%) of the patients were followed-up with profound deficiency and 210 (69.5%) with partial deficiency. A total of 306 variants were detected. Twenty different variants (3 novel - 3 rare) and 31 different genotypes were detected. The 3 most frequently detected variants were c.410G>A (p.Arg137His; 47.3%), c.1270G>C (p.Asp424His; 29.7%), and c.38_44delGCGGCTGinsTCC (p.Cys13Phefs*36; 15.3%). The 3 most frequently identified genotypes were c.410G>A (p.Arg137His) / c.1270G>C (p.Asp424His) compound heterozygous (32.4%), c.410G>A (p.Arg137His) homozygous (24.8%), and c.38_44delGCGGCTGinsTCC (p.Cys13Phefs*36) / c.1270G>C (p.Asp424His) compound heterozygous (12.2%). Patients with c.410G>A (p.Arg137His) homozygous variant, c.38_44delGCGGCTGinsTCC (p.Cys13Phefs*36) homozygous variant and c.38_44delGCGGCTGinsTCC (p.Cys13Phefs*36) / c.410G>A (p.Arg137His) compound heterozygous variant were statistically significantly associated with profound deficiency. Compound heterozygosity of c.410G>A (p.Arg137His) / c.1270G>C (p.Asp424His) variants were significantly associated with partial deficiency. Conclusions. The association between the BTD genotype and biochemical phenotype is not always consistent. Our study provides valuable data by adding variants with genotype-phenotype correlations to the literature and three novel variants, which can provide significant guidance in clinical follow-up.

STEM-11. MULTIDIMENSIONAL PROFILING OF TUMOR CELL HETEROGENEITY REVEALS CELL-LINEAGE SPECIFIC FUNCTIONS IN SUPRATENTORIAL EPENDYMOMAS

Abstract Supratentorial ependymomas (ST-EPN) are aggressive pediatric brain tumors that are categorized into distinct molecular subgroups. However, the developmental origins, tumor microenvironment, and phenotypic characteristics of tumor subpopulations across these subgroups are still poorly understood. In this study, we explored the human developmental signatures, global spatial organization, and the morphological and migratory tumor cell state behaviors in ST-EPN tumors at unprecedented resolution. We profiled 42 ST-EPN patients encompassing ZFTA-RELA (n = 20), ZFTA-Clusters 1 to 4 (n=20), and ST-YAP1 (n=4) subgroups by single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and live-cell imaging. We identified recurrent tumor cell states across tumors, that cover both generic cell processes (including cycling and mesenchymal/hypoxia) and human embryonic and fetal brain developmental signatures. ST-EPN subgroups displayed distinct developmental signatures, mapping to two separate temporally restricted progenitors-neuroepithelial-like and embryonic-like cells. Additionally, tumors showed diverging patterns of neuronal or ependymal differentiation, with ZFTA-Cluster 3 tumors as especially distinct from other subgroups in both developmental origin and differentiation. Furthermore, by utilizing 10X Xenium and novel algorithms we discovered that mesenchymal/hypoxia is critical for driving global tissue architecture to become more organized. Notably, recurrent tumors exhibited higher proportion of mesenchymal/hypoxia cells and greater structure than primary tumors. Lastly, by superimposing molecular and functional assays in both in vivo and in vitro models, we found that cell states exhibit distinct morphological and migratory behaviors, with neuronal-like cells being the most invasive. Neuronal-like cells especially exhibited distinct behavioral patterns reminiscent of neuronal migration during development. Moreover, we demonstrated the crucial role of neuronal microenvironment in promoting plasticity of cells toward this neuronal lineage. Taken together, we present a multidimensional framework for investigating cellular states within ST-EPN tumors, offering novel insights into their developmental origins, patterns of spatial organization, and cellular behavioral characteristics.

