GGPPS1 predicts the biological character of hepatocellular carcinoma in patients with cirrhosis

Background: Hepatocellular carcinoma (HCC) has been associated with diabetes and obesity, but a possible connection with the metabolic syndrome (MetS) and its potential interaction with hepatitis and cirrhosis are open to discussion. Our previous investigations have shown that GGPPS1 plays a critical role during hyperinsulinism. In this report, the expression and distribution of GGPPS1 in liver cancer, and its clinical significance were investigated. Methods: 70 patients with hepatocellular carcinoma (HCC) were included in this study. Three different types of tissues from each HCC patient were assembled immediately after surgical resection: tumor-free tissue >5 cm far from tumor edge (TF), adjacent nonmalignant tissue within 2 cm (AT), and tissue from the tumor (TT). Normal liver tissues from 10 liver transplant donors served as healthy control (HC) while 10 patients with liver cirrhosis as cirrhosis control (CC). The expression and distribution of GGPPS1 were detected by immunohistochemistry, western blots, or real-time PCR. The relationship between the expression of GGPPS1 and clinic pathologic index were analyzed. Results: We found that GGPPS1 was intensified mainly in the cytoplasm of liver tumor cells. Both the expression of GGPPS1 mRNA and protein were upregulated in TT comparing to AT or TF. Meanwhile, HCC patients with cirrhosis had relative higher expression of GGPPS1. In addition, many pathologic characters show close correlation with GGPPS1, such as tumor stage, vessel invasion, and early recurrence. Conclusion: GGPPS1 may play a critical role during the development of HCC from cirrhosis and is of clinical significance for predicting biological character of HCC

The Random Quadratic Assignment Problem

Optimal assignment of classes to classrooms \cite{dickey}, design of DNA microarrays \cite{carvalho}, cross species gene analysis \cite{kolar}, creation of hospital layouts cite{elshafei}, and assignment of components to locations on circuit boards \cite{steinberg} are a few of the many problems which have been formulated as a quadratic assignment problem (QAP). Originally formulated in 1957, the QAP is one of the most difficult of all combinatorial optimization problems. Here, we use statistical mechanical methods to study the asymptotic behavior of problems in which the entries of at least one of the two matrices that specify the problem are chosen from a random distribution $P$. Surprisingly, this case has not been studied before using statistical methods despite the fact that the QAP was first proposed over 50 years ago \cite{Koopmans}. We find simple forms for $C_{\rm min}$ and $C_{\rm max}$, the costs of the minimal and maximum solutions respectively. Notable features of our results are the symmetry of the results for $C_{\rm min}$ and $C_{\rm max}$ and the dependence on $P$ only through its mean and standard deviation, independent of the details of $P$. After the asymptotic cost is determined for a given QAP problem, one can straightforwardly calculate the asymptotic cost of a QAP problem specified with a different random distribution $P$

New CHARMM force field parameters for dehydrated amino acid residues, the key to lantibiotic molecular dynamics simulations

Lantibiotics are an important class of naturally occurring antimicrobial peptides containing unusual dehydrated amino acid residues. In order to enable molecular dynamics simulations of lantibiotics, we have developed empirical force field parameters for dehydroalanine and dehydrobutyrine, which are compatible with the CHARMM all-atom force field. The parameters reproduce the geometries and energy barriers from MP2/6-31G*//MP2/cc-pVTZ quantum chemistry calculations. Experimental, predicted and calculated NMR chemical shifts for the amino protons and alpha-, beta- and carbonyl carbon atoms of the dehydrated residues are consistent with a significant charge redistribution. The new parameters are used to perform the first molecular dynamics simulations of nisin, a widely used but poorly understood lantibiotic, in an aqueous environment and in a phospholipid bilayer. The simulations show surface association of the peptide with membranes in agreement with solid state NMR data and formation of beta-turns in agreement with solution NMR

Comprehensive regulatory networks for tomato organ development based on the genome and RNAome of MicroTom tomato

