Association between week 4 CM and disease status at first restaging after adjusting for CTC

Overall and within batch Coefficient of Variation for CM and each Gene.

Association between week 4 CM and disease status at first restaging after adjusting for CEA.

Supplementary Figure 2 displays the relationship between the week 8 CM level and the change in CM level (Week 8 – baseline). Figure S4B and C use box plots to display the relationship between disease status at first restaging and week 8 CM level or change in CM level (Week 8 – baseline).

Supplementary figure 4 displays time updates ROC curves for week 4 CM level using two additional methods (A) binary thresholding and (B) random forest.

Association between week8 CM and change in CM and disease status at first restaging.

Association between week 4 CM and PFS and OS

Shoot branching, an important agronomic trait, is environmentally and developmentally regulated. Epigenetic modifications play a pivotal role in regulating transcriptional responses to light and temperature cues that control plant growth. Nevertheless, the roles of epigenetic modifiers in regulating shoot branching under varying temperatures remain elusive. In this study, we reveal that elevated temperature suppresses lateral bud outgrowth in tomato (Solanum lycopersicum), accompanied by increased HISTONE DEACETYLASE 4 (HDA4) levels. Loss of function of SlHDA4 augments lateral bud outgrowth, resulting from a reduced auxin response. Notably, increased lateral bud outgrowth observed in slhda4 mutants is insensitive to elevated temperature but can be restored by SlHDA4 overexpression. Furthermore, we found that the histone deacetylase SlHDA4 interacts with the transcription factor SlTCP15 to suppress the expression of genes encoding the light receptor SlPHYB1 and auxin signaling repressor SlIAA12 by decreasing the H3K9ac levels at their promoters. In summary, our work demonstrates that the SlTCP15-SlHDA4 module participates in the regulation of lateral bud outgrowth at warm temperatures by enhancing auxin biosynthesis and signaling in tomato.

Supplementary figure 5 displays time updated ROC curves for (A) CM level at week 8, (B) Change in CM level (Week8 – Week4) and (C) the Combination of week 8 CM level and Change in CM level (Week 8-Week 4) using linear discriminant analysis.

Supplementary Figure 3 displays baseline CM level by disease status at first restaging.

Association between week 4 CM and disease status at first restaging after adjusting for CA27-29.

ABSTRACT Evaluating the cell cycle status during dormancy of multicellular organisms is problematic. This is particularly so for woody perennial buds, where dormant and quiescent states are diffuse, and the organ may remain visibly unchanged for six to nine months of the year. In this study, we investigate cell cycle status of dormant grapevine buds by measuring mitotic index using an optimised method developed for grapevine bud tissue. The experimental material showed a dynamic range in the depth of dormancy, declining from 200 days in March to less than 60 days in May and 30 days in August, measured as the time to reach 50% bud burst in forcing conditions. Despite these differences, flow cytometry analysis showed that most nuclei isolated from these buds were arrested at the G1 phase. Ultrastructure analysis of the cells in the region of the shoot apical meristem confirmed that the mitotic activities of buds remained low at all time points, together with the development of starch grains and the relative absence of organelle development. HIGHLIGHT The cell cycle and ultrastructure data suggest interesting evidence correspond to the growth resumption capacity of grapevine cv. Cabernet Sauvignon buds, i.e., absence of mitosis activities regardless of dormancy depth and starch accumulation irrespective of chilling accumulation.

Uploaded documents are in support of the manuscript and contain: Gene-level quantitation values (transcripts per million - TPM) for the 573 subjects described in the study Metadata with basic information about 573 study subjects

