Regulation of a hair follicle keratin intermediate filament gene promoter

During hair growth, cortical cells emerging from the proliferative follicle bulb rapidly undergo a differentiation program and synthesise large amounts of hair keratin proteins. To identify some of the controls that specify expression of hair genes we have defined the minimal promoter of the wool keratin intermediate filament gene K2.10. The region of this gene spanning nucleotides -350 to +53 was sufficient to direct expression of the lacZ gene to the follicle cortex of transgenic mice but deletion of nucleotides -350 to -150 led to a complete loss of promoter activity. When a four base substitution mutation was introduced into the minimal functional promoter at the binding site for lymphoid enhancer factor 1 (LEF-1), promoter activity in transgenic mice was decreased but specificity was not affected. To investigate the interaction of trans-acting factors within the minimal K2.10 promoter we performed DNase I footprinting analyses and electrophoretic mobility shift assays. In addition to LEF-1, Sp1, AP2-like and NF1-like proteins bound to the promoter. The Sp1 and AP2-like proteins bound sequences flanking the LEF-1 binding site whereas the NF1-like proteins bound closer to the transcription start site. We conclude that the LEF-1 binding site is an enhancer element of the K2.10 promoter in the hair follicle cortex and that factors other than LEF-1 regulate promoter tissue- and differentiation-specificity.S. M. Dunn, R. A. Keough, G. E. Rogers and B. C. Powel

MIUS integration and subsystems test program

The MIUS Integration and Subsystems Test (MIST) facility at the Lyndon B. Johnson Space Center was completed and ready in May 1974 for conducting specific tests in direct support of the Modular Integrated Utility System (MIUS). A series of subsystems and integrated tests was conducted since that time, culminating in a series of 24-hour dynamic tests to further demonstrate the capabilities of the MIUS Program concepts to meet typical utility load profiles for a residential area. Results of the MIST Program are presented which achieved demonstrated plant thermal efficiencies ranging from 57 to 65 percent

The Sensitivity of Auditory-Motor Representations to Subtle Changes in Auditory Feedback While Singing

Singing requires accurate control of the fundamental frequency (F0) of the voice. This study examined trained singers’ and untrained singers’ (nonsingers’) sensitivity to subtle manipulations in auditory feedback and the subsequent effect on the mapping between F0 feedback and vocal control. Participants produced the consonant-vowel /ta/ while receiving auditory feedback that was shifted up and down in frequency. Results showed that singers and nonsingers compensated to a similar degree when presented with frequency-altered feedback (FAF); however, singers’ F0 values were consistently closer to the intended pitch target. Moreover, singers initiated their compensatory responses when auditory feedback was shifted up or down 6 cents or more, compared to nonsingers who began compensating when feedback was shifted up 26 cents and down 22 cents. Additionally, examination of the first 50 ms of vocalization indicated that participants commenced subsequent vocal utterances, during FAF, near the F0 value on previous shift trials. Interestingly, nonsingers commenced F0 productions below the pitch target and increased their F0 until they matched the note. Thus, singers and nonsingers rely on an internal model to regulate voice F0, but singers’ models appear to be more sensitive in response to subtle discrepancies in auditory feedback

Live and recorded group music interventions with active participation for people with dementias: a systematic review

Background: This literature review examined the existing evidence base for the impact of both live and recorded music interventions involving active participation in a dementia population. Methodology: PsycINFO, Medline, CINAHL, Web of Science, PubMed and Cochrane Library were searched and 15 studies met inclusion criteria. Results: There was a positive impact on behavioural and psychological symptoms, quality of life, communication and some aspects of cognitive function; methodological limitations, however, make it difficult to offer firm conclusions. Interventions using recorded music resulted in more consistent positive behavioural and psychological outcomes, whereas interventions using live music reported a benefit to communication and relationships. Conclusions: Although live and recorded music showed benefits, and should be considered in dementia care, the use of different outcome measures made definitive comparisons problematic. In order to better understand mechanisms of change, one future research area should explore how group music interventions affect communication by more closely assessing processes during live and recorded music

Discourses of conflict and collaboration and institutional context in the implementation of forest conservation policies in Soria, Spain

This article examines the emergence of conflict and collaboration in the implementation of forest conservation policies in Soria, Spain. We draw insights from discursive institutionalism and use a comparative case study approach to analyse and compare a situation of social conflict over the Natural Park declaration in the Sierra de Urbión, and a civil society led collaborative process to develop management plans for the “Sierra de Cabrejas” in Soria. The implementation of the EU Habitats Directive generated different outcomes in these two cases, which unfolded in the context of the same nature conservation legislation and national and provincial administrative structures but differed in terms of types of forests involved, property rights arrangements and forest use histories. We critically examine the influence of the institutional context and dominant discourses on the emergence of outcomes: conflict emerged where local institutions and discourses were threatened by the EU directive, while collaboration was possible where local institutions and counter-discourses were weak. We find that the institutional context plays an important part in determining local discourses in the implementation of forest conservation policies. Yet local counter-discourses have limited influence in the implementation and policy processes in the face of contestation by the discourses of regional civil servants conservation activists

