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A bankrupt buyer firm's interactions with its suppliers during bankruptcy have critical implications for both parties and for the broader economy, yet these interactions remain poorly understood. The authors build on research on buyer–supplier relationship dynamics to demonstrate that accommodative and exploitative velocities—the rate and direction of change in the corresponding acts—serve as signals affecting bankruptcy survival. They show how signal characteristics (i.e., the variability in accommodative and exploitative acts) and signaler characteristics (i.e., whether the party undertaking the acts is the buyer or its suppliers) moderate the impact of accommodative and exploitative velocities on bankruptcy survival. Study 1 examines the bankruptcy survival outcome of 310 U.S. bankruptcies over 14 years and finds that a 1% increase in accommodative (exploitative) velocity increases (decreases) the buyer's survival by 39% (33%). Further, variability in accommodative acts weakens their effect, and suppliers' (vs. the buyer's) accommodative and exploitative velocities are less deterministic of the buyer's bankruptcy survival. Study 2 uses a scenario-based experiment to shed light on the mechanism underlying the impact of the two velocities on bankruptcy survival. The findings from both studies demonstrate the key role played by buyer–supplier interactions in a buyer's bankruptcy survival. [ABSTRACT FROM AUTHOR]

Introduction: Program signaling (PS), which enables residency applicants to signal their preference for a specific program, was introduced in emergency medicine (EM) in the 2022–2023 residency application cycle. In this study we evaluated EM program directors’ (PD) utilization of PS in application review and ranking. This study also explores the relationship between program characteristics and number of signals received as well as the relative importance and utilization of signals related to the number of signals received.Methods: This is an institutional review board-approved, cross-sectional study of PDs at Accreditation Council for Graduate Medical Education-accredited EM residency programs. We used descriptive statistics to describe the characteristics of residency programs and practices around PS. Measures of central tendency and dispersion summarized continuous variables. We used chi-square analysis or the Fisher exact test for comparisons between groups for categorical variables. Comparisons for continuous variables were made using the t-test for independent samples or analysis of variance.Results: The response rate was 41% (n = 113/277 EM programs). Most programs participated in PS(n = 261/277 EM programs, 94.2%). Mean number of signals received was 60 (range 2–203). Signals received varied based on program characteristics including geographic location and program type, duration, environment, and longevity. Most used PS in holistic review (52.2%), but other uses varied by proportion of applications that were signaled. The importance of PS in application review (mean 2.9; 1–5scale,1= not important, 5 = extremely important) and rank list preparation (2.1) was relatively low compared to other application elements such as standardized letters of evaluation (4.97 for review, 4.90 for ranking).Conclusion: The study provides insights into PS utilization in EM’s inaugural year. We have identified patterns of signal use based on program characteristics and number of signals received that can inform signal allocation and utilization on an individual applicant and program level. A more nuanced understanding of signal use can provide valuable insight as the specialty of EM grapples with fluctuations in its applicant numbers and shifting demographics of its applicant pool.

Detailed binding experiments reveal new insights into the Norrin/Wnt signaling pathway that helps to control vascularization in the retina.

Plants shed organs such as leaves, petals, or fruits through the process of abscission. Monitoring cues such as age, resource availability, and biotic and abiotic stresses allow plants to abscise organs in a timely manner. How these signals are integrated into the molecular pathways that drive abscission is largely unknown. The INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) gene is one of the main drivers of floral organ abscission in Arabidopsis and is known to transcriptionally respond to most abscission-regulating cues. By interrogating the IDA promoter in silico and in vitro, we identified transcription factors that could potentially modulate IDA expression. We probed the importance of ERF- and WRKY-binding sites for IDA expression during floral organ abscission, with WRKYs being of special relevance to mediate IDA up-regulation in response to biotic stress in tissues destined for separation. We further characterized WRKY57 as a positive regulator of IDA and IDA-like gene expression in abscission zones. Our findings highlight the promise of promoter element-targeted approaches to modulate the responsiveness of the IDA signaling pathway to harness controlled abscission timing for improved crop productivity.

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PIP3-dependent Rac exchanger 1 (P-Rex1) is abundantly expressed in neutrophils and plays central roles in chemotaxis and cancer metastasis by serving as a guanine-nucleotide exchange factor (GEF) for Rac. The enzyme is synergistically activated by PIP3 and heterotrimeric Gβγ subunits, but mechanistic details remain poorly understood. While investigating the regulation of P-Rex1 by PIP3, we discovered that Ins(1,3,4,5)P4 (IP4) inhibits P-Rex1 activity and induces large decreases in backbone dynamics in diverse regions of the protein. Cryo-electron microscopy analysis of the P-Rex1·IP4 complex revealed a conformation wherein the pleckstrin homology (PH) domain occludes the active site of the Dbl homology (DH) domain. This configuration is stabilized by interactions between the first DEP domain (DEP1) and the DH domain and between the PH domain and a 4-helix bundle (4HB) subdomain that extends from the C-terminal domain of P-Rex1. Disruption of the DH-DEP1 interface in a DH/PH-DEP1 fragment enhanced activity and led to a more extended conformation in solution, whereas mutations that constrain the occluded conformation led to decreased GEF activity. Variants of full-length P-Rex1 in which the DH-DEP1 and PH-4HB interfaces were disturbed exhibited enhanced activity during chemokine-induced cell migration, confirming that the observed structure represents the autoinhibited state in living cells. Interactions with PIP3-containing liposomes led to disruption of these interfaces and increased dynamics protein-wide. Our results further suggest that inositol phosphates such as IP4 help to inhibit basal P-Rex1 activity in neutrophils, similar to their inhibitory effects on phosphatidylinositol-3-kinase.

Here, we introduce the EMPH special issue on Evolutionary and Biopsychosocial Perspectives on Sickness Communication. This Commentary provides an overview of each article and places them in the wider context of sickness as a social phenomenon with verbal and nonverbal signals. This Commentary, and the special issue, in general, calls for greater attention to these signals that can affect pathogen transmission and may be at the evolutionary root of our caregiving systems and behaviours.

FGF9 is a potent mitogen and survival factor, but FGF9 protein levels are generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in cancer. However, the mechanism of FGF9 action has not been fully established. Previous studies showed that FGF1 and FGF2 directly bind to integrin αvβ3, and this interaction is critical for signaling functions (FGF-integrin crosstalk). FGF1 and FGF2 mutants defective in integrin binding were defective in signaling, whereas the mutants still bound to FGFR suppressed angiogenesis and tumor growth, indicating that they act as antagonists. We hypothesize that FGF9 requires direct integrin binding for signaling. Here, we show that docking simulation of the interaction between FGF9 and αvβ3 predicted that FGF9 binds to the classical ligand-binding site of αvβ3. We show that FGF9 bound to integrin αvβ3 and generated FGF9 mutants in the predicted integrin-binding interface. An FGF9 mutant (R108E) was defective in integrin binding, activating FRS2α and ERK1/2, inducing DNA synthesis, cancer cell migration, and invasion in vitro. R108E suppressed DNA synthesis and activation of FRS2α and ERK1/2 induced by WT FGF9 (dominant-negative effect). These findings indicate that FGF9 requires direct integrin binding for signaling and that R108E has potential as an antagonist to FGF9 signaling.