Real-time SERS analysis of programmed cell death patterns based on black Phosphorus–gold nanoparticles

Programmed cell death (PCD) plays a crucial role in the biological processes of living organisms and occurs in various forms, such as apoptosis, necroptosis and ferroptosis. However, traditional methods for PCD analysis are time-consuming and complex. In this paper, we propose a facile surface-enhanced Raman spectroscopy (SERS)-based strategy for the real-time analysis of three PCD patterns utilizing black phosphorus–gold nanoparticles (BP–Au NPs) as the ultrasensitive unlabeled Raman probe. BP–Au NPs, which possess excellent biocompatibility, are capable of detecting dye molecules at concentrations as low as [Formula: see text][Formula: see text]M and remain stable for at least one week in different physiological environments. In view of this, BP–Au NPs-based SERS technique can distinguish the tiny differences in the molecular fingerprints of cancer cells undergoing three PCD patterns (apoptosis, necroptosis and ferroptosis) triggered by doxorubicin, shikonin and erastin, respectively. We also have real-time monitoring of the intracellular molecular events during PCD, which spy the fluctuations of some typical SERS bands assigned to protein, DNA and lipid, revealing the unique phenotypic characteristics of each PCD pattern. This strategy provides a detailed and comprehensive analysis of the mechanisms of drug-induced PCD at the Raman level.

A novel ATP2A2 mutation in Darier and genotype phenotype: correlation analysis.

Darier's disease (DD) is a skin disorder caused by mutations in the ATP2A2 gene. Researchers have been investigating the correlation between genotype and phenotype in DD. Understanding the genotype-phenotype relationship in DD can enhance our comprehension of the genetic background and phenotypic characteristics of the condition, as well as the relationship between its systemic and localized manifestations. This study aimed to investigate the molecular pathogenesis of DD in a Chinese family, and to elucidate the genotype-phenotype correlation in DD by summarizing relevant literature. Gene mutations associated with DD were screened by whole-exome sequencing and verified using Sanger sequencing. Genetic analysis assessed the potential impact of these mutations. Genotype-phenotype correlation was obtained by chi-square analysis using literature search test. (1) A novel ATP2A2 Missense mutation, c.2560T>C (p.W854R), was identified and confirmed by Sanger sequencing. Annotation analysis with the ANNOVAR tool indicated that this mutation disrupts normal protein function and is linked to DD clinical manifestations. (2) Genotype-phenotype analysis showed a significant correlation between the prevalence of DD-related mental disorders and geographic regions (P = 0.00), but no association between mutation type and mental disorder prevalence (P = 0.324). The age of onset varied between sporadic and familial cases (P = 0.032), averaging 33years in sporadic cases and 16years in familial cases. By analyzing the genotype-phenotype correlation, we aim to enhance our understanding of the genetic basis of DD. This research could improve early diagnosis, intervention, and the development of personalized long-term health management plans.

Co-existence of antibiotic resistance and virulence factors in carbapenem resistant Klebsiella pneumoniae clinical isolates from Alexandria, Egypt.

The emergence and spread of carbapenem resistance among Enterobacteriaceae, particularly Klebsiella pneumoniae, constitute a serious threat to public health, since carbapenems are the last line of defense in the treatment of life-threatening infections caused by drug-resistant Enterobacteriaceae. The current study investigated the co-existence of different virulence factors and carbapenemases in carbapenem-resistant Klebsiella pneumoniae clinical isolates from Alexandria, Egypt. Phenotypic characterization of virulence factors indicated that 41.5% of the isolates were strong biofilm producers, while hypermucoviscosity was detected in 14.9% of the isolates. All isolates harbored five or more virulence factor encoding genes. entB, ycfM, mrkD and fimH were detected in all isolates, while only one isolate was negative for ybtS. uge, iutA, rmpA and kpn were detected in 61 (64.8%), 55 (58.5%), 41 (43.6%) and 27 (28.7%) isolates, respectively, while all isolates lacked magA and k2A. Phenotypic detection of carbapenemases was explored by performing CarbaNP and mCIM/eCIM. CarbaNP test showed positive results in 98.9% of the isolates and positive mCIM tests were observed in all isolates, while 68 (72.3%) isolates showed positive eCIM tests. blaNDM was the most prevalent carbapenemase encoding gene (92.5%) followed by the blaOXA-48 (51.1%), while blaKPC was detected in only one (1.06%) isolate. blaVIM, blaIMP and blaGES were not detected in any of the tested isolates. The widespread of carbapenem-resistant Klebsiella pneumoniae represents a major problem in health care settings. A significant association between certain virulence factors and carbapenemase-encoding genes was observed. Antibiotic stewardship programs and infection control policies should be effectively implemented especially in hospitals to limit the spread of such highly virulent pathogens.

