Fine mapping of a QTL for ear size on porcine chromosome 5 and identification of high mobility group AT-hook 2 (HMGA2) as a positional candidate gene

<p>Abstract</p> <p>Background</p> <p>Ear size and shape are distinct conformation characteristics of pig breeds. Previously, we identified a significant quantitative trait locus (QTL) influencing ear surface on pig chromosome 5 in a White Duroc × Erhualian F₂resource population. This QTL explained more than 17% of the phenotypic variance.</p> <p>Methods</p> <p>Four new markers on pig chromosome 5 were genotyped across this F₂population. RT-PCR was performed to obtain expression profiles of different candidate genes in ear tissue. Standard association test, marker-assisted association test and F-drop test were applied to determine the effects of single nucleotide polymorphisms (SNP) on ear size. Three synthetic commercial lines were also used for the association test.</p> <p>Results</p> <p>We refined the QTL to an 8.7-cM interval and identified three positional candidate genes i.e. <it>HMGA2</it>, <it>SOX5 </it>and <it>PTHLH </it>that are expressed in ear tissue. Seven SNP within these three candidate genes were selected and genotyped in the F₂population. Of the seven SNP, <it>HMGA2 </it>SNP (JF748727: g.2836 A > G) showed the strongest association with ear size in the standard association test and marker-assisted association test. With the F-drop test, F value decreased by more than 97% only when the genotypes of <it>HMGA2 </it>g.2836 A > G were included as a fixed effect. Furthermore, the significant association between g.2836 A > G and ear size was also demonstrated in the synthetic commercial Sutai pig line. The haplotype-based association test showed that the phenotypic variance explained by <it>HMGA2 </it>was similar to that explained by the QTL and at a much higher level than by <it>SOX5</it>. More interestingly, <it>HMGA2 </it>is also located within the dog orthologous chromosome region, which has been shown to be associated with ear type and size.</p> <p>Conclusions</p> <p><it>HMGA2 </it>was the closest gene with a potential functional effect to the QTL or marker for ear size on chromosome 5. This study will contribute to identify the causative gene and mutation underlying this QTL.</p

Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses

T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis

Structural variation and introgression from wild populations in East Asian cattle genomes confer adaptation to local environment

BACKGROUND: Structural variations (SVs) in individual genomes are major determinants of complex traits, including adaptability to environmental variables. The Mongolian and Hainan cattle breeds in East Asia are of taurine and indicine origins that have evolved to adapt to cold and hot environments, respectively. However, few studies have investigated SVs in East Asian cattle genomes and their roles in environmental adaptation, and little is known about adaptively introgressed SVs in East Asian cattle. RESULTS: In this study, we examine the roles of SVs in the climate adaptation of these two cattle lineages by generating highly contiguous chromosome-scale genome assemblies. Comparison of the two assemblies along with 18 Mongolian and Hainan cattle genomes obtained by long-read sequencing data provides a catalog of 123,898 nonredundant SVs. Several SVs detected from long reads are in exons of genes associated with epidermal differentiation, skin barrier, and bovine tuberculosis resistance. Functional investigations show that a 108-bp exonic insertion in SPN may affect the uptake of Mycobacterium tuberculosis by macrophages, which might contribute to the low susceptibility of Hainan cattle to bovine tuberculosis. Genotyping of 373 whole genomes from 39 breeds identifies 2610 SVs that are differentiated along a "north-south" gradient in China and overlap with 862 related genes that are enriched in pathways related to environmental adaptation. We identify 1457 Chinese indicine-stratified SVs that possibly originate from banteng and are frequent in Chinese indicine cattle. CONCLUSIONS: Our findings highlight the unique contribution of SVs in East Asian cattle to environmental adaptation and disease resistance

The research of device for measuring film thickness of intelligent coating machine

Ion beam sputtering machine uses computer to real time monitor the change of film thickness in the preparation process of soft X ray multilayer element fabrication. It solves the problems of uneven film thickness and too thick film thickness and so on, which exist in the original preparation process. The high-precision quartz crystal converts film thickness measurement into frequency measurement. The equal precision frequency meter based on FPGA measures the frequency. It can reduce the signal delay and interference signal of discrete components, accordingly improving the accuracy of measurement. Then it sents the count value to the host computer through the single chip microcomputer serial port. It calculates and displays the value by the GUI of LabVIEW. The experimental results show that, the relative measurement error can be decreased to 1/10, i.e., the measurement accuracy can be improved by more than ten times

The research of device for measuring film thickness of intelligent coating machine

Ion beam sputtering machine uses computer to real time monitor the change of film thickness in the preparation process of soft X ray multilayer element fabrication. It solves the problems of uneven film thickness and too thick film thickness and so on, which exist in the original preparation process. The high-precision quartz crystal converts film thickness measurement into frequency measurement. The equal precision frequency meter based on FPGA measures the frequency. It can reduce the signal delay and interference signal of discrete components, accordingly improving the accuracy of measurement. Then it sents the count value to the host computer through the single chip microcomputer serial port. It calculates and displays the value by the GUI of LabVIEW. The experimental results show that, the relative measurement error can be decreased to 1/10, i.e., the measurement accuracy can be improved by more than ten times

Transient seizure onset network for localization of epileptogenic zone : effective connectivity and graph theory-based analyses of ECoG data in temporal lobe epilepsy

Objective: Abnormal and dynamic epileptogenic networks cause difficulties for clinical epileptologists in the localization of the seizure onset zone (SOZ) and the epileptogenic zone (EZ) in preoperative assessments of patients with refractory epilepsy. The aim of this study is to investigate the characteristics of time-varying effective connectivity networks in various non-seizure and seizure periods, and to propose a quantitative approach for accurate localization of SOZ and EZ. Methods: We used electrocorticogram recordings in the temporal lobe and hippocampus from seven patients with temporal lobe epilepsy to characterize the effective connectivity dynamics at a high temporal resolution using the full-frequency adaptive directed transfer function (ffADTF) measure and five graph metrics, i.e., the out-degree (OD), closeness centrality (CC), betweenness centrality (BC), clustering coefficient (C), and local efficiency (LE). The ffADTF effective connectivity network was calculated and described in five frequency bands (δ, θ, α, β, and γ) and five seizure periods (pre-seizure, early seizure, mid-seizure, late seizure, and post-seizure). The cortical areas with high values of graph metrics in the transient seizure onset network were compared with the SOZ and EZ identified by clinical epileptologists and the results of epilepsy resection surgeries. Results: Origination and propagation of epileptic activity were observed in the high time resolution ffADTF effective connectivity network throughout the entire seizure period. The seizure-specific transient seizure onset ffADTF network that emerged at seizure onset time remained for approximately 20–50 ms with strong connections generated from both SOZ and EZ. The values of graph metrics in the SOZ and EZ were significantly larger than that in the other cortical areas. More cortical areas with the highest mean of graph metrics were the same as the clinically determined SOZ in the low-frequency δ and θ bands and in Engel Class I patients than in higher frequency α, β, and γ bands and in Engel Class II and III patients. The OD and C were more likely to localize the SOZ and EZ than CC, BC, and LE in the transient seizure onset network. Conclusion: The high temporal resolution ffADTF effective connectivity analysis combined with the graph theoretical analysis helps us to understand how epileptic activity is generated and propagated during the seizure period. The newly discovered seizure-specific transient seizure onset network could be an important biomarker and a promising tool for more precise localization of the SOZ and EZ in preoperative evaluations.peerReviewe

Temporal-spatial characteristics of phase-amplitude coupling in electrocorticogram for human temporal lobe epilepsy

Objective Neural activity of the epileptic human brain contains low- and high-frequency oscillations in different frequency bands, some of which have been used as reliable biomarkers of the epileptogenic brain areas. However, the relationship between the low- and high-frequency oscillations in different cortical areas during the period from pre-seizure to post-seizure has not been completely clarified. Methods We recorded electrocorticogram data from the temporal lobe and hippocampus of seven patients with temporal lobe epilepsy. The modulation index based on the Kullback-Leibler distance and the phase-amplitude coupling co-modulogram were adopted to quantify the coupling strength between the phase of low-frequency oscillations (0.2–10 Hz) and the amplitude of high-frequency oscillations (11–400 Hz) in different seizure epochs. The time-varying phase-amplitude modulogram was used to analyze the phase-amplitude coupling pattern during the entire period from pre-seizure to post-seizure in both the left and right temporal lobe and hippocampus. Channels with strong modulation index were compared with the seizure onset channels identified by the neurosurgeons and the resection channels in the clinical surgery. Results The phase-amplitude coupling strength (modulation index) increased significantly in the mid-seizure epoch and decrease significantly in seizure termination and post-seizure epochs (p < 0.001). The strong phase-amplitude-modulating low- and high-frequency oscillations in the mid-seizure epoch were mainly δ, θ, and α oscillations and γ and ripple oscillations, respectively. The phase-amplitude modulation and strength varied among channels and was asymmetrical in the left and right temporal cortex and hippocampus. The “fall-max” phase-amplitude modulation pattern, i.e., high-frequency amplitudes were largest in the low-frequency phase range [−π, 0], which corresponded to the falling edges of low-frequency oscillations, appeared in the middle period of the seizures at epileptic focus channels. Channels with strong modulation index appeared on the corresponding left or right temporal cortex of surgical resection and overlapped with the clinical resection zones in all patients. Conclusions The “fall-max” pattern between the phase of low-frequency oscillation and amplitude of high-frequency oscillation that appeared in the middle period of the seizures is a reliable biomarker in epileptogenic cortical areas. The modulation index can be used as a good tool for lateralization and localization for the epileptic focus in patients with epilepsy. Significance Phase-amplitude coupling can provide meaningful reference for accurate resection of epileptogenic focus and provide insight into the underlying neural dynamics of the epileptic seizure in patients with temporal lobe epilepsy.peerReviewe

Image_2_Identification of subclusters and prognostic genes based on glycolysis/gluconeogenesis in hepatocellular carcinoma.tif

BackgroundThis study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response.MethodsData analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients.ResultsThirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients.ConclusionResults showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC patients.</p