Cytosolic Sequestration of Prep1 Influences Early Stages of T Cell Development

Objective: Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter. Principal Findings: Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4 2 CD8 2 CD44 2 (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes. Conclusion: The results obtained by genetic (Prep1 hypomorphic) and functional (Pbx1NT transgenic) inactivation of Prep

Aprovechamiento de barros procedentes de central de áridos para la elaboración de piezas cerámicas porosas

Aggregates (gravel and sand) are, after water, the Earth’s second most used natural resource, representing about 50% of all consumed mineral resources. Aggregate production generates a large quantity of waste from the aggregate washing process. This waste is made up of suspended solids – sludge – which has a great environmental impact. It is deposited in huge troughs because of the impossibility of discharging it directly into rivers. Many plants have incorporated decanters and filter presses to separate the solid from the liquid fraction. This paper evaluates the possibility of exploiting the solid fraction (i.e. sludge) in the manufacture of fired clay bricks. The added value of these bricks is, on the one hand, the exploitation of sludge as a currently useless waste product, and on the other, the use of this sludge to enhance the physical and mechanical properties of conventional fired clay bricks.Los áridos son la segunda materia prima más consumida en la Tierra después del agua, representando alrededor del 50% de todos los recursos minerales consumidos. El proceso de elaboración de estos áridos genera una gran cantidad de residuos procedentes de su lavado. Se trata de partículas sólidas en suspensión – lodos – de gran impacto ambiental, que se depositan en grandes charcas ante la imposibilidad de verterlos directamente al rio. Muchas empresas han incorporado decantadores y filtros de prensa para separar la fracción solida de la líquida. El presente trabajo evalúa la posibilidad de utilizar la fracción sólida, es decir el barro, para la fabricación de piezas cerámicas. El valor añadido de estas piezas es por un lado el aprovechamiento del barro como producto residual, que en estos momentos es desechable, y por otro, conseguir que este barro mejore las propiedades físico-mecánicas de la cerámica convencional

Leuconostoc performance in soy-based fermentations – Survival, acidification, sugar metabolism, and flavor comparisons

Leuconostoc spp. is often regarded as the flavor producer, responsible for the production of acetoin and diacetyl in dairy cheese. In this study, we investigate seven plant-derived Leuconostoc strains, covering four species, in their potential as a lyophilized starter culture for flavor production in fermented soy-based cheese alternatives. We show that the process of lyophilization of Leuconostoc can be feasible using a soy-based lyoprotectant, with survivability up to 63% during long term storage. Furthermore, the storage in this media improves the subse-quent growth in a soy-based substrate in a strain specific manner. The utilization of individual raffinose family oligosaccharides was strain dependent, with Leuconostoc pseudomesenteroides NFICC99 being the best consumer. Furthermore, we show that all investigated strains were able to produce a range of volatile flavor compounds found in dairy cheese products, as well as remove certain dairy off-flavors from the soy-based substrate like hexanal and 2-pentylfuran. Also here, NFICC99 was strain producing most cheese-related volatile flavor com-pounds, followed by Leuconostoc mesenteroides NFICC319. These findings provide initial insights into the development of Leuconostoc as a potential starter culture for plant-based dairy alternatives, as well as a promising approach for generation of stable, lyophilized cultures

Enhancing the early home learning environment through a brief group parenting intervention: study protocol for a cluster randomised controlled trial.

BACKGROUND: The quality of the home learning environment has a significant influence on children's language and communication skills during the early years with children from disadvantaged families disproportionately affected. This paper describes the protocol and participant baseline characteristics of a community-based effectiveness study. It evaluates the effects of 'smalltalk', a brief group parenting intervention (with or without home coaching) on the quality of the early childhood home learning environment. METHODS/DESIGN: The study comprises two cluster randomised controlled superiority trials (one for infants and one for toddlers) designed and conducted in parallel. In 20 local government areas (LGAs) in Victoria, Australia, six locations (clusters) were randomised to one of three conditions: standard care (control); smalltalk group-only program; or smalltalk plus (group program plus home coaching). Programs were delivered to parents experiencing socioeconomic disadvantage through two existing age-based services, the maternal and child health service (infant program, ages 6-12 months), and facilitated playgroups (toddler program, ages 12-36 months). Outcomes were assessed by parent report and direct observation at baseline (0 weeks), post-intervention (12 weeks) and follow-up (32 weeks). Primary outcomes were parent verbal responsivity and home activities with child at 32 weeks. Secondary outcomes included parenting confidence, parent wellbeing and children's communication, socio-emotional and general development skills. Analyses will use intention-to-treat random effects ("multilevel") models to account for clustering. RECRUITMENT AND BASELINE DATA: Across the 20 LGAs, 986 parents of infants and 1200 parents of toddlers enrolled and completed baseline measures. Eighty four percent of families demonstrated one or more of the targeted risk factors for poor child development (low income; receives government benefits; single, socially isolated or young parent; culturally or linguistically diverse background). DISCUSSION: This study will provide unique data on the effectiveness of a brief group parenting intervention for enhancing the early home learning environment of young children from disadvantaged families. It will also provide evidence of the extent to which additional one-on-one support is required to achieve change and whether there are greater benefits when delivered in the 1st year of life or later. The program has been designed for scale-up across existing early childhood services if proven effective. TRIAL REGISTRATION: 8 September 2011; ACTRN12611000965909 .This research was commissioned and funded by the Victorian Government Department of Education and Early Childhood (now the Department of Education and Training, DET). JN, MT, SB, TH, VH, EW and NH were employees of the Parenting Research Centre when this study was designed and conducted. JN, SB, EW & NH are currently supported by the Australian Communities Foundation through the Roberta Holmes Transition to Contemporary Parenthood Program (Coronella sub-fund); EW was part-funded by the Centre for Research Excellence in Child Language at Murdoch Children’s Research Institute (NHMRC grant 1023493). OU is funded by the UK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed in this publication are those of the authors and not necessarily those of the funding bodies