Clinical and genetic analysis of a patient with Ataxia and vitamin E deficiency due to homozygous variant of TTPA gene

To explore the clinical phenotype and genetic characteristics of a patient with Ataxia and vitamin E deficiency syndrome (AVED) due to a variant of TTPA gene. A patient diagnosed with AVED (proband), intended for assisted reproductive technology for pregnancy in Zhongnan Hospital of Wuhan University in July 2023, was selected as research subject. Clinical data of the proband were collected, and 2 mL of peripheral venous blood samples were collected from the proband and her father and siblings for serum vitamin E level testing. Whole exome sequencing (WES) was carried out. Pathogenic variants were selected based on American public archive of interpretations of clinically relevant variants (ClinVar). Sanger sequencing was performed to validate the candidate variants detected by WES. Pathogenicity of variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and the impact of variants was analyzed using multiple bioinformatics tools including SIFT, Mutation Taster, CADD, and SpliceAI. Information on the protein domains was obtained from ClinVar and dbSNP databases, and a hotspot map for the variants of protein-coding region was constructed. This study was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (No. 2023068K). The proband has a significantly low serum level of vitamin E (5.186 μg/mL), while her father and siblings were normal. WES revealed that she has harbored a homozygous missense c.2T>A (p.0?) variant of the TTPA gene, for which her father and younger sister were heterozygous carriers. Based on the guidelines from the ACMG, the missense c.2T>A (p.0?) variant of the TTPA gene was classified as pathogenic (PVS1+PM2+PM3). Multiple bioinformatics tools had predicted this variant to be located in the initiation codon region and may lead to abnormal synthesis of the TTPA protein, indicating it was deleterious. The hotspot map based on ClinVar and dbSNP databases showed an even distribution of variants across 5 structural domains of the TTPA protein, with high conservation of the first amino acid residue across various species. The homozygous c.2T>A (p.0?) variant of the TTPA gene probably underlie the AVED in the proband. Above discovery has enriched the mutational spectrum of AVED and provided a basis for the diagnosis, genetic counseling, and assisted reproductive strategies for this family.

Single-cell sequencing reveals cellular heterogeneity of nucleus pulposus in intervertebral disc degeneration

The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further analysis showed that chondrocytes might communicate with immune cells via the MIF, TNFSF9, SPP1 and CCL4L2 signaling pathways. In addition, we found that invading endothelial cells might interact with chondrocytes through the COL4A1, CXCL12, VEGFA and SEMA3E signaling pathways. Our results reveal the cellular complexity and phenotypic characteristics of NP tissues at single-cell resolution, which will contribute to the in-depth investigation of preventative and regenerative strategies for IVDD.

TCR-CD3 signal strength regulates plastic coexpression of IL-4 and IFN-γ in Tfh-like cells

The development of T follicular helper (Tfh) cells is an ongoing process resulting in the formation of various Tfh subsets. Despite advancements, the precise impact of T cell receptor (TCR) stimulation on this process remains incompletely understood. This study explores how TCR-CD3 signaling strength influences naive CD4+ T cell differentiation into Tfh-like cells and the concurrent expression of interleukin-21 (IL-21), interleukin-4 (IL-4), and interferon-gamma (IFN-γ). Strong TCR-CD3 stimulation induces proliferation and increased IL-21 expression in Tfh-like cells, which exhibit a characteristic phenotype expressing CXCR5 and PD1. The coexpression of IL-4 and IFN-γ in IL-21-producing Tfh-like cells is controlled by the strength TCR-CD3 stimulation; low stimulation favors IL-4, while strong stimulation enhances IFN-γ secretion. Exogenous addition of the effector cytokines IL-21 and IL-4 further modulate cytokine coexpression. These findings highlight the intricate regulatory mechanisms governing cytokine production and plasticity in Tfh-like cells, providing insights into B cell response modulation. In vivo, antigen availability may regulate Tfh cell plasticity, impacting subsequent B cell differentiation, emphasizing the need for further exploration through animal models or antigen-specific Tfh cell analyses in human lymph node biopsies

