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Advanced Science (Weinheim,... Jun 2024Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis,...
Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis, transcriptome, and epigenome profiling is conducted across key endosperm developmental stages, revealing that chromatin accessibility, H3K27ac, and H3K27me3 collectively regulate SSP and starch genes with varying impact. Population transcriptome and phenotype analyses highlight accessible promoter regions' crucial role as a genetic variation resource, influencing grain yield and quality in a core collection of wheat accessions. Integration of time-serial RNA-seq and ATAC-seq enables the construction of a hierarchical transcriptional regulatory network governing starch and SSP biosynthesis, identifying 42 high-confidence novel candidates. These candidates exhibit overlap with genetic regions associated with grain size and quality traits, and their functional significance is validated through expression-phenotype association analysis among wheat accessions and loss-of-function mutants. Functional analysis of wheat abscisic acid insensitive 3-A1 (TaABI3-A1) with genome editing knock-out lines demonstrates its role in promoting SSP accumulation while repressing starch biosynthesis through transcriptional regulation. Excellent TaABI3-A1 with enhanced grain weight is selected during the breeding process in China, linked to altered expression levels. This study unveils key regulators, advancing understanding of SSP and starch biosynthesis regulation and contributing to breeding enhancement.
PubMed: 38943260
DOI: 10.1002/advs.202401383 -
Breast Cancer Research : BCR Jun 2024The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to...
BACKGROUND
The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to tumorigenesis. The atypical cell cycle regulator, Spy1 can override cell cycle checkpoints, including those activated by the tumour suppressor p53 which mediates mammary stem cell homeostasis. Spy1 has also been shown to promote expansion of select stem cell populations in other developmental systems. Spy1 protein is elevated during proliferative stages of mammary gland development, is found at higher levels in human breast cancers, and promotes susceptibility to mammary tumourigenesis when combined with loss of p53. We hypothesized that Spy1 cooperates with loss of p53 to increase susceptibility to tumour initiation due to changes in susceptible mammary stem cell populations during development and drives the formation of more aggressive stem like tumours.
METHODS
Using a transgenic mouse model driving expression of Spy1 within the mammary gland, mammary development and stemness were assessed. These mice were intercrossed with p53 null mice to study the tumourigenic properties of Spy1 driven p53 null tumours, as well as global changes in signaling via RNA sequencing analysis.
RESULTS
We show that elevated levels of Spy1 leads to expansion of mammary stem cells, even in the presence of p53, and an increase in mammary tumour formation. Spy1-driven tumours have an increased cancer stem cell population, decreased checkpoint signaling, and demonstrate an increase in therapy resistance. Loss of Spy1 decreases tumor onset and reduces the cancer stem cell population.
CONCLUSIONS
This data demonstrates the potential of Spy1 to expand mammary stem cell populations and contribute to the initiation and progression of aggressive, breast cancers with increased cancer stem cell populations.
Topics: Animals; Female; Mice; Tumor Suppressor Protein p53; Mammary Glands, Animal; Mice, Transgenic; Humans; Cell Cycle Proteins; Neoplastic Stem Cells; Cell Transformation, Neoplastic; Carcinogenesis; Cell Proliferation; Breast Neoplasms; Stem Cells; Cell Cycle; Gene Expression Regulation, Neoplastic
PubMed: 38943151
DOI: 10.1186/s13058-024-01862-1 -
Nature Medicine Jun 2024Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies...
Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.
PubMed: 38942992
DOI: 10.1038/s41591-024-03075-7 -
Biological Trace Element Research Jun 2024The edible mushroom Amanita rubescens Pers., regularly collected and consumed in Slovakia, was assessed for health risk due to the mercury content in its fruiting body...
