BMC Biology最新文献

Background: Molting is a critical yet vulnerable stage in insect development, during which the peritrophic matrix is temporarily disrupted. This transient loss of gut barrier integrity can allow gut bacteria to escape into the hemocoel, where they may proliferate in the nutrient-rich hemolymph, leading to developmental impairments or septicemia. Despite this threat, insects typically complete molting successfully, suggesting the involvement of robust immune mechanisms that control hemolymph bacterial load.

Results: This study identifies the Spätzle gene cluster (HaSpz3-6) in the cotton bollworm (Helicoverpa armigera) as essential for limiting hemolymph bacterial proliferation during molting. Knockdown of HaSpz3-6 suppresses antimicrobial peptide expression, leading to Bacillus spp. overgrowth and delayed molting. The ensuing bacterial proliferation triggers tryptophan catabolism, elevating serotonin and N-acetylserotonin (NAS) levels. Serotonin enhances phagocytosis, which cooperates with reactive oxygen species (ROS) to reduce bacterial burden. NAS subsequently mitigates oxidative stress by scavenging excess ROS.

Conclusions: These findings reveal that Spätzle-mediated immunity is crucial for bacterial regulation during molting. When this pathway is impaired, tryptophan catabolism provides a compensatory defense, albeit with developmental trade-offs. Overall, this study underscores the plasticity of insect immune responses and highlights the critical role of Spätzle in safeguarding developmental transitions.

Water is the most limiting resource for plant growth and development. Heterogeneity in the environmental distribution of water requires plants to direct root growth toward water and to avoid investing resources in areas that lack water. Roots use hydrosignaling pathways-hydrotropism, hydropatterning, and xerobranching-to sense and respond to water availability. While molecular mechanisms of water perception remain unclear, recent studies suggest that organ-level processes using proxies like ethylene help detect spatial water patterns. This review summarizes advances in hydrosignaling and identifies key knowledge gaps to address how plants sense water. Understanding these processes will guide strategies to improve root water capture for sustainable agriculture.

Background: Understanding p53-independent regulatory mechanisms is crucial for predicting outcomes in lung adenocarcinoma (LUAD) and developing improved therapeutic strategies.

Results: We found that PDLIM4 is highly expressed in LUAD tumor tissues, where it induces G2/M phase cell cycle arrest and suppresses cell proliferation, suggesting its potential role in improving patient prognosis. Our study identified BRD4, a bromodomain and extraterminal (BET) family protein, as a key transcriptional regulator of PDLIM4, acting through its BD1 domain. Further analysis revealed that wild-type PDLIM4 stabilizes p21 by blocking its RNA degradation, leading to p21 protein accumulation and subsequent inhibition of cell proliferation. In contrast, the S116 mutation in PDLIM4 abrogates this regulatory effect. Notably, activation of the BRD4/PDLIM4/p21 pathway enhanced chemosensitivity to doxorubicin in both LUAD cells and xenograft tumor models.

Conclusions: Given the high mutation frequency of PDLIM4 recorded in the TCGA cancer database, our findings reveal a critical regulatory signaling pathway that suppresses LUAD progression and augments chemotherapy efficacy.

Background: Nematodes communicate via diverse sex pheromones, including long-range volatile signals, short-range chemical cues, and contact-dependent molecules. While the ascaroside family of small molecules that mediate short-range attraction is well characterized, the identities and roles of volatile sex pheromones (VSPs) that act over longer ranges remain unknown.

Results: Using GC-MS analysis of crude VSP extracts, we identified cyclohexyl acetate (CA) as a candidate mimic, sharing retention time and mass spectral features with natural VSPs. Behavioral assays demonstrated that CA acts as a concentration-dependent, male-specific attractant in Caenorhabditis. Pre-exposure to VSPs induced cross-adaptation to CA, suggesting shared sensory processing. Surprisingly, genetic and calcium imaging analyses revealed that CA perception is mediated primarily by AWC_on (str-2-expressing) neurons and involves VSP chemoreceptor srd-1-independent pathways, which are distinct from the neural pathways involved in natural VSP perception.

Conclusions: These data indicate that CA is unlikely to be a major VSP constituent; rather, it is a structural analog that elicits male-specific attraction via a parallel sensory circuit. The endogenous source of CA in C. remanei remains unresolved; our data do not establish whether females produce CA. Its structural and behavioral mimicry provides new insights into the complexity of chemosensory signaling and the potential for interspecies chemical eavesdropping in nematode ecology.

Background: Intermittent fasting is widely promoted for its potential to improve health and extend lifespan, yet these benefits may come at a reproductive cost, potentially reducing parental fitness and offspring quality. While the inter- and transgenerational effects of fasting are increasingly studied, they remain poorly understood in species with unconventional reproductive roles. Investigating such effects in these systems is crucial, as the evolutionary trade-offs between somatic maintenance and reproductive investment may differ from those in species with conventional reproductive roles. In this study, we investigated the effects of intermittent fasting (IF) in a species with male pregnancy, Syngnathus typhle, by exposing mothers and fathers to either IF or ad libitum (AL) feeding before mating. Upon transfer of maternal eggs to paternal brood pouches, males remained on their assigned diets throughout pregnancy.

Results: Offspring from all parental diet combinations AL(p) × AL(m), IF(p) × IF(m), AL(p) × IF(m), and IF(p) × AL(m) (with p = paternal and m = maternal) were analyzed at birth before first feeding alongside parents for morphology, immune and epigenetic candidate gene expression, and gut microbiota composition. Mothers under IF showed greater condition loss, leading to reduced offspring condition regardless of paternal diet, highlighting the importance of maternal provisioning through eggs. However, IF fathers exhibited increased immune activation and microbiome shifts that were mirrored in offspring, suggesting paternal priming via epigenetic and microbial inheritance. Offspring from mismatched parental diets showed disrupted immune-microbiome correlations, indicating that aligned parental cues support more stable offspring development.