Measure representation and multifractal analysis of complete genomes

This paper introduces the notion of measure representation of DNA sequences. Spectral analysis and multifractal analysis are then performed on the measure representations of a large number of complete genomes. The main aim of this paper is to discuss the multifractal property of the measure representation and the classification of bacteria. From the measure representations and the values of the $D_{q}$ spectra and related $C_{q}$ curves, it is concluded that these complete genomes are not random sequences. In fact, spectral analyses performed indicate that these measure representations considered as time series, exhibit strong long-range correlation. For substrings with length K=8, the $D_{q}$ spectra of all organisms studied are multifractal-like and sufficiently smooth for the $C_{q}$ curves to be meaningful. The $C_{q}$ curves of all bacteria resemble a classical phase transition at a critical point. But the 'analogous' phase transitions of chromosomes of non-bacteria organisms are different. Apart from Chromosome 1 of {\it C. elegans}, they exhibit the shape of double-peaked specific heat function.Comment: 12 pages with 9 figures and 1 tabl

Characterization of the Regulatory Region of the Zebrafish Prep1.1 Gene: Analogies to the Promoter of the Human PREP1

Prep1 is a developmentally essential TALE class homeodomain transcription factor. In zebrafish and mouse, Prep1 is already ubiquitously expressed at the earliest stages of development, with important tissue-specific peculiarities. The Prep1 gene in mouse is developmentally essential and has haploinsufficient tumor suppressor activity [1]. We have determined the human Prep1 transcription start site (TSS) by primer extension analysis and identified, within 20 bp, the transcription start region (TSR) of the zebrafish Prep1.1 promoter. The functions of the zebrafish 5′ upstream sequences were analyzed both by transient transfections in Hela Cells and by injection in zebrafish embryos. This analysis revealed a complex promoter with regulatory sequences extending up to −1.8, possibly −5.0 Kb, responsible for tissue specific expression. Moreover, the first intron contains a conserved tissue-specific enhancer both in zebrafish and in human cells. Finally, a two nucleotides mutation of an EGR-1 site, conserved in all species including human and zebrafish and located at a short distance from the TSS, destroyed the promoter activity of the −5.0 Kb promoter. A transgenic fish expressing GFP under the −1.8 Kb zebrafish promoter/enhancer co-expressed GFP and endogenous Prep1.1 during embryonic development. In the adult fish, GFP was expressed in hematopoietic regions like the kidney, in agreement with the essential function of Prep1 in mouse hematopoiesis. Sequence comparison showed conservation from man to fish of the sequences around the TSS, within the first intron enhancer. Moreover, about 40% of the sequences spread throughout the 5 Kbof the zebrafish promoter are concentrated in the −3 to −5 Kb of the human upstream region

Influence of land-derived stressors and environmental variability on compositional turnover and diversity of estuarine benthic communities

It can be challenging to differentiate community changes caused by human activities from the influence of natural background variability. Using gradient forest analysis, we explored the relative importance of environmental factors, operating across multiple spatio-temporal scales, in influencing patterns of compositional turnover in estuarine benthic macroinvertebrate communities across New Zealand. Both land-derived stressors (represented by sediment mud content and total sediment nitrogen and phosphorus content) and natural environmental variables (represented by sea surface temperature, Southern Oscillation Index, and wind-wave exposure) were important predictors of compositional turnover, reflecting a matrix of processes interacting across space and time. Generalized linear models were used to determine whether measures of benthic macroinvertebrate diversity, which are commonly used as indicators of ecological health on a local scale, changed in a way that was consistent with the compositional turnover along the environmental gradient. As expected, compositional turnover along land-derived stressor gradients was negatively associated with diversity indices, suggesting a decline in ecological health as land-derived stressors increase. This study moves towards an ecosystem-based management approach that focusses on cumulative effects rather than single stressors by considering how multiple land-derived stressors influence indicators of estuarine health, against a background of natural variability across several spatio-temporal scales

Is organizational justice climate at the workplace associated with individual-level quality of care and organizational affective commitment?:A multi-level, cross-sectional study on dentistry in Sweden

Purpose The aim of this study is to investigate whether organizational justice climate at the workplace level is associated with individual staff members’ perceptions of carequality and affective commitment to the workplace.Methods The study adopts a cross-sectional multi-level design. Data were collected using an electronic survey and a response rate of 75% was obtained. Organizational justice climate and affective commitment to the workplace were measured by items from Copenhagen Psychosocial Questionnaire and quality of care by three self-developed items. Non-managerial staff working at dental clinics with at least five respondents (n = 900 from 68 units) was included in analyses. A set of Level-2 random intercept models were built to predict individual-level organizational affective commitment and perceived quality of care from unit-level organizational justice climate, controlling for potential confoundingby group size, gender, age, and occupation.Results The results of the empty model showed substantial between-unit variation for both affective commitment (ICC-1 = 0.17) and quality of care (ICC-1 = 0.12). The overall results showed that the shared perception of organizational justice climate at the clinical unit level was significantly associated with perceived quality of care and affective commitment to the organization (p < 0.001).Conclusions Organizational justice climate at work unit level explained all variation in affective commitment among dental clinics and was associated with both the individualstaff members’ affective commitment and perceived quality of care. These findings suggest a potential for that addressing organizational justice climate may be a way to promote quality of care and enhancing affective commitment. However, longitudinal studies are needed to support causality in the examined relationships. Intervention research is also recommended to probe the effectiveness of actions increasingunit-level organizational justice climate and test their impact on quality of care and affective commitment