Purpose: While comprehensive research exists on the mutation of the DNA repair gene BRCA1, limited information is available regarding the clinical significance of BRCA1 gene expression. Given that cancer cell proliferation is aggrevated by DNA repair, we hypothesized that high BRCA1 gene expression breast cancer (BC) might be linked with aggressive tumor biology and poor clinical outcomes. Methods: The cohorts: The Cancer Genome Atlas (TCGA, n = 1069), METABRIC (n = 1903), and SCAN-B (n = 3273) were utilzed to obtain data of 6245 BC patients. Results: BC patients without BRCA1 mutation exhibited higher BRCA1 expression, which was associated with DNA repair functionality. However, no such correlation was observed with BRCA2 expression. The association of high BRCA1 expression with cancer cell proliferation was evidenced by significant enrichment of cell proliferation-related gene sets, higher histological grade, and proliferation score. Furthermore, increased levels of homologous recombination deficiency, intratumoral heterogeneity, and altered fractions were associated with high BRCA1 expression. Moreover, BC with high BRCA1 expression exhibited reduced infiltration of dendritic cells and CD8 T-cells, while showing increased infiltration of Th1 cells. Surprisingly, BRCA1 expression was not associated with the survival of BC irrespective of the subtypes. Conversely, BC with low BRCA1 expression enriched cancer aggravating pathway gene sets, such as Cancer Stem Cell-related signaling (NOTCH and HEDGEHOG), Angiogenesis, Epithelial-Mesenchymal Transition, Inflammatory Response, and TGF-beta signaling. Conclusion: Despite being linked to heightened proliferation of cancer cells and unassertive phenotype, BRCA1 expression did not show any association with survival in BC. [ABSTRACT FROM AUTHOR]

To combat phage infection, type III CRISPR-Cas systems utilize cyclic oligoadenylates (cA n) signaling to activate various auxiliary effectors, including the CRISPR-associated Lon-SAVED protease CalpL, which forms a tripartite effector system together with an anti-σ factor, CalpT, and an ECF-like σ factor, CalpS. Here, we report the characterization of the Candidatus Cloacimonas acidaminovorans CalpL-CalpT-CalpS. We demonstrate that cA 4 binding triggers CalpL filament formation and activates it to cleave CalpT within the CalpT-CalpS dimer. This cleavage exposes the CalpT C-degron, which targets it for further degradation by cellular proteases. Consequently, CalpS is released to bind to RNA polymerase, causing growth arrest in E. coli. Furthermore, the CalpL-CalpT-CalpS system is regulated by the SAVED domain of CalpL, which is a ring nuclease that cleaves cA 4 in a sequential three-step mechanism. These findings provide key mechanistic details for the activation, proteolytic events, and regulation of the signaling cascade in the type III CRISPR-Cas immunity. [Display omitted] • CalpL filament formation is obligatory for its protease and ring nuclease activities • Within the CalpL filament, CalpT is cleaved by the adjacent CalpL subunit • CalpL cleavage exposes the CalpT C-degron, which targets it for further degradation • CalpL SAVED domain is a ring nuclease cleaving cA 4 via a sequential three-step mechanism Smalakyte et al. report the molecular mechanism of the type III CRISPR-Cas tripartite effector system. cA 4 induces filament formation and activation of Lon-protease CalpL to cleave CalpT, releasing σ-factor CalpS, which binds RNA polymerase, arresting E. coli growth. Signaling cascade is regulated by ring nuclease activity of the CalpL SAVED domain. [ABSTRACT FROM AUTHOR]

The third Asia Pacific Drosophila Neurobiology Conference (APDNC3) was held in the Wako Campus of RIKEN in Tokyo, Japan, from February 27th to March 1st, 2024. While APDNC2 was held in Taiwan in 2019, the global coronavirus pandemic enforced a long hiatus. Hence, APDNC3 was a much‐anticipated meeting that attracted ~218 scientists from 18 different countries and regions, 154 from outside Japan. The meeting was divided into 13 scientific, 2 poster, and 3 career development sessions. Two plenary talks were delivered by Professor Daisuke Yamamoto, from NICT and Professor Claude Desplan from NYU. Thirty‐seven other speakers were invited to give lectures. Eighty‐six poster presenters were selected from submitted abstracts. Talks and posters described how neuronal circuits underlying specific behaviors were identified and how they developed. The presented work also demonstrated circuit‐specific cellular and molecular mechanisms in health and disease. It was clear that technological advances, like molecular genetic tools for identifying, manipulating, and imaging individual neurons and the great granularity of the fly brain connectome, were significantly augmenting research. Overall, the meeting highlighted the remarkable biological insights that fly neurobiologists continue to provide. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) are key orchestrators of development, tissue homeostasis and repair. FGF receptor (FGFR) deficiency in mouse keratinocytes causes an inflammatory skin phenotype with similarities to atopic dermatitis, but the human relevance is unclear. Therefore, we generated human keratinocytes with a CRISPR/Cas9-induced knockout of FGFR2. Loss of this receptor promoted the expression of interferon-stimulated genes and pro-inflammatory cytokines under homeostatic conditions and in particular in response to different inflammatory mediators. Expression of FGFR2 itself was strongly downregulated in cultured human keratinocytes exposed to various pro-inflammatory stimuli. This is relevant in vivo, because bioinformatics analysis of bulk and single-cell RNA-seq data showed strongly reduced expression of FGFR2 in lesional skin of atopic dermatitis patients, which likely aggravates the inflammatory phenotype. These results reveal a key function of FGFR2 in human keratinocytes in the suppression of inflammation and suggest a role of FGFR2 downregulation in the pathogenesis of atopic dermatitis and possibly other inflammatory diseases. [ABSTRACT FROM AUTHOR]

Small peptides produced by plants (SPPs) and microbes (SPMs) function as crucial mediators in plant–rhizosphere microbe interactions, with SPPs facilitating long-distance signaling through extracellular vesicles and SPMs modulating plant immunity and hormone signaling to enhance communication. SPPs may directly alter the rhizosphere microbiomes by modifying microbial gene expression or indirectly by influencing root morphology, exudate release, and immune responses, thus affecting microbial community structure and composition. Leveraging the bidirectional signaling facilitated by SPPs and SPMs between plants and their rhizosphere microbes offers a novel strategy in holobiont engineering, and the potential of exploring transgenic microbes to synthesize small peptides on a large scale merits further investigations. The crucial role of rhizosphere microbes in plant growth and their resilience to environmental stresses underscores the intricate communication between microbes and plants. Plants are equipped with a diverse set of signaling molecules that facilitate communication across different biological kingdoms, although our comprehension of these mechanisms is still evolving. Small peptides produced by plants (SPPs) and microbes (SPMs) play a pivotal role in intracellular signaling and are essential in orchestrating various plant development stages. In this review, we posit that SPPs and SPMs serve as crucial signaling agents for the bidirectional cross-kingdom communication between plants and rhizosphere microbes. We explore several potential mechanistic pathways through which this communication occurs. Additionally, we propose that leveraging small peptides, inspired by plant–rhizosphere microbe interactions, represents an innovative approach in the field of holobiont engineering. [ABSTRACT FROM AUTHOR]

