Gene dosage change of TPTE and BAGE2 and breakpoint analysis in Robertsonian Down syndrome

[[abstract]]Only 4% of Down syndrome (DS) cases have a Robertsonian translocation (ROB). The aim of this study was to define the possible breakage area in 21p where ROB occurs. We prospectively and consecutively collected ten cases ROB DS from three medical centers. Of the ten DS children, six were de novo (60%), and four were due to paternal or maternal inheritance (40%). They consisted of four der(21q;21q), four der(14q;21q), one der(13q;21q), and one der(21q;22q). The origin of the extra chromosome 21q was maternal in five of six de novo ROB and paternal in one case. All four der(21;21) ROB DS were an isochromosome. The result of gene dosage change by real-time quantitative polymerase chain reaction (PCR) was compatible with array-comparative genomic hybridization in one case. We further used real-time PCR to detect the copy number of TPTE and BAGE2 located on 21p11 and SAMSN1 on 21q11. The ratio of copy number in 21p:21q was 1:3 in der(21q;21q) but 2:3 in der(13q;21q), der(14q;21q), and der(21q;22q). Our preliminary results demonstrated the critical breakpoint of chromosome 21 involving ROB might lie between BAGE2 and the centromere, located from 10.1 to 12.3 Mb

Rapid prenatal diagnosis of spinal muscular atrophy by denaturing high-performance liquid chromatography system

[[abstract]]Objective. Use of Denaturing High-Performance Liquid Chromatography (DHPLC) in prenatal diagnosis of spinal muscular atrophy (SMA). Methods. Thirty-three members of 7 families participated in carrier test and disease detection of SMA. Prenatal genetic diagnosis was performed if both parents were carriers or any family members had SMA. DNA extracted from blood, chorionic villi and amniotic fluid was amplified and used for DHPLC. Results. Twenty SMA carriers, seven SMA affected cases, and six normal individuals were identified. SMA status was demonstrated by genotyping and total copy number determinations of SMN1 and SMN2. Families 1-3 were classified as group one (SMA affecting previously born child). Group two, comprising families 4 and 5, had lost a child due to an unknown muscular disease. Group three (SMA-affected parent) comprised families 6 and 7; carrier testing was done. DHPLC prenatal genetic diagnosis was made in seven pregnancies, one in each family (affected, n = 2; carrier, n = 3; normal, n = 2). Pregnancy was terminated for the two affected fetuses. The others were delivered uneventfully and SMA free. Conclusion. DHPLC prenatal diagnosis of SMA and determination of SMA status in adults is possible, and SMN1 and SMN2 copy numbers can be determined

Role of Candida albicans Tem1 in mitotic exit and cytokinesis

Journal ArticleResearch Support, Non-U.S. Gov'tCopyright © 2014 Elsevier Inc. All rights reserved.Candida albicans demonstrates three main growth morphologies: yeast, pseudohyphal and true hyphal forms. Cell separation is distinct in these morphological forms and the process of separation is closely linked to the completion of mitosis and cytokinesis. In Saccharomyces cerevisiae the small GTPase Tem1 is known to initiate the mitotic exit network, a signalling pathway involved in signalling the end of mitosis and initiating cytokinesis and cell separation. Here we have characterised the role of Tem1 in C. albicans, and demonstrate that it is essential for mitotic exit and cytokinesis, and that this essential function is signalled through the kinase Cdc15. Cells depleted of Tem1 displayed highly polarised growth but ultimately failed to both complete cytokinesis and re-enter the cell cycle following nuclear division. Consistent with its role in activating the mitotic exit network Tem1 localises to spindle pole bodies in a cell cycle-dependent manner. Ultimately, the mitotic exit network in C. albicans appears to co-ordinate the sequential processes of mitotic exit, cytokinesis and cell separation.BBSR

Simplifying transformations for nonlinear systems: Part I, an optimisation-based variant of normal form analysis

This paper introduces the idea of a ‘simplifying transformation’ for nonlinear structural dynamic systems. The idea simply stated; is to bring under one heading, those transformations which ‘simplify’ structural dynamic systems or responses in some sense. The equations of motion may be cast in a simpler form or decoupled (and in this sense, nonlinear modal analysis is encompassed) or the responses may be modified in order to isolate and remove certain components. It is the latter sense of simplification which is considered in this paper. One can regard normal form analysis in a way as the removal of superharmonic content from nonlinear system response. In the current paper, this problem is cast in an optimisation form and the differential evolution algorithm is used

Prenatal transplantation of human amniotic fluid stem cell could improve clinical outcome of type III spinal muscular atrophy in mice

Spinal muscular atrophy (SMA) is a single gene disorder affecting motor function in uterus. Amniotic fluid is an alternative source of stem cell to ameliorate SMA. Therefore, this study aims to examine the therapeutic potential of Human amniotic fluid stem cell (hAFSC) for SMA. Our SMA model mice were generated by deletion of exon 7 of Smn gene and knock-in of human SMN2. A total of 16 SMA model mice were injected with 1 × 105 hAFSC in uterus, and the other 16 mice served as the negative control. Motor function was analyzed by three behavioral tests. Engraftment of hAFSC in organs were assessed by flow cytometry and RNA scope. Frequency of myocytes, neurons and innervated receptors were estimated by staining. With hAFSC transplantation, 15 fetuses survived (93.75% survival) and showed better performance in all motor function tests. Higher engraftment frequency were observed in muscle and liver. Besides, the muscle with hAFSC transplantation expressed much laminin α and PAX-7. Significantly higher frequency of myocytes, neurons and innervated receptors were observed. In our study, hAFSC engrafted on neuromuscular organs and improved cellular and behavioral outcomes of SMA model mice. This fetal therapy could preserve the time window and treat in the uterus

Developing an intervention for fall-related injuries in dementia (DIFRID): an integrated, mixed-methods approach

This is the final version. Available on open access from BMC via the DOI in this recordThe datasets generated during and/or analysed during the current study are available from the corresponding author (LA) on reasonable request. The data are not publicly available due to them containing information that could compromise research participant confidentialityBackground: Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. Methods: The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n=81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n=15) on the proposed model, the intervention was manualised and training developed. Results: We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient’s home. Conclusions: A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested.National Institute for Health Research (NIHR

Lung Screen Uptake Trial: results from a single lung cancer screening round

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based 'real-world' LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a 'lung health check'. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment

A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants