Explore the vast range of titles available.

The tomato (Solanum lycopersicum) MADS box FRUITFULL homologs FUL1 and FUL2 act as key ripening regulators and interact with the master regulator MADS box protein RIPENING INHIBITOR (RIN). Here, we report the large-scale identification of direct targets of FUL1 and FUL2 by transcriptome analysis of FUL1/FUL2 suppressed fruits and chromatin immunoprecipitation coupled with microarray analysis (ChIP-chip) targeting tomato gene promoters. The ChIP-chip and transcriptome analysis identified FUL1/FUL2 target genes that contain at least one genomic region bound by FUL1 or FUL2 (regions that occur mainly in their promoters) and exhibit FUL1/FUL2-dependent expression during ripening. These analyses identified 860 direct FUL1 targets and 878 direct FUL2 targets; this set of genes includes both direct targets of RIN and nontargets of RIN. Functional classification of the FUL1/FUL2 targets revealed that these FUL homologs function in many biological processes via the regulation of ripeningrelated gene expression, both in cooperation with and independent of RIN. Our in vitro assay showed that the FUL homologs, RIN, and tomato AGAMOUS-LIKE1 form DNA binding complexes, suggesting that tetramer complexes of these MADS box proteins are mainly responsible for the regulation of ripening.

The myxobacteria are an attractive bioresource for bioactive compounds since the large size genome contains many biosynthetic gene clusters of secondary metabolites. The genome of the myxobacterium Melittangium boletus contains three biosynthetic gene clusters for lanthipeptide production. One of the gene clusters includes genes coding lanthipeptide precursor ( melA ), class II lanthipeptide synthetase ( melM ), and transporter ( melT ). The amino acid sequence of melA indicated similarity with that of known lanthipeptides mersacidin and lichenicidin A1 by the alignment. To perform heterologous production of new lanthipeptides, the expression vector containing the essential genes ( melA and melM ) was constructed by utilizing codon-optimized synthetic genes. The co-expression of two genes in the host bacterial cells of Escherichia coli BL21 (DE3) afforded new lanthipeptides named melittapeptins A–C. The structures of melittapeptins A–C including lanthionine/methyllanthionine bridge pattern were proposed based on protease digestion and MS/MS experiments. The native strain of M. boletus did not produce melittapeptins A–C, so heterologous production using the biosynthetic gene cluster was effective in obtaining the lanthipeptides. Melittapeptins A–C showed specific and potent antibacterial activity to the Gram-positive bacterium Micrococcus luteus . To the best of our knowledge, this is the first report of antibacterial lanthipeptides derived from myxobacterial origin. Key points • New lanthipeptides melittapeptins were heterologously produced in Escherichia coli. • Melittapeptins showed specific antibacterial activity against Micrococcus luteus. • Melittapeptins were the first antibacterial lanthipeptides of myxobacterial origin.

Feeding behaviors are determined by two main factors. One is the internal state, such as hunger or previous experiences; the other is external factors, such as sensory stimulation. During starvation, animals must balance food-seeking behavior with energy conservation. The fruit fly, Drosophila melanogaster , serves as a useful model for studying food selectivity and various behaviors related to food intake. However, few studies have directly connected food selectivity with other behaviors, such as locomotor activity and sleep. In this study, we report that flies exhibited a preference for specific positions and spent more time in the proximity of sweet sugars, such as sucrose and sucralose, but not non-sweet and nutritious sugars like xylitol and sorbitol. On the other hand, prolonged exposure to sorbitol increased the staying time of flies in the proximity of sorbitol. Additionally, after starvation, flies immediately exhibited a position preference in the proximity of sorbitol. These findings suggest that flies prefer the proximity of sweet food, and starvation alters their preference for nutritious food, which may be beneficial for their survival.

