During embryonic development, cells undergo changes in gene expression, signaling pathway activation/inactivation, metabolism, and intracellular organelle structures, which are mediated by ...mitochondria. Mitochondria continuously switch their morphology between elongated tubular and fragmented globular via mitochondrial fusion and fission. Mitochondrial fusion is mediated by proteins encoded by Mfn1, Mfn2, and Opa1, whereas mitochondrial fission is mediated by proteins encoded by Fis1 and Dnm1L. Here, we investigated the expression patterns of mitochondria-related genes during the differentiation of mouse embryonic stem cells (ESCs). Pluripotent ESCs maintain stemness in the presence of leukemia inhibitory factor (LIF) via the JAK-STAT3 pathway but lose pluripotency and differentiate in response to the withdrawal of LIF. We analyzed the expression levels of mitochondrial fusion- and fission-related genes during the differentiation of ESCs. We hypothesized that mitochondrial fusion genes would be overexpressed while the fission genes would be downregulated during the differentiation of ESCs. Though the mitochondria exhibited an elongated morphology in ESCs differentiating in response to LIF withdrawal, only the expression of Mfn2 was increased and that of Dnm1L was decreased as expected, the other exceptions being Mfn1, Opa1, and Fis1. Next, by comparing gene expression and mitochondrial morphology, we proposed an index that could precisely represent mitochondrial changes during the differentiation of pluripotent stem cells by analyzing the expression ratios of three fusion- and two fission-elated genes. Surprisingly, increased Mfn2/Dnm1L ratio was correlated with elongation of mitochondria during the differentiation of ESCs. Moreover, application of this index to other specialized cell types revealed that neural stems cells (NSCs) and mouse embryonic fibroblasts (MEFs) showed increased Mfn2/Dnm1L ratio compared to ESCs. Thus, we suggest that the Mfn2/Dnm1L ratio could reflect changes in mitochondrial morphology according to the extent of differentiation.
Nanometric Lactobacillus plantarum (nLp) is a processed form of Lab. plantarum derived from kimchi and is 0.5–1.0 μm in size. This study was undertaken to determine the effect of nLp and kimchi plus ...nLp (K-nLp) on a dextran sulfate sodium (DSS)-induced mouse model of colitis. Animals fed nLp or K-nLp had longer colons, but lower colon weights per unit length than DSS controls. In addition, nLp- or K-nLp-fed animals showed lower levels of proinflammatory cytokines and inflammatory genes in serum and in colon tissues, lower populations of total bacteria, but higher populations of lactic acid bacteria in feces, and lower activities of fecal β-glucosidase and β-glucuronidase. Furthermore, these suppressive activities of nLp on colitis were equivalent to or higher than those of naive Lab. plantarum. Consequently, nLp was found to exhibit anticolitic effects, and the addition of nLp to kimchi was found to enhance the protective activity of kimchi against DSS-induced colitis. These results suggest that nLp might be an effective substitute for live probiotics and be useful as a functional ingredient with the anticolitic activity by the probiotic and food processing industries.
In this study, half-Heusler (HH) thermoelectric materials Nb0.8Hf0.2FeSb0.98Sn0.02 (p-type) and Hf0.25Zr0.25Ti0.5NiSn0.98Sb0.02 (n-type) were synthesized using induction melting and spark plasma ...sintering. For alloying, a conventional induction melting technique was employed rather than arc melting, for mass production compatibility, and the thermoelectric properties of the materials were analyzed. The maximum dimensionless figures of merit (zTmax) were 0.75 and 0.82 for the p- and n-type material at 650 oC and 600 oC, respectively. These materials were then used to fabricate generator modules, wherein two pairs of p- and nlegs without interfacial metal layers were brazed on direct bonded copper (DBC)/Al2O3 substrates using a Zrbased alloy. A maximum power of 0.57 W was obtained from the module by applying a temperature gradient of 476 oC, which corresponds to a maximum power density of 1.58 W cm -2 when normalized by the area of the material. The maximum electrical conversion efficiency of the module was 3.22% at 476 oC temperature gradient. This value was negatively affected by the non-negligible contact resistivity of the brazed interfaces, which ranged from 6.63 × 10 -9 Ωm2 to 7.54 × 10 -9 Ω m2 at hot-side temperatures of 190 oC and 517 oC, respectively. The low electrical resistivity of the HH materials makes it especially important to develop a brazing technique for ultralow resistance contacts.
