Comparison Of Phenotypes Research Articles

Comparison of Phenotypes of Headaches After COVID-19 Vaccinations Differentiated According to the Vaccine Used

Background/Objectives: In this ongoing, multicenter, global cohort observational study, phenotypes of headaches after COVID-19 vaccination were directly compared between different vaccines. Methods: Phenotypes of postvaccinal headache were recorded in 18,544 participants. The study was launched immediately after the start of the global COVID-19 vaccination campaign on 12 January 2021 and continued until 1 August 2023. Specific aspects of headaches and related variables were collected via an online questionnaire. The clinical headache characteristics of patients vaccinated with the Comirnaty (BioNTech), Jcovden (Johnson & Johnson), Sputnik V (Gamelaya), Covilo (Sinopharm), Spikevax (Moderna), Vaxzevria (AstraZeneca), and Convidecia (CanSino Biologics) vaccines were investigated. Results: Across all vaccines, the median and mean latency of headache onset after vaccine administration were 12 h and 23.3 h, respectively. The median and mean headache duration were 12 h and 23.3 h, respectively. When the nonreplicating viral vector vaccine Sputnik V was used, headaches occurred the fastest, with a latency of 17 h. The latencies for the Vaxzevria and Convidecia nonreplicating viral vector vaccines were 14.9 h and 19.1 h, respectively. The Covilo inactivated whole-virus vaccine had a latency of 20.5 h. The latencies of the mRNA-based Comirnaty and Spikevax vaccines were 26.0 h and 22.02 h, respectively. Analysis of variance revealed no significant differences in the mean duration of postvaccinal headache for the vaccines tested. Compared with the Comirnaty, Covilo, and Vaxzevria vaccines, the Spikevax vaccine induced significantly greater headache intensities. Vaxzevria was associated with a significantly higher frequency of concomitant symptoms than the other vaccines. Conclusions: The phenotype of postvaccinal headache can vary significantly between vaccines. These results have clinical implications for differentiating between postvaccinal headache and other primary and secondary headaches. This knowledge is clinically relevant in differentiating life-threatening vaccination complications, such as thrombotic syndromes, which are also associated with headaches. Based on these results, new diagnostic criteria for postvaccinal headaches can be developed.

Mapping the cellular etiology of schizophrenia and complex brain phenotypes.

Psychiatric disorders are multifactorial and effective treatments are lacking. Probable contributing factors to the challenges in therapeutic development include the complexity of the human brain and the high polygenicity of psychiatric disorders. Combining well-powered genome-wide and brain-wide genetics and transcriptomics analyses can deepen our understanding of the etiology of psychiatric disorders. Here, we leverage two landmark resources to infer the cell types involved in the etiology of schizophrenia, other psychiatric disorders and informative comparison of brain phenotypes. We found both cortical and subcortical neuronal associations for schizophrenia, bipolar disorder and depression. These cell types included somatostatin interneurons, excitatory neurons from the retrosplenial cortex and eccentric medium spiny-like neurons from the amygdala. In contrast we found T cell and B cell associations with multiple sclerosis and microglial associations with Alzheimer's disease. We provide a framework for a cell-type-based classification system that can lead to drug repurposing or development opportunities and personalized treatments. This work formalizes a data-driven, cellular and molecular model of complex brain disorders.

Expanding the Molecular Spectrum of MMP21 Missense Variants: Clinical Insights and Literature Review.