Deciphering Fire Blight: From Erwinia amylovora Ecology to Genomics and Sustainable Control

Fire blight is a highly destructive plant disease that affects the pome fruit value chain, with high economic impacts. Its etiological agent is the Gram-negative bacterium Erwinia amylovora. The origin of fire blight goes back to the late 1700s in North America, and the disease since then has spread to New Zealand, Europe, North Africa, the Middle East, and Asia. Due to its worldwide dissemination, advances have been made to identify and characterize E. amylovora strains from different regions and understand their evolutionary adaptation. Additionally, many efforts have been made in recent decades to stop the occurrence and impacts of fire blight, but in many countries, only preventive measures have been applied, as the application of antibiotics and copper-based compounds has become more restricted. Thus, new sustainable methods to control the pathogen are constantly required. This article presents a comprehensive review of the pathogen, from the phenotypic and molecular characterization methods applied to advances in comparative genomics and the development of new compounds for sustainable control of E. amylovora.

A familial chromosome 4p16.3 terminal microdeletion that does not cause Wolf-Hirschhorn (4p-) syndrome.

Chromosome 4p16.3 microdeletions are known to cause Wolf-Hirschhorn syndrome (WHS), which is characterized by a distinct craniofacial gestalt and multiple congenital malformations. The 4p16.3 region encompasses WHS critical region 1 (WHSCR1) and 2 (WHSCR2). The WHSCR contains several genes that have been implicated in the WHS phenotype including: WHS candidate 1 [WHSC1 (aka NSD2, OMIM 602952)], WHS candidate 2 [WHSC2(akaNELFA, OMIM 606026)],and LETM1 (OMIM 604407). Although several patients harboring 4p16.3 microdeletions that are associated with WHS phenotypes have been reported, the precise molecular underpinnings of WHS are subjects of active investigations. The potential role(s) of genes within the 4p16.3 are increasingly being investigated. Here we report a novel 4p16.3 terminal microdeletion that is not associated with the characteristic WHS phenotype. We studied Individual A (7-months-old female) and her father, Individual B (27-year-old), who both carry a terminal 4p16.3 microdeletion (about 555kb) that is distal to the WHSCR1 and WHSCR2, and does not include WHSC1, WHSC2, or LETM1. Overall,our findings expand thephenotypic spectrumassociated with 4p16.3microdeletionsand support the previous observations that, in some individuals, microdeletions within 4p16.3 regionmay not be sufficient to causeWHS.

A review of deep learning-based stereo vision techniques for phenotype feature and behavioral analysis of fish in aquaculture

The industrialization, high-density, and greener aquaculture requires a more precise and intelligent aquaculture management. Phenotypic and behavioral information of fish, which can reflect fish growth and welfare status, play a crucial role in aquaculture management. Stereo vision technology, which simulates parallax perception of the human eye, can obtain the three-dimensional phenotypic characteristics and movement trajectories of fish through different types of sensors. It can overcome the limitations in dealing with fish deformation, frequent occlusions and understanding three-dimension scenes compared to the traditional two-dimensional computer vision techniques. With the deep learning development and application in aquaculture, stereo vision has become a super computer vision technology that can provide more precise and interpretable information for intelligent aquaculture management, such as size estimation, counting and behavioral analysis of fish. Hence, it is very beneficial for researchers, managers, and entrepreneurs to possess a thorough comprehension about the fast-developing stereo vision technology for modern aquaculture. This study provides a critical review of relevant topics, including the four-layer application structure of stereo vision technology in aquaculture, various deep learning-based technologies used, and specific application scenarios. The review contributes to research development by identifying the current challenges and provide valuable suggestions for future research directions. This review can serve as a useful resource for developing future studies and applications of stereo vision technology in smart aquaculture, focusing on phenotype feature extraction and behavioral analysis of fish.