Terrorist organizations are often described as brands. However, the most important visual representations of these brands – terrorist groups' logos – have remained unexplored. In this article, we demonstrate that logos are signalling devices that provide vital cues on the propensity to use violence. To this end, we code and analyse 562 terrorist logos (2000–16). After providing a descriptive overview of the main colours and symbols used by terrorist groups worldwide, we rely on a zero-inflated negative binomial model to analyse the relationship between these organizations' visual choices and their deadly activities. Our results show that the presence of violent, religious, and extremist symbols in terrorist organizations' logos, as well as the use of black as the main colour, correlates with more frequent and deadlier attacks. These findings have important policy implications, demonstrating that logos serve as behavioural cues predicting the threat posed by terrorist groups not less effectively than their ideology. By highlighting the importance of visual artifacts like logos and their amenability to quantitative research, our article also provides a novel methodological contribution to international relations, helping bridge the gap between explanatory and critical security studies. [ABSTRACT FROM AUTHOR]

Fusarium verticillioides is both an endophyte and pathogen of maize. During growth on maize, the fungus often synthesizes the mycotoxins fumonisins, which have been linked to a variety of diseases, including cancer in some animals. How F. verticillioides responds to other fungi, such as Fusarium proliferatum , Aspergillus flavus , Aspergillus niger , and Penicillium oxalicum , that coinfect maize, has potential to impact mycotoxin synthesis and disease. We hypothesize that low molecular weight acids produced by these fungi play a role in communication between the fungi in planta/nature. To address this hypothesis, we exposed 48-h maize kernel cultures of F. verticillioides to oxalic acid, citric acid, fusaric acid, or kojic acid and then compared transcriptomes after 30 min and 6 h. Transcription of some genes were affected by multiple chemicals and others were affected by only one chemical. The most significant positive response was observed after exposure to fusaric acid which resulted in >2-fold upregulation of 225 genes, including genes involved in fusaric acid synthesis. Exposure of cultures to the other three chemicals increased expression of only 3–15 genes. The predicted function and frequent co-localization of three sets of genes support a role in protecting the fungus from the chemical or a role in catabolism. These unique transcriptional responses support our hypothesis that these chemicals can act as signaling molecules. Studies with gene deletion mutants will further indicate if the initial transcriptional response to the chemicals benefit F. verticillioides. • Low-molecular-weight fungal acids impact the Fusarium verticillioides transcriptome. • Fusaric acid impacted more genes than other acids. • Kojic acid impacted two gene clusters that occur widely in Fusarium. [ABSTRACT FROM AUTHOR]

Background: Normal cells express functional tumor suppressor WW domain-containing oxidoreductase (WWOX), designated WWOXf. UV irradiation induces WWOXf cells to undergo bubbling cell death (BCD) — an event due to the accumulation of nuclear nitric oxide (NO) gas that forcefully pushes the nuclear and cell membranes to form one or two bubbles at room temperature (22 °C) and below. In contrast, when WWOX-deficient or -dysfunctional (WWOXd) cells are exposed to UV and/or cold shock, the cells undergo nuclear pop-out explosion death (POD). We aimed to determine the morphological and biochemical changes in WWOXf cells during BCD versus apoptosis. Methods: WWOXf and WWOXd cells were exposed to UV followed by measuring BCD or POD by time-lapse microscopy and/or time-lapse holographic microscopy at 4, 22, or 37 °C to visualize morphological changes. Live cell stains were used to measure the kinetics of nitric oxide (NO) production and Ca2+ influx. Extent of cell death was measured by uptake of propidium iodide and by internucleosomal DNA fragmentation using agarose gel electrophoresis. Results: WWOXf cells were exposed to UV and then cold shock, or cold shock and then UV, and cultured at 4, 10, and 22 °C, respectively. Initially, UV induced calcium influx and NO production, which led to nuclear bubbling and final death. Cold shock pretreatment completely suppressed UV-mediated bubbling at 37 °C, so the UV/cold shock-treated cells underwent apoptosis. Without cold shock, UV only induced bubbling at all temperatures, whereas the efficiency of bubbling at 37 °C was reduced by greater than 50%. Morphologically, the WWOXf cell height or thickness was significantly increased during cell division or apoptosis, but the event did not occur in BCD. In comparison, when WWOXd cancer cells received UV or UV/cold shock, these cells underwent NO-independent POD. UV/cold shock effectively downregulated the expression of many proteins such as the housekeeping α-tubulin (> 70%) and β-actin (< 50%), and cortactin (> 70%) in WWOXf COS7 cells. UV/cold shock induced relocation of α-tubulin to the nucleus and nuclear bubbles in damaged cells. UV induced co-translocation of the WWOX/TRAF2 complex to the nuclei, in which the prosurvival TRAF2 blocked the proapoptotic WWOX via its zinc finger domain. Without WWOX, TRAF2 did not relocate to the nuclei. Cold shock caused the dissociation of the WWOX/TRAF2 complex in the nucleus needed for BCD. In contrast, the formation of the WWOX/TRAF2 complex, plus p53, was strengthened at 37 °C required for apoptosis. Conclusions: The temperature-sensitive nuclear WWOX/TRAF2 complex acts as a molecular switch, whose dissociation favors BCD at low temperatures, and the association supports apoptosis at 37 °C in UV-treated WWOXf cells. [ABSTRACT FROM AUTHOR]

Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with noncanonical receptors and unidentified coreceptors; however, the effects of which are less understood. Using high-throughput tandem mass tag (TMT) liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomics and gene set enrichment analysis (GSEA), we identified both shared and unique intracellular pathways activated by Reelin through its canonical and noncanonical signaling in primary murine neurons of either sex during dendritic growth and arborization. We observed pathway cross talk related to regulation of cytoskeleton, neuron projection development, protein transport, and actin filament-based process. We also found enriched gene sets exclusively by the noncanonical Reelin pathway including protein translation, mRNA metabolic process, and ribonucleoprotein complex biogenesis suggesting Reelin fine-tunes neuronal structure through distinct signaling pathways. A key discovery is the identification of aldolase A, a glycolytic enzyme and actin-binding protein, as a novel effector of Reelin signaling. Reelin induced de novo translation and mobilization of aldolase A from the actin cytoskeleton. We demonstrated that aldolase A is necessary for Reelin-mediated dendrite growth and arborization in primary murine neurons and mouse brain cortical neurons. Interestingly, the function of aldolase A in dendrite development is independent of its known role in glycolysis. Altogether, our findings provide new insights into the Reelin-dependent signaling pathways and effector proteins that are crucial for dendritic development. [ABSTRACT FROM AUTHOR]

