A study into the conserved nature of yeast and mammalian transcription factors

The study of transcriptional regulation in mammalian cells has led to the identification of a large number of DNA binding transcription factors. Two such activities have been called ATF and AP1. The DNA sequence to which ATF binds to has been shown to mediate transcriptional activation by E1A and cAMP. On the other hand the AP1 binding site has been shown to mediate transcriptional activation by phorbol esters such as TPA. The consensus sequences of these two functional elements differ by only a single nucleotide but this difference is critical in determining specific transcription factor interaction. Previous studies have also defined sequence specific DNA binding proteins which can mediate transcriptional activation in S.cerevisiae. In this thesis I show that there are transcription factors in two yeast systems, that of S.cerevisiae and S.pombe, which have identical DNA binding specificities to the mammalian ATF and AP1 proteins. I have designated these proteins yATF and yAP1. In addition I show that viral promoters which contain binding sites for these transcription factors are expressed in S.pombe utililising transcriptional start sites also used in mammalian cells. By placing ATF and AP1 binding sites upstream of basal promoters I have demonstrated that S.pombe yAP1 and S.cerevisae yATF are most likely transcriptional activators. I have also shown that both the afore mentioned proteins are sensitive to phosphatase treatment indicating they are themselves phosphoproteins, a property which they would share with their mammalian counterparts. I have purified S.cerevisiae yAP1 and identified it as a major species of 85kd. In addition I have obtained a clone for a fission yeast protein which preferentially recognises an ATF site to an AP1 site by using a λgt11 expression library binding site screen. This work has provided the first demonstration of a fission yeast transcription factor. In addition it has shown a remarkable conservation in the DNA binding specificities of yeast and mammalian transcription factors. Together with the parallel developments which have taken place in this field this indicates that certain fundamental properties of the transcriptional machinery have been conserved throughout eukaryotes

Status of the profession

The number of astronomers has grown by about 40 percent over the past decade. The number of astronomers with jobs in industry, or with long-term, non-tenured, jobs has increased dramatically compared with traditional faculty positions. The increase in the number of astronomers and the declining share of the NSF budget going to astronomy has led to extreme difficulties in the NSF grant program and in support of the National Observatories. In 1989, direct NASA support of astronomers through the grants program exceeds that of NSF, although the total of the NSF grants program over decade far exceeds that of NASA. Access to major new telescopes will be important issue for the 1990s. US astronomers, who once had a monopoly on telescopes larger than 3 meters, will, by the year 2000, have access to just half of the world's optical telescope area

Obituary: J. Knox Jones, Jr., 1929-1992

J. Knox Jones, Jr., was born in Lincoln, Nebraska, March 16, 1929, the eldest of the three sons of Virginia Bowen Jones and James Knox Jones. Knox passed away at his home in Lubbock, Texas, on November 15, 1992, after a two-year battle with cancer

The Role of the Private Sector in Supporting Malaria Control in Resource Development Settings.

Industrial operations of the private sector, such as extraction, agriculture, and construction, can bring large numbers of people into new settlement areas and cause environmental change that promotes the transmission of vector-borne diseases. Industry-related workers and communities unduly exposed to infection risk typically lack the knowledge and means to protect themselves. However, there is a strong business rationale for protecting local resident employees through integrated vector control programs, as well as an ethical responsibility to care for these individuals and the affected communities. We discuss the role and challenges of the private sector in developing malaria control programs, which can include extensive collaborations with the public sector that go on to form the basis of national vector control programs or more broadly support local healthcare systems

The effectiveness of anti-stigma interventions for reducing mental health stigma in young people: A systematic review and meta-analysis

Experiencing mental health stigma during adolescence can exacerbate mental health conditions, reduce quality of life and inhibit young people’s help-seeking for their mental health needs. For young people, education and contact have most often been viewed as suitable approaches for stigma reduction. However, evidence on the effectiveness of these anti-stigma interventions has not been consistent. This systematic review evaluated the effectiveness of interventions to reduce mental health stigma among youth aged 10–19 years. The review followed Cochrane and PRISMA guidelines. Eight databases were searched: PubMed, PsycINFO, MEDLINE, Web of Science, Scopus, EMBASE, British Education Index and CNKI. Hand searching from included studies was also conducted. Randomised controlled trials and experimental designs that included randomised allocation to interventions and control groups were included in the review. Narrative synthesis was employed to analyse the results. A meta-analysis was conducted to determine the effectiveness of included interventions. Twenty-two studies were included in the review. Eight studies reported positive effects, 11 studies found mixed effects and 3 studies reported no effect on indicators of mental health stigma among youth. Seven of the effective studies were education-based. Eleven studies were suitable for meta-analysis, and the multivariate meta-analytic model indicated a small, significant effect at post-intervention (d = .21, p < .001), but not at follow-up (d = .069, p = .347). Interventions to reduce stigma associated with mental health conditions showed small, short-term effects in young people. Education-based interventions showed relatively more significant effects than other types of interventions

Impact of Allergic Reactions on Food-Specific IgE Concentrations and Skin Test Results

