Important Phenotypes Research Articles

Fur-mediated regulation of hydrogen sulfide synthesis, stress response, and virulence in Edwardsiella piscicida

The production of endogenous hydrogen sulfide (H2S) is an important phenotype of bacteria. H2S plays an important role in bacterial resistance to ROS and antibiotics, which significantly contributes to bacterial pathogenicity. Edwardsiella piscicida, the Gram-negative pathogen causing fish edwardsiellosis, has been documented to produce hydrogen sulfide. In the study, we revealed that Ferric uptake regulator (Fur) controlled H2S synthesis by activating the expression of phsABC operon. Besides, Fur participated in the bacterial defense against ROS and cationic antimicrobial peptides and modulated T3SS expression. Furthermore, the disruption of fur exhibited a significant in vivo colonization defect. Collectively, our study demonstrated the regulation of Fur in H2S synthesis, stress response, and virulence, providing a new perspective for better understanding the pathogenesis of Edwardsiella.

Expression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3+ T cells in tuberculosis patients

BackgroundHuman T cells play an important role in immunity against tuberculosis (TB) infection. Activating receptor HLA-DR and inhibitory receptor KLRG1 are critical regulators of T cell function during viral infection and tumorigenesis, but they have been less studied in TB infection. MethodsIn this study, we explored the relationship between CD3+ T cell expression of HLA-DR and KLRG1 receptors and function against TB infection. Flow cytometry was conducted to assess the immunomodulatory effects of HLA-DR and KLRG1 receptors on CD3+ T cells in patients with different TB infection status. ResultsWe found activating receptors HLA-DR, NKG2C, CD57 and NKP46, and inhibitory receptors KLRG1 and KIR on CD3+ T cells in different TB infection status showed different distribution patterns; the cytotoxic potential and cytokine secretion capacity of CD3+ T cells after Mtb-specific antigen stimulation were significantly enhanced in TB infection groups. Further studies revealed HLA-DR+ T and KLRG1+ T cells expressed higher activating and inhibitory receptors than the negative population. In addition, the expression of cytotoxic potential and cytokine secretion capacity of HLA-DR+ T and KLRG1+ T cells was significantly higher than that of HLA-DR- T and KLRG1- T cells. ConclusionsExpression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3+ T cells in TB patients, suggesting CD3+ T cells expressing HLA-DR and KLRG1 are important effector cell phenotypes involved in the host anti-TB infection. HLA-DR and KLRG1 expressed by CD3+ T cells may be potential predictive markers of TB disease progression and clinical immune assessment.

Mitochondrial damage and activation of NLRP3 induced by Yersinia ruckeri infection play an important role in the occurrence of diffuse acute inflammation of channel catfish (Ictalurus punctatus)

Yersinia ruckeri, as a facultative intracellular pathogen, can cause two different infection phenotypes of fish. An important phenotype is diffuse acute inflammation (DAI), which is mainly characterized by systemic hemorrhage and multiple tissues damage. Another phenotype is enteric redmouth symptom (EM) with predominantly digestive system damage, while slight damage to other tissues and organs. At present, the causes and mechanisms of heterogeneity of Y. ruckeri infection are not clear. According to our previous research and related bioinformatics analysis, it is suggested that the heterogeneity of infection of Y. ruckeri may be related to the activation of intracellular pattern recognition receptor (NLRP3). Furthermore, combined with the transmission electron microscope observation and ultrastructural pathological analysis of DAI and EM phenotypes, it is hypothesized that Y. ruckeri infection may mediate the occurrence of DAI by inducing mitochondrial damage and activation of NLRP3. In this study, we established DAI and EM phenotypes of channel catfish (Ictalurus punctatus) through the artificial infection experiment. Subsequently, we observed the pathological changes and characteristics of different tissues in DAI and EM phenotypes, such as liver, spleen, kidney, intestine and gill. In addition, the mitochondrial damage of head kidney mediated by Y. ruckeri infection was confirmed by transmission electron microscope observation. Furthermore, by detecting the expression of proinflammatory factors and related pattern recognition receptors in various tissues, we preliminarily clarified the molecular characteristics of immune response in DAI and EM phenotype fish. Moreover, the head kidney macrophages isolated from DAI and EM were observed through transmission electron microscope, and the expression levels of NLRP3, Caspase-1 and IL-1β were detected. Finally, the correlation between mitochondrial damage induced by Y. ruckeri infection and NLRP3 signal transduction was preliminary revealed. Taken together, our results showed that the inflammatory DAI phenotype of fish mediated by Y. ruckeri infection is closely related to mitochondrial damage and NLRP3 activation, which will provide theoretical basis for further study on the pathogenic mechanism of Y. ruckeri infection and clinical diagnosis of the disease, and also provide some insights into the role of NLRP3 in the natural immunity of aquatic animals.

