Lowe syndrome caused by gloss deletion

Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci

Chromosome 1p36 deletion syndrome detected by NGS

Although chromosome 1p36 deletion syndrome is considered clinically recognizable based on characteristic features, the clinical manifestations of patients during infancy are often not consistent with those observed later in life. We report a 4-month-old girl who showed multiple congenital anomalies and developmental delay, but no clinical signs of syndromic disease caused by a terminal deletion in 1p36.32-p36.33 that was first identified by targeted-exome sequencing for molecular diagnosis

ホエーの長期間摂取が老齢ラット唾液腺の萎縮、遺伝子変化、機能低下に及ぼす効果

Salivary glands in elderly individuals commonly exhibit morphological changes and dysfunction resulting in xerostomia. Long-term (4-week) drinking of whey prevented and/or restored age-dependent decline of salivary volume and protein concentration, and atrophy of sublingual glands (SLGs) significantly in 88-week-old rats. The transcripts of 42 genes were up-regulated and 7 genes were down-regulated by more than 1.5-fold change with FDR ≦ 0.1 after whey-drinking. The expression levels of genes associated with salivary proteins and tissue repair were significantly increased, while those associated with lipid metabolism were decreased. Venn diagram analysis revealed that expressions of 13 genes, including Tcfap2b and Abpa, were induced significantly by whey-drinking. Furthermore, secretory protein levels in SLGs and saliva were revealed by immunoblot analysis. This is the first study to report that whey-administration can prevent and/or restore age-dependent atrophy and functional decline of SLGs in relation to gene expression and thus may serve as a functional food ingredient

CXCL10 REGULATION BY THYMIDINE PHOSPHORYLASE IN RA

The sworn affidavit of Stephen R. Wee and attachment, Establishment of the Coeur d\u27Alene Indian Reservation and the Transformation of Coeur d\u27Alene Land and Water Use, From Contract Through Allotment, in support thereof

Reduced marine biogenic sulphate flux in East Antarctica during glacial periods - Based on ion chemistry records from Dome Fuji ice core -

The Tenth Symposium on Polar Science/Ordinary sessions: [OM] Polar Meteorology and Glaciology, Wed. 4 Dec. / 2F Auditorium, National Institute of Polar Researc

A vicious cycle between acid sensing and survival signaling in myeloma cells : acid-induced epigenetic alteration

Myeloma (MM) cells and osteoclasts are mutually interacted to enhance MM growth while creating acidic bone lesions. Here, we explored acid sensing of MM cells and its role in MM cell response to acidic conditions. Acidic conditions activated the PI3K-Akt signaling in MM cells while upregulating the pH sensor transient receptor potential cation channel subfamily V member 1 (TRPV1) in a manner inhibitable by PI3K inhibition. The acid-activated PI3K-Akt signaling facilitated the nuclear localization of the transcription factor Sp1 to trigger the expression of its target genes, including TRPV1 and HDAC1. Consistently, histone deacetylation was enhanced in MM cells in acidic conditions, while repressing a wide variety of genes, including DR4. Indeed, acidic conditions deacetylated histone H3K9 in a DR4 gene promoter and curtailed DR4 expression in MM cells. However, inhibition of HDAC as well as either Sp1 or PI3K was able to restore DR4 expression in MM cells suppressed in acidic conditions. These results collectively demonstrate that acid activates the TRPV1-PI3K-Akt-Sp1 signaling in MM cells while inducing HDAC-mediated gene repression, and suggest that a positive feedback loop between acid sensing and the PI3K-Akt signaling is formed in MM cells, leading to MM cell response to acidic bone lesions

Development of Cysteine-Free Fluorescent Proteins for the Oxidative Environment

Molecular imaging employing fluorescent proteins has been widely used to highlight specific reactions or processes in various fields of the life sciences. Despite extensive improvements of the fluorescent tag, this technology is still limited in the study of molecular events in the extracellular milieu. This is partly due to the presence of cysteine in the fluorescent proteins. These proteins almost cotranslationally form disulfide bonded oligomers when expressed in the endoplasmic reticulum (ER). Although single molecule photobleaching analysis showed that these oligomers were not fluorescent, the fluorescent monomer form often showed aberrant behavior in folding and motion, particularly when fused to cysteine-containing cargo. Therefore we investigated whether it was possible to eliminate the cysteine without losing the brightness. By site-saturated mutagenesis, we found that the cysteine residues in fluorescent proteins could be replaced with specific alternatives while still retaining their brightness. cf(cysteine-free)SGFP2 showed significantly reduced restriction of free diffusion in the ER and marked improvement of maturation when fused to the prion protein. We further applied this approach to TagRFP family proteins and found a set of mutations that obtains the same level of brightness as the cysteine-containing proteins. The approach used in this study to generate new cysteine-free fluorescent tags should expand the application of molecular imaging to the extracellular milieu and facilitate its usage in medicine and biotechnology