Production of Chemokines in Kawasaki Disease, Henoch-Schönlein Purpura and Acute Febrile Illness

We compared the production of three chemokines; interferon-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and growth-related oncogene-α (Gro-α) that attracts monocytes or neutrophils, or both, in peripheral blood at acute stage of Kawasaki disease (n=29), Henoch-Schönlein purpura (n=15) and acute febrile illnesses (n=12). The production of the chemokines was assayed by ELISA. The plasma levels of IP-10 were markedly elevated in Kawasaki disease (538.6±336.4 pg/mL) and acute febrile illnesses (417.1±262.2 pg/mL) compared with in Henoch-Schönlein purpura (58.7±95.7 pg/mL) (p<0.05). The MCP-1 levels were elevated in Kawasaki disease (443.0±473.1 pg/mL) and acute febrile illnesses (328.6±261.1 pg/mL) compared with in Henoch-Schönlein purpura (82.9±79.0 pg/mL) (p<0.05). The Gro-α levels were elevated only in acute febrile illnesses (134.3±153.6 pg/mL) compared with in Kawasaki disease (31.8±22.1 pg/mL) or Henoch-Schönlein purpura (29.4±53.3 pg/mL) (p<0.05). According to these results, monocytes may play an important role in Kawasaki disease. In acute febrile illnesses, both monocytes and neutrophils may play an important role. By contrast, Henoch-Schönlein purpura may not be associated with the role of monocytes and neutrophils. Further studies using a larger number of cases are needed

SCN3A ‐related neurodevelopmental disorder: A spectrum of epilepsy and brain malformation

Objective Pathogenic variants in SCN3A , encoding the voltage‐gated sodium channel subunit Nav1.3, cause severe childhood‐onset epilepsy and malformation of cortical development. Here, we define the spectrum of clinical, genetic, and neuroimaging features of SCN3A ‐related neurodevelopmental disorder. Methods Patients were ascertained via an international collaborative network. We compared sodium channels containing wild‐type vs. variant Nav1.3 subunits co‐expressed with β1 and β2 subunits using whole‐cell voltage clamp electrophysiological recordings in a heterologous mammalian system (HEK‐293 T cells). Results Of 22 patients with pathogenic SCN3A variants, most had treatment‐resistant epilepsy beginning in the first year of life (16/21, 76%; median onset, 2 weeks), with severe or profound developmental delay (15/20; 75%). Many, but not all (15/19; 79%), exhibited malformations of cortical development. Pathogenic variants clustered in transmembrane segments 4–6 of domains II‐IV. Most pathogenic missense variants tested (10/11; 91%) displayed gain of channel function, with increased persistent current and/or a leftward shift in the voltage dependence of activation, and all variants associated with malformation of cortical development exhibited gain of channel function. One variant (p.Ile1468Arg) exhibited mixed effects, with gain and partial loss of function. Two variants demonstrated loss of channel function. Interpretation Our study defines SCN3A‐ related neurodevelopmental disorder along a spectrum of severity, but typically including epilepsy and severe or profound developmental delay/intellectual disability. Malformations of cortical development are a characteristic feature of this unusual channelopathy syndrome, present in over 75% of affected individuals. Gain of function at the channel level in developing neurons is likely an important mechanism of disease pathogenesis

Multicolour photochromic fluorescence of a fluorophore encapsulated in a metal-organic framework

A fluorophore encapsulated in a metal-organic framework showed photochromic multicolour fluorescence. Irradiation with an ultraviolet laser induced the relocation of the fluorophore from a polar to a nonpolar environment, altering the emission from red to blue. This change in emission color can be repeatably recovered by heating the fluorophore-MOF composite

Transcriptome profile of carbon catabolite repression in an efficient l-(+)-lactic acid-producing bacterium Enterococcus mundtii QU25 grown in media with combinations of cellobiose, xylose, and glucose.

Enterococcus mundtii QU25, a non-dairy lactic acid bacterium of the phylum Firmicutes, is capable of simultaneously fermenting cellobiose and xylose, and is described as a promising strain for the industrial production of optically pure l-lactic acid (≥ 99.9%) via homo-fermentation of lignocellulosic hydrolysates. Generally, Firmicutes bacteria show preferential consumption of sugar (usually glucose), termed carbon catabolite repression (CCR), while hampering the catabolism of other sugars. In our previous study, QU25 exhibited apparent CCR in a glucose-xylose mixture phenotypically, and transcriptional repression of the xylose operon encoding initial xylose metabolism genes, likely occurred in a CcpA-dependent manner. QU25 did not exhibit CCR phenotypically in a cellobiose-xylose mixture. The aim of the current study is to elucidate the transcriptional change associated with the simultaneous utilization of cellobiose and xylose. To this end, we performed RNA-seq analysis in the exponential growth phase of E. mundtii QU25 cells grown in glucose, cellobiose, and/or xylose as either sole or co-carbon sources. Our transcriptomic data showed that the xylose operon was weakly repressed in cells grown in a cellobiose-xylose mixture compared with that in cells grown in a glucose-xylose mixture. Furthermore, the gene expression of talC, the sole gene encoding transaldolase, is expected to be repressed by CcpA-mediated CCR. QU25 metabolized xylose without using transaldolase, which is necessary for homolactic fermentation from pentoses using the pentose-phosphate pathway. Hence, the metabolism of xylose in the presence of cellobiose by QU25 may have been due to 1) sufficient amounts of proteins encoded by the xylose operon genes for xylose metabolism despite of the slight repression of the operon, and 2) bypassing of the pentose-phosphate pathway without the TalC activity. Accordingly, we have determined the targets of genetic modification in QU25 to metabolize cellobiose, xylose and glucose simultaneously for application of the lactic fermentation from lignocellulosic hydrolysates

Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

<div><p>The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (<i>HLA-A</i>, <i>-B</i>, <i>-C</i>, <i>-DRB1</i>, and <i>-DPB1</i>) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago.</p> </div

Principal component analysis of Japanese and South Korean.

<p>A) PCA plot. B) PCS plot. The allele frequencies of South Korean were retrieved from the literatures <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060793#pone.0060793-Lee1" target="_blank">[21]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060793#pone.0060793-Song1" target="_blank">[61]</a>. Dotted lines correspond to mean ± one standard deviation of PCSs. HLA alleles that are labeled and in a circle shows high frequency in Japanese but low frequency in South Korean (referred to as cluster 5 [CL5]; <i>A*24:02</i>, <i>C*03:04</i>, <i>C*07:02</i>, <i>B*40:02</i>, and <i>DRB1*09:01</i>). Alleles shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060793#pone-0060793-g003" target="_blank">Figure 3</a> are also labeled.</p

The 10 most common five-locus HLA haplotypes in mainland Japanese.

†<p>Nine mainland groups (Hokkaido, Tohoku, Kanto, Hokuriku, Tokai, Kinki, Chugoku, Shikoku, and Kyushu) were combined.</p