The failure of physiological left-right (LR) patterning, a critical embryological process responsible for establishing the asymmetric positioning of internal organs, leads to a spectrum of congenital abnormalities characterized by laterality defects, collectively known as "heterotaxy". MMP21 biallelic variants have recently been associated with heterotaxy syndrome and congenital heart defects (CHD). However, the genotype-phenotype correlations and the underlying pathogenic mechanisms remain poorly understood. Patients harboring biallelic MMP21 missense variants who underwent diagnostic genetic testing for CHD or heterotaxy were recruited at the Institute for Maternal and Child Health-I.R.C.C.S. "Burlo Garofolo". Additionally, a literature review on MMP21 missense variants was conducted, and clinical data from reported patients, along with molecular data from in silico and modeling tools, were collected. A total of 18 MMP21 missense variants were reported in 26 patients, with the majority exhibiting CHD (94%) and variable extra-cardiac manifestations (64%). In our cohort, through Whole-Exome Sequencing (WES) analysis, the missense p.(Met301Ile) variant was identified in two unrelated patients, who both presented with heterotaxy syndrome. Our comprehensive analysis of MMP21 missense variants supports the pathogenic role of the p.(Met301Ile) variant and provides significant insights into the disease pathogenesis. Specifically, missense variants are distributed throughout the gene without clustering in specific regions, and phenotype comparisons between patients carrying missense variants in compound heterozygosity or homozygosity do not reveal significant differences. These findings may suggest a potential loss-of-function mechanism for MMP21 missense variants, especially those located in the catalytic domain, and highlight their critical role in the pathogenesis of heterotaxy syndrome.

Pseudomonas retamae sp. nov., a novel endophytic bacterium with plant growth-promoting potential, isolated from root nodules of Retama monosperma in Northwestern Algeria.

A thorough polyphasic taxonomic study, integrating genome-based taxonomic approaches, was carried out to characterize the RB5T strain isolated from root nodules of Retama monosperma growing on the coastal dunes of Bousfer Beach (Oran, Algeria). The 16S rRNA gene sequence analysis revealed that strain RB5T had the highest similarity to Pseudomonas granadensis LMG27940T (98.94%) and Pseudomonas gozinkensis IzPS32dT (98.73%). Phylogenetic studies, including both 16S rRNA gene sequence and multilocus sequence analysis using 16S rRNA, gyrB and rpoD housekeeping genes, positioned RB5T in a distinct branch alongside its closest relative, P. granadensis LMG27940T. Phylogenomic analysis using the Bac120 marker set and Type (Strain) Genome Server confirmed the unique position of RB5T and its close relationship with P. granadensis LMG27940T. Similarly, genomic comparisons using average nucleotide identity based on blast (ANIb) and digital DNA-DNA hybridization (dDDH) revealed values of 92.85 and 59.3%, respectively, when compared with its closest relative, P. granadensis LMG27940T. Both values fall below the established species delimitation thresholds of 95-96% for ANIb and 70% for dDDH, providing strong genomic evidence that strain RB5T represents a novel species. Further average nucleotide identity comparisons with unclassified Pseudomonas spp. (384 genomes) and metagenomic-derived genomes from the Genome Taxonomy Database (GTDB) showed values between 84.27 and 89.2%, indicating that strain RB5T belongs to a unique evolutionary line. The genome of RB5T, with a size of 6 311 310 bp and a G+C content of 60%, harbours several key genes associated with plant growth-promoting traits, making it a promising candidate for sustainable agriculture. Phenotypically, RB5T strain is an aerobic, rod-shaped, Gram-negative, non-spore-forming bacterium that is motile with a single polar flagellum. It grows under a wide range of temperature (4-42 °C) and pH (5-10) conditions and tolerates up to 6% (w/v) NaCl. The main cellular fatty acid composition of RB5T includes C16:0, C17:0 cyclo and the summed features 3 consisting of C16:1 ω7c/C16:1 ω6c. Based on the phylogenetic, phenotypic, chemotaxonomic and genome comparison analyses, strain RB5T was identified as a novel species of the genus Pseudomonas, for which the name Pseudomonas retamae sp. nov. is proposed. The type strain is RB5T (=DSM 117471T=LMG 33633T=CIP 112482T).

A Deep Learning Model for Accurate Segmentation of the Drosophila melanogaster Brain from Micro-CT Imaging.

Micro-CT data can be automatically segmented and quantified using a deep learning model trained on as few as 3 samples, facilitating rapid comparison of developmental phenotypes.

Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality.