Abstract Black men are two times more likely to die from prostate cancer (PCa) than White men. We reported that innate immune cell infiltration varies between races, and others have reported differences in androgen receptor (AR) expression by race or ancestry. Herein, we evaluated AR status and immune cell infiltration in primary and metastatic PCa tissues obtained from Black and White men. RNA in situ hybridization (RISH) AR analysis was done on a tissue microarray (TMA) constructed from radical prostatectomy tissues from 120 Black men matched to 60 White men on age, grade and stage. RISH or immunohistochemistry (IHC) analysis of AR, NKX3.1, prostate specific antigen (PSA), mast cells (tryptase), neutrophils (CD66), and macrophages (CD206, CD68, CD80) was done on a TMA containing rapid autopsy tissues from metastatic sites (n=11) collected from Black (n=5) and White (n=16) men. Multiplexing IHC (mIHC) was used to assess AR, neutrophils (CD66ce), mast cells (tryptase), T-cells (CD4, CD8), and M2 macrophages (CD163) on radical prostatectomy whole-tissue sections obtained at Johns Hopkins Medicine, Baltimore, MD and biopsy tissues obtained from the University of Nairobi, Nairobi, Kenya. Tumor regions on TMAs were annotated by a pathologist and signal intensity per unit area measured using TMAJ and FrIDA software. HALO Image Analysis Platform (version 3.6.4134.137; Indica Labs) was used to analyze mIHC stained tissues. Statistical analysis and graphing were done using GraphPad Prism. There was increased AR mRNA expression in primary cancer tissues from Black men compared to White men (p<0.0001) after negative binomial regression with the adjustment of TMA set, age, grade and stage. There was a negative correlation between AR expression and CD66+ neutrophils in tumor and benign tissues from Black men (R = -0.318;p = 0.002) but this correlation was not significant among White men (R= -0.045; p = 0.765). Interestingly, we measured a positive correlation between AR mRNA expression and tryptase+ mast cells among White men (R= 0.320; p=0.016), but a trend toward a negative relationship among Black men (R= -0.252;p = 0.075) We also measured a positive correlation between AR and CD163+(R= 0.324; p<0.001), CD68+(R= 0.514;p<0.001), and CD80+(R= 0.386;p<0.001) macrophages in primary tumor tissues from all men. NKX3.1 and PSA protein were significantly increased in metastatic tissues from White compared to Black men. Conversely, CD68+ and CD80+ macrophages were increased in Black compared to White men. CD66+ neutrophils and CD206+ macrophages were increased in AR- compared to AR intact metastatic tissues. Immune cells appeared to be primarily void of AR expression in primary cancer tissues by mIHC, but there was a subset CD4+ and CD8+ T-cell clusters that express AR. Immune cell infiltration varies by the presence of AR in both primary and metastatic PCa tissues. We observed differences in AR mRNA and AR-related proteins between Black and White patients which may contribute to the differences observed in immune cell infiltration between the two races Citation Format: Kennedy Rains, Katie M. Farkouh, Taylor N. Godwin, Eric Erak, Aakash Parikh, Michael Considine, Elana Fertig, Jiayun Lu, Charles Waihenya, Valerie Odero-Marah, Karen S. Sfanos, Angelo M. De Marzo, Corinne E. Joshu, Janielle P. Maynard. Androgen receptor-mediated regulation of innate immunity in prostate cancer in Black men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C122.

1 Abstract Grapevine leafroll disease (GLD) is a viral disease that affects grapevines ( Vitis vinifera L.) and has a severe economic impact on viticulture. In this study, the effect of grapevine leafroll-associated viruses (GLRaV) on berry quality was investigated in clones of cultivar cv. Crimson Seedless table grapes infected with GLRaV. RT-PCR confirmed the identity of the clones: clone 3236, infected only with GLRaV-3 (termed Single); clone 3215, infected with GLRaV-3, GLRaV-4 strain 9 and grapevine virus A (termed Mixed), and a viral free clone of the same genetic background of the infected clones (termed Control). The berry quality indices of size, sugar, acidity, and anthocyanin content were measured at harvest maturity. RT-qPCR was used to determine viral load. The study was repeated over two years. A two-way, multivariate analysis of variance (MANOVA) was applied with clone and season as independent variables and the measured berry quality parameters as a dependent variable. All dependent variables were significantly affected by viral infection (Wilks, λ, [2,33] = 0.033895, p-value < 0.001), while only titratable acidity (TA) was affected by season. Average berry dry mass decreased (p-value < 0.001). The water content of both infected clones was greater than that of the control (p-value < 0.001). Both infected clones displayed reduced sugar content as a fraction of the berry dry mass (p-value < 0.001). The anthocyanin and the phenol content of the infected clones were significantly reduced compared to the control clone ( p < 0.001, p < 0.05, clone 3236 and clone 3215, respectively). Finally, the viral load was highly variable, and no quantitative relationship between viral load and berry composition was found.

Abstract Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes.

Quiescence is an essential property of meristematic cells, which restrains the cell cycle while retaining the capacity to divide. This crucial process not only facilitates life-long tissue homeostasis and regenerative capacity but also provides protection against adverse environmental conditions, enabling cells to conserve the proliferative potency while minimizing DNA damage. As a survival attribute, quiescence is inherently regulated by the products of aerobic life, in particular reactive oxygen species (ROS) and the redox (reduction/oxidation) mechanisms that plant have evolved to channel these into pervasive signals. Adaptive responses allow quiescent cells to compensate for reduced oxygen tension (hypoxia) in a reversible manner, while the regulated production of the superoxide anion (O2·-) facilitates cell division and the maintenance of stem cells. Here we discuss the role of ROS and redox reactions in the control of the quiescent state in plant meristems, and how this process is integrated with cellular energy and hormone biochemistry. We consider the pathways that sense and transmit redox signals with a focus on the central significance of redox regulation in the mitochondria and nucleus, which is a major regulator of quiescence in meristems. We discuss recent studies that suggest that ROS are a critical component of the feedback loops that control stem cell identity and fate, and suggest that the ROS/hypoxia interface is an important 'outside/in' positional cue for plant cells, particularly in meristems.