Interaction Between The MEC1-Dependent DNA Synthesis Checkpoint And G1 Cyclin Function In Saccharomyces Cerevisiae

The completion of DNA synthesis in yeast is monitored by a checkpoint that requires MEC1 and RAD53. Here we show that deletion of the Saccharomyces cerevisiae G1 cyclins CLN1 and CLN2 suppressed the essential requirement for MEC1 function. Wild-type levels of CLN1 and CLN2, or overexpression of CLN1, CLN2, or CLB5, but not CLN3, killed mec1 strains. We identified RNR1, which encodes a subunit of ribonucleotide reductase, as a high-copy suppressor of the lethality of mec1 GAL1-CLN1. Northern analysis demonstrated that RNR1 expression is reduced by CLN1 or CLN2 overexpression. Because limiting RNR1 expression would be expected to decrease dNTP pools, CLN1 and CLN2 may cause lethality in mec1 strains by causing initiation of DNA replication with inadequate dNTPs. In contrast to mec1 mutants, MEC1 strains with low dNTPs would be able to delay S phase and thereby remain viable. We propose that the essential function for MEC1 may be the same as its checkpoint function during hydroxyurea treatment, namely, to slow S phase when nucleotides are limiting. In a cln1 cln2 background, a prolonged period of expression of genes turned on at the G1-S border, such as RNR1, has been observed. Thus deletion of CLN1 and CLN2 could function similarly to overexpression of RNR1 in suppressing mec1 lethality

Mutations In RAD27 Define A Potential Link Between G₁ Cyclins And DNA Replication

The yeast Saccharomyces cerevisiae has three G1 cyclin (CLN) genes with overlapping functions. To analyze the functions of the various CLN genes, we examined mutations that result in lethality in conjunction with loss of cln1 and cln2. We have isolated alleles of RAD27/ERC11/YKL510, the yeast homolog of the gene encoding flap endonuclease 1, FEN-1.cln1 cln2 rad27/erc11 cells arrest in S phase; this cell cycle arrest is suppressed by the expression of CLN1 or CLN2 but not by that of CLN3 or the hyperactive CLN3-2. rad27/erc11 mutants are also defective in DNA damage repair, as determined by their increased sensitivity to a DNA-damaging agent, increased mitotic recombination rates, and increased spontaneous mutation rates. Unlike the block in cell cycle progression, these phenotypes are not suppressed by CLN1 or CLN2. CLN1 and CLN2 may activate an RAD27/ERC11-independent pathway specific for DNA synthesis that CLN3 is incapable of activating. Alternatively, CLN1 and CLN2 may be capable of overriding a checkpoint response which otherwise causes cln1 cln2 rad27/erc11 cells to arrest. These results imply that CLN1 and CLN2 have a role in the regulation of DNA replication. Consistent with this, GAL-CLN1 expression in checkpoint-deficient, mec1-1 mutant cells results in both cell death and increased chromosome loss among survivors, suggesting that CLN1 overexpression either activates defective DNA replication or leads to insensitivity to DNA damage

Building a health and environment geographical information system :an evaluation, looking at childhood cancer in Northern England

PhD ThesisThe aim of this research was to evaluate a relatively young technology, Geographical Information Systems (GIS), in a specific applications environment. The application adopted was that of searching for environmental causes of childhood cancer, in particular that of Acute Lymphoblastic Leukaemia (ALL), in Northern England. It is also relevant in terms of the WHO's intention to develop a Health and Environment GIS, and therefore the research aims to satisfy their recommendations for pilot studies. The subject matter of this thesis therefore covers two very high profile topics, which it is believed will mutually benefit from the research carried out. Firstly, very little is known about the aetiology of ALL, and thus any new methodology which is introduced to help analyse sensitive issues of causation is welcomed not only by those in the medical field but also the public. The application was made possible with the provision of detailed cancer data for Northern England and a weak but interesting hypothesis that environmental factors may be an attributable mechanism for causation. Key questions which are asked include; Where are incidences of ALL located? Why are they there? Is there a cluster? and What could be the cause? Secondly a Geographical Information System, in this case the proprietary software package ARC/INFO, was considered an excellent medium for tackling this spatial epidemiological problem. Especially with its capability to store large volumes of diverse data, and its inherent flexibility to deal with spatial information pertaining to health and environmental factors. More importantly the application itself offered a means of evaluating the implementation of a GIS. Establishing the advantages and pitfalls which accompany all stages of 'The GIS Process' and an invaluable documentation of the experiences acquired as an initiator, developer and implementor of this new technology. In addition, this research offers fresh ideas and techniques for improving those areas of the technology which appear to be lacking in these early phases of its development. The problems of spatial analysis in GIS and the provision of useful tools such as 'pattern spotters', 'relationship seekers' and 'error handlers' are discussed as alternative techniques. To ensure an exciting future for GIS technology in application environments the latter and other key areas of research which should be persued are highlighted in this thesis

Curating practical theological space : What is it, and who is it for?

