Tissue-specific expression from a compound TATA-dependent and TATA-independent promoter

We have found that the mouse metallothionein-I (MT-I) gene promoter functions in an unusual, compound manner. It directs both TATA-dependent and TATA-independent modes of transcription in vivo. The TATA-dependent message is initiated at the previously characterized +1 transcription start site and is the predominant species in most tissues. In many cell types it is metal inducible. The TATA-independent initiation sites are distributed over the 160 bp upstream of the previously characterized +1 start site, and the RNA products are present in all tissues examined. Only in testis, however, do the TATA-independent transcripts predominate, accumulating to highest levels in pachytene-stage meiotic cells and early spermatids. Unlike the TATA-dependent +1 transcript, these RNAs are not induced by metal, even in cultured cells in which the +1 species is induced. Transfection studies of site-directed mutants show that destruction of the TATA element drastically alters the ratio of the two RNA classes in cells in which the +1 transcripts normally dominates. In TATA-minus mutants, the TATA-independent RNAs become the most prevalent, although they remain refractory to metal induction. Thus, the MT-I promoter utilizes two different types of core promoter function within a single cell population. The two different types of core promoter respond very differently to environmental stimuli, and the choice between them appears to be regulated in a tissue-specific fashion

Ubiquinol Reduces Muscle Wasting but Not Fatigue in Tumor-Bearing Mice

Purpose: Fatigue is the most common and distressing symptom reported by cancer patients during and after treatment. Tumor growth increases oxidative stress and cytokine production, which causes skeletal muscle wasting and cardiac dysfunction. The purpose of this study was to determine whether treatment with the antioxidant ubiquinol improves muscle mass, cardiac function, and behavioral measures of fatigue in tumor-bearing mice. Method: Adult female mice were inoculated with colon26 tumor cells. Half the control and tumor-bearing mice were administered ubiquinol (500 mg/kg/day) in their drinking water. Voluntary wheel running (i.e., voluntary running activity [VRA]) and grip strength were measured at Days 0, 8, 14, and 17 of tumor growth. Cardiac function was measured using echocardiography on Day 18 or 19. Biomarkers of inflammation, protein degradation, and oxidative stress were measured in serum and heart and gastrocnemius tissue. Results: VRA and grip strength progressively declined in tumor-bearing mice. Muscle mass and myocardial diastolic function were decreased, and expression of proinflammatory cytokines was increased in serum and muscle and heart tissue on Day 19 of tumor growth. Oxidative stress was present only in the heart, while biomarkers of protein degradation were increased only in the gastrocnemius muscle. Ubiquinol increased muscle mass in the tumor-bearing and control animals but had no effect on the expression of biomarkers of inflammation, protein degradation, or oxidative stress or on behavioral measures of fatigue

Dynamic Transformations of Genome-wide Epigenetic Marking and Transcriptional Control Establish T Cell Identity

T cell development comprises a stepwise process of commitment from a multipotent precursor. To define molecular mechanisms controlling this progression, we probed five stages spanning the commitment process using RNA-seq and ChIP-seq to track genome-wide shifts in transcription, cohorts of active transcription factor genes, histone modifications at diverse classes of cis-regulatory elements, and binding repertoire of GATA-3 and PU.1, transcription factors with complementary roles in T cell development. The results highlight potential promoter-distal cis-regulatory elements in play and reveal both activation sites and diverse mechanisms of repression that silence genes used in alternative lineages. Histone marking is dynamic and reversible, and though permissive marks anticipate, repressive marks often lag behind changes in transcription. In vivo binding of PU.1 and GATA-3 relative to epigenetic marking reveals distinctive factor-specific rules for recruitment of these crucial transcription factors to different subsets of their potential sites, dependent on dose and developmental context

Evaporites and the salinity of the ocean during the Phanerozoic: Implications for climate, ocean circulation and life

