C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8.

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition.

Mycena genomes resolve the evolution of fungal bioluminescence.

Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life; yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species (Mycena spp.), a diverse lineage comprising the majority of bioluminescent fungi. Two species with haploid genome assemblies ∼150 Mb are among the largest in Agaricales, and we found that a variety of repeats between Mycena species were differentially mediated by DNA methylation. We show that bioluminescence evolved in the last common ancestor of mycenoid and the marasmioid clade of Agaricales and was maintained through at least 160 million years of evolution. Analyses of synteny across genomes of bioluminescent species resolved how the luciferase cluster was derived by duplication and translocation, frequently rearranged and lost in most Mycena species, but conserved in the Armillaria lineage. Luciferase cluster members were coexpressed across developmental stages, with the highest expression in fruiting body caps and stipes, suggesting fruiting-related adaptive functions. Our results contribute to understanding a de novo origin of bioluminescence and the corresponding gene cluster in a diverse group of enigmatic fungal species.

Comparative genomic and transcriptomic analyses of trans-kingdom pathogen Fusarium solani species complex reveal degrees of compartmentalization.

BACKGROUND: The Fusarium solani species complex (FSSC) comprises fungal pathogens responsible for mortality in a diverse range of animals and plants, but their genome diversity and transcriptome responses in animal pathogenicity remain to be elucidated. We sequenced, assembled and annotated six chromosome-level FSSC clade 3 genomes of aquatic animal and plant host origins. We established a pathosystem and investigated the expression data of F. falciforme and F. keratoplasticum in Chinese softshell turtle (Pelodiscus sinensis) host. RESULTS: Comparative analyses between the FSSC genomes revealed a spectrum of conservation patterns in chromosomes categorised into three compartments: core, fast-core (FC), and lineage-specific (LS). LS chromosomes contribute to variations in genomes size, with up to 42.2% of variations between F. vanettenii strains. Each chromosome compartment varied in structural architectures, with FC and LS chromosomes contain higher proportions of repetitive elements with genes enriched in functions related to pathogenicity and niche expansion. We identified differences in both selection in the coding sequences and DNA methylation levels between genome features and chromosome compartments which suggest a multi-speed evolution that can be traced back to the last common ancestor of Fusarium. We further demonstrated that F. falciforme and F. keratoplasticum are opportunistic pathogens by inoculating P. sinensis eggs and identified differentially expressed genes also associated with plant pathogenicity. These included the most upregulated genes encoding the CFEM (Common in Fungal Extracellular Membrane) domain. CONCLUSIONS: The high-quality genome assemblies provided new insights into the evolution of FSSC chromosomes, which also serve as a resource for studies of fungal genome evolution and pathogenesis. This study also establishes an animal model for fungal pathogens of trans-kingdom hosts.

Psychometric properties of the Malay version of motivation scales in drug treatment.

INTRODUCTION: In recognition of the role of motivation in drug use treatment, patient motivational screening instruments are needed for strategic planning and treatment. The aims of this study were to evaluate the reliability and validity of the Malay version of the Treatment Motivation Scale, and to compare the motivational levels of patients receiving substance abuse treatment with different modalities (inpatient vs. outpatient). The motivational scale consists of three scales: problem recognition, desire for help and treatment readiness. METHOD: A convenience sample of 102 patients was recruited from four Cure and Care Service Centres in Malaysia. RESULTS: Principal component analysis with varimax rotation supported two-factor solutions for each subscale: problem recognition, desire for help and treatment readiness, which accounted for 63.5%, 62.7% and 49.1% of the variances, respectively. The Cronbach's alpha coefficients were acceptable for the overall measures (24 items: ∝ = 0.89), the problem recognition scale (10 items; ∝ = 0.89), desire for help (6 items; ∝ = 0.64) and treatment readiness scale (8 items; ∝ = 0.60). The results also indicated significant motivational differences for different modalities, with inpatients having significantly higher motivational scores in each scale compared to outpatients. CONCLUSION: The present study pointed towards the favourable psychometric properties of a motivation for treatment scale, which can be a useful instrument for clinical applications of drug use changes and treatment.

Fast and stable gratings inscription in POFs made of different materials with pulsed 248 nm KrF laser.

