Binding of Upstream Stimulatory Factor to an E-box in the 3′-Flanking Region Stimulates α1(I) Collagen Gene Transcription

Since several lines of evidence implicate the 3'-flanking region in regulating alpha1(I) collagen gene transcription, we analyzed 12. 4-kilobase pairs of 3'-flanking sequence of the murine alpha1(I) collagen gene for transcriptional elements. A region of the 3'-flanking region stimulated expression of the heterologous beta-globin gene promoter in an enhancer trap plasmid and of the alpha1(I) collagen gene promoter in a collagen-luciferase reporter gene construct when located 3' to the luciferase reporter gene. DNase I footprinting analysis demonstrated the presence of three regions where DNA binding proteins specifically interact within this 3'-stimulatory region. Inspection of the DNA sequence revealed a consensus E-box, a binding site for basic helix-loop-helix proteins, in one of the protein binding sites. Mobility shift assays demonstrated that upstream stimulatory factors (USF) USF-1 and USF-2 bind to this E-box. Mutating the E-box in the context of the 3'-flanking region confirmed that it contributes to the enhancement of transcriptional activity of the alpha1(I) collagen gene promoter. Mutations in all three protein binding sites abolished transcriptional activation by the 3'-flanking region, suggesting a complex interaction among the trans-acting factors in enhancing transcriptional activity. Thus, a region of the 3'-flanking region of the alpha1(I) collagen gene stimulates transcription of the alpha1(I) collagen gene promoter, and USF-1 and USF-2 contribute to this transcriptional stimulation

Utilization of a novel digital measurement tool for quantitative assessment of upper extremity motor dexterity: a controlled pilot study.

BackgroundThe current methods of assessing motor function rely primarily on the clinician's judgment of the patient's physical examination and the patient's self-administered surveys. Recently, computerized handgrip tools have been designed as an objective method to quantify upper-extremity motor function. This pilot study explores the use of the MediSens handgrip as a potential clinical tool for objectively assessing the motor function of the hand.MethodsEleven patients with cervical spondylotic myelopathy (CSM) were followed for three months. Eighteen age-matched healthy participants were followed for two months. The neuromotor function and the patient-perceived motor function of these patients were assessed with the MediSens device and the Oswestry Disability Index respectively. The MediSens device utilized a target tracking test to investigate the neuromotor capacity of the participants. The mean absolute error (MAE) between the target curve and the curve tracing achieved by the participants was used as the assessment metric. The patients' adjusted MediSens MAE scores were then compared to the controls. The CSM patients were further classified as either "functional" or "nonfunctional" in order to validate the system's responsiveness. Finally, the correlation between the MediSens MAE score and the ODI score was investigated.ResultsThe control participants had lower MediSens MAE scores of 8.09%±1.60%, while the cervical spinal disorder patients had greater MediSens MAE scores of 11.24%±6.29%. Following surgery, the functional CSM patients had an average MediSens MAE score of 7.13%±1.60%, while the nonfunctional CSM patients had an average score of 12.41%±6.32%. The MediSens MAE and the ODI scores showed a statistically significant correlation (r=-0.341, p<1.14×10⁻⁵). A Bland-Altman plot was then used to validate the agreement between the two scores. Furthermore, the percentage improvement of the the two scores after receiving the surgical intervention showed a significant correlation (r=-0.723, p<0.04).ConclusionsThe MediSens handgrip device is capable of identifying patients with impaired motor function of the hand. The MediSens handgrip scores correlate with the ODI scores and may serve as an objective alternative for assessing motor function of the hand

Utilization of a novel digital measurement tool for quantitative assessment of upper extremity motor dexterity: a controlled pilot study

BACKGROUND: The current methods of assessing motor function rely primarily on the clinician’s judgment of the patient’s physical examination and the patient’s self-administered surveys. Recently, computerized handgrip tools have been designed as an objective method to quantify upper-extremity motor function. This pilot study explores the use of the MediSens handgrip as a potential clinical tool for objectively assessing the motor function of the hand. METHODS: Eleven patients with cervical spondylotic myelopathy (CSM) were followed for three months. Eighteen age-matched healthy participants were followed for two months. The neuromotor function and the patient-perceived motor function of these patients were assessed with the MediSens device and the Oswestry Disability Index respectively. The MediSens device utilized a target tracking test to investigate the neuromotor capacity of the participants. The mean absolute error (MAE) between the target curve and the curve tracing achieved by the participants was used as the assessment metric. The patients’ adjusted MediSens MAE scores were then compared to the controls. The CSM patients were further classified as either “functional” or “nonfunctional” in order to validate the system’s responsiveness. Finally, the correlation between the MediSens MAE score and the ODI score was investigated. RESULTS: The control participants had lower MediSens MAE scores of 8.09%±1.60%, while the cervical spinal disorder patients had greater MediSens MAE scores of 11.24%±6.29%. Following surgery, the functional CSM patients had an average MediSens MAE score of 7.13%±1.60%, while the nonfunctional CSM patients had an average score of 12.41%±6.32%. The MediSens MAE and the ODI scores showed a statistically significant correlation (r=-0.341, p<1.14×10(-5)). A Bland-Altman plot was then used to validate the agreement between the two scores. Furthermore, the percentage improvement of the the two scores after receiving the surgical intervention showed a significant correlation (r=-0.723, p<0.04). CONCLUSIONS: The MediSens handgrip device is capable of identifying patients with impaired motor function of the hand. The MediSens handgrip scores correlate with the ODI scores and may serve as an objective alternative for assessing motor function of the hand. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-0003-11-121) contains supplementary material, which is available to authorized users

