A multi-site study on walkability, data sharing and privacy perception using mobile sensing data gathered from the mk-sense platform

Walking is a fundamental part of a physically active lifestyle, it is one of everyday activities that positively impacts health and wellbeing. In this paper we describe the challenges and experiences of conducting a sensing campaign in the wild. We make use of mk-sense; a software platform to facilitate the deployment of collaborative sensing campaigns. We elaborate on two cross-cultural studies conducted in four different countries (Mexico, Turkey, Spain, and Switzerland) with a total of 77 participants. We present a detailed description of the data collected from one of the studies aimed at measuring walkability around three different university campuses. The analysis of the data shows that walkability can be assessed using information from the sensors in the smartphones and results from surveys answered by participants. In addition, we analyze issues about data sharing and privacy awareness

Parenting Stress in CHARGE Syndrome and the Relationship with Child Characteristics

This study investigates the parental perception of stress related to the upbringing of children with CHARGE syndrome and its association with behavioral and physical child characteristics. Parents of 22 children completed the Nijmegen Parenting Stress Index-Short, Developmental Behavior Checklist, and Dutch Vineland Screener 0-12 and reported their child’s problems with hearing, vision and ability to speak. Parenting stress was high in 59% of the subjects. Behavioral problems on the depression, autism, self-absorbed and disruptive behavior scales correlated positively with parenting stress. A non-significant trend was found, namely higher stress among the parents of non-speaking children. No associations were found with other child characteristics, i.e. level of adaptive functioning and intellectual disability, auditory and visual problems, deafblindness, gender, and age. Raising a child with CHARGE syndrome is stressful; professional support is therefore essential for this population. More research into other possible influencing characteristics is needed to improve family-oriented interventions. Since CHARGE is a rare syndrome, closer international collaboration is needed, not only to expand the group of study subjects to increase statistical power, but also to harmonize research designs and measurement methods to improve the validity, the reliability, and the generalization of the findings

Evolution and Taxonomic Classification of Human Papillomavirus 16 (HPV16)-Related Variant Genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67

Human papillomavirus 16 (HPV16) species group (alpha-9) of the Alphapapillomavirus genus contains HPV16, HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. These HPVs account for 75% of invasive cervical cancers worldwide. Viral variants of these HPVs differ in evolutionary history and pathogenicity. Moreover, a comprehensive nomenclature system for HPV variants is lacking, limiting comparisons between studies.DNA from cervical samples previously characterized for HPV type were obtained from multiple geographic regions to screen for novel variants. The complete 8 kb genomes of 120 variants representing the major and minor lineages of the HPV16-related alpha-9 HPV types were sequenced to capture maximum viral heterogeneity. Viral evolution was characterized by constructing phylogenic trees based on complete genomes using multiple algorithms. Maximal and viral region specific divergence was calculated by global and pairwise alignments. Variant lineages were classified and named using an alphanumeric system; the prototype genome was assigned to the A lineage for all types.The range of genome-genome sequence heterogeneity varied from 0.6% for HPV35 to 2.2% for HPV52 and included 1.4% for HPV31, 1.1% for HPV33, 1.7% for HPV58 and 1.1% for HPV67. Nucleotide differences of approximately 1.0% - 10.0% and 0.5%-1.0% of the complete genomes were used to define variant lineages and sublineages, respectively. Each gene/region differs in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) /noncoding region 2 (NCR2) >upstream regulatory region (URR)> E6/E7 > E2/L2 > E1/L1.These data define maximum viral genomic heterogeneity of HPV16-related alpha-9 HPV variants. The proposed nomenclature system facilitates the comparison of variants across epidemiological studies. Sequence diversity and phylogenies of this clinically important group of HPVs provides the basis for further studies of discrete viral evolution, epidemiology, pathogenesis and preventative/therapeutic interventions

Frequency of Fabry disease in male and female haemodialysis patients in Spain

<p>Abstract</p> <p>Background</p> <p>Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme α-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression.</p> <p>Methods</p> <p>A combined enzymatic and genetic strategy was used, measuring the activity of α-galactosidase A and genotyping the α-galactosidase A gene (<it>GLA</it>) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain.</p> <p>Results</p> <p><it>GLA </it>alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with <it>GLA </it>causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients.</p> <p>Conclusions</p> <p>Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.</p

Identification of Maize Genes Associated with Host Plant Resistance or Susceptibility to Aspergillus flavus Infection and Aflatoxin Accumulation

infection and aflatoxin accumulation. inoculation were compared in two resistant maize inbred lines (Mp313E and Mp04∶86) in contrast to two susceptible maize inbred lines (Va35 and B73) by microarray analysis. Principal component analysis (PCA) was used to find genes contributing to the larger variances associated with the resistant or susceptible maize inbred lines. The significance levels of gene expression were determined by using SAS and LIMMA programs. Fifty candidate genes were selected and further investigated by quantitative RT-PCR (qRT-PCR) in a time-course study on Mp313E and Va35. Sixteen of the candidate genes were found to be highly expressed in Mp313E and fifteen in Va35. Out of the 31 highly expressed genes, eight were mapped to seven previously identified quantitative trait locus (QTL) regions. A gene encoding glycine-rich RNA binding protein 2 was found to be associated with the host hypersensitivity and susceptibility in Va35. A nuclear pore complex protein YUP85-like gene was found to be involved in the host resistance in Mp313E. infection and aflatoxin accumulation. These findings will be important in identification of DNA markers for breeding maize lines resistant to aflatoxin accumulation