Lipids play a critical role in defense against sepsis. We sought to investigate gene expression and lipidomic patterns of lipid dysregulation in sepsis. Data from four adult sepsis studies were analyzed and findings were investigated in two external datasets. Previously characterized lipid dysregulation subphenotypes of hypolipoprotein (HYPO; low lipoproteins, increased mortality) and normolipoprotein (NORMO; higher lipoproteins, lower mortality) were studied. Leukocytes collected within 24h of sepsis underwent RNA sequencing (RNAseq) and shotgun plasma lipidomics was performed. Of 288 included patients, 43% were HYPO and 57% were NORMO. HYPO patients exhibited higher median SOFA scores (9 vs 5, p = < 0.001), vasopressor use (67% vs 34%, p = < 0.001), and 28-day mortality (30% vs 16%, p = 0.004). Leukocyte RNAseq identified seven upregulated lipid metabolism genes in HYPO (PCSK9, DHCR7, LDLR, ALOX5, PLTP, FDFT1, and MSMO1) vs. NORMO patients. Lipidomics revealed lower cholesterol esters (CE, adjusted p = < 0.001), lysophosphatidylcholines (LPC, adjusted p = 0.001), and sphingomyelins (SM, adjusted p = < 0.001) in HYPO patients. In HYPO patients, DHCR7 expression strongly correlated with reductions in CE, LPC, and SM (p < 0.01), while PCSK9, MSMO1, DHCR7, PLTP, and LDLR upregulation were correlated with low LPC (p < 0.05). DHCR7, ALOX5, and LDLR correlated with reductions in SM (p < 0.05). Mortality and phenotype comparisons in two external datasets (N = 824 combined patients) corroborated six of the seven upregulated lipid genes (PCSK9, DHCR7, ALOX5, PLTP, LDLR, and MSMO1). We identified a genetic lipid dysregulation signature characterized by seven lipid metabolism genes. Five genes in HYPO sepsis patients most strongly correlated with low CE, LPC, and SMs that mediate cholesterol storage and innate immunity.

Actinomadura monticuli sp. nov., isolated from Darangshi Oreum (a volcanic cone), and the reclassification of Actinomadura glauciflava Lu et al. 2003 as a later heterotypic synonym of Actinomadura luteofluorescens (Shinobu 1962) Preobrazhenskaya et al. 1975 (Approved Lists 1980).

Two mycelium-forming actinobacterial strains, designated as DLS-47 and DLS-62T, were isolated from volcanic ash collected from the surface of a rock on the peak of Darangshi Oreum (a volcanic cone) in Jeju, Republic of Korea, and their taxonomic positions were investigated by a polyphasic approach. Both of the isolates showed growth at 20-42 °C, pH 6.0-9.0 and 0-1% (w/v) NaCl. Furthermore, DLS-47 was found to grow at 45 °C, while strain DLS-62T grew at pH 10.0 and 3% (w/v) NaCl. The 16S rRNA gene-based phylogeny showed that both of the isolates belonged to the genus Actinomadura; strain DLS-47 was most closely related to Actinomadura chokoriensis DSM 45346T (100% sequence identity), while strain DLS-62T formed a tight cluster with Actinomadura bangladeshensis DSM 45347T (99.5% sequence similarity). Morphological and chemotaxonomic characteristics supported the affiliation of the two isolates to the genus Actinomadura. Phylogenomic analysis based on 92 core gene sequences showed that both of the isolates were most closely related to A. chokoriensis DSM 45346T. Strain DLS-47 shared 100% of orthologous average nucleotide identity and digital DNA-DNA hybridization values with A. chokoriensis DSM 45346T, while strain DLS-62T showed orthologous average nucleotide identity ≤89.8% and digital DNA-DNA hybridization values ≤39.4% with strain DLS-47 and members of the genus Actinomadura. The results of phenotypic assays and comparison of overall genomic relatedness indices support the conclusion that strain DLS-47 (= KACC 23347=DSM 116423) is a strain of A. chokoriensis, while strain DLS-62T (= KACC 23345T = DSM 116424T) represents a new species of the genus Actinomadura, for which the name Actinomadura monticuli sp. nov. is proposed. Also, Actinomadura glauciflava Lu et al. 2003 is reclassified as a later heterotypic synonym of Actinomadura luteofluorescens (Shinobu 1962) Preobrazhenskaya et al. 1975 (Approved Lists 1980) based on analysis of overall genomic relatedness indices and phenotypic similarity.

