The results show that alternative transcript diversity extensively enters translation-supported proteoform space and establish a systematic link between transcript variation and protein functional diversification.
Abstract
Alternative splicing generates extensive transcript diversity, but the extent to which this diversity contributes to the translated proteome and reshapes protein function remains unclear. Here, we develop 3DisoGalaxy, an atlas integrating transcript reconstruction, ribosome profiling, structural modelling and regulatory annotation in breast cancer. We find that 58,292 of 90,929 transcripts are linked to translation-supported ORFs, 71.9% of which arise from non-canonical transcript structures. These products are broadly accommodated within established protein fold space, indicating that alternative isoforms frequently preserve recognizable protein architectures despite substantial sequence variation. Functional divergence is instead concentrated in domains, intrinsically disordered regions, localization determinants and regulatory motifs. Motif-repertoire remodelling is more extensive in cancer-driver genes than in other genes, linking isoform-associated regulatory variation to cancer-relevant proteins. As an example of domain remodelling, we identify an AKT1-ΔPH isoform that lacks the N-terminal PH domain while retaining the kinase core, with immunoblotting revealing a lower-molecular-weight AKT1 species consistent with this isoform. Together, our results show that alternative transcript diversity extensively enters translation-supported proteoform space and establish a systematic link between transcript variation and protein functional diversification. Graphical Abstract
This study constructed a pH-responsive P-TN/SF@Fe-Cur composite coating that demonstrated significant anti-infective, anti-inflammatory, antioxidant, pro-angiogenic, and pro-osteogenic effects in rat subcutaneous infection and femoral defect models.
ProteinReasoner is developed, a multimodal generative protein foundation model that sequentially connects amino acid sequence, evolutionary constraints and three-dimensional structure within a shared autoregressive architecture and suggests a general route towards reasoning across interdependent representations in other scientific domains.
Chaozhong Liu, Linlin Chao, Shaomin Ji et al.· bioRxiv· 1 citation
Due to its importance and wide adoption, wheat cultivation is promptly required to shift towards sustainable practices, reducing the dependency on chemical components. Among bio-based solutions aimed at securing the sustainability of wheat cultivation, biostimulants offer a versatile platform of eco-friendly tools assuring sustainability and profitability. Microalgae present a concrete example of a biostimulant source due to their richness in metabolites and high value products. Therefore, this study evaluated the biostimulant potential of eleven eco-extracts prepared from soil-isolated microalgae strains. Eco-extracts applied via soil drench at low dose (0.1 g/L) were investigated for their biostimulant effects on wheat growth, physiology, yield, and quality under controlled conditions. Results demonstrated significant ameliorations in treated plants as compared to the control, with no phytoinhibitory effects. Remarkable enhancements were notable in growth parameters such as shoot and root lengths (+40-70%), physiological traits such as total chlorophyll and stomatal conductance (+7-52%), yield components in the example of grain number per spike and thousand grain weight (+17-103%), and grain quality namely protein and polyphenol content (+2-fold to 4-fold). Similarly, phosphorus accumulation and uptake were significantly improved, while soil physicochemical status was ameliorated, indicating enhanced fertility. Multivariate analysis and composite index ranking marked Chlorella sp. GA18, Chlorella sp. GA65, Scenedesmus sp. GA69, and Chlorococcum sp. GA63 as eco-extracts with consistent performances across all plant traits. These findings highlighted the promising potential of integrating microalgae-based eco-friendly extracts in sustainable wheat cultivation.
Amer Chabili, Z. Hakkoum, F. Minaoui et al.· Plant Science· 1 citation
HydroGym is introduced, a solver-independent reinforcement learning platform providing more than 60 validated, openly available flow control environments spanning from canonical laminar flows to complex turbulent flows, with systematic progression in the Reynolds number up to Re = 4 × 105, and Mach number variations in two and three dimensions.
Christian Lagemann, Sajeda Mokbel, Miro Gondrum et al.· Nature· 1 citation
ABSTRACT Microplastics (MPs) accumulation in ecosystem and human organs poses urgent environmental and health risks, yet few enzymes efficiently degrade polyethylene terephthalate (PET) under physiological conditions. We leveraged deep learning to mine unexplored sequence space across 246 million proteins, discovering AhPETase, an evolutionarily distinct hydrolase with low homology (<50% sequence identity) to known PET‐degrading enzymes. This noncanonical biocatalyst efficiently depolymerizes PET at 37°C, outperforming all typical PETases and achieving a 7.76‐fold enhancement over IsPETase, one of the most representative mesophilic PETases. Additionally, engineered variant AhPETaseM1 retains functional activity for over 20 days under physiological conditions and can degrade post‐consumer PET MPs 34‐fold faster than recombinant human‐derived enzyme MG8 (rMG8) under equal enzyme loading. Critically, it reversed PET‐induced toxicity in human lung and colon cells, establishing the first proof‐of‐concept for enzymatic MPs detoxification.
Yuxuan Wang, Shijie He, Yuheng Chang et al.· Advancement of science· 0 citations
Alzheimer's disease is characterized by cognitive decline, amyloid-β deposition, tau-related pathology, neuroinflammation, and oxidative stress. Pearl oyster shell-derived nacre extract is used in dietary supplement-related applications, but evidence from animal models should be interpreted cautiously and its effects on Alzheimer's disease-like pathology remain incompletely defined. To evaluate whether long-term oral dietary supplementation with nacre extract is associated with changes in cognitive performance and Alzheimer's disease-like pathological features in APPNL-G-F/NL-G-F knock-in mice. A controlled preclinical animal study was performed using male C57BL/6 wild-type mice and male APPNL-G-F/NL-G-F knock-in mice over a 6-month dietary supplementation period. Six mice were assigned to each group. APP knock-in mice received a standard diet with or without 0.5% (w/w) nacre extract, corresponding to an estimated intake of approximately 20 mg/mouse/day or approximately 600 mg/kg/day. Cognitive performance was assessed using the Y-maze and novel object recognition tests. Brain pathology and molecular responses were evaluated by histology, immunohistochemistry, RNA sequencing, qPCR, Western blotting, and oxidative stress-related assays. Nacre supplementation was associated with improved performance in the Y-maze and novel object recognition tests, reduced amyloid-β deposition and Congo red-positive plaque burden, lower phosphorylated tau immunoreactivity, and fewer histologically degenerated hippocampal neurons. Exploratory RNA sequencing of non-microdissected brain tissue excluding the cerebellum (n = 3/group) identified 53 genes meeting the criteria of an absolute fold change ≥ 1.5 and a valid non-zero FDR-adjusted p value < 0.05. A2M showed a 1.51-fold increase (FDR-adjusted p = 0.00091), and increased A2M abundance was confirmed at the protein level. Iba1 and GFAP immunoreactivity was reduced, and oxidative stress-related parameters were altered in the nacre-supplemented group. Long-term nacre supplementation was associated with improvements in behavioral performance and attenuation of several Alzheimer's disease-like pathological features in male APP knock-in mice. These findings represent an exploratory preclinical signal and do not establish a causal mechanism, dose-response relationship, comprehensive safety profile, or efficacy as a dietary supplement in humans.
Kanae Ohara, Heng Zhang, Hiroto Shibata et al.· Journal of Dietary Supplemen...· 0 citations