This paper presents fiber Bragg grating (FBG) inscription with a pulsed 248 nm UV KrF laser in polymer optical fibers (POFs) made of different polymers, namely polymethyl methacrylate (PMMA), cyclic-olefin polymer and co-polymer, and Polycarbonate. The inscribed gratings and the corresponding inscription parameters are compared with grating inscribed in POFs made of the aforementioned materials but with the hitherto most used laser for inscription, which is a continuous wave 325 nm UV HeCd laser. Results show a reduction of the inscription time of at least 16 times. The maximum time reduction is more than 130 times. In addition, a reflectivity and a bandwidth close to or higher than the ones with the 325 nm laser were obtained. The polymer optical fiber Bragg gratings (POFBGs) inscribed with the 248 nm laser setup present high stability with small variations in their central wavelength, bandwidth, and reflectivity after 40 days.

Ultrasound Strain Relaxation Time Ratio: A Quantitative Marker for the Assessment of Cortical Inflammation/Edema in Renal Allografts.

Purpose: To evaluate the ability of ultrasound strain relaxation time ratio to assess cortical inflammation/edema in renal allografts. Materials and Methods: We prospectively assessed renal allograft cortical inflammation/edema in 16 renal transplants using ultrasound elasticity imaging and correlated the findings with kidney biopsy. Strain relaxation times in the renal cortex and reference soft tissue were produced by free-hand compression with the ultrasound transducer and estimated with 2 D speckle tracking. Compression was performed in 3-second compression-relaxation cycles (push for 1 second, constant pressure for 1 second, and release for 1 second). We propose a strain relaxation time ratio (time of cortical strain to return to zero/time of the reference strain return to zero) to assess the relationship of compression-induced time-dependent strain relaxation in the cortex and reference tissue. 16 patients were divided into a group with ≤ 25 % (n = 8) and a group with > 26 % (n = 8) cortical inflammation/edema based on the Banff score. A t-test was used to examine the difference in the strain relaxation time ratio between the two groups. The diagnostic accuracy, inter-rater reliability, and reproducibility of this technique in discriminating between the groups were tested. Results: The strain relaxation time ratio of cortex/reference tissue was significantly higher in patients with > 26 % than in patients with ≤ 25 % cortical inflammation/edema (1.15 ±â€Š0.10 vs. 0.91 ±â€Š0.08, P = 0.0002). The strain relaxation time ratio has high reliability (Pearson correlation coefficient, R²â€Š= 0.93), reproducibility (intraclass correlation coefficient = 0.98, P = 0.000), and accuracy (area under curve = 1) in determining > 26 % renal cortical inflammation/edema. Conclusion: The strain relaxation time ratio of cortex/reference tissue can be used as a quantitative marker for the assessment of cortical inflammation/edema in renal allografts.

Emerging trends of invasive yeast infections and azole resistance in Beijing intensive care units.

BACKGROUND: Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. METHODS: A two-phase surveillance project was conducted in Beijing, China, involving 37 centres across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. FINDINGS: We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared with the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. CONCLUSIONS: Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

Systematic Reporting of Eosinophils in Transbronchial Biopsies After Lung Transplantation Defines a Distinct Inflammatory Response.

BACKGROUND: Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations. METHODS: A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils. RESULTS: A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic "for-cause" procedures were independently associated with higher quantities of TBBx eosinophils. CONCLUSIONS: Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation.

An acidophilic fungus promotes prey digestion in a carnivorous plant.

Leaves of the carnivorous sundew plants (Drosera spp.) secrete mucilage that hosts microorganisms, but whether this microbiota contributes to prey digestion is unclear. We identified the acidophilic fungus Acrodontium crateriforme as the dominant species in the mucilage microbial communities, thriving in multiple sundew species across the global range. The fungus grows and sporulates on sundew glands as its preferred acidic environment, and its presence in traps increased the prey digestion process. A. crateriforme has a reduced genome similar to other symbiotic fungi. During A. crateriforme-Drosera spatulata coexistence and digestion of prey insects, transcriptomes revealed significant gene co-option in both partners. Holobiont expression patterns during prey digestion further revealed synergistic effects in several gene families including fungal aspartic and sedolisin peptidases, facilitating prey digestion in leaves, as well as nutrient assimilation and jasmonate signalling pathway expression. This study establishes that botanical carnivory is defined by adaptations involving microbial partners and interspecies interactions.

The Aphelenchoides genomes reveal substantial horizontal gene transfers in the last common ancestor of free-living and major plant-parasitic nematodes.

