Crossbrown9385

Differential regulation of stem cell activity in shoot meristems contributes to the wide variation in shoot architecture.1-3 In most Citrus species, a thorn meristem and a dormant axillary meristem co-localize at each leaf base, offset from each other in a spiral phyllotactic pattern. We recently identified THORN IDENTITY1 (TI1) and THORN IDENTITY2 (TI2), encoding TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors, as necessary for the termination of meristem proliferation and concomitant thorn production in Citrus.4 However, how the dormant axillary meristem at the same leaf axil maintains stem cell activity is still unknown. The phosphatidylethanolamine-binding protein (PEBP)-type transcription factors CENTRORADIALIS (CEN) and TERMINAL FLOWER1 (TFL1) maintain inflorescence meristem indeterminacy in many plant species by antagonizing floral meristem identity regulators.5-9 Here, we show that, in Citrus, Citrus CEN (CsCEN) maintains vegetative axillary meristem indeterminacy by antagonizing TI1. CsCEN is expressed in the axillary meristem, but not in the thorn meristem. Disruption of CsCEN function results in termination of the stem cell activity and conversion of dormant axillary meristems into thorns, although ectopic overexpression of CsCEN represses TI1 expression and converts thorns into dormant buds, a phenotype similar to the ti1 mutant. We further show that CsCEN interacts with Citrus FD (CsFD) to repress TI1 expression. CsCEN activity depends on the function of TI1 and TI2, as mutations in TI1 and TI2 rescue the cscen mutant phenotype. We suggest that the antagonistic roles of CsCEN and TI1 define the pattern of axillary meristem determinacy, which shapes vegetative Citrus tree shoot architecture.Expression of the gap and pair-rule genes plays an essential role in body segmentation during Drosophila embryogenesis.1-5 However, it remains unclear how precise expression patterns of these key developmental genes arise from stochastic transcriptional activation at the single-cell level. Here, I employed genome-editing and live-imaging approaches to comprehensively visualize regulation of the gap and pair-rule genes at the endogenous loci. Quantitative image analysis revealed that the total duration of active transcription (transcription period) is a major determinant of spatial patterning of gene expression in early embryos. The length of the transcription period is determined by the continuity of bursting activities in individual nuclei, with the core expression domain producing more bursts than boundary regions. Each gene exhibits a distinct rate of nascent RNA production during transcriptional bursting, which contributes to gene-to-gene variability in the total output. I also provide evidence for "enhancer interference," wherein a distal weak enhancer interferes with transcriptional activation by a strong proximal enhancer to downregulate the length of the transcription period without changing the transcription rate. Analysis of the endogenous hunchback (hb) locus revealed that the removal of the distal shadow enhancer induces strong ectopic transcriptional activation, which suppresses refinement of the initial broad expression domain into narrower stripe patterns at the anterior part of embryos. This study provides key insights into the link between transcriptional bursting, enhancer-promoter interaction, and spatiotemporal patterning of gene expression during animal development.Morinda (Morinda officinalis) is widely consumed as a health-care herb in Asia and reported to possess various biological activities. In this study, anti-inflammatory phytochemicals were investigated and two pairs of new methyl-2-naphthoate enantiomers (1a/1b, 2a/2b), one new anthraquinone (3), three new natural unknown anthraquinones (5-6, 23), and eighteen known anthraquinones were isolated and elucidated from the roots of morinda. Anti-inflammatory activities of the isolated compounds were assessed in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compounds 2b and 19 significantly inhibited the production of NO with IC50 values of 34.32 ± 4.87 and 17.17 ± 4.13 μM (indomethacin, IC50 26.71 ± 6.32 μM), and they were further corroborated via immunoblotting, quantitative real-time PCR and immunofluorescence staining assays. They could dose-dependent suppress lipopolysaccharide-stimulated pro-inflammatory factors (COX-2 and iNOS) production and block nuclear translocation of NF-κB. The results implied that reasonable consumption of morinda may be beneficial for preventing and reducing the occurrence of inflammatory-associated diseases.One of the best ways to design new biocidal agents is synthesizing hybrid molecules by combining two or more bioactive moieties in a single molecular scaffold. So, new series of quinolines bearing a thiazole moiety were synthesized using thiosemicarbazones 2a-f. Cyclization of 2a-f with ethyl chloroacetate, ethyl 2-chloropropanoate or chloroacetone afforded the corresponding thiazoles 3-5. The antimicrobial activity of the new quinoline derivatives was evaluated. The most of tested compounds revealed potent both of the antibacterial and antifungal activities. Fourfold potency of amphotericin B for the inhibition the growth of the A. fumigatus was displayed by ccompound 5e. The latter compound displayed twofold potency of gentamycin for inhibition the growth of N. gonorrhoeae. Moreover, this compound showed equipotent potency of references drugs for inhibition of the growth of S. flexneri, S. pyogenes, P. vulgaris, A. clavatus, G. candidum and P. marneffei. So, quinolines bearing a thiazole moiety