94 research outputs found

    Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation.

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    Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing

    Light response of gametophyte in Adiantum flabellulatum: transcriptome analysis and identification of key genes and pathways

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    Light serves not only as a signaling cue perceived by plant photoreceptors but also as an essential energy source captured by chloroplasts. However, excessive light can impose stress on plants. Fern gametophytes possess the unique ability to survive independently and play a critical role in the alternation of generations. Due to their predominantly shaded distribution under canopies, light availability becomes a limiting factor for gametophyte survival, making it imperative to investigate their response to light. Previous research on fern gametophytes’ light response has been limited to the physiological level. In this study, we examined the light response of Adiantum flabellulatum gametophytes under different photosynthetic photon flux density (PPFD) levels and identified their high sensitivity to low light. We thereby determined optimal and stress-inducing light conditions. By employing transcriptome sequencing, weighted gene co-expression network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we identified 10,995 differentially expressed genes (DEGs). Notably, 3 PHYBs and 5 Type 1 CRYs (CRY1s) were significantly down-regulated at low PPFD (0.1 μmol m-2 s-1). Furthermore, we annotated 927 DEGs to pathways related to photosynthesis and 210 to the flavonoid biosynthesis pathway involved in photoprotection. Additionally, we predicted 34 transcription factor families and identified a close correlation between mTERFs and photosynthesis, as well as a strong co-expression relationship between MYBs and bHLHs and genes encoding flavonoid synthesis enzymes. This comprehensive analysis enhances our understanding of the light response of fern gametophytes and provides novel insights into the mechanisms governing their responses to light

    Ambient temperature regulates root circumnutation in rice through the ethylene pathway: transcriptome analysis reveals key genes involved

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    Plant roots are constantly prepared to adjust their growth trajectories to avoid unfavorable environments, and their ability to reorient is particularly crucial for survival. Under laboratory conditions, this continuous reorientation of the root tip is manifested as coiling or waving, which we refer to as root circumnutation. However, the effect of ambient temperature (AT) on root circumnutation remains unexplored. In this study, rice seedlings were employed to assess the impact of varying ATs on root circumnutation. The role of ethylene in mediating root circumnutation under elevated AT was examined using the ethylene biosynthesis inhibitor aminooxyacetic acid (AOA) and the ethylene perception antagonist silver thiosulfate (STS). Furthermore, transcriptome sequencing, weighted gene co-expression network analysis, and real-time quantitative PCR were utilized to analyze gene expressions in rice root tips under four distinct treatments: 25°C, 35°C, 35°C+STS, and 35°C+AOA. As a result, genes associated with ethylene synthesis and signaling (OsACOs and OsERFs), auxin synthesis and transport (OsYUCCA6, OsABCB15, and OsNPFs), cell elongation (OsEXPAs, OsXTHs, OsEGL1, and OsEXORDIUMs), as well as the inhibition of root curling (OsRMC) were identified. Notably, the expression levels of these genes increased with rising temperatures above 25°C. This study is the first to demonstrate that elevated AT can induce root circumnutation in rice via the ethylene pathway and proposes a potential molecular model through the identification of key genes. These findings offer valuable insights into the growth regulation mechanism of plant roots under elevated AT conditions

    Cytokine concentration in peripheral blood of patients with colorectal cancer

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    IntroductionThe role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared.MethodsPeripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples.ResultsIn peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1β, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis.DiscussionDifferent types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment

    Correlation Between Gait and Near-Infrared Brain Functional Connectivity Under Cognitive Tasks in Elderly Subjects With Mild Cognitive Impairment