MicroTom has a short growth cycle and high transformation efficiency, and is a prospective model plant for studying organ development, metabolism, and plant-microbe interactions. Here, with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments, we constructed multiple gene co-expression networks, which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth, e.g. arbuscular mycorrhizal symbiosis and fruit development. Additionally, non-coding RNAs, including miRNAs, lncRNAs, and circRNAs were also identified, together with their potential targets. Interacting networks between different types of non-coding RNAs (miRNA-lncRNA), and non-coding RNAs and genes (miRNA-mRNA and lncRNA-mRNA) were constructed as well. Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit. Lastly, we established a database (http://eplant.njau.edu.cn/microTomBase/) with genomic and transcriptomic data, as well as details of gene co-expression and interacting networks on MicroTom, and this database should be of great value to those who want to adopt MicroTom as a model plant for research.The Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China, the Outstanding Young Teacher of the QingLan Project of Jiangsu Province, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (833522) and from Ghent University (Methusalem funding).https://academic.oup.com/hram2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-15:Life on lan

New Bending Algorithm for Field-Driven Molecular Dynamics

A field-driven bending method is introduced in this paper according to the coordinate transformation between straight and curved coordinates. This novel method can incorporate with the periodic boundary conditions in analysis along axial, bending, and transverse directions. For the case of small bending, the bending strain can be compatible with the beam theory. Consequently, it can be regarded as a generalized SLLOD algorithm. In this work, the bulk copper beam under bending is analyzed first by the novel bending method. The bending stress estimated here is well consistent to the results predicted by the beam theory. Moreover, a hollow nanowire is also analyzed. The zigzag traces of atomic stress and the corresponding 422 common neighbor type can be observed near the inner surface of the hollow nanowire, which values are increased with an increase of time. It can be seen that the novel bending method with periodic boundary condition along axial direction can provide a more physical significance than the traditional method with fixed boundary condition

Search for Quasi-Periodical Oscillations in Precursors of Short and Long Gamma Ray Bursts

The precursors of short and long Gamma Ray Bursts (SGRBs and LGRBs) can serve as probes of their progenitors, as well as shedding light on the physical processes of mergers or core-collapse supernovae. Some models predict the possible existence of Quasi-Periodically Oscillations (QPO) in the precursors of SGRBs. Although many previous studies have performed QPO search in the main emission of SGRBs and LGRBs, so far there was no systematic QPO search in their precursors. In this work, we perform a detailed QPO search in the precursors of SGRBs and LGRBs detected by Fermi/GBM from 2008 to 2019 using the power density spectrum (PDS) in frequency domain and Gaussian processes (GP) in time domain. We do not find any convinced QPO signal with significance above 3 $\sigma$, possibly due to the low fluxes of precursors. Finally, the PDS continuum properties of both the precursors and main emissions are also studied for the first time, and no significant difference is found in the distributions of the PDS slope for precursors and main emissions in both SGRBs and LGRBs.Comment: submitte

Increases in intracellular calcium perturb blood–brain barrier via protein kinase C-alpha and apoptosis

An increase in intracellular calcium represents one of the early events during an ischaemic stroke. It triggers many downstream processes which promote the formation of brain oedema, the leading cause of death after an ischaemic stroke. As impairment of blood–brain barrier (BBB) accounts for much of oedema formation, the current study explored the impact of intracellular calcium on barrier integrity in relation to protein kinase C, caspase-3/7, plasminogen activators and the pro-oxidant enzyme NADPH oxidase. Human brain microvascular endothelial cells alone or in co-culture with human astrocytes were subjected to 4 h of oxygen–glucose deprivation alone or followed by 20 h of reperfusion (OGD ± R) in the absence or presence of inhibitors for urokinase plasminogen activator (amiloride), NADPH oxidase (apocynin), intracellular calcium (BAPTA-AM) and protein kinase C-α (RO-32-0432). Endothelial cells with protein kinase C-α knockdown, achieved by siRNA, were also exposed to the above conditions. BBB permeability was measured by transendothelial electrical resistance and Evan's blue-albumin and sodium fluorescein flux. Intracellular calcium and total superoxide anion levels, caspase-3/7, NADPH oxidase, plasminogen activator and protein kinase C activities, stress fibre formation, the rate of apoptosis and BBB permeability were increased by OGD ± R. Treatment with the specific inhibitors or knockdown of protein kinase C-α attenuated them. This study reveals successive increases in intracellular calcium levels and protein kinase C-α activity are key mechanisms in OGD ± R-mediated impairment of BBB. Furthermore inhibition of protein kinase C-α may be therapeutic in restoring BBB function by reducing the rate of cytoskeletal reorganisation, oxidative stress and apoptosis