A measurement of the millimetre emission and the Sunyaev-Zel'dovich effect associated with low-frequency radio sources

We present a statistical analysis of the millimetre-wavelength properties of 1.4GHz-selected sources and a detection of the Sunyaev–Zel’dovich (SZ) effect associated with the haloes that host them. We stack data at 148, 218 and 277GHz from the Atacama Cosmology Telescope at the positions of a large sample of radio AGN selected at 1.4GHz. The thermal SZ effect associated with the haloes that host the AGN is detected at the 5σ level through its spectral signature, representing a statistical detection of the SZ effect in some of the lowest mass haloes (average M 200 ≈ 10 13 M. h −1 70 ) studied to date. The relation between the SZ effect and mass (based on weak lensing measurements of radio galaxies) is consistent with that measured by Planck for local bright galaxies. In the context of galaxy evolution models, this study confirms that galaxies with radio AGN also typically support hot gaseous haloes. Adding Herschel observations allows us to show that the SZ signal is not significantly contaminated by dust emission. Finally, we analyse the contribution of radio sources to the angular power spectrum of the cosmic microwave background

Diversification across an altitudinal gradient in the Tiny Greenbul (Phyllastrephus debilis) from the Eastern Arc Mountains of Africa

<p>Abstract</p> <p>Background</p> <p>The Eastern Arc Mountains of Africa have become one of the focal systems with which to explore the patterns and mechanisms of diversification among montane species and populations. One unresolved question is the extent to which populations inhabiting montane forest interact with those of adjacent lowland forest abutting the coast of eastern Africa. The Tiny Greenbul (<it>Phyllastephus debilis</it>) represents the only described bird species within the Eastern Arc/coastal forest mosaic, which is polytypic across an altitudinal gradient: the subspecies <it>albigula </it>(green head) is distributed in the montane Usambara and Nguru Mountains whereas the subspecies <it>rabai </it>(grey head) is found in Tanzanian lowland and foothill forest. Using a combination of morphological and genetic data, we aim to establish if the pattern of morphological differentiation in the Tiny Greenbul (<it>Phyllastrephus debilis</it>) is the result of disruptive selection along an altitudinal gradient or a consequence of secondary contact following population expansion of two differentiated lineages.</p> <p>Results</p> <p>We found significant biometric differences between the lowland (<it>rabai</it>) and montane (<it>albigula</it>) populations in Tanzania. The differences in shape are coupled with discrete differences in the coloration of the underparts. Using multi-locus data gathered from 124 individuals, we show that lowland and montane birds form two distinct genetic lineages. The divergence between the two forms occurred between 2.4 and 3.1 Myrs ago.</p> <p>Our coalescent analyses suggest that limited gene flow, mostly from the subspecies <it>rabai </it>to <it>albigula</it>, is taking place at three mid-altitude localities, where lowland and montane rainforest directly abut. The extent of this introgression appears to be limited and is likely a consequence of the recent expansion of <it>rabai </it>further inland.</p> <p>Conclusion</p> <p>The clear altitudinal segregation in morphology found within the Tiny Greenbul is the result of secondary contact of two highly differentiated lineages rather than disruptive selection in plumage pattern across an altitudinal gradient. Based on our results, we recommend <it>albigula </it>be elevated to species rank.</p

Life Satisfaction, Household Income and Personality Theory

We show that personality traits mediate the e ect of income on Life Satisfaction. The e ect is strong in the case of Neuroticism, which measures the sensitivity to threat and punishment, in both the British Household Panel Survey and the German Socioeconomic Panel. Neuroticism increases the usually observed concavity of the relationship: Individuals with higher Neuroticism score enjoy income more than those with lower score if they are poorer and enjoy income less if they are richer. When the interaction between income and neuroticism is introduced, income does not have signi cant e ect on his own. To interpret the results, we present a simple model where we assume that (i) Life Satisfaction is dependent from the gap between aspired and realized income, and this is modulated by Neuroticism and (ii) income increases in aspirations with a slope less than unity, so that the gap between aspired and realized income increase with aspirations. From the estimation of this model we argue that poorer tend to overshoot in their aspiration, while rich tend to under-shoot. The estimation of the model also shows substantial effect of traits on income

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Listening in on difficult conversations: an observational, multi-center investigation of real-time conversations in medical oncology

BACKGROUND: The quality of communication in medical care has been shown to influence health outcomes. Cancer patients, a highly diverse population, communicate with their clinical care team in diverse ways over the course of their care trajectory. Whether that communication happens and how effective it is may relate to a variety of factors including the type of cancer and the patient’s position on the cancer care continuum. Yet, many of the routine needs of cancer patients after initial cancer treatment are often not addressed adequately. Our goal is to identify areas of strength and areas for improvement in cancer communication by investigating real-time cancer consultations in a cross section of patient-clinician interactions at diverse study sites. METHODS/DESIGN: In this paper we describe the rationale and approach for an ongoing observational study involving three institutions that will utilize quantitative and qualitative methods and employ a short-term longitudinal, prospective follow-up component to investigate decision-making, key topics, and clinician-patient-companion communication dynamics in clinical oncology. DISCUSSION: Through a comprehensive, real-time approach, we hope to provide the fundamental groundwork from which to promote improved patient-centered communication in cancer care