Comparative proteomics using 2-D gel electrophoresis and mass spectrometry as tools to dissect stimulons and regulons in bacteria with sequenced or partially sequenced genomes

We propose two-dimensional gel electrophoresis (2-DE) and mass spectrometry to define the protein components of regulons and stimulons in bacteria, including those organisms where genome sequencing is still in progress. The basic 2-DE protocol allows high resolution and reproducibility and enables the direct comparison of hundreds or even thousands of proteins simultaneously. To identify proteins that comprise stimulons and regulons, peptide mass fingerprint (PMF) with matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS) analysis is the first option and, if results from this tool are insufficient, complementary data obtained with electrospray ionization tandem-MS (ESI-MS/MS) may permit successful protein identification. ESI-MS/MS and MALDI-TOF-MS provide complementary data sets, and so a more comprehensive coverage of a proteome can be obtained using both techniques with the same sample, especially when few sequenced proteins of a particular organism exist or genome sequencing is still in progress

Social Patterning of Screening Uptake and the Impact of Facilitating Informed Choices: Psychological and Ethical Analyses

Screening for unsuspected disease has both possible benefits and harms for those who participate. Historically the benefits of participation have been emphasized to maximize uptake reflecting a public health approach to policy; currently policy is moving towards an informed choice approach involving giving information about both benefits and harms of participation. However, no research has been conducted to evaluate the impact on health of an informed choice policy. Using psychological models, the first aim of this study was to describe an explanatory framework for variation in screening uptake and to apply this framework to assess the impact of informed choices in screening. The second aim was to evaluate ethically that impact. Data from a general population survey (n = 300) of beliefs and attitudes towards participation in diabetes screening indicated that greater orientation to the present is associated with greater social deprivation and lower expectation of participation in screening. The results inform an explanatory framework of social patterning of screening in which greater orientation to the present focuses attention on the disadvantages of screening, which tend to be immediate, thereby reducing participation. This framework suggests that an informed choice policy, by increasing the salience of possible harms of screening, might reduce uptake of screening more in those who are more deprived and orientated to the present. This possibility gives rise to an apparent dilemma where an ethical decision must be made between greater choice and avoiding health inequality. Philosophical perspectives on choice and inequality are used to point to some of the complexities in assessing whether there really is such a dilemma and if so how it should be resolved. The paper concludes with a discussion of the ethics of paternalism

Habitat and Scale Shape the Demographic Fate of the Keystone Sea Urchin Paracentrotus lividus in Mediterranean Macrophyte Communities

Demographic processes exert different degrees of control as individuals grow, and in species that span several habitats and spatial scales, this can influence our ability to predict their population at a particular life-history stage given the previous life stage. In particular, when keystone species are involved, this relative coupling between demographic stages can have significant implications for the functioning of ecosystems. We examined benthic and pelagic abundances of the sea urchin Paracentrotus lividus in order to: 1) understand the main life-history bottlenecks by observing the degree of coupling between demographic stages; and 2) explore the processes driving these linkages. P. lividus is the dominant invertebrate herbivore in the Mediterranean Sea, and has been repeatedly observed to overgraze shallow beds of the seagrass Posidonia oceanica and rocky macroalgal communities. We used a hierarchical sampling design at different spatial scales (100 s, 10 s and <1 km) and habitats (seagrass and rocky macroalgae) to describe the spatial patterns in the abundance of different demographic stages (larvae, settlers, recruits and adults). Our results indicate that large-scale factors (potentially currents, nutrients, temperature, etc.) determine larval availability and settlement in the pelagic stages of urchin life history. In rocky macroalgal habitats, benthic processes (like predation) acting at large or medium scales drive adult abundances. In contrast, adult numbers in seagrass meadows are most likely influenced by factors like local migration (from adjoining rocky habitats) functioning at much smaller scales. The complexity of spatial and habitat-dependent processes shaping urchin populations demands a multiplicity of approaches when addressing habitat conservation actions, yet such actions are currently mostly aimed at managing predation processes and fish numbers. We argue that a more holistic ecosystem management also needs to incorporate the landscape and habitat-quality level processes (eutrophication, fragmentation, etc.) that together regulate the populations of this keystone herbivore

Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach

Background: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the\ud optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access\ud referral strategy for stage 4 (glomerular filtration rate ,30 ml/min/1.73 m2) chronic kidney disease patients using a decision\ud analytic framework.\ud Methods: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an\ud AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the\ud probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy\ud and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were\ud performed using Monte Carlo simulation.\ud Results: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy\ud (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except\ud at higher rates of progression and lower rates of ischemic steal syndrome.\ud Conclusions: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all predialysis\ud patients. Further research on cost implications and patient preferences for treatment options needs to be done\ud before recommending early AVF creation