Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.

SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole.

Wine tasting Demystified: Celebrating Professor Wendy Parr's contribution to the understanding of wine tasting and wine tasters - An Introduction.

Our goal in putting together this special issue was twofold: First, to honour the remarkable career of Professor Wendy Parr and her contribution to the understanding of wine tasting and wine tasters and second, to continue to raise awareness of the importance of the cognitive approach in the wine scientific literature. We present Professor Wendy Parr's insightful reflections on her distinguished career, including her early ventures into psychology and the experiences that shaped her contributions. These are complemented by a concise historical perspective on the evolution of wine sensory science, providing context for her work.

Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent.

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery.

Bee pollen from bracatinga (Mimosa scabrella): Effects of gastrointestinal digestion and epithelial transport in vitro on phenolic profile and bioactivities.

The main objective of the present work was to assess the phenolic profile of bracatinga (Mimosa scabrella) bee pollen, and its antioxidant and anti-inflammatory activities after gastrointestinal digestion in vitro and epithelial transport in a Caco-2 cell monolayer model. The botanical origin of bee pollen was confirmed by optical microscopy and scanning electron microscopy. As major results, 34 phenolic compounds (13 phenylamides, 14 flavonols, and 7 flavanones) were tentatively identified in the extract of bracatinga bee pollen by HPLC-ESI-QTOF-MS.

Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes.

Base editors create precise genomic edits by directing nucleobase deamination or removal without inducing double-stranded DNA breaks. However, a vast chemical space of other DNA modifications remains to be explored for genome editing. Here, we harness the bacterial anti-phage toxin DarT2 to append ADP-ribosyl moieties to DNA, unlocking distinct editing outcomes in bacteria versus eukaryotes.

Clinical outcomes of patients diagnosed with mutated myeloid neoplasms.

SETBP1 mutations (m) have been previously reported in myeloid neoplasms and are associated with poor prognostic co-mutations and cytogenetic abnormalities. We retrospectively analyzed the charts of 113 patients diagnosed with myeloid neoplasms with SETBP1m. The most common diagnosis was MDS (31%).

Optimization of Ultrasonic-Assisted Extraction of Phenolic Compounds and Antioxidant Activity from Araticum Peel Using Response Surface Methodology.

The peel represents a significant portion of the araticum fruit (about 40%), which becomes waste after its consumption or processing. Previous studies have shown that the araticum peel is rich in phenolic compounds; however, little is known about the ideal conditions for recovering these compounds. Therefore, response surface methodology, using a central composite rotatable design, was employed to optimize the extraction process to maximize the total phenolic compounds (TPCs) and enhance the Trolox equivalent antioxidant capacity (TEAC) from araticum peel.

Neural network-assisted humanisation of COVID-19 hamster transcriptomic data reveals matching severity states in human disease.

Background: Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses.

Methods: Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution.

A novel tubular model to recapitulate features of distal airways: the bronchioid.

Background: Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerous models of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems.

Endogenous adenine is a potential driver of the cardiovascular-kidney-metabolic syndrome.

Mechanisms underlying the cardiovascular-kidney-metabolic (CKM) syndrome are unknown, although key small molecule metabolites may be involved. Bulk and spatial metabolomics identified adenine to be upregulated and specifically enriched in coronary blood vessels in hearts from patients with diabetes and left ventricular hypertrophy. Single nucleus gene expression studies revealed that endothelial methylthioadenosine phosphorylase (MTAP) was increased in human hearts with hypertrophic cardiomyopathy.

Characterization and implementation of the MarathonRT template-switching reaction to expand the capabilities of RNA-seq.

End-to-end RNA-sequencing methods that capture 5'-sequence content without cumbersome library manipulations are of great interest, particularly for analysis of long RNAs. While template-switching methods have been developed for RNA sequencing by distributive short-read RTs, such as the MMLV RTs used in SMART-Seq methods, they have not been adapted to leverage the power of ultraprocessive RTs, such as those derived from group II introns. To facilitate this transition, we dissected the individual processes that guide the enzymatic specificity and efficiency of the multistep template-switching reaction carried out by RTs, in this case, by MarathonRT.

L-Wnk1 Deletion in Smooth Muscle Cells Causes Aortitis and Inflammatory Shift.

Background: The long isoform of the Wnk1 (with-no-lysine [K] kinase 1) is a ubiquitous serine/threonine kinase, but its role in vascular smooth muscle cells (VSMCs) pathophysiology remains unknown.

Methods: AngII (angiotensin II) was infused in to induce experimental aortic aneurysm. Mice carrying an allele were cross-bred with mice carrying a floxed allele to specifically investigate the functional role of Wnk1 in VSMCs.

TREM2 protects from atherosclerosis by limiting necrotic core formation.

Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications, myocardial infarction and stroke, are the leading cause of mortality worldwide [1], [2]. Recent studies have identified Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions [3], to be highly expressed in macrophage foam cells in experimental and human atherosclerosis [4]. However, the role of TREM2 in atherosclerosis is not fully known.

The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes.

CD8 T Cells Drive Plaque Smooth Muscle Cell Dedifferentiation in Experimental Atherosclerosis.

Background: Atherosclerosis is driven by the infiltration of the arterial intima by diverse immune cells and smooth muscle cells (SMCs). CD8 T cells promote lesion growth during atherosclerotic lesion development, but their role in advanced atherosclerosis is less clear. Here, we studied the role of CD8 T cells and their effects on SMCs in established atherosclerosis.

Prognostic impact of 'multi-hit' versus 'single-hit' TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases.

While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation (TP53MT) compared to a single-hit (SH) mutation in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an in-depth analysis utilizing data from ten US academic institutions to study differences in molecular characteristics and outcomes of SH (N=139) versus MH (N=243) TP53MT AML. Complex cytogenetics were more common in MH than in SH TP53MT AML (P<0.

Characterization of a Human Respiratory Mucosa Model to Study Odorant Metabolism.

Nasal xenobiotic metabolizing enzymes (XMEs) are important for the sense of smell because they influence odorant availability and quality. Since the major part of the human nasal cavity is lined by a respiratory mucosa, we hypothesized that this tissue contributed to nasal odorant metabolism through XME activity. Thus, we built human respiratory tissue models and characterized the XME profiles using single-cell RNA sequencing.

Quinolinic acid links kidney injury to brain toxicity.

Kidney dysfunction often leads to neurological impairment, yet the complex kidney-brain relationship remains elusive. We employed spatial and bulk metabolomics to investigate a mouse model of rapid kidney failure induced by mouse double minute 2 ( conditional deletion in the kidney tubules to interrogate kidney and brain metabolism. Pathway enrichment analysis of focused plasma metabolomics panel pinpointed tryptophan metabolism as the most altered pathway with kidney failure.