Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification method, was developed for the clinical detection of four species of human malaria parasites: Plasmodium falciparum, P. vivax, P. malariae, and P. ovale. We evaluated the sensitivity and specificity of LAMP in comparison with the results of microscopic examination and nested PCR. LAMP showed a detection limit (analytical sensitivity) of 10 copies of the target 18S rRNA genes for P. malariae and P. ovale and 100 copies for the genus Plasmodium, P. falciparum, and P. vivax. LAMP detected malaria parasites in 67 of 68 microscopically positive blood samples (sensitivity, 98.5%) and 3 of 53 microscopically negative samples (specificity, 94.3%), in good agreement with the results of nested PCR. The LAMP reactions yielded results within about 26 min, on average, for detection of the genus Plasmodium, 32 min for P. falciparum, 31 min for P. vivax, 35 min for P. malariae, and 36 min for P. ovale. Accordingly, in comparison to the results obtained by microscopy, LAMP had a similar sensitivity and a greater specificity and LAMP yielded results similar to those of nested PCR in a shorter turnaround time. Because it can be performed with a simple technology, i.e., with heat-treated blood as the template, reaction in a water bath, and inspection of the results by the naked eye because of the use of a fluorescent dye, LAMP may provide a simple and reliable test for routine screening for malaria parasites in both clinical laboratories and malaria clinics in areas where malaria is endemic.
The replication and infectivity of the lipotropic hepatitis C virus (HCV) are regulated by cellular lipid status. Among differentially expressed microRNAs (miRNAs), we found that miR-27a was preferentially expressed in HCV-infected liver over hepatitis B virus (HBV)-infected liver. Gene expression profiling of Huh-7.5 cells showed that miR-27a regulates lipid metabolism by targeting the lipid synthetic transcription factor RXR␣ and the lipid transporter ATP-binding cassette subfamily A member 1. In addition, miR-27a repressed the expression of many lipid metabolism-related genes, including FASN, SREBP1, SREBP2, PPAR␣, and PPAR␥, as well as ApoA1, ApoB100, and ApoE3, which are essential for the production of infectious viral particles. miR-27a repression increased the cellular lipid content, decreased the buoyant density of HCV particles from 1.13 to 1.08 g/cm 3 , and increased viral replication and infectivity. miR-27a overexpression substantially decreased viral infectivity. Furthermore, miR-27a enhanced in vitro interferon (IFN) signaling, and patients who expressed high levels of miR-27a in the liver showed a more favorable response to pegylated IFN and ribavirin combination therapy. Interestingly, the expression of miR-27a was upregulated by HCV infection and lipid overload through the adipocyte differentiation transcription factor C/EBP␣. In turn, upregulated miR27a repressed HCV infection and lipid storage in cells. Thus, this negative feedback mechanism might contribute to the maintenance of a low viral load and would be beneficial to the virus by allowing it to escape host immune surveillance and establish a persistent chronic HCV infection. MicroRNA (miRNA) is a small, endogenous, single-stranded, noncoding RNA consisting of 20 to 25 bases that regulates gene expression. It plays an important role in various biological processes, including organ development, differentiation, and cellular death and proliferation, and is also involved in infection and diseases such as cancer (1).Previously, we examined miRNA expression in hepatocellular carcinoma (HCC) and noncancerous background liver tissue infected with hepatitis B virus (HBV) and HCV (2). We showed that some miRNAs were differentially expressed according to HBV or HCV infection but not according to the presence of HCC. These infection-specific miRNAs were believed to regulate HBV or HCV replication; however, their functional role has not been elucidated.HCV is described as a lipotropic virus because of its association with serum lipoprotein (3-5). It utilizes the low-density lipoprotein (LDL) receptor for cellular entry (6-8) and forms replication complexes on lipid rafts (9). The HCV core protein surrounds and binds lipid droplets (LDs) and nonstructural proteins on the endoplasmic reticulum (ER) membrane, which is essential for particle formation (10). Moreover, HCV cellular secretion is linked to very LDL (VLDL) secretion (11). In liver tissue histology, steatosis is often observed in chronic hepatitis C (CH-C) and is closely related to resistance ...
We study the modular invariance in magnetized torus models. The modular invariant flavor model is a recently proposed hypothesis for solving the flavor puzzle, where the flavor symmetry originates from modular invariance. In this framework, coupling constants such as Yukawa couplings are also transformed under the flavor symmetry. We show that the low-energy effective theory of magnetized torus models is invariant under a specific subgroup of the modular group. Since Yukawa couplings as well as chiral zero modes transform under the modular group, the above modular subgroup (referred to as modular flavor symmetry) provides a new type of modular invariant flavor models with D 4 × Z 2 , ðZ 4 × Z 2 Þ ⋊ Z 2 , and ðZ 8 × Z 2 Þ ⋊ Z 2. We also find that conventional discrete flavor symmetries which arise in magnetized torus model are noncommutative with the modular flavor symmetry. Combining both symmetries, we obtain a larger flavor symmetry, which is the semidirect product of the conventional flavor symmetry and the modular flavor symmetry for the nonvanishing Wilson line. For the vanishing Wilson line, we have additional Z 2 symmetry, i.e., parity, which is the unique common element between the conventional flavor symmetry and the modular flavor symmetry.
We used the loop-mediated isothermal amplification (LAMP) method developed by our group for malaria diagnosis with genus-specific and species-specific primers for the four human malaria parasites at a field clinic in comparison with standard microscopy. Among 110 blood samples collected from the malaria clinic in Thailand, LAMP detected 59 of 60 samples positive by microscopy (sensitivity = 98.3%) and none of the 50 microscopy-negative samples (specificity = 100%). Negative predictive value (NPV) and positive predictive value (PPV) of LAMP were 98% and 100%, respectively. These results indicate that LAMP is an effective tool for malaria diagnosis at a field clinic in a field setting.
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