Packet recording or capturing is one of the most useful tools for network forensics and surveillance. Since a storage system is of a limited size, de-duplication can be used to save disk space. In ...this article, we present a new scalable de-duplication engine for packet recording that can eliminate redundant contents over multiple packets. Unlike previous work, our proposed scheme is designed for packet-level de-duplication to support any kinds of network from the current Internet to emerging networks. We also present a new fast chunking method and a new indexing scheme that enable multiple engine instances to execute in parallel. We implement the de-duplication engine, and experimental results show that our proposed scheme can remove up to 65 percent of the packet contents in a real campus network. We also confirm that its throughput scalably increases with the number of CPU cores, which means that the proposed scheme can be implemented in a wide range of computing devices from small home gateways to high-end servers.
The tumor-tropic properties of neural stem cells (NSCs) led to the development of a novel strategy for delivering therapeutic genes to tumors in the brain. To apply this strategy to the treatment of ...brain metastases, we made a human NSC line expressing cytosine deaminase (F3.CD), which converts 5-fluorocytosine (5-FC) into 5-fluorouracil, an anticancer agent. In vitro, the F3.CD cells significantly inhibited the growth of tumor cell lines in the presence of the prodrug 5-FC. In vivo, MDA-MB-435 human breast cancer cells were implanted into the brain of immune-deficient mouse stereotactically, and F3.CD cells were injected into the contralateral hemisphere followed by systemic 5-FC administration. The F3.CD cells migrated selectively into the brain metastases located in the opposite hemisphere and resulted in significantly reduced volumes. The F3.CD and 5-FC treatment also decreased both tumor volume and number of tumor mass significantly, when immune-deficient mouse had MDA-MB-435 cells injected into the internal carotid artery and F3.CD cells were transplanted into the contralateral brain hemisphere stereotactically. Taken together, brain transplantation of human NSCs, encoding the suicide enzyme CD, combined with systemic administration of the prodrug 5-FC, is an effective treatment regimen for brain metastases of tumors.
To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge ...traditional beliefs about origins of these infections.PURPOSETo investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections.Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization.MATERIALS AND METHODSPatients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization.In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling.RESULTSIn the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling.Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.CONCLUSIONSUrine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.
This paper describes and reports an analysis of an explosion accident at a wastewater storage pond in South Korea, which resulted in six fatalities and one injury. This study was aimed at analyzing ...and determining the possibility of fracture of concrete structure by vapor cloud explosion (VCE) and ignition point of explosion, using computational fluid dynamics (CFD) for the explosion simulation. The result obtained via CFD analysis was connected with finite element analysis (FEA) to accurately review the structural damages resulting from the explosion. As a result, the mechanism of the accident was determined, and preventive solutions against such accidents are recommended.
This study was aimed at analyzing and determining the possibility of fracture of concrete structure by vapor cloud explosion (VCE) and ignition point of explosion, using computational fluid dynamics (CFD) for the explosion simulation.
Phosphatidylinositol 3-kinase (PI3K) has been implicated in synaptic plasticity and other neural functions in the brain. However, the role of individual PI3K isoforms in the brain is unclear. We ...investigated the role of PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateral-commissural synapses. Both genetic deletion and pharmacological inhibition of PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, is critical for NMDAR LTD and some forms of cognitive function. Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior.
A primary gastrointestinal stromal tumor (GIST) arising in the liver is extremely rare. In our case of GIST, CT and MRI showed a well-defined, weakly enhancing mass with a cystic component in the ...left lateral segment of the liver that showed homogeneous and avid
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F-fluorodeoxyglucose (
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F-FDG) accumulation on positron emission tomography/computed tomography (PET/CT). We herein present a rare case of primary malignant GIST of the liver presenting with peritoneal seeding on CT, gadoxetic acid-enhanced MRI and
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F-FDG PET/CT.
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