Predicted genetic burden and frequency of phenotype-associated variants in the horse

Disease-causing variants have been identified for less than 20% of suspected equine genetic diseases. Whole genome sequencing (WGS) allows rapid identification of rare disease causal variants. However, interpreting the clinical variant consequence is confounded by the number of predicted deleterious variants that healthy individuals carry (predicted genetic burden). Estimation of the predicted genetic burden and baseline frequencies of known deleterious or phenotype associated variants within and across the major horse breeds have not been performed. We used WGS of 605 horses across 48 breeds to identify 32,818,945 variants, demonstrate a high predicted genetic burden (median 730 variants/horse, interquartile range: 613–829), show breed differences in predicted genetic burden across 12 target breeds, and estimate the high frequencies of some previously reported disease variants. This large-scale variant catalog for a major and highly athletic domestic animal species will enhance its ability to serve as a model for human phenotypes and improves our ability to discover the bases for important equine phenotypes.

The cardiovascular changes underlying a low cardiac output with exercise in patients with type 2 diabetes mellitus.

The significant morbidity and premature mortality of type 2 diabetes mellitus (T2DM) is largely associated with its cardiovascular consequences. Focus has long been on the arterial atheromatosis of DM giving rise to early stroke and myocardial infarctions, whereas less attention has been given to its non-ischemic cardiovascular consequences. Irrespective of ischemic changes, T2DM is associated with heart failure (HF) most commonly with preserved ejection fraction (HFpEF). Largely due to increasing population ages, hypertension, obesity and T2DM, HFpEF is becoming the most prevalent form of heart failure. Unfortunately, randomized controlled trials of HFpEF have largely been futile, and it now seems logical to address the important different phenotypes of HFpEF to understand their underlying pathophysiology. In the early phases, HFpEF is associated with a significantly impaired ability to increase cardiac output with exercise. The lowered cardiac output with exercise results from both cardiac and peripheral causes. T2DM is associated with left ventricular (LV) diastolic dysfunction based on LV hypertrophy with myocardial disperse fibrosis and significantly impaired ability for myocardial blood flow increments with exercise. T2DM is also associated with impaired ability for skeletal muscle vasodilation during exercise, and as is the case in the myocardium, such changes may be related to vascular rarefaction. The present review discusses the underlying phenotypical changes of the heart and peripheral vascular system and their importance for an adequate increase in cardiac output. Since many of the described cardiovascular changes with T2DM must be considered difficult to change if fully developed, it is suggested that patients with T2DM are early evaluated with respect to their cardiovascular compromise.

Comprehensive study reveals phenotypic heterogeneity in Klebsiella pneumoniae species complex isolates

Here, we conducted a comprehensive analysis of 356 Klebsiella pneumoniae species complex (KpSC) isolates that were classified as classical (cl), presumptive hypervirulent (p-hv) and hypermucoviscous-like (hmv-like). Overall, K. pneumoniae (82.3%), K. variicola (2.5%) and K. quasipneumoniae (2.5%) were identified. These isolates comprised 321 cl-KpSC, 7 p-hv-KpSC and 18 hmv-like-KpSC. A large proportion of cl-KpSC isolates were extended-spectrum-β-lactamases (ESBLs)-producers (64.4%) and 3.4% of isolates were colistin-resistant carrying carbapenemase and ESBL genes. All p-hv-KpSC showed an antibiotic susceptible phenotype and hmv-like isolates were found to be ESBL-producers (8/18). Assays for capsule production and capsule-dependent virulence phenotypes and whole-genome sequencing (WGS) were performed in a subset of isolates. Capsule amount differed in all p-hv strains and hmv-like produced higher capsule amounts than cl strains; these variations had important implications in phagocytosis and virulence. Murine sepsis model showed that most cl strains were nonlethal and the hmv-like caused 100% mortality with 3 × 108 CFUs. Unexpectedly, 3/7 (42.9%) of p-hv strains required 108 CFUs to cause 100% mortality (atypical hypervirulent), and 4/7 (57.1%) strains were considered truly hypervirulent (hv). Genomic analyses confirmed the diverse population, including isolates belonging to hv clonal groups (CG) CG23, CG86, CG380 and CG25 (this corresponded to the ST3999 a novel hv clone) and MDR clones such as CG258 and CG147 (ST392) among others. We noted that the hmv-like and hv-ST3999 isolates showed a close phylogenetic relationship with cl-MDR K. pneumoniae. The information collected here is important to understand the evolution of clinically important phenotypes such as hypervirulent and ESBL-producing-hypermucoviscous-like amongst the KpSC in Mexican healthcare settings. Likewise, this study shows that mgrB inactivation is the main mechanism of colistin resistance in K. pneumoniae isolates from Mexico.