Characterization of Shigella flexneri serotype 6 strains from geographically diverse low- and middle-income countries.

Shigella flexneri serotype 6 (Sf6) is one of the most common serotypes recovered from surveillance studies of moderate to severe diarrhea. Despite the clinical significance of Sf6, this serotype is understudied. In this work, we have performed both serotype-specific genomic and phenotypic comparisons of Sf6 isolates to one another and non-S. flexneri serotypes. Comparative genomic analyses identified significant nucleotide homology between Sf6 strains (n = 325), despite a broad range of collection timeframes and geographic locations. We identified Sf6 specific factors, including a potential novel Shigella virulence factor (type II secretion system). Additionally, we identified established Shigella virulence genes (ospG) and metabolic genes (rutABCDEFGR) that were absent in Sf6 strains while present in the majority of 728 non-Sf6 strains. Complete sequencing of 11 clinical Sf6 strains, demonstrated that the Sf6 virulence plasmid (pINV) is ~38 kb smaller than the average non-Sf6 pINV (~228 kb). Comparisons of S. flexneri species level antibiotic susceptibility highlighted that clinical Sf6 isolates from Africa in the Global Enteric Multicenter Study (GEMS) and Vaccine Impact on Diarrhea in Africa (VIDA) study demonstrated geographic, serotype-specific susceptibility pattern. Phenotypic analyses of Sf6 identified reduced intracellular invasion and cytokine induction from HT-29 cells, as well as reduced Ipa protein effector secretion, compared with S. flexneri serotype 2a strain 2457T. Together these data highlight conserved and unique serotype-specific genotypic and phenotypic features for Sf6. This level of conservation has not been noted for other S. flexneri serotypes and is promising for vaccine and diagnostic assays to provide global Sf6-specific coverage.IMPORTANCEShigellosis is an ongoing global public health crisis with >270 million annual episodes among all age groups; however, the greatest disease burden is among children in low- and middle-income countries (LMIC). The lack of a licensed Shigella vaccine and the observed rise in antimicrobial-resistant Shigella spp. highlights the urgency for effective preventative and interventional strategies. The inclusion of S. flexneri serotype 6 (Sf6) is a necessary component of a multivalent vaccine strategies based on its clinical and epidemiological importance. Given the genomic diversity of Sf6 compared with other S. flexneri serotypes and Sf6 unique O-antigen core structure, serotype-specific characterization of Sf6 is a critical step to inform Shigella-directed vaccine and alternative therapeutic designs. Herein, we identified conserved genomic content among a large collection of temporally and geographically diverse Sf6 clinical isolates and characterized genotypic and phenotypic properties that separate Sf6 from non-Sf6 S. flexneri serotypes.

Mycoviruses from Aspergillus fungi involved in fermentation of dried bonito

Fungi are exploited for fermentation of foods such as cheese, Japanese sake, and soy sauce. However, the diversity of viruses that infect fungi involved in food fermentation is poorly understood. Fermented dried bonito (“katsuobushi”) is one of the most important processed marine products in Japan. Fungi involved in katsuobushi fermentation are called katsuobushi molds, and Aspergillus spp. have been reported to be dominant on the surface of katsuobushi during fermentation. Because various mycoviruses have been found in members of the genus Aspergillus, we hypothesized that katsuobushi molds are also infected with mycoviruses. Here, we describe seven novel mycoviruses belonging to six families (Chrysoviridae, Fusariviridae, Mitoviridae, Partitiviridae, Polymycoviridae, and Pseudototiviridae) from isolated katsuobushi molds (Aspergillus chevalieri and A. sulphureus) detected by fragmented and primer-ligated double-stranded RNA sequencing. Aspergillus chevalieri fusarivirus 1 has a unique bi-segmented genome, whereas other known fusariviruses have a single genomic segment. Phenotypic comparison between the parental A. chevalieri strain infected with Aspergillus chevalieri polymycovirus 1 (AchPmV1) and isogenic AchPmV1-free isolates indicated that AchPmV1 inhibits the early growth of the host. This study reveals the diversity of mycoviruses that infect katsuobushi molds, and provides insight into the effect of mycoviruses on fungi involved in fermentation.

