[Analysis of KIAA0196 gene mutation in a family with hereditary spastic paraplegia].

OBJECTIVE: To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey. METHODS: Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members. RESULTS: Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet. CONCLUSION: The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.

24-hour-restraint stress induces long-term depressive-like phenotypes in mice.

There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders.

Dental noise exposed mice display depressive-like phenotypes.

BACKGROUND: Studies have indicated that depressive disorders are observed frequently in dentists. It's suggested that dentists encounter numerous sources of stress in their professional career. We noticed that the noises in dental environments are very unpleasant. The animal modeling studies suggested that stressful noise could produce depressive-like phenotypes in rodent animals. We hypothesize that the dental noise may be one of the primary stressors causing depressive disorders in dentists. RESULTS: We treated C57BL/6 mice with programmatically played wide-spectrum dental noise for 8 h/day at 75 ± 10 dB SPL level for 30 days, and then tested the behaviors. After exposure to dental noise, animals displayed the depressive-like phenotypes, accompanied by inhibition of neurogenesis in hippocampus. These deficits were ameliorated by orally administered with antidepressant fluoxetine. CONCLUSIONS: Our results suggested that dental noise could be one of the primary stressors for the pathogenesis of depressive disorders and the dental noise mouse model could be used in further depression studies.

A novel signal transduction pathway that modulates rhl quorum sensing and bacterial virulence in Pseudomonas aeruginosa.

The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs.

Accurate quantification of microRNA via single strand displacement reaction on DNA origami motif.

DNA origami is an emerging technology that assembles hundreds of staple strands and one single-strand DNA into certain nanopattern. It has been widely used in various fields including detection of biological molecules such as DNA, RNA and proteins. MicroRNAs (miRNAs) play important roles in post-transcriptional gene repression as well as many other biological processes such as cell growth and differentiation. Alterations of miRNAs' expression contribute to many human diseases. However, it is still a challenge to quantitatively detect miRNAs by origami technology. In this study, we developed a novel approach based on streptavidin and quantum dots binding complex (STV-QDs) labeled single strand displacement reaction on DNA origami to quantitatively detect the concentration of miRNAs. We illustrated a linear relationship between the concentration of an exemplary miRNA as miRNA-133 and the STV-QDs hybridization efficiency; the results demonstrated that it is an accurate nano-scale miRNA quantifier motif. In addition, both symmetrical rectangular motif and asymmetrical China-map motif were tested. With significant linearity in both motifs, our experiments suggested that DNA Origami motif with arbitrary shape can be utilized in this method. Since this DNA origami-based method we developed owns the unique advantages of simple, time-and-material-saving, potentially multi-targets testing in one motif and relatively accurate for certain impurity samples as counted directly by atomic force microscopy rather than fluorescence signal detection, it may be widely used in quantification of miRNAs.