Euthyroid graves' ophthalmopathy in a Chinese population: A cross-sectional follow-up study.

A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

The 5 Ws of Ambulatory Blood Pressure Monitoring.

Blood pressure (BP) measurement is affected by multiple variables which influence clinical management decisions and patient outcomes. Around 24-hour ambulatory blood pressure monitoring (ABPM) avoids incorrect diagnosis of hypertension (HT), and unnecessary treatment and provides the best prediction of cardiovascular (CV) risk. Clinically important phenotypes of HT such as masked HT (masked HT), white coat HT (white coat HT), and nocturnal HT (nocturnal HT) may be missed by not incorporating ambulatory BP monitoring in practice. However, lack of device availability, operational difficulties, and cost remain barriers to its widespread acceptance in India. In this review, we discuss the when, what, who, why, and where (5Ws) relevant to ABPM measurement.

Novel and rare β-lactamase genes of Bacteroides fragilis group species: Detection of the genes and characterization of their genetic backgrounds

ObjectivesThis study screened the prevalence of rare β-lactamase genes in Bacteroides fragilis group strains from clinical specimens and normal microbiota and examined the genetic properties of the strains carrying these genes. MethodsblaHGD1, blaOXA347, cblA, crxA, and pbbA were detected by real-time polymerase chain reaction in collections of Bacteroides strains from clinical (n = 406) and fecal (n = 184) samples. To examine the genetic backgrounds of the samples, end-point PCR, FT-IR, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used. ResultsAll B. uniformis isolates were positive for cblA in both collections. Although crxA was B. xylanisolvens-specific and associated with carbapenem resistance, it was only found in six fecal and three clinical B. xylanisolvens strains. Moreover, the crxA-positive strains were not clonal among B. xylanisolvens (contrary to cfiA in B. fragilis), implicating a rate of mobility or emergence by independent evolutionary events. The Phocaeicola (B.) vulgatus/P. dorei-specific gene blaHGD1 was detected among all P. vulgatus/P. dorei isolates from fecal (n = 36) and clinical (n = 26) samples. No blaOXA347-carrying isolate was found from European collections, but all US samples (n = 6) were positive. For three clinical isolates belonging to B. thetaiotaomicron (n = 2) and B. ovatus (n = 1), pbbA was detected on mobile genetic elements, and pbbA-positive strains displayed non-susceptibility to piperacillin or piperacillin/tazobactam phenotypically. ConclusionsBased on these observations, β-lactamases produced by rare β-lactamase genes in B. fragilis group strains should not be overlooked because they could encode important resistance phenotypes.

Two sirtuin proteins, Hst3 and Hst4, modulate asexual development, stress tolerance, and virulence by affecting global gene expression in Beauveria bassiana.