The thermophilic bacterium Thermosporothrix hazakensis belongs to a class of Ktedonobacteria in the phylum Chloroflexota. Lanthipeptides are a naturally occurring peptide group that contains antibacterial compounds such as nisin. To find a new lanthipeptide that is a possible candidate for an antibacterial reagent, we performed genome-mining of T. hazakensis and heterologous expression experiments. Based on genome-mining, the presence of a total of ten putative biosynthetic gene clusters for class I and class II lanthipeptides was indicated from the genome sequence of T. hazakensis. New lanthipeptides named hazakensins A and B were produced by heterologous expression of a class I lanthipeptide biosynthetic gene cluster in the expression host Escherichia coli. Co-expression of the biosynthetic gene cluster with tRNA-Glu and glutamyl-tRNA synthetase coding genes derived from T. hazakensis increased the production yield of both lanthipeptides by about 4–6 times. The chemical structures of hazakensins A and B including the bridging pattern of lanthionine/methyllanthionine rings were determined by NMR and MS experiments. Since production of hazakensins A and B was not observed in the native strain T. hazakensis, heterologous production was an effective method to obtain the lanthipeptides derived from the biosynthetic gene cluster. This is the first report of heterologous production of class I lanthipeptides originating from the filamentous green non-sulfur bacteria, to the best of our knowledge. The success of heterologous production of hazakensins may lead to the discovery and development of new lanthipeptides derived from the origins of bacteria in the phylum Chloroflexota.

Background/Objectives: Cancer cachexia (CC) is a prevalent and debilitating syndrome in cancer patients, characterized by severe muscle and weight loss, leading to increased mortality and reduced quality of life. Despite the significant impact, effective treatments are lacking due to an incomplete understanding of its underlying mechanisms. In this study, we aim to develop drugs that ameliorate the inhibition of muscle differentiation induced by CC. We established an advanced, high-content phenotypic screening system using the serum of cancer patients and identified potential compounds. Methods: We used cancer patients’ sera as pathophysiological stimuli in our screening system to evaluate their effects on muscle atrophy and differentiation. Various histone deacetylase (HDAC) inhibitors were tested for their efficacy. The system’s translational relevance was validated by comparing results with clinical data and in vivo cachexia models. Results: Using our screening system, we evaluated several cancer patients’ sera and found that they reflect clinical features of cancer cachexia. In addition, HDAC inhibitors, particularly those with broad-spectrum inhibition, showed promise as agents to ameliorate the inhibition of muscle differentiation induced by CC sera. This system’s findings were consistent with clinical and in vivo data, highlighting its potential for identifying new drugs. Conclusions: The high-content phenotypic screening system effectively mimics some key aspects of CC pathophysiology on skeletal muscle, providing a valuable tool for drug discovery and understanding CC mechanisms. The translational relevance of our system offers a promising avenue for therapeutic advancements in the management of cancer cachexia, with the potential to improve patient outcomes and quality of life.

Octopamine regulates various physiological phenomena including memory, sleep, grooming and aggression in insects. In Drosophila, four types of octopamine receptors have been identified: Oamb, Oct/TyrR, OctβR and Octα2R. Among these receptors, Octα2R was recently discovered and pharmacologically characterized. However, the effects of the receptor on biological functions are still unknown. Here, we showed that Octα2R regulated several behaviors related to octopamine signaling. Octα2R hypomorphic mutant flies showed a significant decrease in locomotor activity. We found that Octα2R expressed in the pars intercerebralis, which is a brain region projected by octopaminergic neurons, is involved in control of the locomotor activity. Besides, Octα2R hypomorphic mutants increased time and frequency of grooming and inhibited starvation‐induced hyperactivity. These results indicated that Octα2R expressed in the central nervous system is responsible for the involvement in physiological functions. Octα2R signaling regulated activation of locomotor activity, inhibition of grooming and starvation‐induced hyperactivity.

Considering that the ultrasonic method is applied for the quality evaluation of concrete, this study experimentally and numerically investigates the effect of inhomogeneity caused by changes in the moisture content of concrete on ultrasonic wave propagation. The experimental results demonstrate that the propagation velocity and amplitude of the ultrasonic wave vary for different moisture content distributions in the specimens. In the analytical study, the characteristics obtained experimentally are reproduced by modeling a system in which the moisture content varies between the surface layer and interior of concrete.