Over the last several decades, there has been an arms race to acquire credentials as higher education has shifted from an elitist system to mass education. From an individual perspective, given the higher education system and labor market conditions, it is rational to pursue advanced qualifications. However, whether the education system delivers improvements in human capital or is principally a signaling mechanism is questionable. Estimates of the proportion of labor market rewards due to signaling range as high as 80%, suggesting that education is not only expensive but inefficient. In an increasingly transactional environment in which education providers are highly motivated by financial considerations, this situation is only likely to be exacerbated by the rapid developments in artificial intelligence (AI). The use of AI has the potential to make learning more effective, but given that many students see credential acquisition as transactional, it may reduce both human capital and the value of the signaling effect. If the credibility of the credentials offered is further damaged, the higher education sector in its present form and scale may well be unsustainable. We examine the evidence on credential inflation, returns to education, and mismatch of graduates to jobs before analyzing how AI is likely to affect these trends. We then suggest possible responses of prospective students, education providers, and employers to the growing adoption of AI in both education and the workplace. We conclude that the current offerings of generalist degrees, as opposed to vocational qualifications, are not sustainable and that to survive, even in a downsized form, the sector must respond to this disruptive technology by changing both the nature of its offerings and its methods of ensuring that the credentials they offer reflect genuine student learning. [ABSTRACT FROM AUTHOR]

Protease-activated receptor 2 (PAR2) is a cell-surface receptor expressed in various cell types, including keratinocytes, neurons, immune and inflammatory cells. Activation of PAR2, whether via its canonical or biased pathways, triggers a series of signaling cascades that mediate numerous functions. This review aims to highlight the emerging roles and interactions of PAR2 in different skin cells. It specifically summarizes the latest insights into the roles of PAR2 in skin conditions such as atopic dermatitis (AD), psoriasis, vitiligo and melasma. It also considers these roles from the perspective of the cutaneous microenvironment in relation to other inflammatory and autoimmune dermatological disorders. Additionally, the review explores PAR2's involvement in associated comorbidities from both cutaneous and extracutaneous diseases. Therefore, PAR2 may serve as a key target for interactions among various cells within the local skin environment. [ABSTRACT FROM AUTHOR]

The chemokine receptors CCR1 and CCR5 display overlapping expression patterns and ligand dependency. Here we find that ligand activation of CCR5, not CCR1, is dependent on N-terminal receptor O-glycosylation. Release from O-glycosylation dependency is obtained by increasing CCR5 N-terminus acidity to the level of CCR1. Ligand activation of CCR5, not CCR1, drastically improves in the absence of glycosaminoglycans (GAGs). Ligand activity at both CCR1 and CCR5 is boosted by positively charged/basic peptides shown to interact with acidic chemokine receptor N-termini. We propose that receptors with an inherent low N-terminus acidity rely on post-translational modifications (PTMs) to efficiently compete with acidic entities in the local environment for ligand capture. Although crucial for initial ligand binding, strong electrostatic interactions between the ligand and the receptor N-terminus may counteract following insertion of the ligand into the receptor binding pocket and activation, a process that seems to be aided in the presence of basic peptides. Basic peptides bind to the naked CCR1 N-terminus, not the CCR5 N-terminus, explaining the loss of boosting of ligand-induced signaling via CCR5 in cells incapable of glycosylation. [ABSTRACT FROM AUTHOR]

Senescent cells produce a Senescence‐Associated Secretory Phenotype (SASP) that involves factors with diverse and sometimes contradictory activities. One key SASP factor, interleukin‐6 (IL‐6), has the potential to amplify cellular senescence in the SASP‐producing cells in an autocrine action, while simultaneously inducing proliferation in the neighboring cells. The underlying mechanisms for the contrasting actions remain unclear. We found that the senescence action does not involve IL‐6 secretion nor the interaction with the receptor expressed in the membrane but is amplified through an intracrine mechanism. IL‐6 sustains intracrine senescence interacting with the intracellular IL‐6 receptor located in anterograde traffic specialized structures, with cytosolic DNA, cGAS‐STING, and NFκB activation. This pathway triggered by intracellular IL‐6 significantly contributes to cell‐autonomous induction of senescence and impacts in tumor growth control. Inactivation of IL‐6 in somatotrophic senescent cells transforms them into strongly tumorigenic in NOD/SCID mice, while re‐expression of IL‐6 restores senescence control of tumor growth. The intracrine senescent IL‐6 pathway is further evidenced in three human cellular models of therapy‐induced senescence. The compartmentalization of the intracellular signaling, in contrast to the paracrine tumorigenic action, provides a pathway for IL‐6 to sustain cell‐autonomous senescent cells, driving the SASP, and opens new avenues for clinical consideration to senescence‐based therapies. [ABSTRACT FROM AUTHOR]

Abstract\nPLAIN LANGUAGE SUMMARYTGF-β is a pivotal cytokine that orchestrates various aspects of cancer progression, including tumor growth, metastasis, and immune evasion. In this review, we present a comprehensive overview of the multifaceted role of transforming growth factor β (TGF-β) in cancer biology, focusing on its intricate interactions with monocytes and macrophages within the tumor microenvironment (TME). We specifically discuss how TGF-β modulates monocyte and macrophage activities, leading to immunosuppression and tumor progression. We conclude with the current translational and clinical efforts targeting TGF-β, recognizing the promising role of this strategy in immunooncology.Transforming growth factor β (TGF-β), a pivotal cytokine, plays a crucial role in maintaining homeostasis and influencing cancer development by affecting various cell types. In cancer, TGF-β initially suppresses tumor cell growth but later contributes to tumor progression and metastasis, presenting challenges in developing therapeutics targeting this cytokine. Mechanistically, TGF-β impacts diverse cellular processes through canonical Smad and non-Smad pathways, that explains its diverse regulation of different, sometimes opposing, cellular processes.In the context of immunity, exposure to TGF-β renders immune cells immunosuppressive, hindering their ability to fight tumor development. This article explores the effects of TGF-β on monocytes and macrophages, highlighting its role in creating an immunosuppressive tumor microenvironment (TME) required for tumor survival and growth. The article provides an update on recent studies that underscore the potential of TGF-β inhibition in modulating the immune response within the TME, thereby enhancing the effectiveness of cancer immunotherapy.Overall, this review article delves into the multifaceted role of TGF-β in cancer biology, with a specific focus on its interactions with monocytes and macrophages. It underscores the knowledge gaps and the importance of targeting TGF-β signaling in tumor-associated monocytes and macrophages as a promising therapeutic approach in TGF-β secreting tumors. [ABSTRACT FROM AUTHOR]

Working within the framework of a conception that makes social practices central to religion, I present an account of religious beliefs as beliefs that are targets of group-specific social practices organized around the norm that these beliefs are to be held. In addition to opening up new avenues of investigation regarding the ways religious adherents negotiate the expectations of their communities around issues of believing, the account generates reasons to resist the idea that religion is characterized by a distinctive kind of doxastic or quasi-doxastic propositional attitude. On my understanding, belief-targeted social practices can generate cognitive dissonance when they make religious adherents responsible for holding beliefs that they do not have good reasons to hold. And the variety of results produced by this dissonance suggests that there is no uniform resolution to this situation, but rather that belief-targeted social practices generate considerable instability within religious communities. [ABSTRACT FROM AUTHOR]