Exome Sequencing Identified Susceptible Genes for High Residual Risks in Early-Onset Coronary Atherosclerotic Disease.

Despite the tremendous improvement in therapeutic medication and intervention for coronary atherosclerotic disease (CAD), residual risks remain. Exome sequencing enables identification of rare variants and susceptibility genes for residual risks of early-onset coronary atherosclerotic disease (EOCAD) with well-controlled conventional risk factors. We performed whole-exome sequencing of subjects who had no conventional risk factors, defined as higher body mass index, smoking, hypertension and dyslipidemia, screened from 1950 patients with EOCAD (age ≤ 45 years, at least 50% stenosis of coronary artery by angiography), and selected control subjects from 1006 elder (age ≥ 65 years) with < 30% coronary stenosis. Gene-based association analysis and clinical phenotypic comparison were conducted. Subjects without defined conventional risk factors accounted for 4.72% of young patients. Totally, 6 genes might be associated with residual risk of EOCAD, namely CABP1 (OR = 22.19, p = 0.02), HLA-E (OR = 22.19, p = 0.02), TOE1 (OR = 33.6, p = 0.002), HPSE2 (OR = 11.1, p = 0.04), CHST14 (OR = 22.19, p = 0.02) as well as KLHL8 (OR = 22.19, p = 0.02). Phenotypic analysis displayed the levels of low-density lipoprotein cholesterol in carriers of mutations from CABP1, HLA-E, TOE1, and HPSE2 were significantly elevated compared to noncarriers. Notably, extracellular matrix-associated CHST14 and fibrinogen-associated KLHL8 both displayed possible correlation with increased neutrophil proportion and decreased monocyte percentage (both p < 0.05), exerting potential effects on the residual inflammatory risks of EOCAD. The study identified six genes related to dyslipidemia and inflammation pathways with potential association with residual risk of EOCAD, which will contribute to precision-based prevention in these patients. The GRAND study was registered at www. gov on July 14, 2015, and the registry number is NCT02496858.

Variability in cadmium tolerance of closely related Listeria monocytogenes isolates originating from dairy processing environments.

Mobile genetic elements in Listeria monocytogenes contribute to its survival in natural and food processing environments. This study focused on how different genetic variants of the efflux pump gene cadAC and group of closely related cadA1C1 strains respond to cadmium exposure. When exposed to two cadmium salts, cadmium chloride and cadmium sulfate, we observed varying growth patterns, with a significantly longer lag phase in cadmium sulfate compared to cadmium chloride. Strains with cadA1 to cadA3 had similar growth trends, whereas a strain with the cadA4 variant had the highest minimum inhibitory concentration value. Among 88 strains from dairy processing facilities, significant phenotypic differences were observed despite core genome similarities, indicating other underlying genetic and physiological factors contribute to cadmium tolerance. Since cadmium tolerance studies in L. monocytogenes are limited, with rare phenotypic comparisons between closely related strains, our study makes an important observation and contribution to understanding of L. monocytogenes tolerance to cadmium by providing phenotypic comparisons between numerous strains within the same clonal group (<16 single nucleotide polymorphisms).

Comparison of basic lymphocyte phenotype results between a diagnostic and a research laboratory.

