Identification of novel mutations in Chinese Hans with autosomal dominant polycystic kidney disease

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: <it>PKD1 </it>(16p13.3) and <it>PKD2 </it>(4q21). Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of <it>PKD1 </it>gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both <it>PKD1 </it>and <it>PKD2 </it>genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC).</p> <p>Methods</p> <p>Both <it>PKD1 </it>and <it>PKD2 </it>genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources.</p> <p>Results</p> <p>A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication) were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65). About 69% (20/29) of the mutations are first reported with a recurrent mutation rate of 31%.</p> <p>Conclusions</p> <p>Mutation study of <it>PKD1 </it>and <it>PKD2 </it>genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.</p

Fibroblast growth factor signalling controls nervous system patterning and pigment cell formation in Ciona intestinalis

During the development of the central nervous system (CNS), combinations of transcription factors and signalling molecules orchestrate patterning, specification and differentiation of neural cell types. In vertebrates, three types of melanin-containing pigment cells, exert a variety of functional roles including visual perception. Here we analysed the mechanisms underlying pigment cell specification within the CNS of a simple chordate, the ascidian Ciona intestinalis. Ciona tadpole larvae exhibit a basic chordate body plan characterized by a small number of neural cells. We employed lineage-specific transcription profiling to characterize the expression of genes downstream of fibroblast growth factor signalling, which govern pigment cell formation. We demonstrate that FGF signalling sequentially imposes a pigment cell identity at the expense of anterior neural fates. We identify FGF-dependent and pigment cell-specific factors, including the small GTPase, Rab32/38 and demonstrated its requirement for the pigmentation of larval sensory organs

Appraising the intention of other people: Ecological validity and procedures for investigating effects of lighting for pedestrians

One of the aims of outdoor lighting public spaces such as pathways and subsidiary roads is to help pedestrians to evaluate the intentions of other people. This paper discusses how a pedestrians’ appraisal of another persons’ intentions in artificially lit outdoor environments can be studied. We review the visual cues that might be used, and the experimental design with which effects of changes in lighting could be investigated to best resemble the pedestrian experience in artificially lit urban environments. Proposals are made to establish appropriate operationalisation of the identified visual cues, choice of methods and measurements representing critical situations. It is concluded that the intentions of other people should be evaluated using facial emotion recognition; eye tracking data suggest a tendency to make these observations at an interpersonal distance of 15 m and for a duration of 500 ms. Photographs are considered suitable for evaluating the effect of changes in light level and spectral power distribution. To support investigation of changes in spatial distribution further investigation is needed with 3D targets. Further data are also required to examine the influence of glare

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease

Nicotinamide delivered in drinking water at about 2 g/kg/day significantly prolonged survival and showed a suggestive improvement on memory in the Npc1 (nih) / Npc1 (nih) mouse model of infantile NPC1 disease. It is likely that this role is due to its function as a histone deacetylase (HDAC) inhibitor although another HDAC inhibitor, valproic acid, was without effect. Nicotinamide could also work by preventing/reversing oxidative stress.Wings Like Eagles Foundation, Tucson, AZ12 month embargo; First Online: 25 October 2016This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Identification and Functional Demonstration of miRNAs in the Fungus Cryptococcus neoformans

microRNAs (miRNAs), endogenous posttranscriptional repressors by base-pairing of their cognate mRNAs in plants and animals, have mostly been thought lost in the kingdom of fungi. Here, we report the identification of miRNAs from the fungus Cryptococcus neoformans. With bioinformatics and Northern blotting approaches, we found that these miRNAs and their hairpin precursors were present in this fungus. The size of miR1 and miR2 is 22 nt and 18 nt, respectively. The precursors are about ∼70 nt in length that is close to mammalian pre-miRNAs. Characteristic features of miRNAs are also found in miR1/2. We demonstrated that the identified miRNAs, miR1 and miR2, caused transgene silencing via the canonical RNAi pathway. Bioinformantics analysis helps to reveal a number of identical sequences of the miR1/2 in transposable elements (TEs) and pseudogenes, prompting us to think that fungal miRNAs might be involved in the regulation of the activity of transposons and the expression of pseudogenes. This study identified functional miRNAs in C. neoformans, and sheds light on the diversity and evolutionary origin of eukaryotic miRNAs