Beauveria bassiana is a widely used entomopathogenic fungus in insect biological control applications. In this study, we investigated the role of two sirtuin homologs, BbHst3 and BbHst4, in the biological activities and pathogenicity of B. bassiana. Our results showed that deletion of BbHst3 and/or BbHst4 led to impaired sporulation, reduced (~50%) conidial production, and decreased tolerance to various stresses, including osmotic, oxidative, and cell wall-disturbing agents. Moreover, BbHst4 plays dominant roles in histone H3-K56 acetylation and DNA damage response, while BbHst3 is more responsible for maintaining cell wall integrity. Transcriptomic analyses revealed significant changes (>1,500 differentially expressed genes) in gene expression patterns in the mutant strains, particularly in genes related to secondary metabolism, detoxification, and transporters. Furthermore, the ΔBbHst3, ΔBbHst4, and ΔBbHst3ΔBbHst4 strains exhibited reduced virulence in insect bioassays, with decreased (~20%) abilities to kill insect hosts through topical application and intra-hemocoel injection. These findings highlight the crucial role of BbHst3 and BbHst4 in sporulation, DNA damage repair, cell wall integrity, and fungal infection in B. bassiana. Our study provides new insights into the regulatory mechanisms underlying the biological activities and pathogenicity of B. bassiana and emphasizes the potential of targeting sirtuins for improving the efficacy of fungal biocontrol agents.IMPORTANCESirtuins, as a class of histone deacetylases, have been shown to play important roles in various cellular processes in fungi, including asexual development, stress response, and pathogenicity. By investigating the functions of BbHst3 and BbHst4, we have uncovered their critical contributions to important phenotypes in Beauveria bassiana. Deletion of these sirtuin homologs led to reduced conidial yield, increased sensitivity to osmotic and oxidative stresses, impaired DNA damage repair processes, and decreased fungal virulence. Transcriptomic analyses showed differential expression of numerous genes involved in secondary metabolism, detoxification, transporters, and virulence-related factors, potentially uncovering new targets for manipulation and optimization of fungal biocontrol agents. Our study also emphasizes the significance of sirtuins as key regulators in fungal biology and highlights their potential as promising targets for the development of novel antifungal strategies.

PRMT5 inhibition shows in vitro efficacy against H3K27M-altered diffuse midline glioma, but does not extend survival in vivo

H3K27-altered Diffuse Midline Glioma (DMG) is a universally fatal paediatric brainstem tumour. The prevalent driver mutation H3K27M creates a unique epigenetic landscape that may also establish therapeutic vulnerabilities to epigenetic inhibitors. However, while HDAC, EZH2 and BET inhibitors have proven somewhat effective in pre-clinical models, none have translated into clinical benefit due to either poor blood–brain barrier penetration, lack of efficacy or toxicity. Thus, there remains an urgent need for new DMG treatments. Here, we performed wider screening of an epigenetic inhibitor library and identified inhibitors of protein arginine methyltransferases (PRMTs) among the top hits reducing DMG cell viability. Two of the most effective inhibitors, LLY-283 and GSK591, were targeted against PRMT5 using distinct binding mechanisms and reduced the viability of a subset of DMG cells expressing wild-type TP53 and mutant ACVR1. RNA-sequencing and phenotypic analyses revealed that LLY-283 could reduce the viability, clonogenicity and invasion of DMG cells in vitro, representing three clinically important phenotypes, but failed to prolong survival in an orthotopic xenograft model. Together, these data show the challenges of DMG treatment and highlight PRMT5 inhibitors for consideration in future studies of combination treatments.

Sex- and strain-dependent effects of ageing on sleep and activity patterns in Drosophila.

The fruit fly Drosophila is a major discovery platform in the biology of ageing due to its balance of relatively short lifespan and relatively complex physiology and behaviour. Previous studies have suggested that some important phenotypes of ageing, for instance increasingly fragmented sleep, are shared from humans to Drosophila and can be useful measures of behavioural change with age: these phenotypes therefore hold potential as readouts of healthy ageing for genetic or pharmacological interventions aimed at the underpinning biology of ageing. However, some age-related phenotypes in Drosophila show differing results among studies, leading to questions regarding the source of discrepancies among experiments. In this study, I have tested females and males from three common laboratory strains of Drosophila to determine the extent to which sex and background strain influence age-related behavioural changes in sleep and activity patterns. Surprisingly, I find that some phenotypes-including age-related changes in total activity, total sleep, and sleep fragmentation-depend strongly on sex and strain, to the extent that some phenotypes show opposing age-related changes in different sexes or strains. Conversely, I identify other phenotypes, including age-related decreases in morning and evening anticipation, that are more uniform across sexes and strains. These results reinforce the importance of controlling for background strain in both behavioural and ageing experiments, and they imply that caution should be used when drawing conclusions from studies on a single sex or strain of Drosophila. At the same time, these findings also offer suggestions for behavioural measures that merit further investigation as potentially more consistent phenotypes of ageing.

Incubation temperature induced developmental plasticity of cold responsive physiological phenotypes in Japanese Quails

Embryonic development is a critical period for phenotype formation. Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals. The thyroxine secretion and aerobic metabolic activity of small birds are important phenotypes closely related to their winter survival. In the context of climate change, it is necessary to determine whether temperature variation during incubation in birds leads to developmental plasticity of these cold responsive phenotypes. We incubated Japanese Quail (Coturnix japonica) eggs at 36.8 °C, 37.8 °C, and 38.8 °C, and raised the chicks to 35-day old at 22 °C with same raising conditions, then all the quails were exposed to gradually temperature dropping environment (from 15 °C to 0 °C). After cold treatment, serum T3 level, resting metabolic rate, skeletal muscle and liver metabolomes of the birds were measured. The serum T3 levels were significantly lower in the 38.8 °C group and significantly higher in the 36.8 °C group compared to the 37.8 °C group. The metabolic rate in the 38.8 °C group was significantly lower compared to the 37.8 °C group. Compared with the 37.8 °C group, metabolites involved in the tricarboxylic acid cycle in the liver were significantly lower in the 38.8 °C group, and metabolites related to lipid oxidation metabolism and fatty acid biosynthesis were significantly lower in the skeletal muscles in the 38.8 °C group but significantly higher in the 36.8 °C group. These results indicate that incubation temperature variation can lead to developmental plasticity in cold responsive physiological phenotypes. Higher incubation temperature may impair the capacity of birds coping with cold challenge.

Genome-Wide Association Analysis of Rapid Decline in Lung Function: Analysis From the Korean Genome and Epidemiology Study.

A rapid decline in forced expiratory volume in 1 second (FEV1) is considered an important phenotype of the development of chronic obstructive pulmonary disease (COPD). However, the associations between specific genetic variants (single-nucleotide polymorphisms; SNPs) and this phenotype remain uncertain. We enrolled 6,516 individuals from the Korean Genome and Epidemiology Study (KoGES). A rapid decline in FEV1 was defined as an annual decrease of FEV1 ≥ 60 mL/year. A multivariable logistic regression model was used to assess the associations between SNP variants and the rapid decline in FEV1. Considering the significant impact of smoking on lung function, a subgroup analysis based on smoking history was also conducted. A genome-wide association analysis of the rapid decline in FEV1 identified 15 association signals (P < 5.0 × 10-8). Among the 15 nucleotide variants, rs9833533 and rs1496255 have been previously reported to be associated with lung function development. In the subgroup analysis, rs16951883 (adjusted odds ratio [aOR], 3.24; P = 5.87 × 10-8) was the most significant SNP associated with rapid decline in FEV1 among never smokers, followed by rs41476549, rs16840064, and rs1350110. Conversely, among ever smokers, rs10959478 (aOR, 4.74; P = 8.27 × 10-7) showed the highest significance, followed by rs6805861, rs9833533, and rs16906215. We identified 15 nucleotide variants linked to a rapid decline in FEV1, including two SNPs previously reported to be associated with lung function development. Additional SNPs, which were associated with COPD, may be found using novel phenotypes.

Tyrosine Kinase Inhibitor-induced Cerebrovascular Occlusion Presenting with Moyamoya Disease-like Stenosis of the Circle of Willis.

Vascular occlusive events are notable adverse effects of tyrosine kinase inhibitors (TKIs), which are promising treatments for chronic myeloid leukemia (CML). We herein report the case of a patient with CML who developed cerebrovascular occlusion of the circle of Willis during TKI treatment. Our patient did not meet the diagnostic criteria for moyamoya disease due to the insignificant development of moyamoya vessels. The lack of moyamoya vessel development may be explained by the suppression of tyrosine kinases that are responsible for angiogenesis. Cerebrovascular occlusion of the circle of Willis, without significant development of moyamoya vessels, may be an important phenotype of TKI-associated vasculopathy.

Encephalitis is an Important Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Diseases: A Single-Center Cohort Study

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. MethodsThis was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. ResultsA total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). ConclusionsThe spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.

RNAseq of diverse spring wheat cultivars released during last 110 years

Here, we performed RNA-seq based expression analysis of root and leaf tissues of a set of 24 historical spring wheat cultivars representing 110 years of temporal genetic variations. This huge 130 tissues RNAseq dataset was initially used to study expression pattern of 97 genes regulating root growth and development in wheat. Root system architecture (RSA) is an important target for breeding stress-resilient and high-yielding wheat cultivars under climatic fluctuations. However, root transcriptome analysis is usually obscured due to challenges in root research due to their below ground presence. We also validated the dataset by performing correlation analysis between expression of RSA related genes in roots and leaves with 25 root traits analyzed under varying moisture conditions and 10 yield-related traits. The Pearson’s correlation coefficients between root phenotypes and expression of root-specific genes varied from −0.72 to 0.78, and strong correlations with genes such as DRO1, TaMOR, ARF4, PIN1 was observed. The presented datasets have multiple uses such as a) studying the change in expression pattern of genes during time, b) differential expression of genes in two very important tissues of wheat i.e., leaf and roots, and c) studying customized expression of genes associated with important phenotypes in diverse wheat cultivars. The initial findings presented here provided key insights into understanding the transcriptomic basis of phenotypic variability of RSA in wheat cultivars.