Lymphocyte phenotyping is a valuable tool for monitoring the effects of antiretroviral therapy on individuals living with HIV-1. A switch study was conducted to compare T-cell subset quantification performed by a research laboratory and a diagnostic, laboratory to understand the impact on the retrospective and prospective results of a long-term study. Using FACSCanto II Flow Cytometers, EDTA anticoagulated peripheral blood from 73 males enrolled in the Multicenter AIDS Cohort Study/Women Interagency HIV Combined Cohort Study was analyzed by both a research (laboratory 1) and a diagnostics laboratory (laboratory 2) for quantification of cluster of differentiation (CD)3, CD4, and CD8 T-cells. There were 47 males living with and 26 living without HIV-1. Bland-Altman (B-A) analysis was applied to assess the agreement between laboratory 1 and laboratory 2 results. There were 69 out of 73 CD3, 71 out of 73CD4, and 72 out of 73 CD8 T-cell results that fell within acceptable B-A limits of agreement. The mean differences between the 2 laboratories were -1.000, -0.945, and +0.685(%), respectively. The strong agreement between results from laboratory 1 and laboratory 2 for CD3, CD4, and CD8 T-cell percentage suggests that the difference between laboratories using the same instrumentation and methodology will have a minimal effect on long-term study results.

Uncovering multiscale structure in the variability of larval zebrafish navigation

Animals chain movements into long-lived motor strategies, exhibiting variability across scales that reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build Markov models of movement sequences that bridge across timescales and enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish responding to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising versus wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive stimuli, or in search for appetitive prey. As our method encodes the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies, we use it to uncover a hierarchical structure in the phenotypic variability that reflects exploration-exploitation trade-offs. Across a wide range of sensory cues, a major source of variation among fish is driven by prior and/or immediate exposure to prey that induces exploitation phenotypes. A large degree of variability that is not explained by environmental cues unravels hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, by extracting the timescales of motor strategies deployed during navigation, our approach exposes structure among individuals and reveals internal states tuned by prior experience.

Measuring Growth, Resistance, and Recovery after Artemisinin Treatment of Plasmodium falciparum in a single semi-high-throughput Assay.

Artemisinin partial resistance (ART-R) has spread throughout Southeast Asia and mutations in pfKelch13, the molecular marker of resistance, are widely reported in East Africa. Effective in vitro assays and robust phenotypes are crucial for monitoring populations for the emergence and spread of resistance. The recently developed extended Recovery Ring-stage Survival Assay used a qPCR-based readout to reduce the labor intensiveness for in vitro phenotyping of ART-R and improved correlation with the clinical phenotype of ART-R. Here, we extend and refine this assay to include measurements of parasite growth and recovery after drug exposure. Clinical isolates and progeny from two genetic crosses were used to optimize and validate the reliability of a straight-from-blood, SYBR Green-based qPCR protocol in a 96-well plate format to accurately measure phenotypes for Growth, Resistance, and Recovery. The assay determined growth between 6 h and 96 h, resistance at 120 h, and recovery from 120 h and 192 h. Growth can be accurately captured by qPCR and is shown by reproduction of previous growth phenotypes from HB3 × Dd2. Resistance measured at 120 h continually shows the most consistent phenotype for ring stage susceptibility. Recovery identifies an additional response to drug than parasites that are determined sensitive by Fold Change at 120 h. Comparison of progeny phenotypes for Growth vs Resistance showed a minor but significant correlation, whereas Growth vs Recovery and Resistance vs Recovery showed no significant correlation. Additionally, dried blood spot (DBS) samples matched Fold Change measured from liquid samples demonstrating Resistance can be easily quantified using either storage method. The qPCR-based methodology provides the throughput needed to quickly measure large numbers of parasites for multiple relevant phenotypes. Growth can reveal fitness defects and illuminate relationships between proliferation rates and drug response. Recovery serves as a complementary phenotype to resistance that quantifies the ability of sensitive parasites to tolerate drug exposure. All three phenotypes offer a comprehensive assessment of parasite-drug interaction each with independent genetic determinants of main effect and overlapping secondary effects that should be further. By adapting our method to include DBS, readouts can be easily extended to ex vivo surveillance applications.