Toll‐like receptors (TLRs) are innate immune sensors for the presence of pathogens and endogenous danger signals. TLR activation results in conserved intracellular signaling events that orchestrate inflammation and antimicrobial defense. While the identity and interplay of key TLR signaling components are well established, how these largely cytosolic proteins are physically connected is not well understood. For the activation of conserved intracellular signaling events, most TLRs engage the adapter MyD88 (myeloid differentiation primary response 88), which assembles into higher‐order protein complexes, myddosomes. In their recent publication, Fisch et al. present evidence that oligomeric myddosomes detach from initiating TLRs and evolve into larger scaffolds that dynamically assemble not only proximal but also distal cytosolic elements required to execute the entire cascade of the TLR–MyD88 signaling pathway. Coinciding with decline in TLR signaling over time, myddosomes progressively recruit autophagy machinery that mediates myddosome clearance. These findings expand the current understanding of TLR signaling by positioning myddosomes as the central structural element that physically assembles the key executors and regulators of TLR–MyD88‐dependent intracellular signaling cascades. [ABSTRACT FROM AUTHOR]

Aim: To investigate how delayed post‐exercise carbohydrate intake affects muscle glycogen, metabolic‐ and mitochondrial‐related molecular responses, and subsequent high‐intensity interval exercise (HIIE) capacity. Methods: In a double‐blind cross‐over design, nine recreationally active men performed HIIE (10 × 2‐min cycling, ~94% W˙peak) in the fed state, on two occasions. During 0–3 h post‐HIIE, participants drank either carbohydrates ("Immediate Carbohydrate" [IC], providing 2.4 g/kg) or water ("Delayed Carbohydrate" [DC]); total carbohydrate intake over 24 h post‐HIIE was matched (~7 g/kg/d). Skeletal muscle (sampled pre‐HIIE, post‐HIIE, +3 h, +8 h, +24 h) was analyzed for whole‐muscle glycogen and mRNA content, plus signaling proteins in cytoplasmic‐ and nuclear‐enriched fractions. After 24 h, participants repeated the HIIE protocol until failure, to test subsequent HIIE capacity; blood lactate, heart rate, and ratings of perceived effort (RPE) were measured throughout. Results: Muscle glycogen concentrations, and relative changes, were similar between conditions throughout (p > 0.05). Muscle glycogen was reduced from baseline (mean ± SD mmol/kg dm; IC: 409 ± 166; DC: 352 ± 76) at post‐HIIE (IC: 253 ± 96; DC: 214 ± 82), +3 h (IC: 276 ± 62; DC: 269 ± 116) and + 8 h (IC: 321 ± 56; DC: 269 ± 116), returning to near‐baseline by +24 h. Several genes (PGC‐1ɑ, p53) and proteins (p‐ACCSer79, p‐P38 MAPKThr180/Tyr182) elicited typical exercise‐induced changes irrespective of condition. Delaying carbohydrate intake reduced next‐day HIIE capacity (5 ± 3 intervals) and increased RPE (~2 ratings), despite similar physiological responses between conditions. Conclusion: Molecular responses to HIIE (performed in the fed state) were not enhanced by delayed post‐exercise carbohydrate intake. Our findings support immediate post‐exercise refueling if the goal is to maximize next‐day HIIE capacity and recovery time is ≤24 h. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a condition that significantly impacts the lifestyle, health, and habits of numerous individuals worldwide. Its diagnosis and classification are based on the Rome criteria, updated periodically to reflect new research findings in this field. IBS can be classified into different types based on symptoms, each with distinct treatment approaches and some differences in their pathophysiology. The exact pathological background of IBS remains unclear, with many aspects still unknown. Recent research developments suggest that disorders in the brain-gut–microbiota axis are key contributors to the symptoms and severity of IBS. The central nervous system (CNS) interacts bidirectionally with intestinal processes within the lumen and the intestinal wall, with the autonomic nervous system, particularly the vagus nerve, playing an important role. However, the enteric nervous system (ENS) is also crucial in the pathophysiological pathway of IBS. The apeline–corticotropin-releasing factor (CRF)–toll-like receptor 4 (TLR4) signaling route via enteric glia and serotonin production in enteroendocrine cells at the enteric barrier are among the most well-understood new findings that affect IBS through the ENS. Additionally, the microbiota regulates neuronal signals, modifying enteric function by altering the number of enteric bacteria and other mechanisms. Given the limited therapeutic options currently available, it is essential to identify new treatment targets, with the brain-gut axis, particularly the enteric nervous system, being a promising focus. This study aims to delineate the molecular mechanisms that induce IBS and to suggest potential targets for future research and treatment of this potentially debilitating disease. [ABSTRACT FROM AUTHOR]

When two parties are engaged in conflict and each distrusts the other's ability to cooperate or make peace, concessions can be used to indicate an interest in cooperation or peacemaking. However, when negotiating parties are concerned that concessions could be used against them in the future, a lack of trust can prevent optimal concessions from being made and therefore reduce the possibility of peace or cooperation. Using a repeated game that is preceded by an opportunity to signal one's commitment to cooperation through the provision of concessions, we formally demonstrate that concerns over the future use of concessions can explain the existence of inefficient concessions. We then use mechanism design to explore ways a third-party mediator can act as a guarantor that promised concessions would be delivered, thereby reducing inefficiencies and increasing the potential for peace and cooperation. In this process, we open up a new rationale for mediation: to increase the efficiency of signaling in a preliminary round of negotiations and to overcome the concern that concessions could be used against the giver in the future. [ABSTRACT FROM AUTHOR]

Nuclear factor kappa-B (NF-κB) signaling-mediated inflammation contributes greatly to the pathogenesis of periodontitis. Neddylation, a ubiquitin-like posttranslational modification, is known to regulate NF-κB signaling. DCUN1D1 (defective in cullin neddylation 1 domain containing 1) is a critical factor in neddylation and has been shown to regulate NF-κB activation. However, the previse roles of DCUN1D1 in periodontitis are not fully elucidated. To explore the roles of DCUN1D1 in periodontitis, the expression of DCUN1D1 was measured in gingival tissues of patients with periodontitis. We inhibited DCUN1D1 by siRNA knocking down or using inhibitor in gingival fibroblasts and the lipopolysaccharides (LPS)-induced expression of IL-6 and TNF-α, and activation of NF-κB were measured. The expression of DCUN1D1 was increased in gingival tissues of patients with periodontitis. Knocking down or inhibiting DCUN1D1 suppressed LPS-induced production of IL-6 and TNF-α, decreased NF-κB activity, and inhibited LPS-induced activation of NF-κB. Inhibiting DCUN1D1 ameliorates periodontitis by suppressing NF-κB signaling. [ABSTRACT FROM AUTHOR]

Mediator, a multiprotein complex, is an important component of the transcription machinery. In plants, the latest studies have established that it functions as a signal processor that conveys transcriptional signals from transcription factors to RNA polymerase II. Mediator has been found to be involved in different developmental and stress-adaptation conditions, ranging from embryo, root, and shoot development to flowering and senescence, and also in responses to different biotic and abiotic stresses. In the last decade, significant progress has been made in understanding the role of Mediator subunits in root development. They have been shown to transcriptionally regulate development of almost all the components of the root system architecture—primary root, lateral roots, and root hairs. They also have a role in nutrient acquisition by the root. In this review, we discuss all the known functions of Mediator subunits during root development. We also highlight the role of Mediator as a nodal point for processing different hormone signals that regulate root morphogenesis and growth. [ABSTRACT FROM AUTHOR]

Phytohormones are signaling substances that control essential elements of growth, development, and reactions to environmental stress. Drought, salt, heat, cold, and floods are a few examples of abiotic factors that have a significant impact on plant development and survival. Complex sensing, signaling, and stress response systems are needed for adaptation and tolerance to such pressures. Abscisic acid (ABA) is a key phytohormone that regulates stress responses. It interacts with the jasmonic acid (JA) and salicylic acid (SA) signaling pathways to direct resources toward reducing the impacts of abiotic stressors rather than fighting against pathogens. Under exposure to nanoparticles, the plant growth hormones also function as molecules that regulate stress and are known to be involved in a variety of signaling cascades. Reactive oxygen species (ROS) are detected in excess while under stress, and nanoparticles can control their formation. Understanding the way these many signaling pathways interact in plants will tremendously help breeders create food crops that can survive in deteriorating environmental circumstances brought on by climate change and that can sustain or even improve crop production. Recent studies have demonstrated that phytohormones, such as the traditional auxins, cytokinins, ethylene, and gibberellins, as well as more recent members like brassinosteroids, jasmonates, and strigolactones, may prove to be significant metabolic engineering targets for creating crop plants that are resistant to abiotic stress. In this review, we address recent developments in current understanding regarding the way various plant hormones regulate plant responses to abiotic stress and highlight instances of hormonal communication between plants during abiotic stress signaling. We also discuss new insights into plant gene and growth regulation mechanisms during stress, phytohormone engineering, nanotechnological crosstalk of phytohormones, and Plant Growth-Promoting Rhizobacteria's Regulatory Powers (PGPR) via the involvement of phytohormones. [ABSTRACT FROM AUTHOR]

Humans display a remarkable tendency to cooperate with strangers; however, identifying prospective cooperation partners accurately before entering any new relationship is essential to mitigate the risk of being exploited. Visual appearance, as inferrable, for example, from facial images on job portals and dating sites, may serve as a potential signal of cooperativeness. This experimental study examines whether static images enable the correct detection of an individual's propensity to cooperate. Participants first played the Prisoner's Dilemma (PD) game, a standard cooperation task. Subsequently, they were asked to predict the cooperativeness of participants from a prior PD study relying solely on their static facial photographs. While our main results indicate only marginal accuracy improvements over random guessing, a more detailed analysis reveals that participants were more successful at identifying cooperative tendencies similar to their own. Despite no detectable main effect in our primary treatment variations (time pressure versus time delay), participants exhibited increased accuracy in identifying male cooperators under time pressure. These findings point towards a limited yet nuanced role of static facial images in predicting cooperativeness, advancing our understanding of non-behavioral cues in cooperative interactions. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of regulated necrosis characterized by iron-dependent lipid peroxidation, leading to irreparable lipid damage, membrane permeabilization, and necrotic cell death. Ferroptosis has recently been implicated in the pathogenesis of multiple forms of heart disease such as myocardial infarction, cardiac hypertrophy, heart failure, and various cardiomyopathies. Important progress has also been made regarding how ferroptosis is regulated in vitro and in vivo as well as its role in cardiac homeostasis and disease pathogenesis. In this review, we discuss molecular mechanisms that regulates ferroptosis in the heart, including pathways leading to iron overload and lipid peroxidation as well as the roles of key organelles in this process. We also discuss recent findings pertaining to the new pathogenic role of ferroptosis in various forms of heart disease as well as genetic and pharmacologic strategies targeting ferroptosis in the heart. [ABSTRACT FROM AUTHOR]

This paper argues that in housing transaction with asymmetric information, sellers may signal their private information with special design of listing prices. We build a cheap-talk signalling model in which sellers strategically choose round number listing prices to signal their weakness, i.e. they are willing to accept lower prices in order to sell their houses more quickly. Using housing market transaction data in Beijing, we find that round number listings sell 0.13% lower and 0.086 months sooner than precise ones. We also show that these results are unlikely to be driven by housing unobserved attributes or round number self-attractiveness. In addition, we find that as the roundness of listing price increases, the signalling effects become more pronounced. Our results present empirical evidence that signalling helps improve negotiation efficiency under asymmetric information. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) in blood circulation causes endotoxemia and is linked to various disease conditions. Current treatments focus on preventing LPS from interacting with its receptor Toll-like receptor 4 (TLR4) and reducing inflammation. However, our body has a natural defense mechanism: reticuloendothelial cells in the liver rapidly degrade and inactivate much of the circulating LPS within minutes. But this LPS clearance mechanism is not perfect. Excessive LPS that escape this clearance mechanism cause systemic inflammatory damage through TLR4. Despite its importance, the role of reticuloendothelial cells in LPS elimination is not well-studied, especially regarding the specific cells, receptors, and mechanisms involved. This gap hampers the development of effective therapies for endotoxemia and related diseases. This review consolidates the current understanding of LPS clearance, narrates known and explores potential mechanisms, and discusses the relationship between LPS clearance and LPS signaling. It also aims to highlight key insights that can guide the development of strategies to reduce circulating LPS by way of bolstering host defense mechanisms. Ultimately, we seek to provide a foundation for future research that could lead to innovative approaches for enhancing the body's natural ability to clear LPS and thereby lower the risk of endotoxin-related inflammatory diseases, including sepsis. [ABSTRACT FROM AUTHOR]

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) associated with viral or metabolic liver diseases is a growing cancer without effective therapy. AMPK is downregulated in HCC and its activation diminishes tumor growth. Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers. We aimed to study its putative action in liver-cancer derived cell lines through AMPK signaling. We performed cytometric studies for apoptosis and cell cycle, and 2D and 3D migration analysis in HepG2/C3A and Hep3B cells. ALA led to significant inhibition of cell migration/invasion only in HepG2/C3A cells. We showed that these effects depended on AMPK, and ALA also increased the levels and nuclear compartmentalization of the AMPK target p53. The anti-invasive effect of ALA was abrogated in stable-silenced (shTP53) versus isogenic-TP53 HepG2/C3A cells. Furthermore, ALA inhibited epithelial-mesenchymal transition (EMT) in control HepG2/C3A but not in shTP53 nor in Hep3B cells. Besides, we spotted that in patients from the HCC-TCGA dataset some EMT genes showed different expression patterns or survival depending on TP53. ALA emerges as a potent activator of AMPK-p53 axis in HCC cells, and it decreases migration/invasion by reducing EMT which could mitigate the disease in wild-type TP53 patients. [ABSTRACT FROM AUTHOR]