Aphelenchoides besseyi is a plant-parasitic nematode (PPN) in the family Aphelenchoididae capable of infecting more than 200 plant species. A. besseyi is also a species complex with strains exhibiting varying pathogenicity to plants. We present the genome and annotations of six Aphelenchoides species, four of which belonged to the A. besseyi species complex. Most Aphelenchoides genomes have a size of 44.7-47.4 Mb and are among the smallest in clade IV, with the exception of A. fujianensis, which has a size of 143.8 Mb and is one of the largest. Phylogenomic analysis successfully delimited the species complex into A. oryzae and A. pseudobesseyi and revealed a reduction of transposon elements in the last common ancestor of Aphelenchoides. Synteny analyses between reference genomes indicated that three chromosomes in A. besseyi were derived from fission and fusion events. A systematic identification of horizontal gene transfer (HGT) genes across 27 representative nematodes allowed us to identify two major episodes of acquisition corresponding to the last common ancestor of clade IV or major PPNs, respectively. These genes were mostly lost and differentially retained between clades or strains. Most HGT events were acquired from bacteria, followed by fungi, and also from plants; plant HGT was especially prevalent in Bursaphelenchus mucronatus. Our results comprehensively improve the understanding of HGT in nematodes.

Factors determining whether diffuse large B-cell lymphoma samples are detected by flow cytometry.

INTRODUCTION: Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. METHODS: Cases with a final diagnosis of DLBCL that were analysed by eight-colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. RESULTS: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B-cell (GCB) and non-GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine-needle aspirates, or between samples from nodal compared to extranodal tissue. CONCLUSION: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight-colour analysis, FCM fails to detect numerous cases of DLBCL.

Characterization of Th1- and Th2-type immune response in human multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a lethal global threat. Insights into the immune regulation of MDR-TB are urgently needed for the development of new treatments; however, the T cell response to an MDR-TB infection in human remains unclear. In the present study, the proportion of Th1 and Th2 cell subsets and the level of related T cell subset cytokines in peripheral blood were investigated. We detected that an MDR-TB infection resulted in suppressed Th1 and Th2 cell activation, which was more remarkable in patients with MDR-TB than that in drug-sensitive tuberculosis (DS-TB) sufferers when compared to healthy controls (HCs). In addition, MDR-TB infection down-regulated the expression of IFN-γ, IL-2, and IL-10, and up-regulated IL-4, IL-6, and TNF-α expression. Our data suggest that the disturbance between protective and pathogenic effects induced by the immunosuppression of Th1- and Th2-type responses is a substantial characteristic of MDR-TB infections.

Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells.

OBJECTIVE: The aim of this study was to examine the anti-invasion effect of Shikonin on human high-metastatic adenoid cystic carcinoma (ACC-M) cells and to explain the possible molecular mechanism involved. METHODS: The ACC-M cells were treated with Shikonin (0, 2.5, 5, 10 µM) for 24 h. The protein levels and gelatinolytic activities of MMP-2 and MMP-9 were analyzed using Western blot and Gelatin zymography test, respectively. Matrigel invasion assays were used to investigate tumor invasive potential and electromobility shift assays were used to determine the activity of NF-κB. RESULTS: The invasiveness of ACC-M cells was reduced in a dose dependent manner following 24-h treatment of up to 10 µM of the Shikonin at which concentration no cytotoxicity occurred. The protein levels and gelatinolytic activities of MMP-9 were significantly suppressed by increasing Shikonin concentrations. The down-regulation of MMP-9 appeared to be via the inactivation of NF-κB as the treatment with Shikonin suppressed the protein level of phosphate-IkBa, which was accompanied by a decrease in DNA-binding level of the factor. CONCLUSIONS: Shikonin inhibits tumor invasion via downregulation of MMP-9 expression in ACC-M cells. Pharmacologic inhibition of the NF-κB-mediated MMP-9 expression by Shikonin might be a powerful treatment option for ACC patients in future.

A Review of Dung Beetle Introductions in the Antipodes and North America: Status, Opportunities, and Challenges.

Following the introduction of cattle, exotic dung beetles (Coleoptera: Aphodiidae, Geotrupidae, Scarabaeidae) were imported into the Antipodes (Australia and New Zealand) and North America (primarily the United States) to accelerate the degradation of cattle dung on pastures. The history of dung beetle introductions between the two regions is similar but has not previously been assessed: this is important as new introductions are continuing in the regions. Here, we review these introduction programs, report on their current status, and discuss methodological advances. In doing so, we examine the accidental introduction of exotic (i.e., adventive) species and the contribution of both deliberately introduced and adventive species to endemic dung beetle faunas. Further, we provide a list of pest and parasite species whose populations can be reduced by dung beetle activity. We also identify a combined total of 37 introduced and 47 adventive dung beetle species that have become established in the Antipodes and North America, with exotic species dominating dung beetle assemblages from pasture habitats. Climatic and edaphic matches, the size of founding populations, abiotic and biotic stressors, and the time of year when releases are made are all critical determinants that affect the success of dung beetle introduction programs. Finally, we discuss opportunities, plus the risks and challenges associated with dung beetle introductions. We hope that this review will aid in the success of future introduction programs, either to enhance ecosystem services in areas that they are needed, or potentially to reestablish native species in regions where they have been extirpated.