Lactococcus lactis strains are used as starter cultures in the production of fermented dairy and vegetable foods, but the species also occurs in other niches such as plant material. Lactococcus lactis subsp. lactis G50 (G50) is a plant-derived strain and potential candidate probiotics. Western blotting of cell-wall proteins using antibodies generated against whole G50 cells detected a 120-kDa protein. MALDI-TOF MS analysis identified it as YwfG, a Leu-Pro-any-Thr-Gly cell-wall-anchor-domain–containing protein. Based on a predicted domain structure, a recombinant YwfG variant covering the N-terminal half (aa 28–511) of YwfG (YwfG 28−511 ) was crystallized and the crystal structure was determined. The structure consisted of an L-type lectin domain, a mucin-binding protein domain, and a mucus-binding protein repeat. Recombinant YwfG variants containing combinations of these domains (YwfG 28–270 , YwfG 28–336 , YwfG 28−511 , MubR4) were prepared and their interactions with monosaccharides were examined by isothermal titration calorimetry; the only interaction observed was between YwfG 28–270 , which contained the L-type lectin domain, and d -mannose. Among four mannobioses, α-1,2-mannobiose had the highest affinity for YwfG 28–270 (dissociation constant = 34 μM). YwfG 28–270 also interacted with yeast mannoproteins and yeast mannan. Soaking of the crystals of YwfG 28–511 with mannose or α-1,2-mannobiose revealed that both sugars bound to the L-type lectin domain in a similar manner, although the presence of the mucin-binding protein domain and the mucus-binding protein repeat within the recombinant protein inhibited the interaction between the L-type lectin domain and mannose residues. Three of the YwfG variants (except MubR4) induced aggregation of yeast cells. Strain G50 also induced aggregation of yeast cells, which was abolished by deletion of ywfG from G50, suggesting that surface YwfG contributes to the interaction with yeast cells. These findings provide new structural and functional insights into the interaction between L . lactis and its ecological niche via binding of the cell-surface protein YwfG with mannose.

Previously, we identified water-soluble compounds with membrane progestin receptor α (mPRα)-binding activity from the marine algae Padina arborescens . The compounds inhibited fish oocyte maturation. These compounds are potentially novel antagonists of mPR and are of interest as novel inhibitors of the nongenomic pathway of steroids. In this study, a compound with mPRα binding activity was purified from the methanol extract of Padina tarries. The structure of one of the major compounds in the fraction was identified as 1-carboxybutyl-2-hydroxypentanoate (1-CB 2-HPNA) using nuclear magnetic resonance spectroscopy and ESI–MS analysis. 1-CB 2-HPNA showed substantial competitive binding affinity for human mPRα (hmPRα) in the graphene quantum dot (GQD)-hmPRα binding assay. The physiological activity of 1-CB 2-HPNA was then evaluated using an in vitro and in vivo zebrafish oocyte maturation and ovulation assay. 1-CB 2-HPNA inhibited the maturation and ovulation of fish oocytes. In addition, 1-CB 2-HPNA inhibited ovulation in mice. These results indicate that 1-CB 2-HPNA, identified from Padina arborescens , is a novel natural mPRα antagonist.

In this study, a disk-type bluff body was installed at the upper part of a nozzle exit, and the circular jet inside the nozzle was controlled using a dielectric barrier discharge (DBD) plasma actuator (DBD-PA). The effects of the changes in the excitation frequency of the jet induced by the DBD-PA on the jet diffusion were elucidated. The experiments included visualization of the jet cross-section, particle image velocimetry analysis, and velocity measurements using an I-type hot-wire anemometer. When the DBD-PA was driven at a specific burst frequency (900–1400 Hz), a lock-in phenomenon occurred, in which the frequency of vortices generated in the initial jet coincided with the burst frequency. This lock-in phenomenon suppressed the merging of vortices by generating vortices at regular intervals. When vortex merging was suppressed, the jet was less likely to be entrained into the recirculation flow generated by the bluff body, thereby increasing the downstream jet width and average flow rate.