Nitrogen (N) and phosphorus (Pi) are essential macronutrients that affect plant growth and development by influencing the molecular, metabolic, biochemical, and physiological responses at the local and whole levels in plants. N and Pi stresses suppress the physiological activities of plants, resulting in agricultural productivity losses and severely threatening food security. Accordingly, plants have elaborated diverse strategies to cope with N and Pi stresses through maintaining N and Pi homeostasis. MicroRNAs (miRNAs) as potent regulators fine-tune N and Pi signaling transduction that are distinct and indivisible from each other. Specific signals, such as noncoding RNAs (ncRNAs), interact with miRNAs and add to the complexity of regulation. Elucidation of the mechanisms by which miRNAs regulate N and Pi signaling transduction aids in the breeding of plants with strong tolerance to N and Pi stresses and high N and Pi use efficiency by fine-tuning MIR genes or miRNAs. However, to date, there has been no detailed and systematic introduction and comparison of the functions of miRNAs in N and Pi signaling transduction from the perspective of miRNAs and their applications. Here, we summarized and discussed current advances in the involvement of miRNAs in N and Pi signaling transduction and highlighted that fine-tuning the MIR genes or miRNAs involved in maintaining N and Pi homeostasis might provide valuable sights for sustainable agriculture. [ABSTRACT FROM AUTHOR]

AbstractTriciribine (TCN) is a tricyclic nucleoside. Its synthesis was first described in 1971. Subsequent studies have indicated that TCN plays a role in inhibiting DNA synthesis and was revealed to possess a higher selectivity for Akt. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARγ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections. [ABSTRACT FROM AUTHOR]

GPR56, an adhesion G-protein coupled receptor (aGPCRs) with constitutive and ligand-promoted activity, is involved in many physiological and pathological processes. Whether the receptor's constitutive or ligand-promoted activation occur through the same molecular mechanism, and whether different activation modes lead to functional selectivity between G proteins is unknown. Here we show that GPR56 constitutively activates both G12 and G13. Unlike constitutive activation and activation with 3-α-acetoxydihydrodeoxygedunin (3αDOG), stimulation with an antibody, 10C7, directed against GPR56's extracellular domain (ECD) led to an activation that favors G13 over G12. An autoproteolytically deficient mutant, GPR56-T383A, was also activated by 10C7 indicating that the tethered agonist (TA) exposed through autocatalytic cleavage, is not required for this activation modality. In contrast, this proteolysis-resistant mutant could not be activated by 3αDOG indicating different modes of activation by the two ligands. We show that an N-terminal truncated GPR56 construct (GPR56-Δ1-385) is devoid of constitutive activity but was activated by 3αDOG. Similarly to 3αDOG, 10C7 promoted the recruitment of β-arrestin-2 but GPR56 internalization was β-arrestin independent. Despite the slow activation mode of 10C7 that favors G13 over G12, it efficiently activated the downstream Rho pathway in BT-20 breast cancer cells. These data show that different GPR56 ligands have different modes of activation yielding differential G protein selectivity but converging on the activation of the Rho pathway both in heterologous expressions system and in cancer cells endogenously expressing the receptor. 10C7 is therefore an interesting tool to study both the processes underlying GPR56 activity and its role in cancer cells. [ABSTRACT FROM AUTHOR]

Metabolism and mRNA translation represent critical steps involved in modulating gene expression and cellular physiology. Being the most energy-consuming process in the cell, mRNA translation is strictly linked to cellular metabolism and in synchrony with it. Indeed, several mRNAs for metabolic pathways are regulated at the translational level, resulting in translation being a coordinator of metabolism. On the other hand, there is a growing appreciation for how metabolism impacts several aspects of RNA biology. For example, metabolic pathways and metabolites directly control the selectivity and efficiency of the translational machinery, as well as post-transcriptional modifications of RNA to fine-tune protein synthesis. Consistently, alterations in the intricate interplay between translational control and cellular metabolism have emerged as a critical axis underlying human diseases. A better understanding of such events will foresee innovative therapeutic strategies in human disease states. This review covers different aspects of translation and metabolism cross-regulation, ranging from how cells receive instructions to reprogram metabolism through translational control to how metabolism and metabolic states influence the protein synthesis machinery and translation control. [ABSTRACT FROM AUTHOR]

During pregnancy, the adipokines leptin and adiponectin can affect placental nutrient transport and inflammatory pathways, potentially leading to altered fetal growth and pregnancy complications including gestational diabetes mellitus (GDM) and preeclampsia (PE). The aim of this systematic review is to gather and analyze research on maternal circulating leptin and adiponectin levels and their relationship to adverse pregnancy and birth outcomes. Additionally, it seeks to determine whether these hormones are linked to alterations in placental transporters and cell signaling pathways. PubMed and MEDLINE were systematically searched to include studies published between 2012 and 2022. All primary data studies reporting serum adiponectin and/or leptin, placental mRNA and protein levels of related transporters, and adverse birth outcomes were eligible. The current systematic review encompasses a total of 14 articles. Abnormal serum maternal leptin and adiponectin levels were associated with changes in fetal growth and placental cellular signaling and nutrient transporters. A majority of studies associated elevated maternal leptin and reduced adiponectin with fetal overgrowth, although this relationship was not consistent and may be complicated when other pathologies are present. The effects of maternal leptin and adiponectin on fetal growth may be driven by placental adaptation in nutrient transporters and mitochondria. Future studies should determine if the placental effects of leptin and adiponectin that have been found in models have mechanistic roles in human pregnancy. [ABSTRACT FROM AUTHOR]

Simple Summary: The current review article focused on the complex interaction between plant hormones and transcription factors in the response to salt stress, a pressing global issue that has a considerable effect on agricultural productivity. The study unveils the effect of salt stress on the ion equilibrium and triggers a cascade of molecular reactions that have a response to plant growth and development. Transcription factors are essential in regulating gene expression under salt stress. The transcription factors function in collaboration with hormones to regulate environmental stress responses. The study sheds light on the underlying regulatory networks, thus providing crucial knowledge for cultivating salt-tolerant crops through selective breeding and genetic engineering. This review significantly contributes to the establishment of sustainable agricultural techniques, which are essential in addressing the increasing problem of soil salinization and securing global food security. The negative impacts of soil salinization on ion homeostasis provide a significant global barrier to agricultural production and development. Plant physiology and biochemistry are severely affected by primary and secondary NaCl stress impacts, which damage cellular integrity, impair water uptake, and trigger physiological drought. Determining how transcriptional factors (TFs) and hormone networks are regulated in plants in response to salt stress is necessary for developing crops that tolerate salt. This study investigates the complex mechanisms of several significant TF families that influence plant responses to salt stress, involving AP2/ERF, bZIP, NAC, MYB, and WRKY. It demonstrates how these transcription factors (TFs) help plants respond to the detrimental effects of salinity by modulating gene expression through mechanisms including hormone signaling, osmotic stress pathway activation, and ion homeostasis. Additionally, it explores the hormonal imbalances triggered by salt stress, which entail complex interactions among phytohormones like jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA) within the hormonal regulatory networks. This review highlights the regulatory role of key transcription factors in salt-stress response, and their interaction with plant hormones is crucial for developing genome-edited crops that can enhance agricultural sustainability and address global food security challenges. [ABSTRACT FROM AUTHOR]