Peer reviewe

The GCC pivot to Asia : the security of US interests in the Arabian Gulf

textThe Gulf Cooperation Council's pivot to Asia began as a slow process of economic integration in the early 2000s but significantly accelerated after the US Shale Revolution, beginning in 2008. As US production increased and imports from foreign oil suppliers declined, many expected the relationships between the US and its GCC partners to similarly decline. The emerging markets of Asia and rising demand from China captured GCC interest. The GCC nations took steps to diversify their markets away from the US. Economic cooperation morphed into budding diplomatic and strategic relationships between the GCC and China. Meanwhile, the US, no longer as reliant on GCC energy, restructured its foreign policy toward the GCC around defense cooperation and human rights. Though US-GCC relationships remained relatively strong, the uprisings of the Arab Spring resulted in mounting US criticism of GCC human rights violations, weakening US leverage in the region. The Chinese took advantage of US-GCC tension, offering an alternative model of diplomatic engagement-- ignoring human rights. Arab populations saw the economic rise of China as an alternative diplomatic model, one that prioritized economic development without attaching political strings to bilateral relationships. Some GCC nations also viewed Chinese influence as a potential foil to US influence in the region. Despite budding local support for stronger ties with China, the Chinese are not able to displace US influence in the Gulf yet because China is unable to provide the quality or quantity of defense sales and cooperation the US provides. In the long-term, though, Chinese policies will likely present a challenge to US influence in the Gulf. The US should reexamine its policies on human rights promotion and reevaluate its strategic interests to protect the short and long term interests of the US in a region of great geostrategic importance.Middle Eastern StudiesGlobal Policy Studie

SpC MS 1790 sc, Letters between Elizabeth Johnston Cross and Diana Forbes-Robertson

Two typewritten letters, one from Elizabeth Johnston Cross to Diana Forbes-Robertson and visa versa. Mrs. Cross is recalling a meeting on ship from Europe to the United States and the continuing friendship between her father, James Wright Johnston, and Diana Forbes-Robertson\u27s mother, Gertrude Elliott, later Lady Forbes-Robertson.https://digitalcommons.library.umaine.edu/manuscripts_20th_century/1000/thumbnail.jp

Music Score Approval Plans in Research Libraries: A Survey of Librarian Satisfaction With and Without Approval Plans

In this study, the researchers submitted a music score approval plan survey to all ARL libraries. Two surveys were created, one for libraries with music score approval plans, one for those without. Forty-four surveys were returned. The authors’ purpose was to analyze and discuss the survey results, incorporating elements of the scholarly work preceding this study. Discussions, roundtables, and listservs participated in by music librarians over the years formed the basis of the topic at hand. The goal was to ascertain whether these discussions and underlying assumptions of approval plans held true to the real world

Using new and innovative technologies to assess clinical stage in early intervention youth mental health services: Evaluation study

Background: Globally there is increasing recognition that new strategies are required to reduce disability due to common mental health problems. As 75% of mental health and substance use disorders emerge during the teenage or early adulthood years, these strategies need to be readily accessible to young people. When considering how to provide such services at scale, new and innovative technologies show promise in augmenting traditional clinic-based services. Objective: The aim of this study was to test new and innovative technologies to assess clinical stage in early intervention youth mental health services using a prototypic online system known as the Mental Health eClinic (MHeC). Methods: The online assessment within the MHeC was compared directly against traditional clinician assessment within 2 Sydney-based youth-specific mental health services (headspace Camperdown and headspace Campbelltown). A total of 204 young people were recruited to the study. Eligible participants completed both face-to-face and online assessments, which were randomly allocated and counterbalanced at a 1-to-3 ratio. These assessments were (1) a traditional 45- to 60-minute headspace face-to-face assessment performed by a Youth Access Clinician and (2) an approximate 60-minute online assessment (including a self-report Web-based survey, immediate dashboard of results, and a video visit with a clinician). All assessments were completed within a 2-week timeframe from initial presentation. Results: Of the 72 participants who completed the study, 71% (51/72) were female and the mean age was 20.4 years (aged 16 to 25 years); 68% (49/72) of participants were recruited from headspace Camperdown and the remaining 32% (23/72) from headspace Campbelltown. Interrater agreement of participants’ stage, as determined after face-to-face assessment or online assessment, demonstrated fair agreement (kappa=.39, P\u3c.001) with concordance in 68% of cases (49/72). Among the discordant cases, those who were allocated to a higher stage by online raters were more likely to report a past history of mental health disorders (P=.001), previous suicide planning (P=.002), and current cannabis misuse (P=.03) compared to those allocated to a lower stage. Conclusions: The MHeC presents a new and innovative method for determining key clinical service parameters. It has the potential to be adapted to varied settings in which young people are connected with traditional clinical services and assist in providing the right care at the right tim

Developing Justice-Oriented Teachers: Personal Transformation through Relationships

The teacher preparation program in a Jesuit liberal arts college prepares future teachers to identify and actively confront inequities in society. Empowering teachers to carry justice-oriented teaching into schools rests on strong relationships among peers and professors on campus, and with students and families from diverse communities in university neighborhoods. The rationale and approach to fostering relationships focuses this first of three essays in Jesuit Higher Education. Future essays will provide practical examples of action in service and reflection in preparing justice-oriented teachers