SAM-ResNet50: A Deep Learning Model for the Identification and Classification of Drought Stress in the Seedling Stage of Betula luminifera

Betula luminifera, an indigenous hardwood tree in South China, possesses significant economic and ecological value. In view of the current severe drought situation, it is urgent to enhance this tree’s drought tolerance. However, traditional artificial methods fall short of meeting the demands of breeding efforts due to their inefficiency. To monitor drought situations in a high-throughput and automatic approach, a deep learning model based on phenotype characteristics was proposed to identify and classify drought stress in B. luminifera seedlings. Firstly, visible-light images were obtained from a drought stress experiment conducted on B. luminifera shoots. Considering the images’ characteristics, we proposed an SAM-CNN architecture by incorporating spatial attention modules into classical CNN models. Among the four classical CNNs compared, ResNet50 exhibited superior performance and was, thus, selected for the construction of the SAM-CNN. Subsequently, we analyzed the classification performance of the SAM-ResNet50 model in terms of transfer learning, training from scratch, model robustness, and visualization. The results revealed that SAM-ResNet50 achieved an accuracy of 1.48% higher than that of ResNet50, at 99.6%. Furthermore, there was a remarkable improvement of 18.98% in accuracy, reaching 82.31% for the spatial transform images generated from the test set images by applying movement and rotation for robustness testing. In conclusion, the SAM-ResNet50 model achieved outstanding performance, with 99.6% accuracy and realized high-throughput automatic monitoring based on phenotype, providing a new perspective for drought stress classification and technical support for B. luminifera-related breeding work.

Changes in clinical features and seasonal variations of Crohn’s disease at diagnosis: a 10-year observational study in China

Background and aimsThe clinical aspects of Crohn’s disease (CD) at diagnosis determine its therapy and management. The onset of CD follows a seasonal pattern. We aimed to analyze changes in the clinical features and seasonal variations of newly CD patients over the last decade.MethodsCD patients were divided into cohort 1 (2012–2016) and cohort 2 (2017–2021). The clinical characteristics were collected and the trends according to the year and season of diagnosis were analyzed.ResultsA total of 2038 patients were included. Cohort 1 had a considerably greater proportion of diarrhea, fever, hematochezia, weight loss and extraintestinal manifestations. The levels of platelet and C-reactive protein were higher in cohort 2 patients, but the opposite was true for albumin levels (p<0.05). The rate of increased eosinophils, increased gangliocyte and abundant lymphoplasmacytic infiltrate significantly decreased over the years. Patients with granulomas were diagnosed with CD at an earlier age (p = 0.006). Cohort 1 patients used more conventional drugs, while cohort 2 patients apply more biologics (p<0.05). The diagnosis occurred more frequently in summer and less frequently in winter. Patients diagnosed in winter had notably higher BMI, lower frequency of perianal disease and lowest incidence of asthenia and weight loss.ConclusionThe clinical phenotype, laboratory and pathological characteristics of CD has changed over time in China. The diagnosis of CD tends to have a seasonal trend with the highest incidence in summer. CD patients diagnosed in winter appear to have a milder form of the disease.

Phenotypic and genetic characteristics of retinal vascular parameters and their association with diseases

Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extract 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, main temporal angles, vascular density, central retinal equivalents, the number of bifurcations, and tortuosity, from over 130,000 fundus images of close to 72,000 UK Biobank subjects. We perform genome-wide association studies of these phenotypes. From this, we estimate their heritabilities, ranging between 5 and 25%, and genetic cross-phenotype correlations, which mostly mirror the corresponding phenotypic correlations, but tend to be slightly larger. Projecting our genetic association signals onto genes and pathways reveals remarkably low overlap suggesting largely decoupled mechanisms modulating the different phenotypes. We find that diameter variability, especially for the veins, associates with diseases including heart attack, pulmonary embolism, and age of death. Mendelian Randomization analysis suggests a causal influence of blood pressure and body mass index on retinal vessel morphology, among other results. We validate key findings in two independent smaller cohorts. Our analyses provide evidence that large-scale analysis of image-derived vascular phenotypes has sufficient power for obtaining functional and causal insights into the processes modulating the retinal vasculature.