The edible mushroom Amanita rubescens Pers., regularly collected and consumed in Slovakia, was assessed for health risk due to the mercury content in its fruiting body parts. For this purpose, 364 both from the soil/substrate and mushroom samples from 40 localities in Slovakia were evaluated. At the same time, 21 samples of 7 developmental stages of the fruiting body of A. rubescens were taken in the Žakýlske pleso locality. The total mercury content in the soil and mushroom samples was determined using an AMA-254 analyzer. The contamination factor (C) and index of geoaccumulation (I) were used to detect the level of soil pollution by mercury. The ability of A. rubescens to accumulate mercury from the soil environment was evaluated using the bioconcentration factor (BCF), and the distribution of mercury in the mushroom body was evaluated using the translocation quotient (Q). To determine the health risks resulting from mushroom consumption, the percentages of provisional tolerable weekly intake (%PTWI) and target hazard quotient (THQ) were used. The obtained results have confirmed serious content of mercury soil pollution, especially in former mining areas, where the situation is alarming from a health risk point of view. Consumption of A. rubescens was found to be risky, not only in former mining areas, but higher values of mercury were also detected in other parts of Slovakia. Evaluation of the developmental stages of the fruiting body of A. rubescens showed that the highest bioconcentration factor was determined at developmental stage no. VI for caps with a value of 2.47 mg kg and developmental stage VII for stipes with a value of 1.65 mg kg DW.
PubMed: 38942969
DOI: 10.1007/s12011-024-04280-8 -
Biological Psychiatry Jun 2024Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations...
BACKGROUND
Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages is not fully established.
METHODS
We analyzed blood-derived genotype arrays from 9,715 SCZ patients and 28,822 controls of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mCAs. We focused on probable early developmental sCNVs through stringent filtering. We assessed the sCNVs' burden across varying cell fraction (CF) cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the Psychiatric Genomics Consortium (PGC) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 subjects (449 cases and 487 controls).
RESULTS
Patients with SCZ had a significantly higher somatic losses detection rate than control subjects (1.00% vs 0.52%; odds ratio (OR) = 1.91; 95% CI, 1.47-2.49; two-sided Fisher's exact test, p=1.49×10). Further analysis indicated that the ORs escalated proportionately (from 1.91 to 2.78) with the increment in CF cutoffs. Recurrent sCNVs associated with SCZ (OR>8; Fisher's exact test, p<0.05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, some regions validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2.
CONCLUSIONS
The study highlights mCAs' significant impact on SCZ, suggesting their pivotal role in the disorder's genetic etiology.
PubMed: 38942348
DOI: 10.1016/j.biopsych.2024.06.015 -
Journal of Thermal Biology Jun 2024Phenotypic links are the potential for "carryover" of effects of experience during one life history stage into performance and selection at subsequent stages. They...
Phenotypic links are the potential for "carryover" of effects of experience during one life history stage into performance and selection at subsequent stages. They reflect plastic responses to the environment experienced during an early phase on the phenotype of subsequent phases. We are studying these effects by following individuals of the shrimp Palaemon serratus from the embryonic (eggs carried by females) through the larval phase (pelagic) to the juvenile phase (benthic). In experiment 1, we investigated the effects of larval prey concentration (10, 4 and 2 Artemia/mL) and larval incubation temperature (16 and 22 °C) on larval performance (metamorphosis rate, developmental duration and growth) and then on juvenile performance (survival and Specific Growth Rate, SGR, at 18 and 24 °C in 14 days). In experiment 2, we investigated the effects of embryonic incubation temperature (larval biomass and lipid content of newly hatched larvae from embryos incubated at 12 and 18 °C) and larval prey concentration on larval performance and then on juvenile performance. In both experiments, the larvae plastically increased their development time in response to the reduction in temperature and prey concentration, whereas their survival decreased with temperature and prey concentration. The quantity of lipids available at hatching decreased with decreasing embryonic incubation temperature, which reduced the larval performance, particularly with a low concentration of prey. Survival at 14 days post-metamorphosis was significantly reduced when the embryos were incubated at 12 °C compared with those incubated at 18 °C, regardless of the subsequent larval incubation conditions, revealing phenotypic links between overconsumption of embryonic yolk reserves and post-metamorphic fitness. Overall, juveniles had a better SGR at 24 than at 18 °C, and even better when incubated under stressful embryo-larval conditions (temperature and prey concentration). This study highlighted phenotypic links between developmental stages and over developmental periods of several months.
PubMed: 38941824
DOI: 10.1016/j.jtherbio.2024.103892 -
Molecular Biotechnology Jun 2024Huanglongbing (HLB), a global citrus threat, is transmitted by Diaphorina citri Kuwayama, a widespread insect pest. The disease's rapid spread and incurability...
