Unveiling 14 novel 2-hydroxy acid racemization and epimerization reactions in the lactate racemase superfamily.

2-hydroxy acids are organic carboxylic acids ubiquitous in the living world and are important building blocks in organic synthesis. Recently, the lactate racemase (LarA) superfamily, a diverse superfamily of 2-hydroxy acid racemases and epimerases using the nickel-pincer nucleotide (NPN) cofactor, has been uncovered. In this study, we performed a taxonomic analysis of the LarA superfamily, showing the distribution of lactate racemase homologs (LarAHs) sequences across the three domains of life.

Acid-exposed and hypoxic cancer cells do not overlap but are interdependent for unsaturated fatty acid resources.

Cancer cells in acidic tumor regions are aggressive and a key therapeutic target, but distinguishing between acid-exposed and hypoxic cells is challenging. Here, we use carbonic anhydrase 9 (CA9) antibodies to mark acidic areas in both hypoxic and respiring tumor areas, along with an HRE-GFP reporter for hypoxia, to isolate distinct cell populations from 3D tumor spheroids. Transcriptomic analysis of CA9-positive, hypoxia-negative cells highlights enriched fatty acid desaturase activity.

The elastic system: A review of elastin-related techniques and hematoxylin-eosin/phloxine applicability for normal and pathological tissue description.

The elastic system is one of the most developed interstitial elements in connective tissue. With diverse functions, pre-elastic and elastic fibers contribute to the distensibility and malleability of several organs. Also, microanalyses of the elastic system were obtained by different histological techniques that were employed over years to describe normal and pathological conditions.

Chemo-enzymatic synthesis of NPN cofactor taking advantage of ADP-ribosyl cyclase and LarC cyclometallase promiscuous activities.

The nickel-pincer nucleotide cofactor (NPN) is a widespread organometallic cofactor required for lactate racemase (LarA) and for α-hydroxy acid racemases and epimerases of the LarA superfamily. Its biosynthesis, which starts with nicotinic acid adenine dinucleotide (NaAD), requires three enzymes: LarB, LarC, and LarE, and can be performed in vitro with purified enzymes. Nevertheless, as LarE and LarC are single turnover enzymes, the in vitro NPN biosynthesis requires huge amounts of enzymes (particularly 2 equivalents of LarE), which hampers the study of NPN and of NPN-dependent enzymes.

Occurrence and Synthesis Pathways of (Suspected) Genotoxic α,β-Unsaturated Carbonyls in Chocolate and Other Commercial Sweet Snacks.

α,β-Unsaturated carbonyls are highly reactive and described as structural alerts for genotoxicity. Ten of them (either commercially available or synthesized here by combinatorial chemistry) were first investigated throughout the chocolate-making process by solvent-assisted flavor evaporation (SAFE) coupled to GC-MS/SIM. Monitored α,β-unsaturated aldehydes were formed during chocolate production, primarily through aldol condensation of Strecker aldehydes triggered by bean roasting.

Use of Botanical Ingredients: Nice Opportunities to Avoid Premature Oxidation of NABLABs by Increasing Their ORAC Values Strongly Impacted by Dealcoholization or Pasteurization.

Even when fresh, non-alcoholic, and low-alcoholic beers (NABLABs) exhibit significant staling defects due to premature oxidation. In this study, the antioxidant power of eleven fresh commercial NABLABs was assessed by means of three different assays: the oxygen radical absorbance capacity (ORAC), the linoleic acid-induced oxidation (TINH), and the indicator time test (ITT). Only the first two assays, both involving radicalar degradations initiated by AAPH, were found to correlate with each other.

Possible crosstalk between the Arabidopsis TSPO-related protein and the transcription factor WRINKLED1.

This study uncovers a regulatory interplay between WRINKLED1 (WRI1), a master transcription factor for glycolysis and lipid biosynthesis, and Translocator Protein (TSPO) expression in Arabidopsis thaliana seeds. We identified potential WRI1-responsive elements upstream of AtTSPO through bioinformatics, suggesting WRI1's involvement in regulating TSPO expression. Our analyses showed a significant reduction in AtTSPO levels in wri1 mutant seeds compared to wild type, establishing a functional link between WRI1 and TSPO.

