An Arabidopsis Cell Culture With Weak Circadian Rhythms Under Constant Light Compared With Constant Dark Can Be Rescued by ELF3.

Callus and cell suspension culture techniques are valuable tools in plant biotechnology and are widely used in fundamental and applied research. For studies in callus and cell suspension cultures to be relevant, it is essential to know if the underlying biochemistry is similar to intact plants. This study examined the expression of core circadian genes in Arabidopsis callus from the cell suspension named AT2 and found that the circadian rhythms were impaired.

A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogen Candida glabrata.

Drug-resistant microbes typically carry mutations in genes involved in critical cellular functions and may therefore be less fit under drug-free conditions than susceptible strains. Candida glabrata is a prevalent opportunistic yeast pathogen with a high rate of fluconazole resistance (FLZR), echinocandin resistance (ECR), and multidrug resistance (MDR) relative to other Candida. However, the fitness of C.

The Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence.

Unlabelled: , a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic infections have now been reported in more than 50 countries, with mortality rates of 30%-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that unlike most species, displays unique skin tropism and can stay on human skin for a prolonged period.

Ancient Schwannoma Along the Patellar Tendon: Unveiling a Rare Clinical Phenomenon With Literature Review.

Ancient schwannoma, a rare subtype of schwannoma, a benign tumor originating from nerve sheaths, can arise from various nerves, except for the optic, olfactory, spinal, and autonomic nervous systems. Schwannomas are typically characterized by the presence of neoplastic Schwann cells and tend to develop eccentrically. Malignant transformations of schwannomas are exceptionally uncommon.

Discovery of aminopiperidine based potent & novel topoisomerase inhibitor with broad spectrum anti-bacterial activity.

Bacterial DNA gyrase and topoisomerase IV inhibition has emerged as a promising strategy for the cure of infections caused by antibiotic-resistant bacteria. The Novel Bacterial Topoisomerase Inhibitors (NBTIs) bind to a different site from that of the quinolones with novel mechanism of action. This evades the existing target-mediated bacterial resistance associated with quinolones.

The Influence of Body Fat Dynamics on Pulmonary Immune Responses in Murine Tuberculosis: Unraveling Sex-Specific Insights.

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence () burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose -HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD).

BTK drives neutrophil activation for sterilizing antifungal immunity.

We describe a previously-unappreciated role for Bruton's tyrosine kinase (BTK) in fungal immune surveillance against aspergillosis, an unforeseen complication of BTK inhibitors (BTKi) used for treating B-cell lymphoid malignancies. We studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, BTKi-treated patients, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcγR-dependent manner, triggering the oxidative burst.

The Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence.

Unlabelled: , a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic infections have now been reported in more than 50 countries, with mortality rates of 30-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that unlike most species, displays unique skin tropism and can stay on human skin for a prolonged period.

Evaluation of murine renal phagocyte-fungal interactions using intravital confocal microscopy and flow cytometry.

Myeloid phagocytes are essential for antifungal host defense during systemic candidiasis. Here, we present a protocol for assessing phagocyte-fungal interactions in vivo in the kidney, the primary target organ of the murine systemic candidiasis model. We describe steps for intravital confocal microscopy and flow cytometry.

Overlooked petites are echinocandin tolerant, induce host inflammatory responses, and display poor fitness.

is a major fungal pathogen, which is able to lose mitochondria and form small and slow-growing colonies, called "petite." This attenuated growth rate has created controversies and questioned the clinical importance of petiteness. Herein, we have employed multiple omics technologies and mouse models to critically assess the clinical importance of petite phenotype.

Overlooked petites are echinocandin tolerant, induce host inflammatory responses, and display poor fitness.

Unlabelled: Small colony variants (SCVs) are relatively common among some bacterial species and are associated with poor prognosis and recalcitrant infections. Similarly, - a major intracellular fungal pathogen - produces small and slow-growing respiratory-deficient colonies, termed "petite." Despite reports of clinical petite .

Weed-induced changes in the maize root transcriptome reveal transcription factors and physiological processes impacted early in crop-weed interactions.

A new paradigm suggests weeds primarily reduce crop yield by altering crop developmental and physiological processes long before the weeds reduce resources through competition. Multiple studies have implicated stress response pathways are activated when crops such as maize are grown in close proximity with weeds during the first 4-8 weeks of growth-the point at which weeds have their greatest impact on subsequent crop yields. To date, these studies have mostly focused on the response of above-ground plant parts and have not examined the early signal transduction processes associated with maize root response to weeds.

C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection.

Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identified transcription of complement system genes as the top biological pathway induced in candidemic patients and as predictive of candidemia.

Impact of stereopure chimeric backbone chemistries on the potency and durability of gene silencing by RNA interference.

Herein, we report the systematic investigation of stereopure phosphorothioate (PS) and phosphoryl guanidine (PN) linkages on siRNA-mediated silencing. The incorporation of appropriately positioned and configured stereopure PS and PN linkages to N-acetylgalactosamine (GalNAc)-conjugated siRNAs based on multiple targets (Ttr and HSD17B13) increased potency and durability of mRNA silencing in mouse hepatocytes in vivo compared with reference molecules based on clinically proven formats. The observation that the same modification pattern had beneficial effects on unrelated transcripts suggests that it may be generalizable.

pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells.

Plasmacytoid dendritic cells (pDCs) have been shown to play an important role during immune responses, ranging from initial viral control through the production of type I interferons to antigen presentation. However, recent studies uncovered unexpected heterogeneity among pDCs. We identified a previously uncharacterized immune subset, referred to as pDC-like cells, that not only resembles pDCs but also shares conventional DC (cDC) features.

Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes.

The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPs through metabolic network analysis applied to three large-scale transcriptional datasets: we introduce (1) an ImmGen MNP open-source dataset of 337 samples across 26 tissues; (2) a myeloid subset of ImmGen Phase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) dataset (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we develop a network-based computational approach, genes and metabolites (GAM) clustering, for unbiased identification of the key metabolic subnetworks based on transcriptional profiles.

Efficacy of Cochleated Amphotericin B in Mouse and Human Mucocutaneous Candidiasis.

Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC) and in patients with azole-resistant CMC.

Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria.

Antibiotics are a modifiable iatrogenic risk factor for the most common human nosocomial fungal infection, invasive candidiasis, yet the underlying mechanisms remain elusive. We found that antibiotics enhanced the susceptibility to murine invasive candidiasis due to impaired lymphocyte-dependent IL-17A- and GM-CSF-mediated antifungal immunity within the gut. This led to non-inflammatory bacterial escape and systemic bacterial co-infection, which could be ameliorated by IL-17A or GM-CSF immunotherapy.

Predicting exon criticality from protein sequence.

Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting Exon skipping Based on Protein amino acid SequenceS), to assess the criticality of exon inclusion based solely on information contained in the amino acid sequence upstream and downstream of the exon junctions. By focusing on protein sequence, Exon ByPASS predicts exon skipping independent of tissue and species in the absence of any intronic information.