Single cell RNA-seq reveals cellular and transcriptional heterogeneity in the splenic CD11b+Ly6Chigh monocyte population expanded in sepsis-surviving mice

BackgroundSepsis survivors exhibit immune dysregulation that contributes to poor long-term outcomes. Phenotypic and functional alterations within the myeloid compartment are believed to be a contributing factor. Here we dissect the cellular and transcriptional heterogeneity of splenic CD11b+Ly6Chigh myeloid cells that are expanded in mice that survive the cecal ligation and puncture (CLP) murine model of polymicrobial sepsis to better understand the basis of immune dysregulation in sepsis survivors.MethodsSham or CLP surgeries were performed on C57BL/6J and BALB/c mice. Four weeks later splenic CD11b+Ly6Chigh cells from both groups were isolated for phenotypic (flow cytometry) and functional (phagocytosis and glycolysis) characterization and RNA was obtained for single-cell RNA-seq (scRNA-seq) and subsequent analysis.ResultsCD11b+Ly6Chigh cells from sham and CLP surviving mice exhibit phenotypic and functional differences that relate to immune function, some of which are observed in both C57BL/6J and BALB/c strains and others that are not. To dissect disease-specific and strain-specific distinctions within the myeloid compartment, scRNA-seq analysis was performed on CD11b+Ly6Chigh cells from C57BL/6J and BALB/c sham and CLP mice. Uniform Manifold Approximation and Projection from both strains identified 13 distinct clusters of sorted CD11b+Ly6Chigh cells demonstrating significant transcriptional heterogeneity and expressing gene signatures corresponding to classical-monocytes, non-classical monocytes, M1- or M2-like macrophages, dendritic-like cells, monocyte-derived dendritic-like cells, and proliferating monocytic myeloid-derived suppressor cells (M-MDSCs). Frequency plots showed that the percentages of proliferating M-MDSCs (clusters 8, 11 and 12) were increased in CLP mice compared to sham mice in both strains. Pathway and UCell score analysis in CLP mice revealed that cell cycle and glycolytic pathways were upregulated in proliferating M-MDSCs in both strains. Notably, granule protease genes were upregulated in M-MDSCs from CLP mice. ScRNA-seq analyses also showed that phagocytic pathways were upregulated in multiple clusters including the classical monocyte cluster, confirming the increased phagocytic capacity in CD11b+Ly6Chigh cells from CLP mice observed in ex vivo functional assays in C57BL/6J mice.ConclusionThe splenic CD11b+Ly6Chigh myeloid populations expanded in survivors of CLP sepsis correspond to proliferating cells that have an increased metabolic demand and gene signatures consistent with M-MDSCs, a population known to have immunosuppressive capacity.

Characterisation of a Mesophilic Aeromonas salmonicida and the Development of a PCR to Differentiate Atypical and Typical Strains.

This study describes the identification and characterisation of a new mesophilic Aeromonas salmonicida strain, named HMes1 isolated from Atlantic salmon (Salmo salar L.) in Tasmania. Isolates were identified as Aeromonas salmonicida through phenotypic, phylogenetic and genetic characterisation. After characterisation, the diagnostic phenotypic identification system MicroSys A24 was updated and a new multiplex conventional PCR was developed to enable rapid and inexpensive identification of atypical A. salmonicida, and exclusion of the exotic strain, A. salmonicida ssp. salmonicida.

Influence of Nutrition on Growth and Development of Metabolic Syndrome in Children

Obesity is currently an increasing public health burden due to its related metabolic and cardiovascular complications. In Western countries, a significant number of people are overweight or obese, and this trend is, unfortunately, becoming increasingly common even among the pediatric population. In this narrative review, we analyzed the role of nutrition during growth and its impact on the risk of developing metabolic syndrome and cardiovascular complications later in life. An impactful role in determining the phenotypic characteristics of the offspring is the parental diet carried out before conception. During intrauterine growth, the main risk factors are represented by an unbalanced maternal diet, excessive gestational weight gain, and impaired glycemic status. Breastfeeding, on the other hand, has many beneficial effects, but at the same time the quality of breast milk may be modified if maternal overweight or obesity subsists. Complementary feeding is likewise pivotal because an early introduction before 4 months of age and a high protein intake contribute to weight gain later. Knowledge of these mechanisms may allow early modification of risk factors by implementing targeted preventive strategies.

Mutation spectrum and genotype-phenotype correlation of pediatric patients with methylmalonic acidemia.