can be suggested as interesting scaffolds for the development both of the novel antibacterial and antifungal agents. Some new derivatives were studied as peptide deformylase enzyme inhibitors. Thiazolidin-4-one derivative 3d and 2,3-dihydrothiazole derivative 5c had shown good PDF inhibition activity, which had been supported by the docking results with highest binding affinity and lowest docking energy score. These results suggested that the most potent compounds might be possible agents as novel bacterial PDF inhibitor.Recent studies in both mice and humans have suggested that gut microbiota could modulate tumor responsiveness to chemo- or immunotherapies. However, the underlying mechanism is not clear yet. Here, we found that gut microbial metabolites, especially butyrate, could promote the efficacy of oxaliplatin by modulating CD8+ T cell function in the tumor microenvironment. Butyrate treatment directly boosted the antitumor cytotoxic CD8+ T cell responses both in vitro and in vivo in an ID2-dependent manner by promoting the IL-12 signaling pathway. In humans, the oxaliplatin responder cancer patients exhibited a higher amount of serum butyrate than did non-responders, which could also increase ID2 expression and function of human CD8+ T cells. Together, our findings suggest that the gut microbial metabolite butyrate could promote antitumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity, indicating that gut microbial metabolites could be effective as a part of cancer therapy.Associative learning allows animals to adapt their behavior in response to environmental cues. For example, sensory cues associated with food availability can trigger overconsumption even in sated animals. However, the neural mechanisms mediating cue-driven non-homeostatic feeding are poorly understood. To study this, we recently developed a behavioral task in which contextual cues increase feeding even in sated mice. Here, we show that an insular cortex to central amygdala circuit is necessary for conditioned overconsumption, but not for homeostatic feeding. This projection is marked by a population of glutamatergic nitric oxide synthase-1 (Nos1)-expressing neurons, which are specifically active during feeding bouts. Finally, we show that activation of insular cortex Nos1 neurons suppresses satiety signals in the central amygdala. The data, thus, indicate that the insular cortex provides top-down control of homeostatic circuits to promote overconsumption in response to learned cues.The initiation of DNA replication involves cell cycle-dependent assembly and disassembly of protein complexes, including the origin recognition complex (ORC) and CDC6 AAA+ ATPases. We report that multiple short linear protein motifs (SLiMs) within intrinsically disordered regions (IDRs) in ORC1 and CDC6 mediate cyclin-CDK-dependent and independent protein-protein interactions, conditional on the cell cycle phase. A domain within the ORC1 IDR is required for interaction between the ORC1 and CDC6 AAA+ domains in G1, whereas the same domain prevents CDC6-ORC1 interaction during mitosis. Then, during late G1, this domain facilitates ORC1 destruction by a SKP2-cyclin A-CDK2-dependent mechanism. During G1, the CDC6 Cy motif cooperates with cyclin E-CDK2 to promote ORC1-CDC6 interactions. The CDC6 IDR regulates self-interaction by ORC1, thereby controlling ORC1 protein levels. Protein phosphatase 1 binds directly to a SLiM in the ORC1 IDR, causing ORC1 de-phosphorylation upon mitotic exit, increasing ORC1 protein, and promoting pre-RC assembly.Managing chronic diseases is an important issue for older adults to pursue healthy aging. Prior studies have found that self-management has positive results. A better understanding of the self-management behaviours of older adults with chronic diseases and different activities of daily living abilities will lead to effective support and assistance. This qualitative study used interview data from Chinese older adults with chronic diseases to compare self-management behaviours between different activities of daily living groups. A self-management behavioural model was constructed that included three behaviours self-monitoring, self-evaluating and self-intervening. The similarities and differences in these behaviours between three types of older adults (i.e. energetic, self-care and semi self-care) were identified. Study findings enrich the research on self-management behaviour from a patient perspective, providing insights for older adults and care providers in understanding and supporting chronic disease self-management.Based on developing, implementing, and evaluating postgraduate interprofessional case-based learning, we have written these twelve tips for health education planners who wish to apply case-based learning in the clinical setting. Interprofessional case-based learning engages participants in a structured manner towards uncovering decisions processes and patterns of action that resemble the clinical reality in which various healthcare professionals handle multifaceted tasks related to the optimal patient treatment. Laduviglusib Postgraduate interprofessional case-based learning has the potential to break down traditional hierarchical structures as interactions generate respectful behaviour. We present two models of case-based learning to assist in standardising, structuring, and systematising postgraduate interprofessional case-based learning. We have created 12 practical tips for the design, implementation, and evaluation of successful postgraduate interprofessional case-based learning integrated into the existing clinical setting.