Parasalinivibrio latis gen. nov., sp. nov., isolated from the distal gut of healthy farmed Asian Seabass (Lates calcarifer).

Asian Seabass (Lates calcarifer) is widely farmed as a sustainable source of protein for countries in the tropical Indo-West Pacific region. However, microbial species of the gut microbiome of healthy Asian Seabass remain largely uncharacterized and uncultured. Here, we analysed the microbial composition along the gastrointestinal tract of a farmed healthy Asian Seabass. We used different cultivation approaches to obtain isolates from the seabass intestinal tract and describe the isolation and characterization of a novel strain, TLL-SE01T. Analysis of the strain's 16S rRNA gene indicates that the strain belongs to the family Vibrionaceae with Photobacterium damselae as its closest relative, albeit sharing only 94.8% (aligned region 1553bp) nucleotide identity. Comparative genomic analysis with all validly published Vibrionaceae species with available genomes revealed average nucleotide identity (ANI) and DNA-DNA hybridisation (DDH) values of around 70% and 24% respectively to strain TLL-SE01T, which are well below proposed thresholds for species delineation (ANI, 95-96%; DDH, 70%). The alignment fraction and ANI genus demarcation boundaries for all genera in the Vibrionaceae family were determined for which strain TLL-SE01T is well below the calculated values, indicating that it belongs to a novel genus. Single- and core-gene phylogenetic analysis places strain TLL-SE01T in a monophyletic clade, further supporting its designation to a novel genus. Phenotypic comparison between strain TLL-SE01T and its close relatives indicated additional differences, such as growth response at different salt concentrations and different metabolic capabilities. Based on genotypic, phylogenetic and phenotypic differences to other Vibrionaceae species, we propose a novel species in a new genus, Parasalinivibrio latis gen. nov. sp. nov. and strain TLL-SE01T (= BCRC 81435T = JCM 36283T) as the type strain.

A phenotypic comparison of the Romanian and French ATTRv cohorts: Glu54Gln founder pathogenic variant vs the most common variants in Western Europe

Aim and methodsWe conducted a retrospective observational study of the ATTRv heterozygous mutation frequency, phenotype, and all-cause mortality at two cardiac amyloidosis centers in Romania and France. Results291 patients were included: 26 Glu54Gln (all Romanian), 200 Val122Ile, 47 Val30Met and 18 Ser77Tyr. On diagnosis, Gu54Gln patients were younger than Val122Ile or late-onset Val30Met (median age: 46 [42–50], 76 [71–80] and 70 [61–76], respectively; p < 0.001) and had more autonomic dysfunction (50 %, 6.3 %, and 7.7 %, respectively; p < 0.001) and similar cardiac symptom profiles. They had fewer conduction disorders (11.5 %) than early-onset Val30Met (76.9 %, p < 0.001) and Ser77Tyr group, notably less cardiac pacemaker present on diagnosis: 3.8 % for Glu54Gln vs. 23.5 % for Ser77Tyr; p = 0.014. Glu54Gln, Val122Ile, late-onset Val30Met and Ser77Tyr patients had similar left ventricular mass and systolic function values. Median survival for Glu54Gln patients was 58.7 years (95 %CI 55.9 – upper bound indeterminable), significantly lower than that of Val122Ile (83.6 years 95 %CI 81.6–85.5, log-rank test p < 0.001), late-onset Val30Met (83.4 years 95 %CI 81.9–84.9, log-rank test p < 0.001) and Ser77Tyr (74.8 years 95 %CI 68.7–80.9, log-rank test p = 0.022). Median survival after diagnosis was 5.7 years for Glu54Gln patients (95 %CI 4.7–6.4). ConclusionWe established that the Glu54Gln variant has an aggressive, mixed phenotype, with an early onset of autonomic dysfunction and heart failure symptoms. We emphasize the need for systematic genetic testing in patients with ATTR as understanding genotype-phenotype correlations is key for the management and the counseling of patients and their family members.