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    Older adults with mild cognitive impairment (MCI) have a high risk of developing Alzheimer’s disease. Gait performance is a potential clinical marker for the progression of MCI into dementia. However, the relationship between gait and brain functional connectivity (FC) in older adults with MCI remains unclear. Forty-five subjects [MCI group, n = 23; healthy control (HC) group, n = 22] were recruited. Each subject performed a walking task (Task 01), counting backward–walking task (Task 02), naming animals–walking task (Task 03), and calculating–walking task (Task 04). The gait parameters and cerebral oxygenation signals from the left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), right motor cortex (RMC), left occipital leaf cortex (LOL), and right occipital leaf cortex (ROL) were obtained simultaneously. Wavelet phase coherence was calculated in two frequency intervals: low frequency (interval I, 0.052–0.145 Hz) and very low frequency (interval II, 0.021–0.052 Hz). Results showed that the FC of RPFC–RMC is significantly lower in interval I in Task 03 compared with that in Task 02 in the MCI group (p = 0.001). Also, the right relative symmetry index (IDpsR) is significantly lower in Task 03 compared with that in Task 02 (p = 0.000). The IDpsR is positively correlated with the FC of RPFC–RMC in interval I in the MCI group (R = 0.205, p = 0.041). The gait symmetry such as left relative symmetry index (IDpsL) and IDpsR is significantly lower in the dual-task (DT) situation compared with the single task in the two groups (p < 0.05). The results suggested that the IDpsR might reflect abnormal change in FC of RPFC–RMC in interval I in the MCI population during Task 03. The gait symmetry is affected by DTs in both groups. The findings of this study may have a pivotal role in the early monitoring and intervention of brain dysfunction among older adults with MCI

    Abnormalities of White Matter Microstructure in Unmedicated Obsessive-Compulsive Disorder and Changes after Medication

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    BACKGROUND: Abnormalities of myelin integrity have been reported in obsessive-compulsive disorder (OCD) using multi-parameter maps of diffusion tensor imaging (DTI). However, it was still unknown to what degree these abnormalities might be affected by pharmacological treatment. OBJECTIVE: To investigate whether the abnormalities of white matter microstructure including myelin integrity exist in OCD and whether they are affected by medication. METHODOLOGY AND PRINCIPAL FINDINGS: Parameter maps of DTI, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were acquired from 27 unmedicated OCD patients (including 13 drug-naïve individuals) and 23 healthy controls. Voxel-based analysis was then performed to detect regions with significant group difference. We compared the DTI-derived parameters of 15 patients before and after 12-week Selective Serotonin Reuptake Inhibitor (SSRI) therapies. Significant differences of DTI-derived parameters were observed between OCD and healthy groups in multiple structures, mainly within the fronto-striato-thalamo-cortical loop. An increased RD in combination with no change in AD among OCD patients was found in the left medial superior frontal gyrus, temporo-parietal lobe, occipital lobe, striatum, insula and right midbrain. There was no statistical difference in DTI-derived parameters between drug-naive and previously medicated OCD patients. After being medicated, OCD patients showed a reduction in RD of the left striatum and right midbrain, and in MD of the right midbrain. CONCLUSION: Our preliminary findings suggest that abnormalities of white matter microstructure, particularly in terms of myelin integrity, are primarily located within the fronto-striato-thalamo-cortical circuit of individuals with OCD. Some abnormalities may be partly reversed by SSRI treatment

    Determination of band alignment at the CdTe/SnTe heterojunction interface for CdTe thin-film solar cells

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    The Ohmic back contact for CdTe is a key issue to realize high-efficiency CdTe thin film solar cells because of the high work function of CdTe. CdTe/SnTe heterojunctions (HJs) have been implemented to address this issue which shows promising potential, but the band alignment at the HJs is unknown. The valence band offsets in MBE-grown cadmium telluride (CdTe)/tin telluride (SnTe) (111) heterostructures were measured with X-ray photoelectron spectroscopy (XPS). The XPS results show that the heterostructure has an ideal type-I band structure for CdTe solar cells applications, with a valence band offset of −1.33±0.18 eV-1.33 \pm 0.18\ \text{eV} and a conduction band offset of 0.09±0.18 eV0.09 \pm 0.18\ \text{eV} , which expedites hole transport from the CdTe absorber to the hole electrode and improves the Ohmic contact for CdTe. Experimental determination of the band structure of CdTe/SnTe HJs can help improve the photovoltaic performance of CdTe thin film solar cells and facilitate the design and fabrication of CdTe/SnTe related devices. Furthermore, we inserted a SnTe back contact buffer layer into the CdTe thin film solar cells, and it was compared with the cell structure without the SnTe buffer layer. The feasibility of using SnTe as a solar cell back contact is confirmed
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