A compilation of data on volumes and masses of evaporite deposits is used as the basis for reconstruction of the salinity of the ocean in the past. Chloride is tracked as the only ion essentially restricted to the ocean, and past salinities are calculated from reconstructed chlorine content of the ocean. Models for ocean salinity through the Phanerozoic are developed using maximal and minimal estimates of the volumes of existing evaporite deposits, and using constant and declining volumes of ocean water through the Phanerozoic. We conclude that there have been significant changes in the mean salinity of the ocean accompanying a general decline throughout the Phanerozoic. The greatest changes are related to major extractions of salt into the young ocean basins which developed during the Mesozoic as Pangaea broke apart. Unfortunately, the sizes of these salt deposits are also the least well known. The last major extractions of salt from the ocean occurred during the Miocene, shortly after the large scale extraction of water from the ocean to form the ice cap of Antarctica. However, these two modifications of the masses of H2O and salt in the ocean followed in sequence and did not cancel each other out. Accordingly, salinities during the Early Miocene were between 37‰ and 39‰. The Mesozoic was a time of generally declining salinity associated with the deep sea salt extractions of the North Atlantic and Gulf of Mexico (Middle to Late Jurassic) and South Atlantic (Early Cretaceous). The earliest of the major extractions of the Phanerozoic occurred during the Permian. There were few large extractions of salt during the earlier Palaeozoic. The models suggest that this was a time of relatively stable but slowly increasing salinities ranging through the upper 40‰'s into the lower 50‰'s. Higher salinities for the world ocean have profound consequences for the thermohaline circulation of the ocean in the past. In the modern ocean, with an average salinity of about 34.7‰, the density of water is only very slightly affected by cooling as it approaches the freezing point. Consequently, salinization through sea-ice formation or evaporation is usually required to make water dense enough to sink into the ocean interior. At salinities above about 40‰ water continues to become more dense as it approaches the freezing point, and salinization is not required. The energy-consuming phase changes involved in sea-ice formation and evaporation would not be required for vertical circulation in the ocean. The hypothesized major declines in salinity correspond closely to the evolution of both planktonic foraminifera and calcareous nannoplankton. Both groups were restricted to shelf regions in the Jurassic and early Cretaceous, but spread into the open ocean in the mid-Cretaceous. Their availability to inhabit the open ocean may be directly related to the decline in salinity. The Permian extraction may have created stress for marine organisms and may have been a factor contributing to the end-Permian extinction. The modeling also suggests that there was a major salinity decline from the Late Precambrian to the Cambrian, and it is tempting to speculate that this may have been a factor in the Cambrian explosion of life

Quasar 3C 298: a test-case for meteoritic nanodiamond 3.5 µm emission

Aims. We calculate the dust emission expected at 3.43 and 3.53 µm if meteoritic (i.e. hydrogenated) nanodiamonds are responsible for most of the far-UV break observed in quasars. Methods. We integrate the UV flux that hydrogenated nanodiamonds must absorb to reproduce the far-UV break. Based on laboratory spectra of H-terminated diamond surfaces, we analyse the radiative energy budget and derive theoretically the IR emission profiles expected for possible C-H surface stretch modes of the diamonds. Results. Using as test case a spectrum of 3C 298 provided by the Spitzer Observatory, we do not find evidence of these emission bands. Conclusions. While diamonds without surface adsorbates remain a viable candidate for explaining the far-UV break observed in quasars, hydrogenated nanodiamonds appear to be ruled out, as they would give rise to IR emission bands, which have not been observed so far

Fruit quality in strawberry (Fragaria x ananassa Duch. cv. Korona) at three times during the season and with two fertilizer strategies

Effects on fruit quality of preplant fertilization and fertigation in strawberry were studied in a field experiment established August 2003 in South East Norway. Half the field was fertilized at planting and fertigated with a low nutrient rate from spring 2004 (T1), while the second half was unfertilized at planting but fertigated with a relatively high nutrient rate from spring 2004 (T2). Berries were harvested three times per week during the first harvesting year. Samples of berries from early season, mid season and late season were analysed for soluble solids, pH, titratable acidity, colour, vitamin C, antioxidant activity (FRAP) and mineral concentration. The results were correlated to leaf mineral concentration in dry matter. T1 gave larger and darker berries compared to T2. The other quality parameters and mineral content in strawberry fruits were not significantly influenced by the two fertilizer strategies. Soluble solids, pH, titratable acidity and colour varied significantly through the season, while vitamin C and antioxidant activity (FRAP) was unaffected by fertilizer treatment, berry size and time of season. The results gave a general view of the quality parameters in the strawberry cultivar ‘Korona’

New Equity Performance Following Chapter 11 Emergence

This body of research investigates how the performance of exchange-traded common equity from firms in Chapter 11 bankruptcy emergence compares with common stock from non-bankrupt competitors and recently public peers in short and long-term time horizons.  Return data are gathered for a sample of sixteen financially restructured companies, each paired with two non-distressed industry competitors and one recently-public peer.  Using the Capital Asset Pricing Model as a primary analytical tool, empirical tests show a positive correlation in equity returns among the samples of restructured and non-distressed market competitors and a stock underperformance from the sample of IPO competitors.  These results suggest that markets are better at judging the value of post-Chapter 11 companies relative to newly public companies and refute the theory of IPO price momentum