Twice Bitten, Thrice Shy: A Case of Recurrent Isolated Cardiac Sarcoidosis in the Transplanted Heart.

We present a case of recurrent isolated cardiac sarcoidosis, 3 years post-heart transplantation. The case highlights the scarcity of data on the utility of immunosuppression in cardiac sarcoidosis and, in particular, raises questions about the optimal immunosuppression regimen in transplant recipients. (Level of Difficulty: Advanced.).

PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality.

Breast cancer is a common malignancy with current biological therapies tailored to steroid hormone (ER, PR) and HER2 receptor status. Understanding the biological basis of resistance to current targeted therapies and the identification of new potential therapeutic targets is an ongoing challenge. The PI3K pathway is altered in a high proportion of breast cancers and may contribute to therapeutic resistance. We undertook an integrative study of mutational, copy number and expression analyses of key regulators of the PI3K pathway in a cohort of 292 invasive breast cancer patients with known treatment outcomes. The alterations identified in this cohort included PIK3CA mutations (12/168, i.e. 7%), PIK3CA copy number gain (28/209, i.e. 14%), PTEN loss (73/258, i.e. 28%) and AKT activation (62/258, i.e. 24%). Overall at least 1 parameter was altered in 72% (139/193) of primary breast cancers. PI3K pathway activation was significantly associated with ER negative (p = 0.0008) and PR negative (p = 0.006) status, high tumor grade (p = 0.032) and a "basal-like" phenotype (p = 0.01), where 92% (25/27) of tumors had an altered pathway. In univariate analysis, PI3K pathway aberrations were associated with death from breast cancer; however, this relationship was not maintained in multivariate analysis. No association was identified between an activated pathway and outcome in tamoxifen- or chemotherapy-treated patients. We concluded that >70% of breast cancers have an alteration in at least 1 component of the PI3K pathway and this might be exploited to therapeutic advantage especially in "basal-like" cancers.

MicroRNA-381 inhibits metastasis and epithelial-mesenchymal transition of glioblastoma cells through targeting LEF1.

OBJECTIVE: Glioblastoma is a common intracranial malignancy that is extremely harmful to human life and health. Various microRNAs (miRNAs) have been reported to be involved in the progression of glioblastoma, except miR-381. Therefore, the purpose of this study is to investigate the role of miR-381 in glioblastoma. MATERIALS AND METHODS: The expression of miR-381 and LEF1 (lymphoid enhancer-binding factor-1) was quantified using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot analysis. Transwell and Dual-Luciferase reporter assays were used to investigate the regulatory mechanism of miR-381/LEF1 in glioblastoma. RESULTS: Downregulation of miR-381 was observed in A172 cells. In addition, the overexpression of miR-381 restrained migration and invasion of glioblastoma cells. Furthermore, overexpression of miR-381 inhibited epithelial-mesenchymal transition (EMT) in A172 cells. Further, miR-381 was confirmed to directly target LEF1 and negatively regulates its expression in glioblastoma cells. Downregulation of LEF1 also inhibited cell migration, invasion, and EMT in glioblastoma cells. More importantly, the upregulation of LEF1 abolished the inhibitory effect of miR-381 in glioblastoma cells. CONCLUSIONS: MiR-381 inhibits cell metastasis and EMT in glioblastoma by suppressing LEF1 expression.

Dung beetle species introductions: when an ecosystem service provider transforms into an invasive species.