Comparison of Genetic, Auditory Features, and Systemic Clinical Phenotype in 14 Families with Syndromic Hearing Loss.

Syndromic hearing loss (SHL) is characterized by distinctive clinical phenotypes as well as genetic and phenotypic heterogeneity. More than 400 species of SHL have been described, the majority of which are autosomal dominant. 11 forms of SHL were obtained from 14 unrelated families with probands ranging in age from 5 to 78 months. The results of whole exome sequencing(WES), audiological characteristics, middle and inner ear radiological findings, and additional clinical phenotype characteristics were retrospectively analyzed. Fourteen people with SHL were found. Two of them had Waardenburg syndrome, two had Branchio-Oto-Renal syndrome, two had CHARGE syndrome, and one had Treacher Collins syndrome, Kleefstra syndrome, Muenke syndrome, Osteopathia Striata with Cranial Sclerosis, Ayme-Gripp syndrome, Tatton-Brown-Rahman syndrome, Stickler syndrome, or Stapes Ankylosis with Broad Thumbs and Toes. In this investigation, ten variants were first reported. The combination of a neonatal hearing screening and WES can diagnose syndrome-type hearing loss in infancy and childhood, according to our findings, expansion of the gene variant spectrum and phenotype for various age groups of SHL is essential and can provide valuable guidelines for clinical intervention decisions. It is imperative for medical practitioners to conduct diligent and prolonged patient monitoring due to the inherent variability in both the auditory impairment and the comprehensive clinical manifestation of SHL.

Malassezia gallinae sp. nov., a new basidiomycetous yeast species isolated from skins of chickens.

Species of Malassezia are lipid-dependent yeasts and integral components of the skin microbiome. Most of the currently known species are isolated from mammals. However, the presence and distribution of Malassezia yeasts on the skin of avian species have not been fully understood or elucidated. During a survey on the occurrence of Malassezia species in chickens, 23 Malassezia strains isolated from the healthy skins of chickens may represent two candidate new species of this genus based on the sequence analysis of the internal transcribed spacer (ITS) (including 5.8S rRNA) and the D1/D2 domains of 26S rRNA. The combined ITS and D1/D2 phylogenetic analysis showed that those two candidate new species were closely related to Malassezia slooffiae, and differed from the type of M. slooffiae by 51-62 nucleotides in the ITS region and four nucleotides in the D1/D2 domains, respectively. Based on the phylogenetic analysis and the phenotypic comparison, we propose a new species, named M. gallinae sp. nov., to include the 21 isolated strains.

Genomic and phenotypic characterization of a Clostridioides difficile strain of the epidemic ST37 type from China.

Clostridioides difficile strains of sequence type (ST) 37, primarily including PCR ribotype (RT) 017, are prevalent in mainland China. Our study aimed to compare the major virulence factors of an epidemic C. difficile isolate of ST37 type (Xy06) from China with the well-characterized C. difficile reference strains R20291 (RT027) and CD630E (ST54), as well as a Chinese ST54 strain (Xy07) isolated from the same hospital. The Xy06 genome was predicted to harbor two complete prophages and several transposon-like elements. Comparative analysis of PaLoc revealed a truncated tcdA gene, a functional tcdB gene, a functional tcdC gene, and well-conserved tcdR and tcdE genes. Phenotypic comparisons showed that Xy06 was a robust producer of TcdB, readily sporulated and germinated, and strongly bound to human gut epithelial cells. In a mouse model of C. difficile infection, Xy06 was more virulent than strains CD630E and Xy07 and was comparable to strain R20291 in virulence. Our data suggest the potential threat of the epidemic ST37 strains in China.

X- vs. Y-chromosome influences on human behavior: a deep phenotypic comparison of psychopathology in XXY and XYY syndromes

BackgroundDo different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders.MethodsUsing a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)—Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences.ResultsWe show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r = .75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ.ConclusionsThis work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior.