Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling.

Spy1, a unique cell cycle regulator, alters viability in ALS motor neurons and cell lines in response to mutant SOD1-induced DNA damage.

Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). Human SpeedyA1 (Spy1), a member of the Speedy/Ringo family, enhances cell proliferation and promotes tumorigenesis. Further studies have demonstrated that Spy1 promotes cell survival and inhibits DNA damage-induced apoptosis. We showed that the Spy1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro by qRT-PCR, western blotting, and Immunoassay tests. In addition, we established that over-expression of human SOD1 mutant G93A led to a decreased expression of Spy1. Furthermore, DNA damage response was activated in SOD1G93A-transfected cells (mSOD1 cells). Moreover, decreased Spy1 expression reduced cell viability and further activated the DNA damage response in mSOD1 cells. In contrast, increased Spy1 expression improved cell viability and inhibited the DNA damage response in mSOD1 cells. These results suggest that Spy1 plays a protective role in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS as well as for trial designs, such as investigating the role of oncogenic proteins in ALS.

Corpus callosum atrophy associated with the degree of cognitive decline in patients with Alzheimer's dementia or mild cognitive impairment: a meta-analysis of the region of interest structural imaging studies.

Individual structural neuroimaging studies of the corpus callosum (CC) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) with the region of interest (ROI) analysis have yielded inconsistent findings. The aim of this study was to conduct a meta-analysis of structural imaging studies using ROI technique to measure the CC midsagittal area changes in patients with AD or MCI. Databases of PubMed, the Cochrane Library, the ISI Web of Science, and Science Direct from inception to June 2014 were searched with key words "corpus callosum" or "callosal", plus "Alzheimer's disease" or "mild cognitive impairment". Twenty-three studies with 603 patients with AD, 146 with MCI, and 638 healthy controls were included in this meta-analysis. Effect size was used to measure the difference between patients with AD or MCI and healthy controls. Significant callosal atrophy was found in MCI patients with an effect size of -0.36 (95% CI, -0.57 to -0.14; P = 0.001). The degree of the CC atrophy in mild AD was less severe than that in moderate AD with a mean effect size -0.69 (95% CI, -0.89 to -0.49) versus -0.92 (95% CI, -1.16 to -0.69), respectively. Comparing with healthy controls, patients with MCI had atrophy in the anterior portion of the CC (i.e., rostrum and genu). In contrast, patients with AD had atrophy in both anterior and posterior portions (i.e., splenium). These results suggest that callosal atrophy may be related to the degree of cognitive decline in patients with MCI and AD, and it may be used as a biomarker for patients with cognitive deficit even before meeting the criteria for AD.

[Differential gene expression of liver carcinoma cell after transfection of by ARL-1 with microarray].

OBJECTIVE: To study the difference of the gene expression profile and to identify the different expression after transfection of the ARL-1 gene. METHODS: The cDNA probes were synthesized from total RNA of study group and control group, which was differentially hybridized to cDNA chips and confirmed by a gene specific semiquantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Six kinds of gene expression were increased and 9 kinds of gene expression were decreased. The findings were correlated with protein metabolism, signal pathway, metastasis, and drug resistance. CONCLUSIONS: cDNA chips showed that gene expression profile of liver carcinoma cell was changed after transfection of the ARL-1 gene. It is a useful method in understanding the mechanism of drug resistance.