Although there is concern that food allergic reactions may negatively affect the natural history of food allergy, the impact of reactions on food-specific IgE (sIgE) or skin prick tests is unknown

Detection of Planetary and Stellar Companions to Neighboring Stars via a Combination of Radial Velocity and Direct Imaging Techniques

13 pages, 6 figures, 4 tables, accepted for publication in the Astronomical Journal (submitted 25 Feb 2019; accepted 28 April 2019). Machine readable tables and Posteriors from the RadVel fits are available here: http://stephenkane.net/rvfits.tarThe sensitivities of radial velocity (RV) surveys for exoplanet detection are extending to increasingly longer orbital periods, where companions with periods of several years are now being regularly discovered. Companions with orbital periods that exceed the duration of the survey manifest in the data as an incomplete orbit or linear trend, a feature that can either present as the sole detectable companion to the host star, or as an additional signal overlain on the signatures of previously discovered companion(s). A diagnostic that can confirm or constrain scenarios in which the trend is caused by an unseen stellar rather than planetary companion is the use of high-contrast imaging observations. Here, we present RV data from the Anglo-Australian Planet Search (AAPS) for 20 stars that show evidence of orbiting companions. Of these, six companions have resolved orbits, with three that lie in the planetary regime. Two of these (HD 92987b and HD 221420b) are new discoveries. Follow-up observations using the Differential Speckle Survey Instrument (DSSI) on the Gemini South telescope revealed that 5 of the 20 monitored companions are likely stellar in nature. We use the sensitivity of the AAPS and DSSI data to place constraints on the mass of the companions for the remaining systems. Our analysis shows that a planetary-mass companion provides the most likely self-consistent explanation of the data for many of the remaining systems.Peer reviewedFinal Accepted Versio

Early-life gut microbiome composition and milk allergy resolution

Gut microbiota may play a role in the natural history of cow’s milk allerg

Evaluation and Treatment in Urology for Nocturia Caused by Nonurological Mechanisms:Guidance from the PLANET Study

Patients with nocturia are commonly referred to urology clinics, including many for whom a nonurological medical condition is responsible for their symptoms. The PLanning Appropriate Nocturia Evaluation and Treatment (PLANET) study was established to develop practical approaches to equip healthcare practitioners to deal with the diverse causes of nocturia, based on systematic reviews and expert consensus. Initial assessment and therapy need to consider the possibility of one or more medical conditions falling into the “SCREeN” areas of Sleep medicine (insomnia, periodic limb movements of sleep, parasomnias, and obstructive sleep apnoea), Cardiovascular (hypertension and congestive heart failure), Renal (chronic kidney disease), Endocrine (diabetes mellitus, thyroid disease, pregnancy/menopause, and diabetes insipidus), and Neurology. Medical and medication causes of xerostomia should also be considered. Some key indicators for these conditions can be identified in urology clinics, working in partnership with the primary care provider. Therapy of the medical condition in some circumstances lessens the severity of nocturia. However, in many cases there is a conflict between the two, in which case the medical condition generally takes priority on safety grounds. It is important to provide patients with a realistic expectation of therapy and awareness of limitations of current therapeutic options for nocturia.Patient summaryNocturia is the symptom of waking at night to pass urine. Commonly, this problem is referred to urology clinics. However, in some cases, the patient does not have a urological condition but actually a condition from a different speciality of medicine. This article describes how best the urologist and the primary care doctor can work together to assess the situation and make sensible and safe treatment suggestions. Unfortunately, there is sometimes no safe or effective treatment choice for nocturia, and treatment needs to focus instead on supportive management of symptoms

A Super-Earth and Two Neptunes Orbiting the Nearby Sun-like Star 61 Virginis

We present precision radial velocity data that reveal a multiple exoplanet system orbiting the bright nearby G5V star 61 Virginis. Our 4.6 years of combined Keck/HIRES and Anglo-Australian Telescope precision radial velocities indicate the hitherto unknown presence of at least three planets orbiting this well-studied star. These planets are all on low-eccentricity orbits with periods of 4.2, 38.0, and 124.0 days, and projected masses (Msin i) of 5.1, 18.2, and 24.0 M_⊕, respectively. Test integrations of systems consistent with the radial velocity data suggest that the configuration is dynamically stable. Depending on the effectiveness of tidal dissipation within the inner planet, the inner two planets may have evolved into an eccentricity fixed-point configuration in which the apsidal lines of all three planets corotate. This conjecture can be tested with additional observations. We present a 16-year time series of photometric observations of 61 Virginis, which comprise 1194 individual measurements, and indicate that it has excellent photometric stability. No significant photometric variations at the periods of the proposed planets have been detected. This new system is the first known example of a G-type Sun-like star hosting a Super-Earth mass planet. It joins HD 75732 (55 Cnc), HD 69830, GJ 581, HD 40307, and GJ 876 in a growing group of exoplanet systems that have multiple planets orbiting with periods less than an Earth-year. The ubiquity of such systems portends that space-based transit-search missions such as Kepler and CoRoT will find many multi-transiting systems