Dung beetle introduction programmes were designed to accelerate exotic livestock dung degradation and to control dung breeding pestiferous flies and livestock parasites. The introduction programmes provided exotic dung beetle species with an opportunity to cross natural barriers and spread beyond their native range. There are no reports that explain what probable adaptation mechanisms enable particular dung beetle species to be the most successful invader. Here we identify the morphological, biological, physiological, ecological and behavioural attributes of the four most widespread and successful dung beetle species in introduced areas on a global scale in relation to the assumption that these species are different from other exotic and native dung beetles. We have recognised Digitonthophagus gazella (Fabricius), Onthophagus taurus (Schreber), Euoniticellus intermedius (Reiche) and Aphodius fimetarius (Linnaeus) as the most successful invaders based on their spread, predominance, distribution range and the reports of invasion. Each of these four species has different natural history traits that increase their fitness making them successful invaders. D. gazella has high fecundity and spreading ability, can instantly locate and colonise fresh and nutritious dung, and has a broad thermal window. O. taurus has morphological plasticity, high fecundity, high brood survival rate due to bi-parenting, and is adapted to extreme thermal and moisture conditions. E. intermedius has remnant-dung feeding abilities, a wide thermal window, functioning best at upper-temperature levels, and successful breeding and survival abilities at extremely low soil moisture conditions. A. fimetarius is small-sized, has high breeding and dispersal abilities, and is adapted to lower thermal and upper moisture extremes and variable soil conditions. Discussed here are perspectives on adaptive attributes of dung beetle species that are important to consider during their selection for redistributions. We have elaborated on the fitness and success characteristics of the four species individually. Further, we recommend a prior-introduction baseline monitoring of native dung beetle assemblages so as to evaluate the future impact of exotic dung beetle introductions on the recipient ecosystem.

Comparative Transcriptomics across Nematode Life Cycles Reveal Gene Expression Conservation and Correlated Evolution in Adjacent Developmental Stages.

Nematodes are highly abundant animals with diverse habitats and lifestyles. Some are free living whereas others parasitize animals or plants, and among the latter, infection abilities change across developmental stages to infect hosts and complete life cycles. To determine the relationship between transcriptome evolution and morphological divergences among nematodes, we compared 48 transcriptomes of different developmental stages across eight nematode species. The transcriptomes were clustered broadly into embryo, larva, and adult stages, with the developmental plastic stages were separated from common larval stages within the larval branch. This suggests that development was the major determining factor after lifestyle changes, such as parasitism, during transcriptome evolution. Such patterns were partly accounted for by tissue-specific genes-such as those in oocytes and the hypodermis-being expressed at different proportions. Although nematodes typically have 3-5 larval stages, the transcriptomes for these stages were found to be highly correlated within each species, suggesting high similarity among larval stages across species. For the Caenorhabditis elegans-Caenorhabditis briggsae and Strongyloides stercoralis-Strongyloides venezuelensis comparisons, we found that ∼50% of genes were expressed at multiple stages, whereas half of their orthologs were also expressed in multiple but different stages. Such frequent changes in expression have resulted in concerted transcriptome evolution across adjacent stages, thus generating species-specific transcriptomes over the course of nematode evolution. Our study provides a first insight into the evolution of nematode transcriptomes beyond embryonic development.

A Multicenter Study of Neutrophil-to-Lymphocyte Ratio in Primary Aldosteronism.

BACKGROUND: Hypertensive patients with primary aldosteronism (PA) have a higher risk of cardiovascular complications than those with blood pressure-matched essential hypertension. The excess cardiovascular consequences of PA can be attributed to the proinflammatory effect of excessive aldosterone and mineralocorticoid receptor activation in a range of peripheral tissues and cell types. The neutrophil-to-lymphocyte ratio (NLR) is a widely available marker of inflammation which has been shown to predict cardiovascular outcome in the general population. This study aims to evaluate the use of NLR as a potential biomarker of PA and PA severity. METHODS: Patients with PA (n = 355) were identified from 2 large PA databases in Australia and China, while controls (n = 222) were patients with hypertension who were referred for assessment but did not meet the diagnostic criteria for PA. The NLR was retrospectively collected from routine full blood examination, prior to commencement of targeted treatment for PA. RESULTS: The NLR did not differ between PA patients and hypertensive controls (median 2.3 and 2.4, P = 0.563). However, among patients with PA, the NLR was positively correlated with baseline and post-saline aldosterone levels (r = 0.22 and P < 0.001 for both) and negatively correlated with serum potassium (r = -0.15, P = 0.006). Furthermore, in a logistic regression analysis of data from patients with PA, the NLR predicted the presence of comorbid chronic kidney disease (CKD) (defined as estimated glomerular filtration rate <60 mL/min/1.73m2) with an odds ratio of 1.5 (P = 0.003). CONCLUSION: While the NLR did not distinguish PA from controls, it was a marker of PA severity, being associated with aldosterone concentration as well as the presence of CKD. A prospective study is needed to further clarify the role of NLR in predicting end-organ damage associated with PA.