Huanglongbing (HLB), a global citrus threat, is transmitted by Diaphorina citri Kuwayama, a widespread insect pest. The disease's rapid spread and incurability necessitate efficient, sustainable control strategies. This study investigates heat shock protein 70 (HSP70) genes in D. citri, known to play a pivotal role in insect survival and stress response. The genome-wide identification, gene structure analysis, and conserved protein domain analysis of 22 HSP70 genes in D. citri were performed. Furthermore, the expression of these genes during HLB infection or developmental processes was gauged. Phylogenetic analysis revealed the functional categorization of the identified genes, while gene structure and conserved motifs offered insights into gene function. The expression analysis unveiled dynamic profiles in response to infection and across development stages, potentially aiding future targeted pest control strategies. These findings offer promising leads for the design of novel inhibitors or RNAi strategies targeting D. citri and HLB.
PubMed: 38940979
DOI: 10.1007/s12033-024-01232-4 -
Annals of Agricultural and... Jun 2024Morphological anomalies are considered a rare phenomenon among natural tick populations. New cases of abnormalities in ticks are being described, such as body...
Morphological anomalies are considered a rare phenomenon among natural tick populations. New cases of abnormalities in ticks are being described, such as body assymetries, nanism, gynandromorphism and limb malformations. The tick removed from a cat was morphologically identified to species and developmental stage. The time of feeding on the host was determined. The specimen was tested using PCR and Real-Time PCR methods for the presence of the common tick-borne pathogens: , spp, spp., , spp. For visualisation of the anomalous structures, scanning electron microscopy (SEM) was performed. The tick was identified as a slightly engorged adult female of I. ricinus exhibiting ectromely of leg I on the left side of the idiosoma. The specimen was tested positive for two medically important pathogens: and . The case report describes a rare case of a morphological anomaly in an tick from Poland.
Topics: Animals; Poland; Ixodes; Female; Cats; Cat Diseases; Anaplasma phagocytophilum; Tick Infestations
PubMed: 38940115
DOI: 10.26444/aaem/172533 -
Frontiers in Psychology 2024An emerging body of research attends to grasp the concept of authenticity. Nonetheless, a view on the developmental part with its underlying facets of processes, is...
An emerging body of research attends to grasp the concept of authenticity. Nonetheless, a view on the developmental part with its underlying facets of processes, is rare. In this paper, we aim to take a deeper look into the dynamics of inner work processes, that define certain authenticity developmental stages. Building upon our recently proposed "4C-view" of authenticity, we approach this developmental perspective from two different angles: from a angle and a angle. Using vignettes of authentic client personality coaching processes, we propose that the interwoven dynamic between those two aspects yields several combinations of maturity levels within the individual. Continuity as an overarching concept thus contains various developmental authenticity stages that could be identified through different markers and vary in particular contexts.
PubMed: 38939224
DOI: 10.3389/fpsyg.2024.1231484 -
Journal of Child & Adolescent Trauma Jun 2024Pubertal status/stage of maturation and pubertal timing have been linked with emotional symptoms of problems among youth, particularly in vulnerable developmental...
Pubertal status/stage of maturation and pubertal timing have been linked with emotional symptoms of problems among youth, particularly in vulnerable developmental contexts at risk for stress exposure. The present study tested the extent to which pubertal status/stage of maturation and pubertal timing were associated with anxious/depressed, withdrawn/depressed, and somatic complaint symptoms in Kosovar adolescents. It also tested whether sex moderated these relationships. Data were collected from N = 1,342 Kosovar adolescents (665 girls; M age = 13.26 years, SD = 1.27; 677 boys M age = 13.19 years, SD = 1.31). Regression analyses provided evidence that pubertal status/stage was positively associated with rates of anxious/depressed, withdrawn/depressed, and somatic complaint symptoms in girls, but only with withdrawn/depressed symptoms in boys. Additionally, pubertal timing was positively associated with anxious/depressed, and somatic complaint symptoms in girls; no significant links were found for boys. The present study provided evidence that advanced pubertal status/stage as well as timing is positively associated with internalizing symptoms in girls; however, only pubertal status/stage was positively associated with withdrawn/depressed symptoms in boys. The study highlights the importance of pubertal development for internalizing symptoms in a developmental context known for high stress exposure, particularly for girls.
PubMed: 38938975
DOI: 10.1007/s40653-024-00610-z