Conclusion: These findings highlight how parental nutritional history differentially shapes offspring phenotype through maternal and paternal pathways in a species with male pregnancy. Our results emphasize the value of studying species with diverse reproductive strategies and life histories to understand the full spectrum of trans-generational plasticity in nature.

Background: Mesenchymal stromal/stem cells (MSC) may represent the cell-of-origin for sarcoma development. A collection of human MSCs sequentially mutated with an increasing number of oncogenic hits served to recreate a step-wise process of sarcomagenesis. To identify potential protein targets of interest in the MSC-sarcoma transformation process, quantitative mass spectrometry-based (LC-MS/MS) proteomics was performed.

Results: Among the protein hits identified as significantly regulated in the transformation process, ALDH1A3 and CD99 were selected and further studied. Both ALDH1A3 abundance levels and activity were significantly upregulated in early-phase (immortalized) and fully transformed (sarcoma forming) cells as compared to normal MSCs. Inversely, CD99 total protein and cell-surface abundance levels were downregulated in immortalized and transformed MSCs. Downregulated CD99 was also identified in several human bone and soft tissue sarcoma subtypes.

Conclusions: Proteomics investigation of a MSC-transformation model of sarcoma has yielded ALDH1A3 and CD99 as potential targets for sarcomagenesis that may contribute to a greater understanding of the disease and the development of novel therapeutic approaches.

Background: To combat infection, an immune system needs to be promptly activated but tightly controlled to avoid destruction of host tissues. IbinA and IbinB are related short peptides with robust expression upon microbial challenge in Drosophila melanogaster.

Results: Ibin genes are ubiquitously present in flies of the Drosophila subgenus Sophophora, replacing the likely evolutionarily older, related gene, Mibin, which is found across a much wider range of cyclorrhaphan flies and is also upregulated following infection. We observed no direct bactericidal or bacteriostatic activity for IbinA or IbinB in vitro. Using single and double Ibin mutant Drosophila lines, we examined their roles in development and during microbial infections. IbinA is expressed in early pupae, and a lack of IbinA and IbinB leads to temperature-dependent formation of melanized tissue during metamorphosis, frequently around the trachea. IbinA and IbinB have distinct effects on susceptibility to microbial infection. For example, flies lacking IbinB had improved survival when challenged with Listeria monocytogenes, an intracellular pathogen, whereas a lack of IbinA alone had no effect. RNA sequencing following L. monocytogenes infection showed enhanced Toll target gene expression in flies lacking IbinB, suggesting that IbinB acts as a negative regulator of the Toll pathway. In contrast, IbinA mutants had decreased Toll target gene expression. Correspondingly, IbinB mutant flies had improved, and IbinA compromised survival in septic fungal infection, where the Toll pathway has a major role.

Conclusions: Our study provides insight into the roles of IbinA and IbinB in regulation of the immune response in Drosophila.

Background: Transposable elements (TEs) are critical in shaping genomic architecture and evolutionary processes, driving genome size expansion and functional innovation. TE dynamics and their contribution to genome expansions have been reported extensively; yet, there is a gap in information regarding their role in gene family expansions and the evolution of new genes, particularly in arthropods.

Results: In this study, we examine the TE dynamics across 80 species from all four major subphyla in Arthropoda, revealing a substantial variation in TE contents and their significant impacts on genome expansion. Our analysis of protein-coding transcripts demonstrates that TEs were frequently integrated into protein-coding regions, with an average of 15.1% of protein-coding transcripts harboring TE-derived fragments. We reported the dynamics of retrocopies in selected species and highlighted the role of retroposition in driving the expansion and diversification of key protein families. We find that certain species-specific key protein families such as Calreticulin-like, Acaloleptin-A, and Ctenidins proteins have undergone substantial expansion and structural diversification.

Conclusions: Our study provides new insights into the impact of TEs on genome evolution, exonization of TEs into host genes, and TE-aided retroposition for gene family expansion.

Background: Atopic dermatitis (AD) is a highly prevalent inflammatory skin disease, affecting up to 30% of children at some point in their life and frequently persisting into adulthood. Insufficiency in the late epidermal protein filaggrin is frequently observed in the lesional skin of patients, with direct and indirect impact on the skin barrier quality and function. We hypothesized that filaggrin reduction influences intracellular, surface, and derived extracellular membranes of keratinocytes with multiple impacts on the cell function.

Results: Using filaggrin knockdown keratinocytes generated by shRNA interference (shFLG), we determined that the physical characteristics of the cellular membranes (reported by refractive index) are changed on a filaggrin insufficiency background. Using proteomics, protein binding modeling, and functional assays, we established that filaggrin insufficiency in keratinocytes results in changes in both organelles comprised of internal cellular membranes (i.e., small extracellular vesicles, sEVs) and the plasma membrane. We detected increased association of anti-adhesive proteins (tenascin-C and matrilin-2) with sEVs, resulting in a reduction of the fibronectin-1-mediated sEV uptake by dendritic cell subsets. At the same time, dysregulation of the tight junction and cell adhesion molecules at the level of the cell increased keratinocyte adhesiveness to reconstituted basement membrane substratum as well as faster gap closure in the wound healing assay. We also independently confirmed the findings on sEV uptake and wound healing in filaggrin knockout N/TERT-2G keratinocytes, which more closely resemble primary cells.

Conclusions: We conclude that the alterations in different membrane compartments in filaggrin insufficiency are reflected in changes in keratinocyte functions of relevance to AD pathology, and strategies to target those could open up new therapeutic approaches.