Nuclear microenvironments modulate transcription from low-affinity enhancers

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation

Reducing Biomass Recalcitrance by Heterologous Expression of a Bacterial Peroxidase in Tobacco (\u3cem\u3eNicotiana benthamiana\u3c/em\u3e)

Commercial scale production of biofuels from lignocellulosic feed stocks has been hampered by the resistance of plant cell walls to enzymatic conversion, primarily owing to lignin. This study investigated whether DypB, the lignin-degrading peroxidase from Rodococcus jostii, depolymerizes lignin and reduces recalcitrance in transgenic tobacco (Nicotiana benthamiana). The protein was targeted to the cytosol or the ER using ER-targeting and retention signal peptides. For each construct, five independent transgenic lines were characterized phenotypically and genotypically. Our findings reveal that expression of DypB in the cytosol and ER does not affect plant development. ER-targeting increased protein accumulation, and extracts from transgenic leaves showed higher activity on classic peroxidase substrates than the control. Intriguingly, in situ DypB activation and subsequent saccharification released nearly 200% more fermentable sugars from transgenic lines than controls, which were not explained by variation in initial structural and non-structural carbohydrates and lignin content. Pyrolysis-GC-MS analysis showed more reduction in the level of lignin associated pyrolysates in the transgenic lines than the control primarily when the enzyme is activated prior to pyrolysis, consistent with increased lignin degradation and improved saccharification. The findings reveal for the first time that accumulation and in situ activation of a peroxidase improves biomass digestibility

Real-World Evidence from the Integrative Medicine Primary Care Trial (IMPACT): Assessing Patient-Reported Outcomes at Baseline and 12-Month Follow-Up

Purpose. The University of Arizona Integrative Health Center (UAIHC) was an innovative membership-supported integrative medicine (IM) adult primary care clinic in Phoenix, Arizona. UAIHC delivered healthcare using an integrative medicine model that combined conventional and complementary medical treatments, including nutrition, mind-body medicine, acupuncture, manual medicine, health coaching, educational classes, and groups. Results from pre-post evaluation of patient-reported outcomes on several standardized measures are presented here. Methods. UAIHC patients completed surveys at baseline and after 12 months of continuous integrative primary care. Patients reported on perceived changes in health outcomes as measured by Short-Form Health Survey (SF-12 general, mental, and physical health), Perceived Stress Scale (PSS4), Work Productivity and Activity Impairment Questionnaire (WPAI), World Health Organization Well-Being Index (WHO-5), Pain Visual Analog Scale (VAS), Fatigue Severity Scale (VAS; FSS), Generalized Anxiety Disorder Scale (GAD2), Patient Health Questionnaire for depression (PHQ2), Pittsburgh Sleep Quality Index (PSQI) global rating of sleep quality, and the Behavioral Risk Factor Surveillance System (BRFSS; nutrition, exercise, and physical activity). Overall differences between time points were assessed for statistical significance. Patient demographics are also described. Results. 177 patients completed baseline and follow-up outcome measures. Patients were predominantly white, female, college-educated, and employed. Baseline to one-year follow-up results indicate statistically significant improvements (p < .05) on all but perceived stress (PSS-4) and work absenteeism (WPAI). Clinical impact and/or practical effects are reported as percent change or standardized effect sizes whenever possible. Other demographic and descriptive information is summarized. Conclusions. Following one year of IM primary care at UAIHC, patient-reported outcomes indicated positive impacts in several areas of patients' lives: mental, physical, and overall health; work productivity; sleep quality; pain; fatigue; overall well-being; and physical activity.Adolph Coors Family Foundation; Andrew Weil Center for Integrative Medicine, University of ArizonaOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Integrated Pest Management of Texas Turfgrass.

26 p

Nuclear microenvironments modulate transcription from low-affinity enhancers

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation

Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals

Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species’ blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors’ lipid metabolism and/or bloodstream oxidative environment affecting PON1’s role in fatty acid oxidation. PON1 loss also eliminates marine mammals’ main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environment

Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals

Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species’ blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors’ lipid metabolism and/or bloodstream oxidative environment affecting PON1’s role in fatty acid oxidation. PON1 loss also eliminates marine mammals’ main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environment

The First Hour of Extra-galactic Data of the Sloan Digital Sky Survey Spectroscopic Commissioning: The Coma Cluster