Prevalence and molecular basis of null blood group phenotypes in the Korean population: Analysis using a public database.

Null phenotypes are characterized by complete absence of all antigens within a blood group system and caused by null variants (e.g., nonsense, frameshift, initiation codon, and canonical splice site variants) in the genes encoding the antigens. Knowing the prevalence and molecular basis of null phenotypes is essential to establish a rare donor program, and the aim of this study was to reveal the prevalence and molecular basis of null phenotypes using the Korean Reference Genome Database (KRGDB) containing whole-genome sequences of 1722 Korean individuals. Population allele frequencies of null alleles in 39 blood group systems except ABO, MNS, Rh, Lewis, and FORS were obtained from the KRGDB. The prevalence of null phenotypes was calculated using Hardy-Weinberg equation. The prevalence of null phenotypes were estimated to be less than 0.001% in all blood group systems except JR and SID. The prevalence of the Jr(a-) and Sd(a-) phenotypes were estimated to be 0.0453% and 0.2323%, respectively. The most frequent null allele of the JR system was ABCG2*01N.01, accounting for approximately 85% of null alleles. Our approach using a public database allowed us to investigate the prevalence and molecular basis of null phenotypes in the Korean population, which will serve as a guide for establishing a rare donor program in Korea. Considering the clinical significance, Jr(a-) is an important null phenotype that should be typed in the Korean population, and molecular assays targeting the most frequent allele ABCG2*01N.01 may be useful in detecting this phenotype.

Regulation of the physiology and virulence of Ralstonia solanacearum by the second messenger 2′,3′-cyclic guanosine monophosphate

Previous studies have demonstrated that bis-(3',5')-cyclic diguanosine monophosphate (bis-3',5'-c-di-GMP) is a ubiquitous second messenger employed by bacteria. Here, we report that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions, quorum sensing (QS) signaling systems and virulence in Ralstonia solanacearum through the transcriptional regulator RSp0980. This signal specifically binds to RSp0980 with high affinity and thus abolishes the interaction between RSp0980 and the promoters of target genes. In-frame deletion of RSp0334, which contains an evolved GGDEF domain with a LLARLGGDQF motif required to catalyze 2',3'-cGMP to (2',5')(3',5')-cyclic diguanosine monophosphate (2',3'-c-di-GMP), altered the abovementioned important phenotypes through increasing the intracellular 2',3'-cGMP levels. Furthermore, we found that 2',3'-cGMP, its receptor and the evolved GGDEF domain with a LLARLGGDEF motif also exist in the human pathogen Salmonella typhimurium. Together, our work provides insights into the unusual function of the GGDEF domain of RSp0334 and the special regulatory mechanism of 2',3'-cGMP signal in bacteria.

Infant gut microbiota and negative and fear reactivity.

Studies indicate that gut microbiota is related to neurodevelopmental and behavioral outcomes. Accordingly, early gut microbiota composition (GMC) has been linked to child temperament, but research is still scarce. The aim of this study was to examine how early GMC at 2.5 months is associated with child negative and fear reactivity at 8 and 12 months since they are potentially important intermediate phenotypes of later child psychiatric disorders. Our study population was 330 infants enrolled in the longitudinal FinnBrain Birth Cohort Study. Gut microbiota composition was analyzed using stool sample 16s rRNA sequencing. Negative and fear reactivity were assessed using the Laboratory Temperament Assessment Battery (Lab-TAB) at child's age of 8 months (n =150) and the Infant Behavior Questionnaire-Revised Short Form (IBQ-R SF) at child's age of 12 months (n = 276). We found a positive association between alpha diversity and reported fear reactivity and differing microbial community composition based on negative reactivity for boys. Isobutyric acid correlated with observed negative reactivity, however, this association attenuated in the linear model. Several genera were associated with the selected infant temperament traits. This study adds to the growing literature on links between infant gut microbiota and temperament informing future mechanistic studies.