Characterization of ERK Docking Domain Inhibitors that Induce Apoptosis by Targeting Rsk-1 and Caspase-9

<p>Abstract</p> <p>Background</p> <p>The extracellular signal-regulated kinase-1 and 2 (ERK1/2) proteins play an important role in cancer cell proliferation and survival. ERK1/2 proteins also are important for normal cell functions. Thus, anti-cancer therapies that block all ERK1/2 signaling may result in undesirable toxicity to normal cells. As an alternative, we have used computational and biological approaches to identify low-molecular weight compounds that have the potential to interact with unique ERK1/2 docking sites and selectively inhibit interactions with substrates involved in promoting cell proliferation.</p> <p>Methods</p> <p>Colony formation and water soluble tetrazolium salt (WST) assays were used to determine the effects of test compounds on cell proliferation. Changes in phosphorylation and protein expression in response to test compound treatment were examined by immunoblotting and <it>in vitro </it>kinase assays. Apoptosis was determined with immunoblotting and caspase activity assays.</p> <p>Results</p> <p><it>In silico </it>modeling was used to identify compounds that were structurally similar to a previously identified parent compound, called <b>76</b>. From this screen, several compounds, termed <b>76.2</b>, <b>76.3</b>, and <b>76.4 </b>sharing a common thiazolidinedione core with an aminoethyl side group, inhibited proliferation and induced apoptosis of HeLa cells. However, the active compounds were less effective in inhibiting proliferation or inducing apoptosis in non-transformed epithelial cells. Induction of HeLa cell apoptosis appeared to be through intrinsic mechanisms involving caspase-9 activation and decreased phosphorylation of the pro-apoptotic Bad protein. Cell-based and <it>in vitro </it>kinase assays indicated that compounds <b>76.3 </b>and <b>76.4 </b>directly inhibited ERK-mediated phosphorylation of caspase-9 and the p90Rsk-1 kinase, which phosphorylates and inhibits Bad, more effectively than the parent compound <b>76</b>. Further examination of the test compound's mechanism of action showed little effects on related MAP kinases or other cell survival proteins.</p> <p>Conclusion</p> <p>These findings support the identification of a class of ERK-targeted molecules that can induce apoptosis in transformed cells by inhibiting ERK-mediated phosphorylation and inactivation of pro-apoptotic proteins.</p

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation

Early Markers of Glycaemic Control in Children with Type 1 Diabetes Mellitus

Background: Type 1 diabetes mellitus (T1DM) may lead to severe long-term health consequences. In a longitudinal study, we aimed to identify factors present at diagnosis and 6 months later that were associated with glycosylated haemoglobin (HbA 1c) levels at 24 months after T1DM diagnosis, so that diabetic children at risk of poor glycaemic control may be identified. Methods: 229 children,15 years of age diagnosed with T1DM in the Auckland region were studied. Data collected at diagnosis were: age, sex, weight, height, ethnicity, family living arrangement, socio-economic status (SES), T1DM antibody titre, venous pH and bicarbonate. At 6 and 24 months after diagnosis we collected data on weight, height, HbA 1c level, and insulin dose. Results: Factors at diagnosis that were associated with higher HbA1c levels at 6 months: female sex (p,0.05), lower SES (p,0.01), non-European ethnicity (p,0.01) and younger age (p,0.05). At 24 months, higher HbA1c was associated with lower SES (p,0.001), Pacific Island ethnicity (p,0.001), not living with both biological parents (p,0.05), and greater BMI SDS (p,0.05). A regression equation to predict HbA1c at 24 months was consequently developed. Conclusions: Deterioration in glycaemic control shortly after diagnosis in diabetic children is particularly marked in Pacific Island children and in those not living with both biological parents. Clinicians need to be aware of factors associated wit

WW domain interactions regulate the Hippo tumor suppressor pathway

The Hippo kinase pathway is emerging as a conserved signaling pathway that is essential for organ growth and tumorigenesis in Drosophila and mammalians. Although the signaling of the core kinases is relatively well understood, less is known about the upstream inputs, downstream outputs and regulation of the whole cascade. Enrichment of the Hippo pathway components with WW domains and their cognate proline-rich interacting motifs provides a versatile platform for further understanding the mechanisms that regulate organ growth and tumorigenesis. Here, we review recently discovered mechanisms of WW domain-mediated interactions that contribute to the regulation of the Hippo signaling pathway in tumorigenesis. We further discuss new insights and future directions on the emerging role of such regulation