Potential Roles of Specific Subclasses of Premotor Interneurons in Spinal Cord Function Recovery after Traumatic Spinal Cord Injury in Adults.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach might not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults.

Flexible metallic core-shell nanostructured electrodes for neural interfacing.

Electrodes with nanostructured surface have emerged as promising low-impedance neural interfaces that can avoid the charge-injection restrictions typically associated to microelectrodes. In this work, we propose a novel approximation, based on a two-step template assisted electrodeposition technique, to obtain flexible nanostructured electrodes coated with core-shell Ni-Au vertical nanowires. These nanowires benefit from biocompatibility of the Au shell exposed to the environment and the mechanical properties of Ni that allow for nanowires longer and more homogeneous in length than their only-Au counterparts.

Versatile capillary electrophoresis method for the direct chiral separation of aliphatic and aromatic α-hydroxy acids, β-hydroxy acids and polyhydroxy acids using vancomycin as chiral selector.

Hydroxy acids (HAs) are ubiquitous in nature and play significant roles in various industrial and biological processes. Most HAs harbor at least one chiral center, therefore the development of efficient chiral analysis techniques for HA stereoisomers is of crucial importance across a wide range of fields. A capillary electrophoresis (CE) method was developed for the chiral analysis and quantification of aliphatic and aromatic α‑hydroxy acid (AHA) enantiomers, aliphatic β‑hydroxy acid (BHA) enantiomers and aliphatic polyhydroxy acid (PHA) stereoisomers.

Issue when expressing a recombinant protein under the control of p in BY-2 cells.

Several recombinant proteins have been successfully produced in plants. This usually requires -mediated cell transformation to deliver the T-DNA into the nucleus of plant cells. However, some genetic instability may threaten the integrity of the expression cassette during its delivery via , especially when the protein of interest is toxic to the bacteria.

Occurrence of Perillaldehyde and Other (Suspected) Genotoxic Flavoring Substances in Water-Based Beverages Consumed by Belgian Children.

Despite the extensive use of flavoring substances in food, their monitoring for regulatory purposes is currently limited. This raises public health issues, especially as some compounds are prohibited due to (geno)toxicity. A solvent-assisted flavor evaporation (SAFE) method coupled with GC/MS (SIM) was validated here for diverse water-based beverages.

Dietary methylmercury and fatty acids affect the lipid metabolism of adipose tissue and liver in rainbow trout.

Methylmercury (MeHg) is a pervasive environmental contaminant in aquatic ecosystems that can reach elevated concentrations in fish of high trophic levels, such as salmonids. The present study aims at investigating the individual and combined impacts of dietary MeHg and fatty acids on lipid metabolism in juvenile rainbow trout (Oncorhynchus mykiss) with a focus on two key organs, adipose tissue and liver. MeHg and fatty acids are both known to act on energy homeostasis although little is known about their interplay on lipid metabolism in fish.

Evidence of Enzymatic and Chemical Interconversions of Barley Malt 3-Sulfanylhexanol Conjugates during Mashing.

Recent studies have highlighted in malt the occurrence of the glutathionylated precursor of 3-sulfanylhexanol (G-3SHol) at concentrations reaching hundreds of μg/kg. Here, SIDA-LC-MS/MS was used to investigate the potential conversion of G-3SHol to its dipeptide and cysteinyl analogues during mashing. At 45 and 55 °C, malt γGT and carboxypeptidase activities quickly degrade G-3SHol (up to 90% loss), first to the cysteinylglycine conjugate and then to the cysteine conjugate (up to 205% increase).

The yeast Gdt1 protein mediates the exchange of H for Ca and Mn influencing the Golgi pH.

The GDT1 family is broadly spread and highly conserved among living organisms. GDT1 members have functions in key processes like glycosylation in humans and yeasts and photosynthesis in plants. These functions are mediated by their ability to transport ions.

Discriminating Aroma Compounds in Five Cocoa Bean Genotypes from Two Brazilian States: White Kerosene-like Catongo, Red Whisky-like FL89 (Bahia), Forasteros IMC67, PA121 and P7 (Pará).

Fine-grade cocoa beans are characterized by their great organoleptic quality. Brazilian cocoa producers increasingly privilege organoleptic quality over yield. Catongo and FL89, fine Brazilian cocoa genotypes from Bahia, are characterized by particular flavors (respectively, kerosene and whisky).

Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains.

Myoblast migration is crucial for myogenesis and muscular tissue homeostasis. However, its spatiotemporal control remains elusive. Here, we explored the involvement of plasma membrane cholesterol and sphingolipids in this process.

Beyond the Lab: What We Can Learn about Cancer from Wild and Domestic Animals.

Cancer research has benefited immensely from the use of animal models. Several genetic tools accessible in rodent models have provided valuable insight into cellular and molecular mechanisms linked to cancer development or metastasis and various lines are available. However, at the same time, it is important to accompany these findings with those from alternative or non-model animals to offer new perspectives into the understanding of tumor development, prevention, and treatment.

A plant-specific bridging adaptor for amphisome biogenesis.

The fusion of autophagosomes with endocytic compartments to form amphisomes has only been described in metazoans. In this issue, Zhao et al. (2022.

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer?

The treatment of obesity can no longer be reduced to a simplistic view of weight loss. Metabolic adaptation leads to systematic weight regain following weight-loss efforts, and new obesity treatments should therefore aim to induce long-standing double-digit weight loss, and thus improve and even reverse obesity-associated comorbidities such as type 2 diabetes. Until now, only metabolic surgery has been able to achieve such a goal, but this invasive procedure cannot be offered on a large scale.

Surface cholesterol-enriched domains specifically promote invasion of breast cancer cell lines by controlling invadopodia and extracellular matrix degradation.

Tumor cells exhibit altered cholesterol content. However, cholesterol structural subcellular distribution and implication in cancer cell invasion are poorly understood mainly due to difficulties to investigate cholesterol both quantitatively and qualitatively and to compare isogenic cell models. Here, using the MCF10A cell line series (non-tumorigenic MCF10A, pre-malignant MCF10AT and malignant MCF10CAIa cells) as a model of breast cancer progression and the highly invasive MDA-MB-231 cell line which exhibits the common TP53 mutation, we investigated if cholesterol contributes to cancer cell invasion, whether the effects are specific to cancer cells and the underlying mechanism.

Rac1, the actin cytoskeleton and microtubules are key players in clathrin-independent endophilin-A3-mediated endocytosis.

Endocytic mechanisms actively regulate plasma membrane composition and sustain fundamental cellular functions. Recently, we identified a clathrin-independent endocytic (CIE) modality mediated by the BAR domain protein endophilin-A3 (endoA3, encoded by SH3GL3), which controls the cell surface homeostasis of the tumor marker CD166 (also known as ALCAM). Deciphering the molecular machinery of endoA3-dependent CIE should therefore contribute to a better understanding of its pathophysiological role, which remains so far unknown.

HOXA1, a breast cancer oncogene.

More than 25 years ago, the first literature records mentioned HOXA1 expression in human breast cancer. A few years later, HOXA1 was confirmed as a proper oncogene in mammary tissue. In the following two decades, molecular data about the mode of action of the HOXA1 protein, the factors contributing to activate and maintain HOXA1 gene expression and the identity of its target genes have accumulated and provide a wider view on the association of this transcription factor to breast oncogenesis.

Incretin-induced changes in the transcriptome of skeletal muscles of fa/fa Zucker rat (ZFR) with obesity, without diabetes.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1ra) are increasingly used in treating type 2 diabetes and obesity. Exendin-4 (Ex-4), a long acting GLP-1ra, was previously reported to decrease oxidative stress in hepatocytes, adipocytes and skeletal muscle cells in obese nondiabetic fa/fa Zucker rats (ZFR), thereby improving insulin resistance.

Aim: We aimed first to identify Ex-4-induced changes in the transcriptome of skeletal muscle cells in ZFR.