Global Functional Atlas of \u3cem\u3eEscherichia coli\u3c/em\u3e Encompassing Previously Uncharacterized Proteins

One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans’ biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a “systems-wide” functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins

Women’s Sexual Fantasies in Context: The Emotional Content of Sexual Fantasies, Psychological and Interpersonal Distress, and Satisfaction in Romantic Relationships

Background: Psychoanalytic thinkers propose that aspects of an individual’s sexual fantasies are related to her psychological and interpersonal functioning. The present study aims to elucidate the significance of sexual fantasies with respect to women’s emotional and interpersonal lives. The study evaluated a model, which hypothesized that internal representations of self and others (e.g. attachment security, maturity of object relations) along with psychological and interpersonal factors would predict both the emotional content (guilt, fear, affection) of written sexual fantasy narratives, and overall romantic satisfaction in heterosexual women. Methods: Five hundred and thirty four women completed self-report questionnaires online. Subsequently, the sexual fantasies of 20 women (10 with higher levels of psychological and interpersonal distress, 10 with lower levels of psychological and interpersonal distress) were qualitatively examined and compared with respect to differences in their emotional and thematic content. Results: The hypotheses were partially supported: women with more attachment anxiety, as well as more psychological symptoms and interpersonal difficulties, had more negative emotional reactions to their fantasies, were less satisfied with their current romantic relationship and reported less frequent sexual activity and orgasm with their current partner. Confirmatory factor analyses lead to revisions of the theoretical model. Respecification of the study model found that psychological and interpersonal distress mediated the relationship between negative emotional reactivity to sexual fantasy and lower romantic satisfaction, and between negative emotional reactivity to fantasy and less frequent sexual activity with current partner. Conclusions: Current findings suggest links between women’s negative emotional reactivity to their sexual fantasies and lower satisfaction with both the emotional and sexual components of their current romantic relationship. The mediation model suggests that this relationship is explained by each of these factors association with psychological and interpersonal distress

The Utilisation of Craniomaxillofacial Radiology in Preventative Medicine

This thesis discusses the importance of the maximal utilisation of dental, maxillofacial and antenatal craniofacial imaging in preventative healthcare. Many craniomaxillofacial imaging techniques can provide added diagnostic information which assist in the diagnosis of conditions other than those that the study was performed to investigate. The first publication describes use of panoramic dental radiographs in the assessment of stroke risk in the individual patient. The second publication discusses the uses and limitations of panoramic dental radiographs in the evaluation of maxillary sinus disease. The final three articles establish the normal fetal cephalic index, and its value in the antenatal detection of sagittal craniosynostosis. The results of these studies will assist dental and medical professionals in the appropriate investigation and management of patients with carotid artery calcification detected incidentally on orthopantomograms, and the selection of the most suitable imaging studies to evaluate the maxillary sinuses. The antenatal diagnosis of sagittal craniosynostosis can provide valuable information to the expectant mother and her obstetrician with regards to delivery options and choices where there is an increased risk of obstructed labour that could injure mother, child or both. The full utilisation of these imaging studies will provide an increased clinical benefit to the patient and referrer, and can benefit the population as a whole by assisting with preserving the health of the community and managing spiralling healthcare costs. Craniomaxillofacial Radiology Declaration Declaration I, Sarah Christine Constantine, certify that this work contains no material which has been accepted for the award of any other degree or diploma in my name, in any university or other tertiary institution and, to the best of my knowledge and belief, contains no material previously published or written by another person, except where due reference has been made in the text. In addition, I certify that no part of this work will, in the future, be used in a submission in my name, for any other degree or diploma in any university or other tertiary institution without the prior approval of the University of Adelaide and where applicable, any partner institution responsible for the joint-award of this degree. I acknowledge that copyright of published works contained within this thesis resides with the copyright holder(s) of those works. I also give permission for the digital version of my thesis to be made available on the web, via the University’s digital research repository, the Library Search and also through web search engines, unless permission has been granted by the University to restrict access for a period of time. I acknowledge the support I have received for my research through the provision of an Australian Government Research Training Program Scholarship.Thesis (Ph.D.) -- University of Adelaide, Adelaide Dental School, 201

High intensity interval training improves liver and adipose tissue insulin sensitivity

Objective: Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods: In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results: HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC

The Confluence of Stereotactic Ablative Radiotherapy and Tumor Immunology

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses

Earlier post-operative hypocortisolemia may predict durable remission from Cushings disease.

CONTEXT: Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushings disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. OBJECTIVE: We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. METHODS: A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 μg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. RESULTS: Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 μg/dL and 6% of cases with cortisol nadir ≤2 μg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 μg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 μg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. CONCLUSIONS: In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ≤2 µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term

Book Reviews

Reviews of the following books: The Long Argument: English Puritanism and the Shaping of New England Culture, 1570-1700 by Stephen Foster; The Salem Witch Crisis by Larry Gragg; A Home for Everyman: The Greek Revival and Maine Domestic Architecture by Joyce K. Bibber; The Gunpowder Mills of Maine by Maurice W. Hitten; In the Hands of Providence: Joshua L. Chamberlain And The American Civil War by Alice Rains Trulock; Hurricane Island: The Town That Disappeared by Eleanor Motley Richardson; Home Front On Penobscot Bay: Rockland During The War Years, 1940-1945by Paul G. Merriam, Thomas J. Molloy, and Theodore W. Sylvester, Jr.; The History of Broadcasting in Maine: The First Fifty Yearsby Ellie Thompson; New Compass Points by Roy P. Fairfiel