MMA incidence is significantly greater in China than in the rest of the world, but the mutation spectrum of MMA in China has not yet been mapped. We summarized published MMA-related articles and conducted a systematic meta-analysis of the literature. We analyzed the gene variants information of 926 pediatric MMA patients in China; 517 were children with combined MMA, and 409 were children with isolated MMA. Almost all combined MMA cases were caused by MMACHC gene mutations (cblC-type). The c.609G>A variation was the most common in cblC-type children, accounting for 43.01%, followed by c.658_660delAAG, c.482G>A, c.80A>G, and c.394C>T variations. Mut-type MMA patients accounted for 98.8% (404/409) of all isolated MMA cases. The variant MMUT c.729_730insTT accounted for 10.30% (80/802) of all variants and was the most common variant in mut-type children, followed by c.323G>A and c.1106G>A. Our study summarized and characterized the mutation spectrum of Chinese pediatric patients with MMACHC and MMUT variants, and we also analyzed the relationships between common variants, onset time, and clinical phenotype. These findings will contribute to understanding the phenotypic characteristics and overall pathogenesis of MMA patients, supporting the goal of gene therapy. The incidence of methylmalonic academia (MMA) in China is significantly greater than that in the rest of the world, but the mutation spectrum of MMA in China has not yet been mapped. In this paper, for the first time, we investigated hot-spot gene variants in MMA patients in China and comprehensively described the MMA gene mutation spectrum of the Chinese population. We explored the relationship between MMA genotype and clinical phenotype in patients, providing a basis for family genetic counseling, prenatal diagnosis, and newborn screening.

RETRACTION: Genotypic and phenotypic characterization of a large, diverse population of maize near-isogenic lines.

L. Morales, A. C. Repka, K. L. Swarts, W. C. Stafstrom, Y. He, S. M. Sermons, Q. Yang, L. O. Lopez-Zuniga, E.Rucker, W. E. Thomason, R. J. Nelson, P. J. Balint-Kurti. "Genotypic and phenotypic characterization of a large, diverse population of maize near-isogenic lines," The Plant Journal 103, no. 3 (2020): 1246-1255. https://doi.org/10.1111/tpj.14787. The above article, published online on 29 April 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Katherine Denby; Society for Experimental Biology (SEB); and John Wiley & Sons Ltd. The retraction has been agreed following a report submitted by the authors indicating that the imputation of genotypes outlined in the article caused errors in the reported positions of introgressions in the lines. The authors also declared that some of the pedigree information is inaccurate. As a result, all authors agree that the paper must be retracted. The authors have stated their intention to publish a corrected report with improved analyses of introgression positions.

Genomic Characterization and Comparative Analysis of Streptococcus zhangguiae sp. nov. Isolated from the Respiratory Tract of Marmota Himalayana.

Two Gram-stain-positive, oxidase-negative, non-motile, facultative anaerobic, α-hemolytic, coccus-shaped bacteria (zg-86T and zg-70) were isolated from the respiratory tracts of marmots (Marmota Himalayana) on the Qinghai-Tibet Plateau of China. Phylogenetic analysis of the 16S rRNA gene and 545 core genes revealed that these two strains belong to the Streptococcus genus. These strains were most closely related to Streptococcus respiraculi HTS25T, Streptococcus cuniculi CCUG 65085T, and Streptococcus marmotae HTS5T. The average nucleotide identity (ANI) and digital DNA‒DNA hybridization (dDDH) were below the threshold for species delineation. The predominant cellular fatty acids (CFAs) in this novel species were C16:0, C18:0, and C18:1ω9c, whereas the primary polar lipids were phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and an unknown phosphoglycolipid (PGL). The optimal growth conditions for the strains were 37°C, pH 7.0, and 0.5% (w/v) NaCl on brain-heart infusion (BHI) agar supplemented with 5% defibrinated sheep blood. Comparative genomics analyses revealed the potential pathogenicity of strain zg-86T through comparisons with suis subclade strains in terms of virulence factors, pathogen-host interactions (PHIs) and mobile genetic factors (MGEs). Based on the phenotypic characteristics and phylogenetic analyses, we propose that these two isolates represent novel species in the genus Streptococcus, for which the names Streptococcus zhangguiae sp. nov. (the type strain zg-86T=GDMCC 1.1758T=JCM 34273T) is proposed.