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Mutations in theTP53tumor suppressor gene occur in >80% of the triple-negative or basal-like breast cancer. To test whether neomorphic functions of specificTP53missense mutations contribute to phenotypic heterogeneity, we characterized phenotypes of non-transformed MCF10A-derived cell lines expressing the ten most common missense mutant p53 proteins and observed a wide spectrum of phenotypic changes in cell survival, resistance to apoptosis and anoikis, cell migration, invasion and 3D mammosphere architecture. The p53 mutants R248W, R273C, R248Q, and Y220C are the most aggressive while G245S and Y234C are the least, which correlates with survival rates of basal-like breast cancer patients. Interestingly, a crucial amino acid difference at one position—R273C vs. R273H—has drastic changes on cellular phenotype. RNA-Seq and ChIP-Seq analyses show distinct DNA binding properties of different p53 mutants, yielding heterogeneous transcriptomics profiles, and MD simulation provided structural basis of differential DNA binding of different p53 mutants. Integrative statistical and machine-learning-based pathway analysis on gene expression profiles with phenotype vectors across the mutant cell lines identifies quantitative association of multiple pathways including the Hippo/YAP/TAZ pathway with phenotypic aggressiveness. Further, comparative analyses of large transcriptomics datasets on breast cancer cell lines and tumors suggest that dysregulation of the Hippo/YAP/TAZ pathway plays a key role in driving the cellular phenotypes towards basal-like in the presence of more aggressive p53 mutants. Overall, our study describes distinct gain-of-function impacts on protein functions, transcriptional profiles, and cellular behaviors of different p53 missense mutants, which contribute to clinical phenotypic heterogeneity of triple-negative breast tumors.

 

Spinach is a nutritious leafy vegetable belonging to the family Chenopodiaceae. Here we report a high-quality chromosome-scale reference genome assembly of spinach and genome resequencing of 305 cultivated and wild spinach accessions. Reconstruction of ancestral Chenopodiaceae karyotype indicates substantial genome rearrangements in spinach after its divergence from ancestral Chenopodiaceae, coinciding with high repeat content in the spinach genome. Population genomic analyses provide insights into spinach genetic diversity and population differentiation. Genome-wide association studies of 20 agronomical traits identify numerous significantly associated regions and candidate genes for these traits. Domestication sweeps in the spinach genome are identified, some of which are associated with important traits (e.g., leaf phenotype, bolting and flowering), demonstrating the role of artificial selection in shaping spinach phenotypic evolution. This study provides not only insights into the spinach evolution and domestication but also valuable resources for facilitating spinach breeding.

 

We present the first Greenlandic tree ring oxygen isotope record (δ18OGTR), derived from four birch trees collected from the Qinguadalen Valley in southwestern Greenland in 1999. Our δ18O record spans from 1950–1999 and is significantly and positively correlated with winter ice core δ18O from southern Greenland. δ18OGTR records are positively correlated with southwestern Greenland January–August mean temperatures. North Atlantic Oscillation (NAO) reconstructions have been developed from a variety of proxies, but never with Greenlandic tree rings, and our δ18OGTR record is significantly correlated with NAO (r = −0.64), and spatial correlations with sea-level pressure indicate a classic NAO pressure seesaw pattern. These results may facilitate a longer NAO reconstruction based on long time series of tree ring δ18O records from Greenland, provided that subfossil wood can be found in areas vacated by melting glaciers. 

Water system operations require subannual streamflow data—e.g., monthly or weekly—that are not readily achievable with conventional streamflow reconstructions from annual tree rings. This mismatch is particularly relevant to highly seasonal rivers such as Thailand's Chao Phraya. Here, we combine tree ring width and stable oxygen isotope ratios (δ¹⁸O) from Southeast Asia to produce 254‐year, monthly‐resolved reconstructions for all four major tributaries of the Chao Phraya. From the reconstructions, we derive subannual streamflow indices to examine past hydrological droughts and pluvials, and find coherence and heterogeneity in their histories. The monthly resolution reveals the spatiotemporal variability in wet season timing, caused by interactions between early summer typhoons, monsoon rains, catchment location, and topography. Monthly‐resolved reconstructions, like the ones presented here, not only broaden our understanding of past hydroclimatic variability, but also provide data that are functional to water management and climate‐risk analyses, a significant improvement over annual reconstructions.

 

Despite having offered important hydroclimatic insights, streamflow reconstructions still see limited use in water resources operations, because annual reconstructions are not suitable for decisions at finer time scales. The few attempts toward sub‐annual reconstructions have relied on statistical disaggregation, which uses none or little proxy information. Here, we develop a novel framework that optimizes proxy combinations to simultaneously produce seasonal and annual reconstructions. Importantly, the framework ensures that total seasonal flow matches annual flow closely. This mass balance criterion is necessary to avoid misguiding water management decisions, such as the allocation of water rights or dam release decisions. Using the framework, and leveraging a multi‐species network of ring width and celluloseO in Southeast Asia, we reconstruct seasonal and annual inflow to Thailand's largest reservoir. The reconstructions are statistically skillful. Furthermore, they preserve the mass balance well: the differences are mostly within 10% of the mean annual flow. As a result, the reconstructions provide more reliable estimates of the seasonal and annual surface water availability. This work is one step closer toward operational usability of streamflow reconstruction in water resources management.

 

We present a statistically robust reconstruction of Thailand's Chao Phraya River peak season streamflow (CPRPF) that spans the 202 years from 1804 to 2005 CE. Our reconstruction is based on tree ring δ¹⁸O series derived from threePinus merkusiisites from Laos and Thailand. The regional δ¹⁸O index accounts for 57% of the observed variance of CPRPF. Spatial correlation and 21‐year running correlation analyses reveal that CPRPF is greatly influenced by regional precipitation variations associated with the El Niño–Southern Oscillation (ENSO). Periods of enhanced and reduced ENSO activity are associated with strong and weak ENSO‐streamflow correlation, respectively. At the longer timescale, the Pacific Decadal Oscillation (PDO) appears to modulate the ENSO‐streamflow correlations, with the most extreme flood events along the Chao Phraya River occurring during periods of increased frequency of La Niña events that coincide with extended cold phases of the PDO. The CPRPF reconstruction could aid management planning for Thailand's water resources.