On 26 May 1999, one of the Sloan Digital Sky Survey (SDSS) fiber-fed spectrographs saw astronomical first light. This was followed by the first spectroscopic commissioning run during the dark period of June 1999. We present here the first hour of extra-galactic spectroscopy taken during these early commissioning stages: an observation of the Coma cluster of galaxies. Our data samples the Southern part of this cluster, out to a radius of 1.5degrees and thus fully covers the NGC 4839 group. We outline in this paper the main characteristics of the SDSS spectroscopic systems and provide redshifts and spectral classifications for 196 Coma galaxies, of which 45 redshifts are new. For the 151 galaxies in common with the literature, we find excellent agreement between our redshift determinations and the published values. As part of our analysis, we have investigated four different spectral classification algorithms: spectral line strengths, a principal component decomposition, a wavelet analysis and the fitting of spectral synthesis models to the data. We find that a significant fraction (25%) of our observed Coma galaxies show signs of recent star-formation activity and that the velocity dispersion of these active galaxies (emission-line and post-starburst galaxies) is 30% larger than the absorption-line galaxies. We also find no active galaxies within the central (projected) 200 h-1 Kpc of the cluster. The spatial distribution of our Coma active galaxies is consistent with that found at higher redshift for the CNOC1 cluster survey. Beyond the core region, the fraction of bright active galaxies appears to rise slowly out to the virial radius and are randomly distributed within the cluster with no apparent correlation with the potential merger of the NGC 4839 group. [ABRIDGED]Comment: Accepted in AJ, 65 pages, 20 figures, 5 table

Star Formation Rates in Resolved Galaxies: Calibrations with Near- and Far-infrared Data for NGC 5055 and NGC 6946

We use the near-infrared Brγ hydrogen recombination line as a reference star formation rate (SFR) indicator to test the validity and establish the calibration of the Herschel/PACS 70 μm emission as a SFR tracer for sub-galactic regions in external galaxies. Brγ offers the double advantage of directly tracing ionizing photons and of being relatively insensitive to the effects of dust attenuation. For our first experiment, we use archival Canada-France-Hawaii Telescope Brγ and Ks images of two nearby galaxies: NGC 5055 and NGC 6946, which are also part of the Herschel program KINGFISH (Key Insights on Nearby Galaxies: a Far-Infrared Survey with Herschel). We use the extinction corrected Brγ emission to derive the SFR(70) calibration for H II regions in these two galaxies. A comparison of the SFR(70) calibrations at different spatial scales, from 200 pc to the size of the whole galaxy, reveals that about 50% of the total 70 μm emission is due to dust heated by stellar populations that are unrelated to the current star formation. We use a simple model to qualitatively relate the increase of the SFR(70) calibration coefficient with decreasing region size to the star formation timescale. We provide a calibration for an unbiased SFR indicator that combines the observed Hα with the 70 μm emission, also for use in H II regions. We briefly analyze the PACS 100 and 160 μm maps and find that longer wavelengths are not as good SFR indicators as 70 μm, in agreement with previous results. We find that the calibrations show about 50% difference between the two galaxies, possibly due to effects of inclination

Patch-augmented rotator cuff surgery (PARCS) study-protocol for a feasibility study

Background: A rotator cuff tear is a common disabling shoulder problem. Symptoms include pain, weakness, lack of shoulder mobility and sleep disturbance. Many patients require surgery to repair the tear; however, there is a high failure rate. There is a pressing need to improve the outcome of rotator cuff surgery and the use of patch augmentation to provide support to the healing process and improve patient outcomes holds new promise. Patches have been made using different materials (e.g. human/animal skin or intestine tissue, and completely synthetic materials) and processes (e.g. woven or a mesh). However, clinical evidence on their use is limited. The aim of the patch-augmented rotator cuff surgery (PARCS) feasibility study is to determine, using a mixed method approach, the design of a definitive randomised trial assessing the effectiveness and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and feasible. Methods: The objectives of this six-stage mixed methods feasibility study are to determine current practice, evidence and views about patch use; achieve consensus on the design of a randomised trial to evaluate patch-augmented rotator cuff surgery; and assess the acceptability and feasibility of the proposed design. The six stages will involve a systematic review of clinical evidence, two surveys of surgeons, focus groups and interviews with stakeholders, a Delphi study and a consensus meeting. The various stakeholders (including patients, surgeons, and representatives from industry, the NHS and regulatory bodies) will be involved across the six stages. Discussion: The PARCS feasibility study will inform the feasibility and acceptability of a randomised trial of the effectiveness and cost-effectiveness of a patch-augmented rotator cuff surgery. Consensus opinion on the basic design of a randomised trial will be sought. Trial registration: Not applicable