Cell adhesion proteins localize to epithelial and endothelial cell membranes to form junctional complexes between neighboring cells or between cells and the underlying basement membrane. The structural and functional integrities of these junctions are critical to establish cell polarity and maintain tissue barrier function, while also facilitating leukocyte migration and adhesion to sites of inflammation. In addition to their adhesive properties, however, junctional proteins can also serve important noncanonical functions in inflammatory signaling and transcriptional regulation. Intriguingly, recent work has unveiled novel roles for cell adhesion proteins as both signaling initiators and downstream targets during inflammation. In this review, we discuss both the traditional functions of junction proteins in cell adhesion and tissue barrier function as well as their noncanonical signaling roles that have been implicated in facilitating diverse inflammatory pathologies. [ABSTRACT FROM AUTHOR]

The hormone renin is produced in the kidney by the juxtaglomerular cells. It is the rate-limiting factor in the circulating renin–angiotensin–aldosterone system (RAAS), which contributes to electrolyte, water, and blood pressure homeostasis. In the kidneys, the distal tubule and the collecting duct are the key target segments for RAAS. The collecting duct is important for urine production and also for salt, water, and acid–base homeostasis. The critical functional role of the collecting duct is mediated by the principal and the intercalated cells and is regulated by different hormones like aldosterone and vasopressin. The collecting duct is not only a target for hormones but also a place of hormone production. It is accepted that renin is produced in the collecting duct at a low level. Several studies have described that the cells in the collecting duct exhibit plasticity properties because the ratio of principal to intercalated cells can change under specific circumstances. This narrative review focuses on two aspects of the collecting duct that remain somehow aside from mainstream research, namely the cell plasticity and the renin expression. We discuss the link between these collecting duct features, which we see as a promising area for future research given recent findings. [ABSTRACT FROM AUTHOR]

Land plants grow throughout their life cycle via the continuous activity of stem cell reservoirs contained within their apical meristems. The shoot apical meristem (SAM) of Arabidopsis and other land plants responds to a variety of environmental cues, yet little is known about the response of meristems to seasonal changes in day length, or photoperiod. Here, the vegetative and reproductive growth of Arabidopsis wild-type and clavata3 (clv3) plants in different photoperiod conditions was analyzed. It was found that SAM size in wild-type Arabidopsis plants grown in long-day (LD) conditions gradually increased from embryonic to reproductive development. clv3 plants produced significantly more leaves as well as larger inflorescence meristems and more floral buds than wild-type plants in LD and short-day (SD) conditions, demonstrating that CLV3 signaling limits vegetative and inflorescence meristem activity in both photoperiods. The clv3 phenotypes were more severe in SDs, indicating a greater requirement for CLV3 restriction of SAM function when the days are short. In contrast, clv3 floral meristem size and carpel number were unchanged between LD and SD conditions, which shows that the photoperiod does not affect the regulation of floral meristem activity through the CLV3 pathway. This study reveals that CLV3 signaling specifically restricts vegetative and inflorescence meristem activity in both LD and SD photoperiods but plays a more prominent role during short days. [ABSTRACT FROM AUTHOR]

Pollen grains are central to sexual plant reproduction and their viability and longevity/storage are critical for plant physiology, ecology, plant breeding, and many plant product industries. Our goal is to present progress in assessing pollen viability/longevity along with recent advances in our understanding of the intrinsic and environmental factors that determine pollen performance: the capacity of the pollen grain to be stored, germinate, produce a pollen tube, and fertilize the ovule. We review current methods to measure pollen viability, with an eye toward advancing basic research and biotechnological applications. Importantly, we review recent advances in our understanding of how basic aspects of pollen/stigma development, pollen molecular composition, and intra- and intercellular signaling systems interact with the environment to determine pollen performance. Our goal is to point to key questions for future research, especially given that climate change will directly impact pollen viability/longevity. We find that the viability and longevity of pollen are highly sensitive to environmental conditions that affect complex interactions between maternal and paternal tissues and internal pollen physiological events. As pollen viability and longevity are critical factors for food security and adaptation to climate change, we highlight the need to develop further basic research for better understanding the complex molecular mechanisms that modulate pollen viability and applied research on developing new methods to maintain or improve pollen viability and longevity. [ABSTRACT FROM AUTHOR]

Autophagy is essential for the adaptive response to exercise and physiological skeletal muscle functionality. However, the mechanisms leading to the activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle in response to high-intensity exercise remain elusive. Our findings demonstrate that macroautophagy and chaperone-mediated autophagy are stimulated by high-intensity exercise in normoxia (P I O 2 : 143 mmHg) and severe acute hypoxia (P I O 2 : 73 mmHg) in healthy humans. High-intensity exercise induces macroautophagy initiation through AMPKα phosphorylation, which phosphorylates and activates ULK1. ULK1 phosphorylates BECN1 at Ser15, eliciting the dissociation of BECN1-BCL2 crucial for phagophore formation. Besides, high-intensity exercise elevates the LC3B-II:LC3B–I ratio, reduces total SQSTM1/p62 levels, and induces p -Ser349 SQSTM1/p62 phosphorylation, suggesting heightened autophagosome degradation. PHAF1/MYTHO, a novel macroautophagy biomarker, is highly upregulated in response to high-intensity exercise. The latter is accompanied by elevated LAMP2A expression, indicating chaperone-mediated autophagy activation regardless of post-exercise HSPA8/HSC70 downregulation. Despite increased glycolytic metabolism, severe acute hypoxia does not exacerbate the autophagy signaling response. Signaling changes revert within 1 min of recovery with free circulation, while the application of immediate post-exercise ischemia impedes recovery. Our study concludes that macroautophagy and chaperone-mediated autophagy pathways are strongly activated by high-intensity exercise, regardless of PO 2 , and that oxygenation is necessary to revert these signals to pre-exercise values. PHAF1/MYTHO emerges as a pivotal exercise-responsive autophagy marker positively associated with the LC3B-II:LC3B–I ratio. [Display omitted] • It is unknown whether and how macroautophagy and chaperone-mediated autophagy are activated by exercise in human skeletal muscle. • We show that macroautophagy and chaperone-mediated autophagy are activated by acute exercise to exhaustion in normoxia and severe acute hypoxia. • Simultaneously, protein synthesis signaling is blunted. • Macroautophagy and chaperone-mediated autophagy remain activated during ischemic recovery. • MYTHO, a FOXO-regulated protein is markedly upregulated after exercise in normoxia, hypoxia, and post-exercise ischemia. [ABSTRACT FROM AUTHOR]